Patent Application
20150105386
The present invention relates to novel 4-(4-pyridyl)-benzamides. The compounds possess valuable therapeutic properties and are suitable, in particular, for treating diseases that respond to modulation of Rho kinases (ROCKs).
An important large family of enzymes is the protein kinase enzyme family. Currently, there are about 500 different known protein kinases. Protein kinases serve to catalyze the phosphorylation of an amino acid side chain in various proteins by the transfer of the y-phosphate of the ATP-Mg2+ complex to said amino acid side chain.
These enzymes control the majority of the signalling processes inside cells, thereby governing cell function, growth, differentiation and destruction (apoptosis) through reversible phosphorylation of the hydroxyl groups of serine, threonine and tyrosine residues in proteins. Studies have shown that protein kinases are key regulators of many cell functions, including signal transduction, transcriptional regulation, cell motility, and cell division. Several oncogenes have also been shown to encode protein kinases, suggesting that kinases play a role in oncogenesis. These processes are highly regulated, often by complex intermeshed pathways where each kinase will itself be regulated by one or more kinases. Consequently, aberrant or inappropriate protein kinase activity can contribute to the rise of disease states associated with such aberrant kinase activity. Due to their physiological relevance, variety and ubiquitousness, protein kinases have become one of the most important and widely studied families of enzymes in biochemical and medical research.
The protein kinase family of enzymes is typically classified into two main subfamilies: Protein Tyrosine Kinases and Protein SerineThreonine Kinases, based on the amino acid residue they phosphorylate. The serinethreonine kinases (PSTK), includes cyclic AMP- and cyclic GMP-dependent protein kinases, calcium- and phospholipid-dependent protein kinase, calcium- and calmodulin-dependent protein kinases, casein kinases, cell division cycle protein kinases and others. These kinases are usually cytoplasmic or associated with the particulate fractions of cells, possibly by anchoring proteins. Aberrant protein serinethreonine kinase activity has been implicated or is suspected in a number of pathologies such as rheumatoid arthritis, psoriasis, septic shock, bone loss, many cancers and other proliferative diseases.
Accordingly, serinethreonine kinases and the signal transduction pathways which they are part of are important targets for drug design. The tyrosine kinases phosphorylate tyrosine residues. Tyrosine kinases play an equally important role in cell regulation. These kinases include several receptors for molecules such as growth factors and hormones, including epidermal growth factor receptor, insulin receptor, platelet derived growth factor receptor and others. Studies have indicated that many tyrosine kinases are transmembrane proteins with their receptor domains located on the outside of the cell and their kinase domains on the inside. Much work is also under progress to identify modulators of tyrosine kinases as well.
A major signal transduction systems utilized by cells is the RhoA-signalling pathways. RhoA is a small GTP binding protein that can be activated by several extracellular stimuli such as growth factor, hormones, mechanic stress, osmotic change as well as high concentration of metabolite like glucose. RhoA activation involves GTP binding, conformation alteration, post-translational modification (geranylization and farnesylation) and activation of its intrinsic GTPase activity. Activated RhoA is capable of interacting with several effector proteins including ROCKs (Rho kinase) and transmit signals into cellular cytoplasm and nucleus.
Rho kinase is found in two isoforms encoded by two different genes of ROCK, ROCK 1 (also known as ROCKβ or p160-ROCK) and ROCK 2 (also known as ROCKα). Both ROCK 1 and ROCK 2 contain an amino-terminal catalytic kinase domain, a central coiled-coil domain of about 600 amino acids, and a carboxyl-terminal pleckstrin homology (PH) domain that is split by a cysteine-rich region. RhoGTP interacts with the Cterminal portion of the central coiled-coil domain and activates the kinase activity of ROCK.
Thus, ROCK1 and 2 constitute a family of serinethreonine kinases that can be activated by RhoA-GTP complex via physical association. Activated ROCKs phosphorylate a number of substrates and play important roles in pivotal cellular functions. The substrates for ROCKs include myosin binding subunit of myosin light chain phosphatase (MBS, also named MYPT1), adducin, moesin, myosin light chain (MLC), LIM kinase as well as transcription factor FHL. The phosphorylation of theses substrates modulate the biological activity of the proteins and thus provide a means to alter cell's response to external stimuli. One well documented example is the participation of ROCK in smooth muscle contraction. Upon stimulation by phenylephrine, smooth muscle from blood vessels contracts. Studies have shown that phenylephrine stimulates alpha-adrenergic receptors and leads to the activation of RhoA. Activated RhoA in turn stimulates kinase activity of ROCK1 and which in turn phosphorylates MBS. Such phosphorylation inhibits the enzyme activity of myosin light chain phosphatase and increases the phosphorylation of myosin light chain itself by a calcium-dependent myosin light chain kinase (MLCK) and consequently increases the contractility of myosin-actin bundle, leading to smooth muscle contraction. This phenomenon is also sometimes called calcium sensitization. In addition to smooth muscle contraction, ROCKs have also been shown to be involved in cellular functions including apoptosis, cell migration, transcriptional activation, fibrosis, cytokinesis, inflammation and cell proliferation. Moreover, in neurons ROCK plays a critical role in the inhibition of axonal growth by myelin-associated inhibitory factors such as myelin-associated glycoprotein (MAG). ROCK-activity also mediates the collapse of growth cones in developing neurons. Both processes are thought to be mediated by ROCK-induced phosphorylation of substrates such as LIM kinase and myosin light chain phosphatase, resulting in increased contractility of the neuronal actin-myosin system.
Abnormal activation of the RhoROCK pathway has been observed in various disorders (1Wettschureck, N., Offermanns, S., RhoRho-kinase mediated signaling in physiology and pathophysiology. J. Mol. Med. 80, 2002, 629-638; 2Müller, B. K., Mack, H., Teusch, N., Rho kinase, a promising drug target for neurological discorders. Nat. Drug Discov. Rev. 4, 2005, 387-398; 3Hu, E, Lee, D., ROCK inhibitors as potential therapeutic agents for cardiovascular diseases. Curr. Opin. Investig. Drugs. 4, 2003, 1065-1075). As already mentioned, ROCKs phosphorylate the myosin binding subunit of myosin light chain (MLC) phosphatase (MLCP), resulting in increased myosin phosphorylation and actin-myosin contraction (Somlyo, A. P., Somlyo, A. V., Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol. Rev. 83, 2003, 1325-1358). Examples of disease states related with abnormal RhoROCK activity, in particular with vasospasm activity, include cardiovascular diseases such as hypertension (9Satoh S., Kreutz R., Wilm C., Ganten D., Pfitzer G., Augmented agonist-induced Ca2+-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells. J. Clin. Invest. 94, 1994, 1397-1403; 10Mukai, Y., Shimokawa, H., Matoba, T., Kandabashi, T., Satoh, S., Hiroki, J., Kaibuchi, K., Takeshita, A., Involvement of Rho-kinase in hypertensive vascular disease: a novel therapeutic target in hypertension. FASEB J. 15, 2001, 1062-1064; 11Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M., Narumiya, S., Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389, 1997, 990-994; 12Masumoto, A., Hirooka, Y., Shimokawa, H., Hironaga, K., Setoguchi, S., Takeshita, A., Possible involvement of Rhokinase in the pathogenesis of hypertension in humans. Hypertension 38, 2001, 1307-1310), chronic and congestive heart failure (18Fuster, V., Badimon, L., Badimon, J J, Chesebro, J H, The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 326, 1992, 310-318; 19Shimokawa, H., Cellular and molecular mechanisms of coronary artery spasm: lessons from animal models. Jpn Circ J 64, 2000, 1-12; 20Shimokawa, H., Morishige, K., Miyata, K., Kandabashi, T., Eto, Y., Ikegaki, I., Asano, T., Kaibuchi, K., Takeshita, A., Longterm inhibition of Rho-kinase induces a regression of arteriosclerotic coronary lesions in a porcine model in vivo. Cardiovasc Res 51, 2001, 169-177; 21Utsunomiya, T., Satoh, S., Ikegaki, I., Toshima, Y., Asano, T., Shimokawa, H., Antianginal effects of hydroxyfasudil, a Rho-kinase inhibitor, in a canine model of effort angina. Br J Pharmacol 134, 201, 1724-1730), cardiac hypertrophy (40Hoshijima, M., Sah, V. P., Wang, Y., Chien, K. R., Brown, J. H., The low molecular weight GTPase Rho regulates myofibril formation and organization in neonatal rat ventricular myocytes. Involvement of Rho kinase. J Biol Chem 273, 1998, 7725-77230; 41Sah, V. P., Hoshijima, M., Chien, K. R., Brown, J. H., Rho is required for Galphaq and alpha1-adrenergic receptor signal-637 ing in cardiomyocytes. Dissociation of Ras and Rho pathways. J Biol Chem 271, 1996, 31185-1190; 42Kuwahara, K., Saito, Y., Nakagawa, O., Kishimoto, I., Harada, M., Ogawa, E., Miyamoto, Y., Hamanaka, I., Kajiyama, N., Takahashi, N., Izumi, T., Kawakami, R., Tamura, N., Ogawa, Y., Nakao, K., The effects of the selective ROCK inhibitor, Y27632, on ET-1-induced hypertrophic response in neonatal rat cardiacmyocytes-possible involvement of Rho/ROCK pathway in cardiac muscle cell hypertrophy. FEBS Lett 452, 1999, 314-318), chronic renal failure (7Sharpe, C. C., Hendry, B., M. Signaling: focus on Rho in renal disease. J. Am. Soc. Nephrol. 14, 2003, 261-264), cerebral vasospasm after subarachnoid bleeding (13Shibuya, M., Suzuki, Y., Sugita, K., Saito, I., Sasaki, T., Takakura, K., Okamoto, S., Kikuchi, H., Takemae, T., Hidaka, H., Dose escalation trial of a novel calcium antagonist, AT877, in patients 636 with aneurysmal subarachnoid haemorrhage. Acta Neurochir (Wien) 107, 1990, 11-15; 14Shibuya, M., Suzuki, Y., Sugita, K., Saito, I., Sasaki, T., Takakura, K., Nagata, I., Kikuchi, H., Takemae, T., Hidaka, H., et. al, Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial. J Neurosurg 76, 1992, 571-577; 15Sato, M., Tani, E., Fujikawa, H., Kaibuchi, K., Involvement of Rhokinase-mediated phosphorylation of myosin light chain in enhancement of cerebral vasospasm. Circ Res 87, 2000, 195-200; 16Miyagi, Y., Carpenter, R. C., Meguro, T., Parent, A. D., Zhang, J. H., Upregulation of rho A and rho kinase messenger RNAs in the basilar artery of a rat model of subarachnoid hemorrhage. J Neurosurg 93, 2000, 471-476; 17Tachibana, E., Harada, T., Shibuya, M. Saito, K., Takayasu, M., Suzuki, Y., Yoshida, J., Intra-arterial infusion of fasudil hydrochloride for treating vasospasm following subarachnoid haemorrhage. Acta Neurochir (Wien) 141, 1999, 13-19), pulmonary hypertension (5Sylvester, J. T., The tone of pulmonary smooth muscle: ROK and Rho music? Am. J. Physiol. Lung Cell. Mol. Physiol. 287, 2004, L624-L630) and ocular hypertension (34Honjo, M., Inatani, M., Kido, N., Sawamura, T., Yue, B. Y., Honda, Y., Tanihara H., Effects of protein kinase inhibitor, HA1077, on intraocular pressure and outflow facility in rabbit eyes. Arch Ophthalmol 119, 2001, 1171-1178; 35Rao, P. V, Deng, P. F., Kumar, J. Epstein, D. L., Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y-27632. Invest Ophthalmol V is Sci 42, 2001, 1029-1037). Further diseases related to abnormal RhoROCK activity are cancer (6Aznar, S., Fernandez-Valeron, P., Espina, C., Lacal, J. C., Rho GTPases: potential candidates for anticancer therapy. Cancer Lett. 206, 2004, 181-191; 43Yin, L. et al., Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro and in vivo. Mol Cancer Ther 5, 2007, 1517-25; 44Itoh, K., Yoshioka, K., Akedo, H., Uehata, M., Ishizaki, T., Narumiya, S., An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. Nat Med 5, 1999, 221-225; 45Genda, T. Sakamoto, M., Ichida, T., Asakura, H., Kojiro, M., Narumiya, S., Hirohashi, S., Cell motility mediated by rho and Rho-associated protein kinase plays a critical role inintrahepatic metastasis of human hepatocellular carcinoma. Hepatology 30, 1999, 1027-1036; 46Somlyo, A. V., Bradshaw, D., Ramos, S., Murphy, C., Myers, C. E., Somlyo, A. P., Rho-kinase inhibitor retards migration and in vivo dissemination of human prostate cancer cells. Biochem Biophys Res Commun 269, 2000, 652-659), asthma (24Roberts, J. A., Raeburn, D., Rodger, I. W., Thomson, N. C., Comparison of in vivo airway responsiveness and in vitro smooth muscle sensitivity to methacholine in man. Thorax 39; 1984, 837-843; 25Chiba, Y., Misawa, M., Characteristics of muscarinic cholinoceptors in airways of antigen-induced airway hyperresponsive rats. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 111, 1995, 351-357; 26Chiba, Y., Takada, Y., Miyamoto, S., MitsuiSaito, M., Karaki, H., Misawa, M., Augmented acetylcholine-induced, Rho mediated Ca2+ sensitization of bronchial smooth muscle contraction in antigen-induced airway hyperresponsive rats. Br J Pharmacol 127, 1999, 597-600; 27Chiba, Y., Sakai, H. Misawa, M., Augmented acetylcholine-induced translocation of RhoA in bronchial smooth muscle from antigen-induced airway hyperresponsive rats. BrJ Pharmacol 133, 2001, 886-890; 28lizuka, K., Shimizu, Y., Tsukagoshi, H., Yoshii, A., Harada, T. Dobashi, K., Murozono, T., Nakazawa, T., Mori, M., Evaluation of Y-27632, a rho-kinase inhibitor, as a bronchodilator in guinea pigs. Eur J Pharmacol 406, 2000, 273-279), male erectile dysfunctions (8Andersson, K. E., Hedlund, P., New directions for erectile dysfunction therapies. Int. J. Impot. Res. 14 (Suppl. 1), 2002, S82-S92; 32Chitaley, K., Wingard, C. J., Clinton Webb, R., Branam, H., Stopper, V. S., Lewis, R. W., Mills, T. M., Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxideindependent pathway. Nat Med 7, 2001, 119-122; 33 Mills, T. M., Chitaley, K., Wingard, C. J., Lewis, R. W., Webb, R. C., Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation. J Appl Physiol 91, 2001, 1269-1273), female sexual dysfunction, over-active bladder syndrome (64Peters, S. L. et al., Rho kinase: a target for treating urinary bladder dysfunction? Trends Pharmacol Sci. 27, 2006, 492-7) and preterm labor (29Niiro, N., Nishimura, J., Sakihara, C., Nakano, H., Kanaide, H., Up-regulation of rho A and rho-kinase mRNAs in the rat myometrium during pregnancy. Biochem Biophys Res Commun 230, 1997, 356-359; 30Tahara, M., Morishige, K., Sawada, K., Ikebuchi, Y., Kawagishi, R., Tasaka, K., Murata, Y., RhoARho-kinase cascade is involved in oxytocin-induced rat uterine contraction. Endocrinology 143, 2002, 920-929; 31Kupittayanant, S., Burdyga, T., Wray, S., The effects of inhibiting Rho-associated kinase with Y-27632 on force and intracellular calcium in human myometrium. Pflugers Arch. 443, 2001, 112-114).
Inhibitors of ROCKs have been suggested for use in the treatments of a variety of diseases. They include cardiovascular diseases such as hypertension (see above 9-12), chronic and congestive heart failure18-21, and cardiac hypertrophy40-42, chronic renal failure7, furthermore cerebral vasospasm after subarachnoid bleeding13-17, pulmonary hypertension5 and ocular hypertension34, 35. In addition, because of their muscle relaxing properties, they are also suitable for asthma24-28, male erectile dysfunctions8, 32, 33, female sexual dysfunction and over-active bladder syndrome and preterm labor29-31. Several recent studies have reported the beneficial effects of ROCK inhibitors in ischemia—reperfusion and myocardial infarction. In these studies, the ROCK inhibitors Y-27632 and fasudil were shown to decrease ischemiareperfusion injury, myocardial infarct size, and myocardial fibrosis in response to experimental myocardial infarction (MI) and in a rat model of chronic hypertension induced congestive heart failure (see above 18-21 and 22Masumoto, A., Mohri, M., Shimokaw, a H., Urakami, L., Usui, M., Takeshita, A., Suppression of coronary artery spasm by the rho-kinase inhibitor fasudil in patients with vasospastic angina. Circulation 105, 2002, 1545-1547; 23Shimokawa, H., linuma, H., Kishida, H., et al., Antianginal effect of fasudil, a Rho-kinase inhibitor, in patients with stable effort angina: a multicenter study (abstract). Circulation 104 [Suppl II], 2001, 11691; 36Morishige K, Shimokawa H, Eto Y, Kandabashi T, Miyata K, Matsumoto Y, Hoshijima M, Kaibuchi K, Takeshita A, Adenovirus-mediated transfer of dominant-negative rho-kinase induces a regression of coronary arteriosclerosis in pigs in vivo. Arterioscler Thromb Vasc Biol 21, 2001, 548-554; 37Kandabashi T, Shimokawa H, Mukai Y, Matoba T, Kunihiro I, Morikawa K, Ito M, Takahashi S, Kaibuchi K, Takeshita A, Involvement of rho-kinase in agonists-induced contractions of arteriosclerotic human arteries. Arterioscler Thromb Vasc Biol 22, 2002, 243-248; 38Liu M W, Roubin G S, King SB 3rd, Restenosis after coronary angioplasty. Potential biologic determinants and role of intimal hyperplasia. Circulation 79, 1989, 1374-1387; 39Shibata R, Kai H, Seki Y, Kato S, Morimatsu M, Kaibuchi K, Imaizumi T, Role of Rho-associated kinase in neointima formation after vascular injury. Circulation 103, 2001, 284-289).
Additionally, ROCKs can interact with other signalling pathways resulting in inhibition of phosphoinositide-3 kinase (PI-3K), endothelial nitric oxide synthase (eNOS) pathways, and activation of plasminogen activator inhibitor-1 (PAI-1) which may contribute to endothelial dysfunction like restenosis and atherosclerosis. Thus ROCK inhibitors have been suggested for the treatment of restenosis and atherosclerosis (see above38-39 and Iwasaki, H. et al., High glucose induces plasminogen activator inhibitor-1 expression through Rho/Rho-kinase-mediated NF-kappaB activation in bovine aortic endothelial cells. Atherosclerosis, 2007, Jan 31).
Vascular intimal thickening in vein grafts after surgery is the major cause of late graft failure. In a study with the ROCK inhibitor fasudil, the intimal thickening and vascular smooth muscle cell (VSMC) proliferation was significantly suppressed, whereas VSMC apoptosis was enhanced in the weeks following the procedure, suggesting that ROCK inhibitors can be used as a therapeutic agent for the prevention of graft failure36-39, 67.
Injury to the adult vertebrate brain and spinal cord activates ROCKs, thereby causing neurodegeneration and inhibition of neuroregeneration like neurite growth and sprouting (56 Bito, H., Furuyashiki, T., Ishihara, H., Shibasaki, Y., Ohashi, K., Mizuno, K., Maekawa, M., Ishizaki, T., Narumiya, S., A critical role for a Rho-associated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons. Neuron 26, 2000, 431-441). Inhibition of ROCKs results in induction of new axonal growth, axonal rewiring across lesions within the CNS, accelerated regeneration and enhanced functional recovery after acute neuronal injury in mammals (spinal-cord injury, traumatic brain injury) (see above 64 and 60Hara, M. et al., Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats. J. Neurosurg. Spine 93, 94-101; 61Fournier, A. E., Takizawa, B. T. & Strittmatter, S. M., ROCK inhibition enhances axonal regeneration in the injured CNS. J. Neurosci. 23, 2003, 1416-1423; 62Sung, J. K. et al., A possible role of RhoARho-kinase in experimental spinal cord injury in rat. Brain Res. 959, 2003, 29-38; 63Tanaka, H. et al., Cytoplasmic p21 (Cip1/WAF1) enhances axonal regeneration and functional recovery after spinal cord injury in rats. Neuroscience 127, 2004, 155-164). ROCK inhibitors are therefore likely to be useful for regenerative (recovery) treatment of CNS disorders such as spinal cord injury, acute neuronal injury (stroke, traumatic brain injury) (52Okamura N et al., Vasodilator effects of fasudil, a Rho-kinase inhibitor, on retinal arterioles in strokeprone spontaneously hypertensive rats. J Ocul Pharmacol Ther. 23, 2007, 207-12; 53Yagita Y et al., Rho-kinase activation in endothelial cells contributes to expansion of infarction after focal cerebral ischemia. J Neurosci Res. 85, 2007, 2460-9), Parkinson's disease, Alzheimer disease (54Pedrini S et al., Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK. PLoS Med. 2, 2005, 18; 55Burton A., NSAIDS and Alzheimer's disease: its only Rock and Rho. Lancet Neurol. 3(1), 2004, 6) and other neurodegenerative disorders. Other neurodegenetarive disorders for which ROCK inhibitors are expected to be useful are Huntington's disease (Shao J, Welch W J, Diprospero N A, Diamond M I. Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation. Mol Cell Biol. 2008 September; 28(17):5196-208; Shao J, Welch W J, Diamond M I. ROCK and PRK-2 mediate the inhibitory effect of Y-27632 on polyglutamine aggregation. FEBS Lett. 2008 May 28; 582(12):1637-42), spinal muscular atrophy (Bowerman M, Shafey D, Kothary R. Smn depletion alters profilin II expression and leads to upregulation of the RhoAROCK pathway and defects in neuronal integrity. J Mol. Neurosci. 2007; 32(2):120-31) and amyotrophic lateral sclerosis. Inhibition of the RhoROCK pathway has also proved to be efficacious in other animal models of neurodegeneration like stroke52, 53 and in inflammatory and demyelinating diseases like multiple sclerosis (51Sun X et al., The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis. J Neuroimmunol. 180, 2006, 126-34), acute and chronic pain (57Inoue, M. et al., Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nature Med. 10, 2004, 712-718; 58Ramer, L. M., Borisoff, J. F. & Ramer, M. S., Rho-kinase inhibition enhances axonal plasticity and attenuates cold hyperalgesia after dorsal rhizotomy. J. Neurosci. 24, 2004, 10796-10805; 59Tatsumi, S. et al., Involvement of Rho-kinase in inflammatory and neuropathic pain through phosphorylation of myristoylated alanine-rich Ckinase substrate (MARCKS). Neuroscience 131, 2005, 491-498).
ROCK inhibitors have been shown to possess anti-inflammatory properties by decreased cytokine release, e.g. TNFα. Thus they can be used as treatment for neuroinflammatory diseases such as stroke, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and inflammatory pain, as well as other inflammatory diseases such as rheumatoid arthritis, osteoarthritis, osteoporosis, asthma, irritable bowel syndrome, or inflammatory bowel disease (70Segain J. P., Rho kinase blockade prevents inflammation via nuclear factor kappa B inhibition: evidence in Crohn's disease and experimental colitis. Gastroenterology. 124(5), 2003, 1180-7). In addition, recent reports have demonstrated that inhibition of ROCK results in disruption of inflammatory cell chemotaxis as well as inhibition of smooth muscle contraction in models of pulmonary inflammation associated with asthma. Therefore, the inhibitors of the Rho/ROCK pathway should be useful for the treatment of asthma (see above 51 and 47Kawaguchi A, Ohmori M, Harada K, Tsuruoka S, Sugimoto K, Fujimura A., The effect of a Rho kinase inhibitor Y-27632 on superoxide production, aggregation and adhesion inhuman polymorphonuclear leukocytes. Eur J Pharmacol 403, 2000, 203-208; 48Lou Z, Billadeau D D, Savoy D N, Schoon R A, Leibson P. J., A role for a RhoA/ROCK/LIM-kinase pathway in the regulation of cytotoxic lymphocytes. J Immunol 167, 2001, 5749-5757; 49Vicente-Manzanares M, Cabrero J R, Rey M, Perez-Martinez M, Ursa A, Itoh K, Sanchez-Madrid F., A role for the Rho-p160 Rho coiled-coil kinase axis in the chemokine stromal cell-derived factor-1alpha-induced lymphocyte actomyosinand microtubular organization and chemotaxis. J Immunol 168, 2002, 400-410; 50Thorlacius K et al., Protective effect of fasudil, a Rho-kinase inhibitor, on chemokine expression, leukocyte recruitment, and hepatocellular apoptosis in septic liver injury. J Leukoc Biol. 79, 2006, 923-31).
Since ROCK inhibitors reduce cell proliferation and cell migration, they could be useful in treating cancer and tumor metastasis6, 43-46. ROCK inhibitors can also be beneficial in diseases with impaired blood brain barrier function, e.g. HIV-1 encephalitis (71Persidski Y et al., Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE). Blood. 107, 2006, 4770-4780) and Alzheimer's disease (72Man S-M et al., Peripheral T cells overexpress MIP-1α to enhance its transendothelial migration in Alzheimer's disease. Neurobiol. Of Aging 28, 2007, 485-496).
Furthermore, there is evidence suggesting that ROCK inhibitors suppress cytoskeletal rearrangement upon virus invasion, thus they also have potential therapeutic value in anti-viral and anti-bacterial applications (69Favoreel H W, Cytoskeletal rearrangements and cell extensions induced by the US3 kinase of an alphaherpesvirus are associated with enhanced spread. Proc Natl Acad Sci USA. 102(25), 2006, 8990-5).
ROCKs have been reported to interfere with insulin signalling through serine phosphorylation of insulin receptor substrate-1 (IRS-1), in cultured VSMC. Activation of RhoAROCK was observed in skeletal muscles and aortic tissues of Zucker obese rats. Inhibition of ROCK, by fasudil for 4 weeks, reduced blood pressure, corrected glucose and lipid metabolism, improved insulin signalling and endothelial dysfunction. In another experiment administration of high dose fasudil completely suppressed the development of diabetes, obesity, and dyslipidemia and increased serum adiponectin levels in OLETF rats. ROCK inhibitors may therefore be useful for the treatment of insulin resistance and diabetes (see above 67 and 65Nakamura Y et al., Marked increase of insulin gene transcription by suppression of the RhoRho-kinase pathway. Biochem Biophys Res Commun. 350(1), 2006, 68-73; 66Kikuchi Y et al., A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin-resistant diabetic rats. J Endocrinol. 192(3), 2007, 595-603; 68Goyo A et al., The Rho-kinase inhibitor, fasudil, attenuates diabetic nephropathy in streptozotocin-induced diabetic rats. Eur J. Pharmacol. 568(1-3), 2007, 242-7).
The ROCK inhibitor Fasudil increased cerebral blood flow and was neuroprotective under CNS ischemic conditions. ROCK inhibitors are expected to be useful for the treatment of ischemic CNS disorders and may therefore improve functional outcome in patients suffering from stroke, vascular or AD type dementia52, 53.
Due to the efficacy of Y-27632 and fasudil in animal models of epileptogenesis, of ROCK inhibitors have been suggested for the use in the treatments of epilepsy and seizure disorders (Inan S Y, Buyukafsar K. Antiepileptic effects of two Rho-kinase inhibitors, Y-27632 and fasudil, in mice. Br. J. Pharmacol. advance online publication, 9 Jun. 2008; doi:10.1038bjp.2008.225)
ROCK inhibitors are also expected to be useful for the treatment of glaucoma34, 35, psoriasis, retinopathy and benign prostatic hypertrophy.
As ROCK's have been implicated in neuronal morphogenesis, connectivity, and plasticity in general, they are expected to be useful for the treatment of psychiatric disorders, e.g. maior depression, schizophrenia, obsessive compulsive disorder and bipolar disorders.
ROCK inhibitors have been described in the prior art, e.g. in WO 2007026920, WO 2005074643 and WO 2004016597. However, their affinity and selectivity or their pharmacological profile is not yet satisfactory.
It is an object of the present invention to provide compounds which have a high affinity and selectivity for the ROCKs, thus allowing the treatment of disorders associated with inappropriate ROCK activity.
This object is surprisingly achieved by means of compounds of the formula I
wherein
The present invention therefore relates to compounds of the general formula I and to their physiologically tolerated acid addition salts.
The present invention also relates to a pharmaceutical composition which comprises at least one compound of the formula I and/or at least one physiologically tolerated acid addition salt of I, and at least one physiologically acceptable carrier and/or at least one auxiliary substance.
The present invention also relates to a method for treating disorders which respond to influencing by ROCK ligands, said method comprising administering an effective amount of at least one compound of the formula I and/or at least one physiologically tolerated acid addition salt of I to a subject in need thereof.
The present invention further relates to the use of a compound of the formula I and/or physiologically tolerated acid addition salts thereof, for preparing a medicament for the treatment of a medical disorder susceptible to treatment with a ROCK ligand.
Preferably, the compounds of the invention are ROCK inhibitors.
The remarks made in the following with respect to preferred aspects of the invention, e.g. to preferred meanings of the variables of compound I, to preferred compounds I and to preferred embodiments of the method or the use according to the invention, apply in each case on their own or to combinations thereof.
The diseases which respond to the influencing of ROCKs, in particular to ROCK inhibitors, include, in particular, cardiovascular diseases such as hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, atherosclerosis, asthma, male erectile dysfunctions, female sexual dysfunction, over-active bladder syndrome, neuroinflammatory diseases such as stroke, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and inflammatory pain, as well as other inflammatory diseases such as rheumatoid arthritis, irritable bowel syndrome, or inflammatory bowel disease. In addition, based on their neurite outgrowth inducing effects, ROCK inhibitors can be used as drugs for neuronal regeneration, inducing new axonal growth and axonal rewiring across lesions within the CNS. ROCK inhibitors are therefore useful for regenerative (recovery) treatment of CNS disorders such as spinal cord injury, acute neuronal injury (stroke, traumatic brain injury), Parkinson's disease, Alzheimer disease and other neurodegenerative disorders, such as, in particular, Huntington's disease, spinal muscular atrophy, and amyotrophic lateral sclerosis. Since ROCK inhibitors reduce cell proliferation and cell migration, they could be useful in treating cancer and tumor metastasis. Furthermore, there is evidence suggesting that ROCK inhibitors suppress cytoskeletal rearrangement upon virus invasion, thus they also have potential therapeutic value in anti-viral and anti-bacterial applications. ROCK inhibitors may also be useful for the treatment of insulin resistance and diabetes. ROCK inhibitors may furthermore be useful for the treatment of ischemic CNS disorders, vascular or AD type dementia, glaucoma, psoriasis, retinopathy, benign prostatic hypertrophy, psychiatric disorders, in particular depression, schizophrenia, obsessive compulsive disorder and bipolar disorder, epilepsy and seizure disorders, for decreasing ischemia-reperfusion injury, myocardial infarct size and myocardial fibrosis, and for the prevention of graft failure. Accordingly, the compounds I of the present invention can be used for treating the above-listed disorders. More preferably, they are used for treating pain, asthma, Alzheimer's disease, multiple sclerosis, rheumatoid arthritis and spinal cord injuries.
Provided the compounds of the formula I of a given constitution may exist in different spatial arrangements, for example if they possess one or more centers of asymmetry, polysubstituted rings or double bonds, or as different tautomers, it is also possible to use enantiomeric mixtures, in particular racemates, diastereomeric mixtures and tautomeric mixtures, preferably, however, the respective essentially pure enantiomers, diastereomers and tautomers of the compounds of formula I and/or of their salts.
Particularly, the carbon atom of the CH group carrying R8 and R9 may have (S) or (R) configuration in case these are different. In one preferred embodiment, this carbon atom has following absolute configuration (which, in the CIP terminology, can be R or S, depending on the respective radicals XW and YZ):
It is likewise possible to use physiologically tolerated salts of the compounds of the formula I, especially acid addition salts with physiologically tolerated acids. Examples of suitable physiologically tolerated organic and inorganic acids are hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, C1-C4-alkylsulfonic acids, such as methanesulfonic acid, aromatic sulfonic acids, such as benzenesulfonic acid and toluenesulfonic acid, oxalic acid, maleic acid, fumaric acid, lactic acid, tartaric acid, citric acid, adipic acid and benzoic acid. Other utilizable acids are described in Fortschritte der Arzneimittelforschung [Advances in drug research], Volume 10, pages 224 ff., Birkhä user Verlag, Basel and Stuttgart, 1966.
The organic moieties mentioned in the above definitions of the variables are—like the term halogen—collective terms for individual listings of the individual group members. The prefix Cn—Cm indicates in each case the possible number of carbon atoms in the group.
The term halogen denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine, chlorine or bromine.
C1-C4-Alkyl is a straight-chain or branched alkyl group having from 1 to 4 carbon atoms. Examples of an alkyl group are methyl, ethyl, n-propyl, iso-propyl, n-butyl, 2-butyl, iso-butyl or tert-butyl. C1-C2 Alkyl is methyl or ethyl, C1-C3 alkyl is additionally n-propyl or isopropyl.
C1-C6-Alkyl is a straight-chain or branched alkyl group having from 1 to 6 carbon atoms. Examples include C1-C4-alkyl as mentioned above and also pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl.
C1-C8-Alkyl is a straight-chain or branched alkyl group having from 1 to 8 carbon atoms. Examples include C1-C6-alkyl as mentioned above and also heptyl, octyl, 2-ethylhexyl and positional isomers thereof.
Haloalkyl is an alkyl group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, haloalkyl is fluorinated alkyl. Fluorinated C1-C8-alkyl is a straight-chain or branched alkyl group having from 1 to 8, preferably 1 to 6 (=fluorinated C1-C6-alkyl), especially 1 to 4 carbon atoms (=fluorinated C1-C4-alkyl), in particular 1 to 3 carbon atoms (=fluorinated C1-C3-alkyl), wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by a fluorine atom such as in fluoromethyl, difluoromethyl, trifluoromethyl, (R)-1-fluoroethyl, (S)-1-fluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl, (R)-1-fluoropropyl, (S)-1-fluoropropyl, 2-fluoropropyl, 3-fluoropropyl, 1,1-difluoropropyl, 2,2-difluoropropyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, (R)-2-fluoro-1-methylethyl, (S)-2-fluoro-1-methylethyl, (R)-2,2-difluoro-1-methylethyl, (S)-2,2-difluoro-1-methylethyl, (R)-1,2-difluoro-1-methylethyl, (S)-1,2-difluoro-1-methylethyl, (R)-2,2,2-trifluoro-1-methylethyl, (S)-2,2,2-trifluoro-1-methylethyl, 2-fluoro-1-(fluoromethyl)ethyl, 1-(difluoromethyl)-2,2-difluoroethyl, 1-(trifluoromethyl)-2,2,2-trifluoroethyl, 1-(trifluoromethyl)-1,2,2,2-tetrafluoroethyl, (R)-1-fluorobutyl, (S)-1-fluorobutyl, 2-fluorobutyl, 3-fluorobutyl, 4-fluorobutyl, 1,1-difluorobutyl, 2,2-difluorobutyl, 3,3-difluorobutyl, 4,4-difluorobutyl, 4,4,4-trifluorobutyl, and the like.
C1-C8-Alkoxy is a straight-chain or branched alkyl group having from 1 to 8, preferably 1 to 6 (═C1-C6-alkoxy), in particular 1 to 4 carbon atoms (═C1-C4-alkoxy), which is bound to the remainder of the molecule via an oxygen atom. Examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, 2-butoxy, iso-butoxy, tert.-butoxy pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexyloxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, n-hexyloxy, 1-methylpentyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 4-methylpentyloxy, 1,1-dimethylbutyloxy, 1,2-dimethylbutyloxy, 1,3-dimethylbutyloxy, 2,2-dimethylbutyloxy, 2,3-dimethylbutyloxy, 3,3-dimethylbutyloxy, 1-ethylbutyloxy, 2-ethylbutyloxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy, 1-ethyl-2-methylpropoxy, heptyloxy and octyloxy.
Haloalkoxy is an alkoxy group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, haloalkoxy is fluorinated alkoxy. Fluorinated C1-C8-alkoxy is a straight-chain or branched alkoxy group having from 1 to 8, preferably 1 to 6 (=fluorinated C1-C6-alkoxy), in particular 1 to 4 carbon atoms (=fluorinated C1-C4-alkoxy), wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by a fluorine atoms such as in fluoromethoxy, difluoromethoxy, trifluoromethoxy, (R)-1-fluoroethoxy, (S)-1-fluoroethoxy, 2-fluoroethoxy, 1,1-difluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, (R)-1-fluoropropoxy, (S)-1-fluoropropoxy, (R)-2-fluoropropoxy, (S)-2-fluoropropoxy, 3-fluoropropoxy, 1,1-difluoropropoxy, 2,2-difluoropropoxy, 3,3-difluoropropoxy, 3,3,3-trifluoropropoxy, (R)-2-fluoro-1-methylethoxy, (S)-2-fluoro-1-methylethoxy, (R)-2,2-difluoro-1-methylethoxy, (S)-2,2-difluoro-1-methylethoxy, (R)-1,2-difluoro-1-methylethoxy, (S)-1,2-difluoro-1-methylethoxy, (R)-2,2,2-trifluoro-1-methylethoxy, (S)-2,2,2-trifluoro-1-methylethoxy, 2-fluoro-1-(fluoromethyl)ethoxy, 1-(difluoromethyl)-2,2-difluoroethoxy, (R)-1-fluorobutoxy, (S)-1-fluorobutoxy, 2-fluorobutoxy, 3-fluorobutoxy, 4-fluorobutoxy, 1,1-difluorobutoxy, 2,2-difluorobutoxy, 3,3-difluorobutoxy, 4,4-difluorobutoxy, 4,4,4-trifluorobutoxy, and the like.
C1-C8-Hydroxyalkyl is a straight-chain or branched alkyl group having from 1 to 8, preferably 1 to 6 (═C1-C6-hydroxyalkyl), especially 1 to 4 carbon atoms (═C1-C4-hydroxyalkyl), in particular 1 to 3 carbon atoms (═C1-C3-hydroxyalkyl), wherein one of the hydrogen atoms is replaced by a hydroxy group, such as in 2-hydroxyethyl or 3-hydroxypropyl.
C1-C6-Alkoxy-C1-C6-alkyl is a straight-chain or branched alkyl group having from 1 to 6, especially 1 to 4 carbon atoms, in particular 1 to 3 carbon atoms, wherein one of the hydrogen atoms is replaced by a C1-C6-alkoxy group, such as in methoxymethyl, 2-methoxyethyl, ethoxymethyl, 3-methoxypropyl, 3-ethoxypropyl and the like.
C1-C6-Alkoxy-C1-C6-alkoxy is a straight-chain or branched alkyl group having from 1 to 6, especially 1 to 4 carbon atoms, in particular 1 to 3 carbon atoms, wherein one of the hydrogen atoms is replaced by a C1-C6-alkoxy group, such as in 2-methoxyethoxy, ethoxymethoxy, 2-ethoxyethoxy, 3-methoxypropoxy, 3-ethoxypropoxy and the like.
C1-C8-Alkylcarbonyl is a straight-chain or branched alkyl group having from 1 to 8, preferably 1 to 6 (═C1-C6-alkylcarbonyl), especially 1 to 4 carbon atoms (═C1-C4-alkylcarbonyl), in particular 1 to 3 carbon atoms (═C1-C3-alkylcarbonyl), which is bound via a carbonyl group (CO) to the remainder of the molecule. Examples for C1-C3-alkylcarbonyl are acetyl and propionyl. Examples for C1-C4-alkylcarbonyl are, apart those mentioned for C1-C3-alkylcarbonyl, butylcarbonyl, sec-butylcarbony, isobutylcarbonyl and tert-butylcarbonyl. Examples for C1-C6-alkylcarbonyl are, apart those mentioned for C1-C4-alkylcarbonyl, pentylcarbonyl and hexylcarbonyl. Examples for C1-C8-alkylcarbonyl are, apart those mentioned for C1-C6-alkylcarbonyl, heptylcarbonyl, octylcarbonyl and 2-ethylhexylcarbonyl.
Haloalkylcarbonyl is an alkylcarbonyl group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, haloalkylcarbonyl is fluorinated alkylcarbonyl. Fluorinated C1-C6-alkylcarbonyl is a straight-chain or branched alkyl group having from 1 to 6 (=fluorinated C1-C6-alkylcarbonyl), especially 1 to 4 carbon atoms (=fluorinated C1-C4-alkylcarbonyl), in particular 1 to 3 carbon atoms (=fluorinated C1-C3-alkylcarbonyl), wherein one of the hydrogen atoms is replaced by a carbonyl group (CO) and wherein at least one of the remaining hydrogen atoms, e.g. 1, 2, 3, or 4 of the hydrogen atoms are replaced by a fluorine atom, such as in trifluoroacetyl and 3,3,3-trifluoropropionyl.
C1-C3-Alkylcarbonyloxy is a straight-chain or branched alkyl group having from 1 to 8, preferably 1 to 6 (═C1-C6-alkylcarbonyloxy), especially 1 to 4 carbon atoms (═C1-C4-alkylcarbonyloxy), in particular 1 to 3 carbon atoms (═C1-C3-alkylcarbonyloxy), which is bound via a carbonyloxy group (C(O)—O) to the remainder of the molecule. Examples for C1-C3-alkylcarbonyloxy are acetyloxy and propionyloxy. Examples for C1-C4-alkylcarbonyl are, apart those mentioned for C1-C3-alkylcarbonyl, butylcarbonyloxy, sec-butylcarbonyoxy, isobutylcarbonyloxy and tert-butylcarbonyloxy. Examples for C1-C6-alkylcarbonyl are, apart those mentioned for C1-C4-alkylcarbonyl, pentylcarbonyloxy and hexylcarbonyloxy. Examples for C1-C8-alkylcarbonyl are, apart those mentioned for C1-C6-alkylcarbonyl, heptylcarbonyloxy, octylcarbonyloxy and 2-ethylhexylcarbonyloxy.
Haloalkylcarbonyloxy is an alkylcarbonyloxy group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, haloalkylcarbonyloxy is fluorinated alkylcarbonyloxy Fluorinated C1-C6-alkylcarbonyloxy is a straight-chain or branched alkyl group having from 1 to 6 (=fluorinated C1-C6-alkylcarbonyloxy), especially 1 to 4 carbon atoms (=fluorinated C1-C4-alkylcarbonyloxy), in particular 1 to 3 carbon atoms (=fluorinated C1-C3-alkylcarbonyloxy), which is bound via a carbonyloxy group (CO—O—) to the remainder of the molecule and wherein at least one of the remaining hydrogen atoms, e.g. 1, 2, 3, or 4 of the hydrogen atoms are replaced by a fluorine atom, such as in trifluoroacetyloxy and 3,3,3-trifluoropropionyloxy.
C1-C6-Alkylcarbonylamino is a straight-chain or branched alkyl group having from 1 to 6, especially 1 to 4 carbon atoms (═C1-C4-alkylcarbonylamino), in particular 1 to 3 carbon atoms (═C1-C3-alkylcarbonylamino), which is bound via a carbonylamino group (CO—NH—) to the remainder of the molecule, such as in acetamido (acetylamino) (CH3CONH—) and propionamido (CH3CH2CONH—).
Haloalkylcarbonylamino is an alkylcarbonylamino group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, haloalkylcarbonylamino is fluorinated alkylcarbonylamino. Fluorinated Cr C6-alkylcarbonylamino is a straight-chain or branched alkyl group having from 1 to 6 (=fluorinated C1-C6-alkylcarbonylamino), especially 1 to 4 carbon atoms (=fluorinated C1-C4-alkylcarbonylamino), in particular 1 to 3 carbon atoms (=fluorinated C1-C3-alkylcarbonylamino), which is bound via a carbonylamino group (CO—NH—) to the remainder of the molecule and wherein at least one of the remaining hydrogen atoms, e.g. 1, 2, 3, or 4 of the hydrogen atoms are replaced by a fluorine atom, such as in trifluoroacetylamino and 3,3,3-trifluoropropionylamino.
C1-C8-Alkoxycarbonyl is a straight-chain or branched alkoxy group having from 1 to 8, preferably 1 to 6 (═C1-C6-alkoxycarbonyl), especially 1 to 4 carbon atoms (═C1-C4-alkoxycarbonyl), in particular 1 to 3 carbon atoms (═C1-C3-alkoxycarbonyl), which is bound via a carbonyl group (CO) to the remainder of the molecule. Examples for C1-C3-alkoxycarbonyl are methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl and isopropoxycarbonyl. Examples for C1-C4-alkoxycarbonyl are, apart those mentioned for C1-C3-alkoxycarbonyl, butoxycarbonyl, sec-butoxycarbony, isobutoxycarbonyl and tert-butoxycarbonyl. Examples for C1-C6-alkoxycarbonyl are, apart those mentioned for C1-C4-alkoxycarbonyl, pentoxycarbonyl and hexoxycarbonyl. Examples for C1-C8-alkoxycarbonyl are, apart those mentioned for C1-C6-alkoxycarbonyl, heptoxycarbonyl, octoxycarbonyl and 2-ethylhexoxycarbonyl.
Haloalkoxycarbonyl is an alkoxycarbonyl group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, haloalkoxycarbonyl is fluorinated alkoxycarbonyl. Fluorinated C1-C6-alkoxycarbonyl is a straight-chain or branched alkoxy group having from 1 to 6 (=fluorinated C1-C6-alkoxycarbonyl), especially 1 to 4 carbon atoms (=fluorinated C1-C4-alkoxycarbonyl), in particular 1 to 3 carbon atoms (=fluorinated C1-C3-alkoxycarbonyl), which is bound via a carbonyl group (CO) to the remainder of the molecule and wherein at least one of the remaining hydrogen atoms, e.g. 1, 2, 3, or 4 of the hydrogen atoms are replaced by a fluorine atom, such as in fluoromethoxycarbonyl, difluoromethxycarbonyl, trifluoromethoxycarbonyl, 1,1-difluoroethoxycarbonyl, 2,2-difluoroethoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl, 1,1,2,2,2-pentafluoroethpxycarbonyl, 1,1-difluoropropoxycarbonyl, 2,2-difluoropropoxycarbonyl, 3,3,3-trifluoropropoxycarbonyl and the like.
C1-C6-Alkylthio (also termed as C1-C6-alkylsulfanyl) refers to straight-chain or branched alkyl groups having 1 to 6 carbon atoms, e.g. 1 to 4 carbon atoms (═C1-C6-alkylthio), which are bound to the remainder of the molecule via a sulfur atom at any bond in the alkyl group. Examples for C1-C4-alkylthio include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, sec-butylthio, isobutylthio and tert-butylthio. Examples for C1-C6-alkylthio are, apart those mentioned for C1-C4-alkylthio, 1-, 2- and 3-pentylthio, 1-, 2- and 3-hexylthio and the positional isomers thereof.
Haloalkylthio is an alkylthio group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, haloalkylthio is fluorinated alkylthio. Fluorinated C1-C6 alkylthio (also termed fluorinated C1-C6-alkylsulfanyl) is a straight-chain or branched alkylthio group having from 1 to 6, in particular 1 to 4 carbon atoms (═C1-C4-alkylthio), wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by fluorine atoms. Examples include fluoromethylthio, difluoromethylthio, trifluoromethylthio, 1,1-difluoroethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 1,1,2,2,2-pentafluoroethylthio, 1,1-difluoropropylthio, 2,2-difluoropropylthio, 3,3-difluoropropylthio, 3,3,3-trifluoropropylthio, 2,2,3,3,3-pentafluoropropylthio and the like.
C1-C6-Alkylsulfinyl refers to straight-chain or branched alkyl groups having 1 to 6 carbon atoms, e.g. 1 to 4 carbon atoms, which are bound to the remainder of the molecule via a S(O) group. Examples for C1-C4-alkylsulfinyl include methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, sec-butylsulfinyl, isobutylsulfinyl and tertbutylsulfinyl. Examples for C1-C6-alkylsulfinyl are, apart those mentioned for C1-C4-alkylsulfinyl, 1-, 2- and 3-pentylsulfinyl, 1-, 2- and 3-hexylsulfinyl and the positional isomers thereof.
Haloalkylsulfinyl is an alkylsulfinyl group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, haloalkylsulfinyl is fluorinated alkylsulfinyl. Fluorinated C1-C6 alkylsulfinyl is a straight-chain or branched alkylsulfinyl group having from 1 to 6, in particular 1 to 4 carbon atoms, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by fluorine atoms. Examples include fluoromethylsulfinyl, difluoromethylsulfinyl, trifluoromethylsulfinyl, 1,1-difluoroethylsulfinyl, 2,2-difluoroethylsulfinyl, 2,2,2-trifluoroethylsulfinyl, 1,1,2,2,2-pentafluoroethylsulfinyl, 1,1-difluoropropylsulfinyl, 2,2-difluoropropylsulfinyl, 3,3-difluoropropylsulfinyl, 3,3,3-trifluoropropylsulfinyl, 2,2,3,3,3-pentafluoropropylsulfinyl and the like.
C1-C6-Alkylsulfonyl refers to straight-chain or branched alkyl groups having 1 to 6 carbon atoms, e.g. 1 to 4 carbon atoms, which are bound to the remainder of the molecule via a S(O)2 group. Examples for C1-C4-alkylsulfonyl include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, sec-butylsulfonyl, isobutylsulfonyl and tert-butylsulfonyl. Examples for C1-C6-alkylsulfonyl are, apart those mentioned for C1-C4-alkylsulfonyl, 1-, 2- and 3-pentylsulfonyl, 1-, 2- and 3-hexylsulfonyl and the positional isomers thereof.
Haloalkylsulfonyl is an alkylsulfonyl group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, haloalkylsulfonyl is fluorinated alkylsulfonyl. Fluorinated C1-C6 alkylsulfonyl is a straight-chain or branched alkylsulfonyl group having from 1 to 6, in particular 1 to 4 carbon atoms, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by fluorine atoms. Examples include fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl, 1,1-difluoroethylsulfonyl, 2,2-difluoroethylsulfonyl, 2,2,2-trifluoroethylsulfonyl, 1,1,2,2,2-pentafluoroethylsulfonyl, 1,1-difluoropropylsulfonyl, 2,2-difluoropropylsulfonyl, 3,3-difluoropropylsulfonyl, 3,3,3-trifluoropropylsulfonyl, 2,2,3,3,3-pentafluoropropylsulfonyl and the like.
C3-C6-Cycloalkyl is a cycloaliphatic radical having from 3 to 6 C atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. C3-C8-Cycloalkyl is a cycloaliphatic radical having from 3 to 8 C atoms. Examples are, apart those mentioned for C3-C6-cycloalkyl, cycloheptyl and cyclooctyl
Halocycloalkyl is a cycloalkyl group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, halo cycloalkyl is fluorinated cycloalkyl. Fluorinated C3-C6-cycloalkyl is a cycloaliphatic radical having from 3 to 6 C atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by a fluorine atoms such as in 1-fluorocyclopropyl, 2-fluorocyclopropyl, (S)- and (R)-2,2-difluorocyclopropyl, 1,2-difluorocyclopropyl, 2,3-difluorocyclopropyl, pentafluorocyclopropyl, 1-fluorocyclobutyl, 2-fluorocyclobutyl, 3-fluorocyclobutyl, 2,2-difluorocyclobutyl, 3,3-difluorocyclobutyl, 1,2-difluorocyclobutyl, 1,3-difluorocyclobutyl, 2,3-difluorocyclobutyl, 2,4-difluorocyclobutyl, or 1,2,2-trifluorocyclobutyl.
C3-C6-Cycloalkoxy is C3-C6-cycloalkyl as defined above which is bound via an oxygen atom to the remainder of the molecule. Examples are cyclopropoxy, cyclobutoxy, cyclopentoxy and cyclohexoxy.
C3-C8-Cycloalkyl-C1-C4-alkyl is C1-C4-alkyl as defined above in which one hydrogen atom is replaced by a C3-C8-cycloalkyl group as defined above. C3-C6-Cycloalkyl-C1-C4-alkyl is C1-C4-alkyl as defined above in which one hydrogen atom is replaced by a C3-C6-cycloalkyl group as defined above. Examples are cyclopropylmethyl, cyclopropyl-1-ethyl, cyclopropyl-2-ethyl, cyclopentylmethyl, cyclopentyl-1-ethyl, cyclopentyl-2-ethyl, cyclohexyl methyl, cyclohexyl-1-ethyl, cyclohexyl-2-ethyl, and the like.
C2-C6-Alkenyl is a singly unsaturated hydrocarbon radical having 2, 3, 4, 5 or 6 C-atoms, e.g. vinyl, allyl (2-propen-1-yl), 1-propen-1-yl, methallyl (2-methylprop-2-en-1-yl) and the like. C3-C6-Alkenyl is, in particular, allyl, 1-methylprop-2-en-1-yl, 2-buten-1-yl, 3-buten-1-yl, methallyl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-en-1-yl or 2-ethylprop-2-en-1-yl.
Haloalkenyl is an alkenyl group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, haloalkenyl is fluorinated alkenyl. Fluorinated C2-C6-alkenyl is a singly unsaturated hydrocarbon radical having 2, 3, 4, 5 or 6 C-atoms, I, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by a fluorine atoms such as in 1-fluorovinyl, 2-fluorovinyl, 2,2-fluorovinyl, 3,3,3-fluoropropenyl, 1,1-difluoro-2-propenyl 1-fluoro-2-propenyl and the like.
C2-C6-Alkenyloxy is C2-C6-alkenyl as defined above which is bound via an oxygen atom to the remainder of the molecule. Examples are vinyloxy, allyloxy (2-propen-1-yloxy), 1-propen-1-yloxy, methallyloxy (2-methylprop-2-en-1-yloxy) and the like. C3-C6-Alkenyloxy is, in particular, allyloxy, 1-methylprop-2-en-1-yloxy, 2-buten-1-yloxy, 3-buten-1-yloxy, methallyloxy, 2-penten-1-yloxy, 3-penten-1-yloxy, 4-penten-1-yloxy, 1-methyl but-2-en-1-yloxy or 2-ethylprop-2-en-1-yloxy.
C2-C6-Alkenylthio is C2-C6-alkenyl as defined above which is bound via a sulfur atom to the remainder of the molecule. Examples are vinylthio, allylthio (2-propen-1-ylthio), 1-propen-1-ylthio, methallylthio (2-methylprop-2-en-1-ylthio) and the like. C3-C6-Alkenyl is, in particular, allylthio, 1-methylprop-2-en-1-ylthio, 2-buten-1-ylthio, 3-buten-1-ylthio, methallylthio, 2-penten-1-ylthio, 3-penten-1-ylthio, 4-penten-1-ylthio, 1-methylbut-2-en-1-ylthio or 2-ethylprop-2-en-1-ylthio.
C2-C6-Alkenylsulfinyl is C2-C6-alkenyl as defined above which is bound via an S(O) group to the remainder of the molecule. Examples are vinylsulfinyl, allylsulfinyl (2-propen-1-ylsulfinyl), 1-propen-1-ylsulfinyl, methallylsulfinyl (2-methylprop-2-en-1-ylsulfinyl) and the like. C3-C6-Alkenyl is, in particular, allylsulfinyl, 1-methylprop-2-en-1-ylsulfinyl, 2-buten-1-ylsulfinyl, 3-buten-1-ylsulfinyl, methallylsulfinyl, 2-penten-1-ylsulfinyl, 3-penten-1-ylsulfinyl, 4-penten-1-ylsulfinyl, 1-methylbut-2-en-1-ylsulfinyl or 2-ethylprop-2-en-1-ylsulfinyl.
C2-C6-Alkenylsulfonyl is C2-C6-alkenyl as defined above which is bound via an S(O)2, group to the remainder of the molecule. Examples are vinylsulfonyl, allylsulfonyl (2-propen-1-ylsulfonyl), 1-propen-1-ylsulfonyl, methallylsulfonyl (2-methylprop-2-en-1-ylsulfonyl) and the like. C3-C6-Alkenyl is, in particular, allylsulfonyl, 1-methylprop-2-en-1-ylsulfonyl, 2-buten-1-ylsulfonyl, 3-buten-1-ylsulfonyl, methallylsulfonyl, 2-penten-1-ylsulfonyl, 3-penten-1-ylsulfonyl, 4-penten-1-ylsulfonyl, 1-methylbut-2-en-1-ylsulfonyl or 2-ethylprop-2-en-1-ylsulfonyl.
C2-C6-Alkenylcarbonyl is C2-C6-alkenyl as defined above which is bound via a CO group to the remainder of the molecule. Examples are vinylcarbonyl, allylcarbonyl (2-propen-1-ylcarbonyl), 1-propen-1-ylcarbonyl, methallylcarbonyl (2-methylprop-2-en-1-ylcarbonyl) and the like. C3-C6-Alkenyl is, in particular, allylcarbonyl, 1-methylprop-2-en-1-ylcarbonyl, 2-buten-1-ylcarbonyl, 3-buten-1-ylcarbonyl, methallylcarbonyl, 2-penten-1-ylcarbonyl, 3-penten-1-ylcarbonyl, 4-penten-1-ylcarbonyl, 1-methylbut-2-en-1-ylcarbonyl or 2-ethylprop-2-en-1-ylcarbonyl.
C2-C6-Alkenylcarbonyloxy is C2-C6-alkenyl as defined above which is bound via a C(O)—O group to the remainder of the molecule. Examples are vinylcarbonyloxy, allylcarbonyloxy (2-propen-1-ylcarbonyloxy), 1-propen-1-ylcarbonyloxy, methallylcarbonyl (2-methylprop-2-en-1-ylcarbonyloxy) and the like. C3-C6-Alkenylcarbonyloxy is, in particular, allylcarbonyloxy, 1-methylprop-2-en-1-ylcarbonyloxy, 2-buten-1-ylcarbonyloxy, 3-buten-1-ylcarbonyloxy, methallylcarbonyloxy, 2-penten-1-ylcarbonyloxy, 3-penten-1-ylcarbonyloxy, 4-penten-1-ylcarbonyloxy, 1-methylbut-2-en-1-ylcarbonyloxy or 2-ethylprop-2-en-1-ylcarbonyloxy.
C2-C6-Alkenyloxycarbonyl is C2-C6-alkenyl as defined above which is bound via a O—C(O) group to the remainder of the molecule. Examples are vinyloxycarbonyl, allyloxycarbonyl (2-propen-1-yloxycarbonyl), 1-propen-1-yloxycarbonyl, methallyloxycarbonyl (2-methylprop-2-en-1-yloxycarbonyl) and the like. C3-C6-Alkenyl is, in particular, allyloxycarbonyl, 1-methylprop-2-en-1-yloxycarbonyl, 2-buten-1-yloxycarbonyl, 3-buten-1-yloxycarbonyl, methallyloxycarbonyl, 2-penten-1-yloxycarbonyl, 3-penten-1-yloxycarbonyl, 4-penten-1-yloxycarbonyl, 1-methylbut-2-en-1-yloxycarbonyl or 2-ethylprop-2-en-1-yloxycarbonyl.
C2-C6-Alkynyl is a straight-chain or branched hydrocarbon group having 2 to 6 carbon atoms and one or two triple bonds in any position, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl, 1-ethyl-1-methyl-2-propynyl and the like.
Haloalkynyl is an alkynyl group wherein a part or all of the hydrogen atoms are replaced by a halogen atom, in particular by fluorine and/or chlorine. Preferably, haloalkynyl is fluorinated alkynyl. Fluorinated C2-C6-alkynyl is a singly unsaturated hydrocarbon radical having 2, 3, 4, 5 or 6 C-atoms, I, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by a fluorine atoms.
C2-C6-Alkynyloxy is C2-C6-alkynyl as defined above which is bound via an oxygen atom to the remainder of the molecule. Examples are ethynyloxy, 1-propynyloxy, 2-propynyloxy, 1-butynyloxy, 2-butynyloxy, 3-butynyloxy, 1-methyl-2-propynyloxy, 1-pentynyloxy, 2-pentynyloxy, 3-pentynyloxy, 4-pentynyloxy, 1-methyl-2-butynyloxy, 1-methyl-3-butynyloxy, 2-methyl-3-butynyloxy, 3-methyl-1-butynyloxy, 1,1-dimethyl-2-propynyloxy, 1-ethyl-2-propynyloxy, 1-hexynyloxy, 2-hexynyloxy, 3-hexynyloxy, 4-hexynyloxy, 5-hexynyloxy, 1-methyl-2-pentynyloxy, 1-methyl-3-pentynyloxy, 1-methyl-4-pentynyloxy, 2-methyl-3-pentynyloxy, 2-methyl-4-pentynyloxy, 3-methyl-1-pentynyloxy, 3-methyl-4-pentynyloxy, 4-methyl-1-pentynyloxy, 4-methyl-2-pentynyloxy, 1,1-dimethyl-2-butynyloxy, 1,1-dimethyl-3-butynyloxy, 1,2-dimethyl-3-butynyloxy, 2,2-dimethyl-3-butynyloxy, 3,3-dimethyl-1-butynyloxy, 1-ethyl-2-butynyloxy, 1-ethyl-3-butynyloxy, 2-ethyl-3-butynyloxy, 1-ethyl-1-methyl-2-propynyloxy and the like.
C2-C6-Alkynylthio is C2-C6-alkynyl as defined above which is bound via a sulfur atom to the remainder of the molecule. Examples are ethynylthio, 1-propynylthio, 2-propynylthio, 1-butynylthio, 2-butynylthio, 3-butynylthio, 1-methyl-2-propynylthio, 1-pentynylthio, 2-pentynylthio, 3-pentynylthio, 4-pentynylthio, 1-methyl-2-butynylthio, 1-methyl-3-butynylthio, 2-methyl-3-butynylthio, 3-methyl-1-butynylthio, 1,1-dimethyl-2-propynylthio, 1-ethyl-2-propynylthio, 1-hexynylthio, 2-hexynylthio, 3-hexynylthio, 4-hexynylthio, 5-hexynylthio, 1-methyl-2-pentynylthio, 1-methyl-3-pentynylthio, 1-methyl-4-pentynylthio, 2-methyl-3-pentynylthio, 2-methyl-4-pentynylthio, 3-methyl-1-pentynylthio, 3-methyl-4-pentynylthio, 4-methyl-1-pentynylthio, 4-methyl-2-pentynylthio, 1,1-dimethyl-2-butynylthio, 1,1-dimethyl-3-butynylthio, 1,2-dimethyl-3-butynylthio, 2,2-dimethyl-3-butynylthio, 3,3-dimethyl-1-butynylthio, 1-ethyl-2-butynylthio, 1-ethyl-3-butynylthio, 2-ethyl-3-butynylthio, 1-ethyl-1-methyl-2-propynylthio and the like.
C2-C6-Alkynylsulfinyl is C2-C6-alkynyl as defined above which is bound via an S(O) group to the remainder of the molecule. Examples are ethynylsulfinyl, 1-propynylsulfinyl, 2-propynylsulfinyl, 1-butynylsulfinyl, 2-butynylsulfinyl, 3-butynylsulfinyl, 1-methyl-2-propynylsulfinyl, 1-pentynylsulfinyl, 2-pentynylsulfinyl, 3-pentynylsulfinyl, 4-pentynylsulfinyl, 1-methyl-2-butynylsulfinyl, 1-methyl-3-butynylsulfinyl, 2-methyl-3-butynylsulfinyl, 3-methyl-1-butynylsulfinyl, 1,1-dimethyl-2-propynylsulfinyl, 1-ethyl-2-propynylsulfinyl, 1-hexynylsulfinyl, 2-hexynylsulfinyl, 3-hexynylsulfinyl, 4-hexynylsulfinyl, 5-hexynylsulfinyl, 1-methyl-2-pentynylsulfinyl, 1-methyl-3-pentynylsulfinyl, 1-methyl-4-pentynylsulfinyl, 2-methyl-3-pentynylsulfinyl, 2-methyl-4-pentynylsulfinyl, 3-methyl-1-pentynylsulfinyl, 3-methyl-4-pentynylsulfinyl, 4-methyl-1-pentynylsulfinyl, 4-methyl-2-pentynylsulfinyl, 1,1-dimethyl-2-butynylsulfinyl, 1,1-dimethyl-3-butynylsulfinyl, 1,2-dimethyl-3-butynylsulfinyl, 2,2-dimethyl-3-butynylsulfinyl, 3,3-dimethyl-1-butynylsulfinyl, 1-ethyl-2-butynylsulfinyl, 1-ethyl-3-butynylsulfinyl, 2-ethyl-3-butynylsulfinyl, 1-ethyl-1-methyl-2-propynylsulfinyl and the like.
C2-C6-Alkynylsulfonyl is C2-C6-alkynyl as defined above which is bound via an S(O)2, group to the remainder of the molecule. Examples are ethynylsulfonyl, 1-propynylsulfonyl, 2-propynylsulfonyl, 1-butynylsulfonyl, 2-butynylsulfonyl, 3-butynylsulfonyl, 1-methyl-2-propynylsulfonyl, 1-pentynylsulfonyl, 2-pentynylsulfonyl, 3-pentynylsulfonyl, 4-pentynylsulfonyl, 1-methyl-2-butynylsulfonyl, 1-methyl-3-butynylsulfonyl, 2-methyl-3-butynylsulfonyl, 3-methyl-1-butynylsulfonyl, 1,1-dimethyl-2-propynylsulfonyl, 1-ethyl-2-propynylsulfonyl, 1-hexynylsulfonyl, 2-hexynylsulfonyl, 3-hexynylsulfonyl, 4-hexynylsulfonyl, 5-hexynylsulfonyl, 1-methyl-2-pentynylsulfonyl, 1-methyl-3-pentynylsulfonyl, 1-methyl-4-pentynylsulfonyl, 2-methyl-3-pentynylsulfonyl, 2-methyl-4-pentynylsulfonyl, 3-methyl-1-pentynylsulfonyl, 3-methyl-4-pentynylsulfonyl, 4-methyl-1-pentynylsulfonyl, 4-methyl-2-pentynylsulfonyl, 1,1-dimethyl-2-butynylsulfonyl, 1,1-dimethyl-3-butynylsulfonyl, 1,2-dimethyl-3-butynylsulfonyl, 2,2-dimethyl-3-butynylsulfonyl, 3,3-dimethyl-1-butynylsulfonyl, 1-ethyl-2-butynylsulfonyl, 1-ethyl-3-butynylsulfonyl, 2-ethyl-3-butynylsulfonyl, 1-ethyl-1-methyl-2-propynylsulfonyl and the like.
C2-C6-Alkynylcarbonyl is C2-C6-alkynyl as defined above which is bound via a CO group to the remainder of the molecule. Examples are ethynylcarbonyl, 1-propynylcarbonyl, 2-propynylcarbonyl, 1-butynylcarbonyl, 2-butynylcarbonyl, 3-butynylcarbonyl, 1-methyl-2-propynylcarbonyl, 1-pentynylcarbonyl, 2-pentynylcarbonyl, 3-pentynylcarbonyl, 4-pentynylcarbonyl, 1-methyl-2-butynylcarbonyl, 1-methyl-3-butynylcarbonyl, 2-methyl-3-butynylcarbonyl, 3-methyl-1-butynylcarbonyl, 1,1-dimethyl-2-propynylcarbonyl, 1-ethyl-2-propynylcarbonyl, 1-hexynylcarbonyl, 2-hexynylcarbonyl, 3-hexynylcarbonyl, 4-hexynylcarbonyl, 5-hexynylcarbonyl, 1-methyl-2-pentynylcarbonyl, 1-methyl-3-pentynylcarbonyl, 1-methyl-4-pentynylcarbonyl, 2-methyl-3-pentynylcarbonyl, 2-methyl-4-pentynylcarbonyl, 3-methyl-1-pentynylcarbonyl, 3-methyl-4-pentynylcarbonyl, 4-methyl-1-pentynylcarbonyl, 4-methyl-2-pentynylcarbonyl, 1,1-dimethyl-2-butynylcarbonyl, 1,1-dimethyl-3-butynylcarbonyl, 1,2-dimethyl-3-butynylcarbonyl, 2,2-dimethyl-3-butynylcarbonyl, 3,3-dimethyl-1-butynylcarbonyl, 1-ethyl-2-butynylcarbonyl, 1-ethyl-3-butynylcarbonyl, 2-ethyl-3-butynylcarbonyl, 1-ethyl-1-methyl-2-propynylcarbonyl and the like.
C2-C6-Alkynylcarbonyloxy is C2-C6-alkynyl as defined above which is bound via a C(O)—O group to the remainder of the molecule. Examples are ethynylcarbonyloxy, 1-propynylcarbonyloxy, 2-propynylcarbonyloxy, 1-butynylcarbonyloxy, 2-butynylcarbonyloxy, 3-butynylcarbonyloxy, 1-methyl-2-propynylcarbonyloxy, 1-pentynylcarbonyloxy, 2-pentynylcarbonyloxy, 3-pentynylcarbonyloxy, 4-pentynylcarbonyloxy, 1-methyl-2-butynylcarbonyloxy, 1-methyl-3-butynylcarbonyloxy, 2-methyl-3-butynylcarbonyloxy, 3-methyl-1-butynylcarbonyloxy, 1,1-dimethyl-2-propynylcarbonyloxy, 1-ethyl-2-propynylcarbonyloxy, 1-hexynylcarbonyloxy, 2-hexynylcarbonyloxy, 3-hexynylcarbonyloxy, 4-hexynylcarbonyloxy, 5-hexynylcarbonyloxy, 1-methyl-2-pentynylcarbonyloxy, 1-methyl-3-pentynylcarbonyloxy, 1-methyl-4-pentynylcarbonyloxy, 2-methyl-3-pentynylcarbonyloxy, 2-methyl-4-pentynylcarbonyloxy, 3-methyl-1-pentynylcarbonyloxy, 3-methyl-4-pentynylcarbonyloxy, 4-methyl-1-pentynylcarbonyloxy, 4-methyl-2-pentynylcarbonyloxy, 1,1-dimethyl-2-butynylcarbonyloxy, 1,1-dimethyl-3-butynylcarbonyloxy, 1,2-dimethyl-3-butynylcarbonyloxy, 2,2-dimethyl-3-butynylcarbonyloxy, 3,3-dimethyl-1-butynylcarbonyloxy, 1-ethyl-2-butynylcarbonyloxy, 1-ethyl-3-butynylcarbonyloxy, 2-ethyl-3-butynylcarbonyloxy, 1-ethyl-1-methyl-2-propynylcarbonyloxy and the like.
C2-C6-Alkynyloxycarbonyl is C2-C6-alkynyl as defined above which is bound via a O—C(O) group to the remainder of the molecule. Examples are ethynyloxycarbonyl, 1-propynyloxycarbonyl, 2-propynyloxycarbonyl, 1-butynyloxycarbonyl, 2-butynyloxycarbonyl, 3-butynyloxycarbonyl, 1-methyl-2-propynyloxycarbonyl, 1-pentynyloxycarbonyl, 2-pentynyloxycarbonyl, 3-pentynyloxycarbonyl, 4-pentynyloxycarbonyl, 1-methyl-2-butynyloxycarbonyl, 1-methyl-3-butynyloxycarbonyl, 2-methyl-3-butynyloxycarbonyl, 3-methyl-1-butynyloxycarbonyl, 1,1-dimethyl-2-propynyloxycarbonyl, 1-ethyl-2-propynyloxycarbonyl, 1-hexynyloxycarbonyl, 2-hexynyloxycarbonyl, 3-hexynyloxycarbonyl, 4-hexynyloxycarbonyl, 5-hexynyloxycarbonyl, 1-methyl-2-pentynyloxycarbonyl, 1-methyl-3-pentynyloxycarbonyl, 1-methyl-4-pentynyloxycarbonyl, 2-methyl-3-pentynyloxycarbonyl, 2-methyl-4-pentynyloxycarbonyl, 3-methyl-1-pentynyloxycarbonyl, 3-methyl-4-pentynyloxycarbonyl, 4-methyl-1-pentynyloxycarbonyl, 4-methyl-2-pentynyloxycarbonyl, 1,1-dimethyl-2-butynyloxycarbonyl, 1,1-dimethyl-3-butynyloxycarbonyl, 1,2-dimethyl-3-butynyloxycarbonyl, 2,2-dimethyl-3-butynyloxycarbonyl, 3,3-dimethyl-1-butynyloxycarbonyl, 1-ethyl-2-butynyloxycarbonyl, 1-ethyl-3-butynyloxycarbonyl, 2-ethyl-3-butynyloxycarbonyl, 1-ethyl-1-methyl-2-propynyloxycarbonyl and the like.
C1-C6-Alkylene is a linear or bridged hydrocarbon bridging group having 1, 2, 3, 4, 5 or 6 carbon atoms. Examples for C1-C2-alkylene are methylene, 1,1-ethylene and 1,2-ethylene. Examples for C1-C3-alkylene are, apart those mentioned for C1-C2-alkylene, 1,1-propylene, 2,2-propylene, 1,2-propylene, 2,3-propylene and 1,3-propylene. Examples for C1-C4-alkylene are, apart those mentioned for C1-C3-alkylene, 1,1-butylene, 2,2-butylene, 1,2-butylene, 1,3-butylene, 1,4-butylene, 2-methyl-1,2-propylene, 2-methyl-2,3-propylene and the like. Examples for C1-C6-alkylene are, apart those mentioned for C1-C4-alkylene, 1,1-pentylene, 2,2-pentylene, 3,3-pentylene, 1,2-pentylene, 2,3-pentylene, 3,4-pentylene, 2,4-pentylene, 2,2-dimethyl-1,3-propylene, 1,5-pentylene, 1,6-hexylene and the like.
Aryl is a carbocyclic aromatic radical having 6 to 14 carbon atoms, such as phenyl, naphthyl, anthracenyl or phenanthrenyl. C6-C10-Aryl is phenyl or naphthyl.
Aryloxy is carbocyclic aromatic radical having 6 to 14 carbon atoms which is attached via oxygen, such as phenoxy, naphthyloxy, anthracenyloxy or phenanthrenyloxy. C6-C10-Aryloxy is phenoxy or naphthoxy.
Arylthio is a carbocyclic aromatic radical having 6 to 14 carbon atoms which is attached via sulfur, such as phenylthio, naphthylthio, anthracenylthio or phenanthrenylthio. C6-C10-Arylthio is phenylthio or naphthylthio.
Arylsulfinyl is a carbocyclic aromatic radical having 6 to 14 carbon atoms which is attached via an SO group, such as phenylsulfinyl, naphthylsulfinyl, anthracenylsulfinyl or phenanthrenylsulfinyl. C6-C10-Arylsulfinyl is phenylsulfinyl or naphthylsulfinyl.
Arylsulfonyl is a carbocyclic aromatic radical having 6 to 14 carbon atoms which is attached via an S(O)2 group, such as phenylsulfonyl, naphthylsulfonyl, anthracenylsulfonyl or phenanthrenylsulfonyl. C6-C10-Arylsulfonyl is phenylsulfonyl or naphthylsulfonyl.
Arylcarbonyl is a carbocyclic aromatic radical having 6 to 14 carbon atoms which is attached via a CO group, such as phenylcarbonyl, naphthylcarbonyl, anthracenylcarbony) or phenanthrenylcarbonyl. C6-C10-Arylcarbonyl is phenylcarbonyl or naphthylcarbonyl.
Arylcarbonyloxy is a carbocyclic aromatic radical having 6 to 14 carbon atoms which is attached via a CO—O— group, such as phenylcarbonyloxy, naphthylcarbonyloxy, anthracenylcarbonyloxy or phenanthrenylcarbonyloxy. C6-C10-Arylcarbonyloxy is phenylcarbonyloxy or naphthylcarbonyloxy.
Aryloxycarbonyl is a carbocyclic aromatic radical having 6 to 14 carbon atoms which is attached via a O—CO group, such as phenoxycarbonyl, naphthyloxycarbonyl, anthracenyloxycarbonyl or phenanthrenyloxycarbonyl. C6-C10-Aryloxycarbonyl is phenoxycarbonyl or naphthyloxycarbonyl.
Arylalkyl is an alkyl radical (as defined above), for example C1-C8-alkyl, C1-C6-alkyl or in particular C1-C4-alkyl, where a hydrogen atom is replaced by an aryl group, such as benzyl, phenethyl and the like.
Arylalkoxy is an alkoxy radical (as defined above), for example C1-C8-alkoxy, C1-C6-alkoxy or in particular C1-C4-alkoxy, where one hydrogen atom is replaced by an aryl group, such as benzyloxy, phenethyloxy and the like.
Aryloxyalkyl is an alkyl radical (as defined above), for example C1-C8-alkyl, C1-C6-alkyl or in particular C1-C4-alkyl, where a hydrogen atom is replaced by an aryloxy group as defined above, such as phenoxymethyl, naphthoxymethyl, 2-phenoxyethyl, 2-naphthoxyethyl and the like.
Arylalkylthio is an alkylthio radical (as defined above), for example C1-C8alkylthio, C1-C6-alkylthio or in particular C1-C4-alkylthio, where a hydrogen atom is replaced by an aryl group as defined above, such as benzylthio, naphthylmethyltho, phenethylthio, 2-naphthylethylthio and the like.
Arylthioalkyl is an alkyl radical (as defined above), for example C1-C8-alkyl, C1-C6-alkyl or in particular C1-C4-alkyl, where a hydrogen atom is replaced by an arylthio group as defined above, such as phenylthiomethyl, naphthylthiomethyl, 2-phenylthioethyl, 2-naphthylthioethyl and the like.
Arylalkylcarbonyl is an arylalkyl radical (as defined above), for example aryl-C1-C8-alkyl, aryl-C1-C6-alkyl or in particular aryl-C1-C4-alkyl, which is bound via a CO group, such as benzoyl, phenethylcarbonyl and the like.
Arylalkoxycarbonyl is an arylalkoxy radical (as defined above), for example aryl-C1-C8-alkoxy, aryl-C1-C6-alkoxy or in particular aryl-C1-C4-alkoxy, which is bound via a CO group, such as benzoxycarbonyl, 2-phenylethoxycarbonyl and the like.
Arylalkylcarbonyloxy is an arylalkyl radical (as defined above), for example aryl-C1-C8-alkyl, aryl-C1-C6-alkyl or in particular aryl-C1-C4-alkyl, which is bound via a CO—Ogroup, such as benzoyloxy, phenethylcarbonyloxy and the like.
Aryl-C2-C4-alkenyl is a C2-C4-alkenyl radical (as defined above), where a hydrogen atom is replaced by an aryl group, such as 2-phenylethenyl, 3-phenyl-prop-2-enyl, 3-phenyl-prop-1-enyl and the like.
Aryl-C2-C4-alkynyl is a C2-C4-alkynyl radical (as defined above), where a hydrogen atom is replaced by an aryl group, such as 2-phenylethynyl, 3-phenyl-prop-2-ynyl, 3-phenyl-prop-1-ynyl and the like.
5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic rings containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups are either 5- or 6-membered saturated heterocyclic rings containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups as ring members, i.e. rings without any (C—C/C—N/N—N) double bonds in the ring scaffold (C—C/C—N/N—N), or 5- or 6-membered partly unsaturated heterocyclic rings containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups as ring members, i.e. a 5-membered ring with one (C—C/C—N/N—N) double bond or a 6-membered ring with one or two (C—C/C—N/N—N) double bonds in the ring scaffold, or are 5- or 6-membered aromatic heterocyclic rings containing 1, 2, 3 or 4 heteroatoms selected from O, S and N as ring members, i.e. rings with aromatic unsaturation. In the heterocyclic rings, the N atoms can be present as such (then, they are part of a ring double bond) or as NR groups where R is H or an appropriate substituent such as alkyl, alkoxy, formyl, alkylcarbonyl arylcarbonyl arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl or arylalkylsulfonyl. The rings can be bound via a carbon atom or via a nitrogen atom to the remainder of the molecule. In 5-membered heteroaromatic rings containing 1 heteroatom, this is selected from O, S and N. In 5-membered heteroaromatic rings containing 2 heteroatoms, one is selected from O, S and N and the second heteroatom is N. In 5-membered heteroaromatic rings containing 3 heteroatoms, one is selected from O, S and N and the other two heteroatoms are N. In 5-membered heteroaromatic rings containing 4 heteroatoms, all four heteroatoms are N. In 6-membered heteroaromatic rings, all heteroatoms are N (1, 2 or 3 nitrogen atoms).
Examples of 5- or 6-membered saturated heterocyclic rings containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups are pyrrolidinyl, e.g. 1-, 2- or 3-pyrrolidinyl, pyrrolidinonyl, e.g. pyrrolidin-2-on-1-yl, pyrrolidin-2-on-3-yl, pyrrolidin-2-on-4-yl, pyrrolidin-2-on-5-yl, pyrrolidin-3-on-1-yl, pyrrolidin-3-on-2-yl, pyrrolidin-3-on-4-yl or pyrrolidin-3-on-5-yl, pyrrolidindionyl, e.g. pyrrolidin-2,5-dion-1-yl or pyrrolidin-2,5-dion-3-yl, tetrahyrofuranyl, e.g. tetrahyrofuran-2-yl or tetrahyrofuran-3-yl, tetrahydrothienyl, e.g. tetrahydrothien-2-yl or tetrahydrothien-3-yl, pyrazolidinyl, e.g. pyrazolidin-1-yl, pyrazolidin-3-yl or pyrazolidin-4-yl, imidazolidinyl, e.g. imidazolidin-1-yl, imidazolidin-2-yl or imidazolidin-4-yl, imidazolidinonyl, e.g. imidazolidin-2-on-1-yl or imidazolidin-2-on-4-yl, dioxolanyl, e.g. 1,3-dioxolan-2-yl or 1,3-dioxolan-4-yl, oxazolidinyl, e.g. oxazolidin-2-yl, oxazolidin-3-yl, oxazolidin-4-yl or oxazolidin-5-yl, oxazolidinonyl, e.g. oxazolidin-2-on-3-yl, oxazolidin-2-on-4-yl or oxazolidin-2-on-5-yl, isoxazolidinyl, e.g. isoxazolidin-2-yl, isoxazolidin-3-yl, isoxazolidin-4-yl or isoxazolidin-5-yl, isoxazolidinonyl, e.g. isoxazolidin-3-on-2-yl, isoxazolidin-3-on-4-yl or isoxazolidin-3-on-5-yl, 1,3-dithiolan-2-yl or 1,3-dithiolan-4-yl, thiazolidinyl, e.g. thiazolidin-2-yl, thiazolidin-3-yl, thiazolidin-4-yl or thiazolidin-5-yl, thiazolidinonyl, e.g. thiazolidin-2-on-3-yl, thiazolidin-2-on-4-yl or thiazolidin-2-on-5-yl, isothiazolidinyl, e.g. isothiazolidin-2-yl, isothiazolidin-3-yl, isothiazolidin-4-yl or isothiazolidin-5-yl, isothiazolidinonyl, e.g. isothiazolidin-3-on-2-yl, isothiazolidin-3-on-4-yl or isothiazolidin-3-on-5-yl, triazolidinyl, e.g. [1,2,3]triazolidin-1-yl, [1,2,3]triazolidin-2-yl, [1,2,3]triazolidin-4-yl, [1,2,4]triazolidin-1-yl, [1,2,4]triazolidin-2-yl, [1,2,4]triazolidin-3-yl or [1,2,4]triazolidin-4-yl, oxadiazolidinyl, e.g. [1,2,3]oxadiazolidin-2-yl, [1,2,3]oxadiazolidin-3-yl, [1,2,3]oxadiazolidin-4-yl, [1,2,3]oxadiazolidin-5-yl, [1,2,5]oxadiazolidin-2-yl, [1,2,5]oxadiazolidin-3-yl, [1,2,4]oxadiazolidin-2-yl, [1,2,4]oxadiazolidin-3-yl, [1,2,4]oxadiazolidin-4-yl, [1,2,4]oxadiazolidin-5-yl, [1,3,4]oxadiazolidin-2-yl or [1,3,4]oxadiazolidin-3-yl, thiadiazolidinyl, e.g. [1,2,3]thiadiazolidin-2-yl, [1,2,3]thiadiazolidin-3-yl, [1,2,3]thiadiazolidin-4-yl, [1,2,3]thiadiazolidin-5-yl, [1,2,5]thiadiazolidin-2-yl, [1,2,5]thiadiazolidin-3-yl, [1,2,4]thiadiazolidin-2-yl, [1,2,4]thiadiazolidin-3-yl, [1,2,4]thiadiazolidin-4-yl, [1,2,4]thiadiazolidin-5-yl, [1,3,4]thiadiazolidin-2-yl or [1,3,4]thiadiazolidin-3-yl, tetrazolidinyl, e.g. [1,2,3,4]tetrazolidin-1-yl, [1,2,3,4]tetrazolidin-2-yl or [1,2,3,4]tetrazolidin-5-yl, piperidinyl, e.g. piperidin-1-yl, piperidin-2-yl, piperidin-3-yl or piperidin-4-yl, piperidinonyl, e.g. piperidin-2-on-1-yl, piperidin-2-on-3-yl, piperidin-2-on-4-yl, piperidin-2-on-5-yl, piperidin-2-on-6-yl, piperidin-3-on-1-yl, piperidin-3-on-2-yl, piperidin-3-on-4-yl, piperidin-3-on-5-yl, piperidin-3-on-6-yl, piperidin-4-on-1-yl, piperidin-4-on-2-yl or piperidin-4-on-3-yl, piperidindionyl, e.g. piperidin-2,6-dion-1-yl, piperidin-2,6-dion-3-yl or piperidin-2,6-dion-4-yl, tetrahydropyranyl, e.g. tetrahydropyran-2-yl or tetrahydropyran-3-yl, tetrahydropyranonyl, e.g. tetrahydropyran-2-on-3-yl, tetrahydropyran-2-on-4-yl, tetrahydropyran-2-on-5-yl or tetrahydropyran-2-on-6-yl, tetrahydrothiopyranyl, e.g. tetrahydrothiopyran-2-yl or tetrahydrothiopyran-3-yl, piperazinyl, e.g. piperazin-1-yl or piperazin-2-yl, dioxanyl, e.g. 1,3-dioxan-2-yl, 1,3-dioxan-4-yl, 1,3-dioxan-5-yl or 1,4-dioxan-2-yl, morpholinyl, e.g. morpholin-2-yl, morpholin-3-yl or morpholin-4-yl, thiomorpholinyl, e.g. thiomorpholin-2-yl, thiomorpholin-3-yl or thiomorpholin-4-yl and the like.
Examples of 5- or 6-membered partly unsaturated heterocyclic rings containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups are pyrrolinyl, e.g. 2,3-dihydropyrrol-1-yl, 2,3-dihydropyrrol-2-yl, 2,3-dihydropyrrol-3-yl, 2,3-dihydropyrrol-4-yl, 2,3-dihydropyrrol-5-yl, 2,5-dihydropyrrol-1-yl, 2,5-dihydropyrrol-2-yl or 2,5-dihydropyrrol-3-yl, pyrrolinonyl, e.g. 2,3-dihydropyrrol-2-on-1-yl, 2,3-dihydropyrrol-2-on-3-yl, 2,3-dihydropyrrol-2-on-4-yl or 2,3-dihydropyrrol-2-on-5-yl, dihydrofuranyl, e.g. 2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3-yl, 2,3-dihydrofuran-4-yl, 2,3-dihydrofuran-5-yl, 3,4-dihydrofuran-2-yl or 3,4-dihydrofuran-4-yl, dihydrothienyl, e.g. 2,3-dihydrothien-2-yl, 2,3-dihydrothien-3-yl, 2,3-dihydrothien-4-yl, 2,3-dihydrothien-5-yl, 3,4-dihydrothien-2-yl or 3,4-dihydrothien-4-yl, pyrazolinyl, e.g. 2,3-dihydropyrazol-1-yl, 2,3-dihydropyrazol-2-yl, 2,3-dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl, 2,3-dihydropyrazol-5-yl, 2,5-dihydropyrazol-1-yl, 2,5-dihydropyrazol-2-yl, 2,5-dihydropyrazol-3-yl, 2,5-dihydropyrazol-4-yl, 2,5-dihydropyrazol-5-yl, 4,5-dihydropyrazol-1-yl, 4,5-dihydropyrazol-2-yl, 4,5-dihydropyrazol-3-yl, 4,5-dihydropyrazol-4-yl or 4,5-dihydropyrazol-5-yl, imidazolinyl, e.g. 2,3-dihydroimidazol-1-yl, 2,3-dihydroimidazol-2-yl, 2,3-dihydroimidazol-3-yl, 2,3-dihydroimidazol-4-yl, 2,3-dihydroimidazol-5-yl, 2,5-dihydroimidazol-1-yl, 2,5-dihydroimidazol-2-yl, 2,5-dihydroimidazol-4-yl, 2,5-dihydroimidazol-5-yl, 4,5-dihydroimidazol-1-yl, 4,5-dihydroimidazol-2-yl, 4,5-dihydroimidazol-4-yl or 4,5-dihydroimidazol-5-yl, oxazolinyl, e.g. 2,3-dihydrooxazol-2-yl, 2,3-dihydrooxazol-3-yl, 2,3-dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl, 2,5-dihydrooxazol-2-yl, 2,5-dihydrooxazol-4-yl, 2,5-dihydrooxazol-5-yl, 4,5-dihydrooxazol-2-yl, 4,5-dihydrooxazol-4-yl or 4,5-dihydrooxazol-5-yl, thiazolinyl, e.g. 2,3-dihydrothiazol-2-yl, 2,3-dihydrothiazol-3-yl, 2,3-dihydrothiazol-4-yl, 2,3-dihydrothiazol-5-yl, 2,5-dihydrothiazol-2-yl, 2,5-dihydrothiazol-4-yl, 2,5-dihydrothiazol-5-yl, 4,5-dihydrothiazol-2-yl, 4,5-dihydrothiazol-4-yl or 4,5-dihydrothiazol-5-yl, triazolinyl, e.g. [1,2,3]-2,3-dihydrotriazol-1-yl, [1,2,3]-2,3-dihydrotriazol-2-yl, [1,2,3]-2,3-dihydrotriazol-3-yl, [1,2,3]-2,3-dihydrotriazol-4-yl, [1,2,3]-2,3-dihydrotriazol-5-yl, [1,2,3]-2,5-dihydrotriazol-1-yl, [1,2,3]-2,5-dihydrotriazol-2-yl, [1,2,3]-2,5-dihydrotriazol-4-yl, [1,2,3]-2,5-dihydrotriazol-5-yl, [1,2,3]-4,5-dihydrotriazol-1-yl, [1,2,3]-4,5-dihydrotriazol-4-yl, [1,2,3]-4,5-dihydrotriazol-5-yl, [1,2,4]-2,3-dihydrotriazol-1-yl, [1,2,4]-2,3-dihydrotriazol-2-yl, [1,2,4]-2,3-dihydrotriazol-3-yl, [1,2,4]-2,3-dihydrotriazol-5-yl, [1,2,4]-2,5-dihydrotriazol-1-yl, [1,2,4]-2,5-dihydrotriazol-2-yl, [1,2,4]-2,5-dihydrotriazol-3-yl, [1,2,4]-2,5-dihydrotriazol-5-yl, [1,2,4]-4,5-dihydrotriazol-1-yl, [1,2,4]-4,5-dihydrotriazol-3-yl, [1,2,4]-4,5-dihydrotriazol-4-yl or [1,2,4]-4,5-dihydrotriazol-5-yl, dihydropyridinyl, e.g. 1,2-dihydropyridin-1-yl, 1,2-dihydropyridin-2-yl, 1,2-dihydropyridin-3-yl, 1,2-dihydropyridin-4-yl, 1,2-dihydropyridin-5-yl, 1,2-dihydropyridin-6-yl, 1,4-dihydropyridin-1-yl, 1,4-dihydropyridin-2-yl, 1,4-dihydropyridin-3-yl, 1,4-dihydropyridin-4-yl, 1,4-dihydropyridin-5-yl, 1,4-dihydropyridin-6-yl, 2,3-dihydropyridin-2-yl, 2,3-dihydropyridin-3-yl, 2,3-dihydropyridin-4-yl, 2,3-dihydropyridin-5-yl or 2,3-dihydropyridin-6-yl, dihydropyridinonyl, e.g. 1,2-dihydropyridin-2-on-1-yl, 1,2-dihydropyridin-2-on-3-yl, 1,2-dihydropyridin-2-on-4-yl, 1,2-dihydropyridin-2-on-5-yl or 1,2-dihydropyridin-2-on-6-yl, tetrahydropyridinyl, e.g. 1,2,3,4-tetrahydropyridin-1-yl, 1,2,3,4-tetrahydropyridin-2-yl, 1,2,3,4-tetrahydropyridin-3-yl, 1,2,3,4-tetrahydropyridin-4-yl, 1,2,3,4-tetrahydropyridin-5-yl, 1,2,3,4-tetrahydropyridin-6-yl, 1,2,5,6-tetrahydropyridin-1-yl, 1,2,5,6-tetrahydropyridin-2-yl, 1,2,5,6-tetrahydropyridin-3-yl, 1,2,5,6-tetrahydropyridin-4-yl, 1,2,5,6-tetrahydropyridin-5-yl, 1,2,5,6-tetrahydropyridin-6-yl, 3,4,5,6-tetrahydropyridin-2-yl, 3,4,5,6-tetrahydropyridin-3-yl, 3,4,5,6-tetrahydropyridin-4-yl, 3,4,5,6-tetrahydropyridin-5-yl or 3,4,5,6-tetrahydropyridin-6-yl, tetrahydropyridinonyl, e.g. 1,2,3,4-tetrahydropyridin-2-on-1-yl, 1,2,3,4-tetrahydropyridin-2-on-3-yl, 1,2,3,4-tetrahydropyridin-2-on-4-yl, 1,2,3,4-tetrahydropyridin-2-on-5-yl, 1,2,3,4-tetrahydropyridin-2-on-6-yl, 1,2,5,6-tetrahydropyridin-2-on-1-yl, 1,2,5,6-tetrahydropyridin-2-on-3-yl, 1,2,5,6-tetrahydropyridin-2-on-4-yl, 1,2,5,6-tetrahydropyridin-2-on-5-yl or 1,2,5,6-tetrahydropyridin-2-on-6-yl, dehydromorpholinyl, e.g. 2,3-dehydromorpholin-2-yl, 2,3-dehydromorpholin-3-yl, 2,3-dehydromorpholin-4-yl, 2,3-dehydromorpholin-5-yl or 2,3-dehydromorpholin-6-yl, dehydrothiomorpholinyl, e.g. 2,3-dehydrothiomorpholin-2-yl, 2,3-dehydrothiomorpholin-3-yl, 2,3-dehydrothiomorpholin-4-yl, 2,3-dehydrothiomorpholin-5-yl or 2,3-dehydrothiomorpholin-6-yl and the like.
Examples of 5- or 6-membered heteroaromatic radicals comprise 1-, 2- or 3-pyrrolyl, 2- or 3-furyl, 2- or 3-thienyl, 1-, 3-, 4- or 5-pyrazolyl, 1-, 2-, 4- or 5-imidazolyl, 2-, 3- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 3- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2- or 5-[1,3,4]oxadiazolyl, 4- or 5-[1,2,3]oxadiazolyl, 3- or 5-[1,2,4]oxadiazolyl, 2- or 5-[1,3,4]thiadiazolyl, 2- or 5-[1,3,4]thiadiazolyl, 4- or 5-[1,2,3]thiadiazolyl, 3- or 5-[1,2,4]thiadiazolyl, 1H—, 2H— or 3H-1,2,3-triazol-4-yl, 2H-triazol-3-yl, 1H—, 2H—, or 4H-1,2,4-triazolyl and 1H— or 2H-tetrazolyl, 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, pyrazinyl, 3- or 4-pyridazinyl or 2-[1,3,5]triazinyl.
Examples of a phenyl ring fused to phenyl, to a saturated or partly unsaturated 5- or 6-membered carbocyclic ring or to a saturated, partly unsaturated or aromatic heterocyclic ring which contains as ring members 1, 2 or 3 heteroatoms selected from O, S and N and optionally 1 or 2 CO groups comprise naphthyl, indenyl, indanyl, 1,2- or 2,3-dihydronaphthyl, tetralinyl, indolyl, 2,3-dihydroindolyl, indazolyl, indoxylyl, oxindolyl, benzimidazolyl, 2,3-dihydrobenzimidazolyl, cumaronyl (benzo[b]furanyl), 2,3-dihydrobenzofuranyl, benzo-1,3-dioxyl, benzo-1,4-dioxanyl, benzoxazolyl, 2,3-dihydrobenzoxazolyl, benzo[b]thienyl, 2,3-dihydrobenzothienyl, benzothiazolyl, 2,3-dihydrobenzothiazolyl, benzoxathiazolyl, benzoxadiazolyl, benzothiadiazolyl, benzoxazinyl, dihydrobenzoxazinyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, tetrahydroisoquinolinyl, chromenyl, chromonyl, icochromenyl, chromanyl, chromanonyl, isochromanyl and the like. This fused system may be bonded to the remainder of the molecule via carbon atoms of the phenyl moiety (this corresponds to the definition “phenyl fused to phenyl or a carbocyclic or heterocyclic ring) or via ring atoms (C— or Natoms) of the ring fused to phenyl (this corresponds to the definition “heterocyclic ring fused to phenyl).
Examples of this fused system being for its part fused to phenyl are anthracenyl, phenanthrenyl, acenaphthenyl, dihydroacenaphthenyl, fluorenyl, carbazolyl, dibenzofuranyl, dibenzothienyl, acridinyl, carbazinyl (acridanyl), phenazinyl, 9,10-dihydrophenazinyl, dibenzomorpholinyl (phenoxazinyl) and dibenzothiomorpholinyl (phenothiazinyl).
If R8 and R9 form together with the CH group to which they are bound a CH-bound 5- or 6-membered saturated or partly unsaturated carbocyclic ring which is fused to a phenyl group, this is for example indanyl, such as indan-1-yl, indenyl, such as inden-3-yl, indanonyl, such as indan-2-on-1-yl or indan-3-on-1-yl, tetralinyl, such as tetralin-1-yl, or dihydronaphthyl, such as 1,4-dihydronaphth-1-yl or 2,3-dihydronaphth-1-yl.
If R8 and R9 form together with the CH group to which they are bound a CH-bound 5- or 6-membered saturated or partly unsaturated carbocyclic ring which is fused to a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which contains as ring members 1, 2 or 3 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups, this is for example 2,3-cyclopentenopyridyl, 2,3-cyclohexenopyridyl, 4,5,6,7-tetrahydroindolyl, 4,5,6,7-tetrahydrobenzimidazolyl and the like.
If R8 and R9 form together with the CH group to which they are bound a CH-bound 5- or 6-membered saturated or partly unsaturated heterocyclic ring which is fused to a phenyl group, this is for example 2,3-dihydroindolyl, e.g. 2,3-dihydroindol-2-yl or 2,3-dihydroindol-3-yl, indoxylyl, e.g. indoxyl-2-yl, oxindolyl, e.g. oxindol-3-yl, 2,3-dihydrobenzimidazolyl, e.g. 2,3-dihydrobenzimidazol-2-yl, 2,3-dihydrobenzofuranyl, e.g. 2,3-dihydrobenzofuran-2-yl or 2,3-dihydrobenzofuran-3-yl, 1,3-benzodioxolyl, e.g. 1,3-benzodioxol-2-yl, benzo-1,4-dioxanyl, e.g. benzo-1,4-dioxan-2-yl, 2,3-dihydrobenzoxazolyl, e.g. 2,3-dihydrobenzoxazol-2-yl, 2,3-dihydrobenzothienyl, e.g. 2,3-dihydrobenzothien-2-yl or 2,3-dihydrobenzothien-3-yl, 2,3-dihydrobenzothiazolyl, e.g. 2,3-dihydrobenzothiazol-2-yl, 1,3-benzoxazinyl, 1,4-benzoxazinyl, dihydro-1,3-benzoxazinyl, dihydro-1,4-benzoxazinyl, dihydroquinolinyl, e.g. 1,2-dihydroquinolin-2-yl, 3,4-dihydroquinolin-3-yl or 3,4-dihydroquinolin-4-yl, tetrahydroquinolinyl, e.g. 1,2,3,4-tetrahydroquinolin-2-yl, 1,2,3,4-tetrahydroquinolin-3-yl or 1,2,3,4-tetrahydroquinolin-4-yl, dihydroisoquinolinyl, e.g. 1,2-dihydroisoquinolin-1-yl, 3,4-dihydroisoquinolin-3-yl or 3,4-dihydroisoquinolin-4-yl, tetrahydroisoquinolinyl, e.g. 1,2,3,4-tetrahydroisoquinolin-1-yl, 1,2,3,4-tetrahydroisoquinolin-3-yl or 1,2,3,4-tetrahydroisoquinolin-4-yl, 2,3-dihydroquinoxalinyl, e.g. 2,3-dihydroquinoxalin-2-yl, tetrahydroquinoxalinyl, e.g. 1,2,3,4-tetrahydroquinoxalin-2-yl, dihydroquinazolinyl, e.g. 1,2-dihydroquinazolin-2-yl or 3,4-dihydroquinazolin-4-yl, tetrahydroquinazolinyl, e.g. 1,2,3,4-tetrahydroquinazolin-2-yl or 1,2,3,4-tetrahydroquinazolin-4-yl, dihydrocinnolinyl, e.g. 3,4-dihydrocinnolin-3-yl or 3,4-dihydrocinnolin-4-yl, tetrahydrocinnolinyl, e.g. 1,2,3,4-tetrahydrocinnolin-3-yl or 1,2,3,4-tetrahydrocinnolin-4-yl, chromenyl, e.g. chromen-4-yl, isochromenyl, e.g. isochromen-1-yl, chromanyl, e.g. chroman-2-yl, chroman-3-yl or chroman-4-yl, chroman-4-onyl, e.g. chroman-4-on-2-yl or chroman-4-on-3-yl, or isochromanyl, e.g. isochroman-1-yl, isochroman-3-yl or isochroman-4-yl.
If R12 and R13, together with the nitrogen atom to which they are bound, form a 4-, 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which may contain as ring members 1 or 2 further heteroatoms selected from O, S and N and/or 1 or 2 carbonyl groups, this is an N-bound 4-, 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which may contain further heteroatoms, in particular one further N, O or S or one further N and an O or an S atom. Additionally or alternatively the heterocyclic ring may contain 1 or 2 carbonyl groups. Examples of such rings are 1-azetidinyl, 1-pyrrolidinyl, pyrrolidin-2-on-1-, pyrrolidin-2,5-dion-1-yl, 1-pyrrolinyl, 1-pyrrolyl, 1-pyrazolidinyl, 1-pyrazolinyl, 1-pyrazolyl, 1-imidazolidinyl, imidazolidin-2-on-1-yl, 1-imidazolinyl, 1-imidazolyl, 3-oxazolidinyl, 3-thiazolidinyl, 1-[1,2,3]-1H-triazolidinyl, 4-[1,2,4]-4-H-triazolidinyl, 1-[1,2,3]-1H-triazolyl, 4-[1,2,4]-4-H-triazolyl, 1-piperidinyl, 1-piperazinyl, 4-morpholinyl, 4-thiomorpholinyl and the like.
The below remarks to suitable and preferred embodiments of the variables are to be understood to refer the single variable as well as in particular in combination with preferred meanings of other variables.
In compounds I, R1 and R2 are independently of each other preferably H, halogen or C1-C4-alkyl, more preferably H, fluorine, chlorine or methyl, in particular H or methyl and specifically H. Preferably, one of R1 and R2 is H and the other is selected from H, halogen and C1-C4-alkyl and more preferably from H, fluorine, chlorine and methyl.
Preferably, R3 and R4 are independently of each other H, halogen, C1-C4-alkyl or C1-C4-haloalkyl. In a preferred embodiment, one of R3 and R4 is H and the other is H, halogen, C1-C4-alkyl or C1-C4-haloalkyl. More preferably, R3 and R4 are independently of each other H, halogen or C1-C4-alkyl and even more preferably, one of R3 and R4 is H and the other is H, halogen or C1-C4-alkyl. Preferably, halogen is fluorine and C1-C4-alkyl is methyl. In particular R3 and R4 are independently of each other H or C1-C4alkyl, particularly methyl, and even more preferably, one of R3 and R4 is H and the other is H or C1-C4-alkyl, particularly methyl. Specifically, both R3 and R4 are H.
Preferably, R5 and R6 are independently of each other H, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy or C1-C4-haloalkoxy. In a preferred embodiment, one of R5 and R6 is H and the other is H, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy or Crat-haloalkoxy. More preferably, R5 and R6 are independently of each other H, halogen, C1-C4-alkyl or C1-C4alkoxy and even more preferably, one of R5 and R6 is H and the other is H, halogen, C1-C4-alkyl or C1-C4-alkoxy. Preferably, halogen is fluorine, C1-C4-alkyl is methyl and C1-C4-alkoxy is methoxy. It is preferred that the substituent(s) which is (are) different from H be located ortho relative to the CO—NR7 group. Specifically, both R5 and R6 are H.
R7 is preferably H or C1-C8-alkyl, more preferably H or C1-C4-alkyl, even more preferably H, methyl or ethyl and in particular H or methyl. Specifically, R7 is H.
In groups R8, X is preferably a single bond, CH2, CH(OH) or CH2CH2. More preferably, X is a single bond, CH2 or CH(OH) and in particular a single bond or CH2.
W is preferably selected from phenyl, naphthyl, anthracenyl, phenanthrenyl, indenyl, indanyl, dihydronaphthyl, tetralinyl, indolyl, 2,3-dihydroindolyl, indoxylyl, oxindolyl, indazolyl, 2,3-dihydroindazolyl, benzimidazolyl, 2,3-dihydrobenzimidazolyl, cumaronyl (benzo[b]furanyl), 2,3-dihydrobenzofuranyl, benzo-1,3-dioxyl, benzo-1,4-dioxanyl, benzoxazolyl, 2,3-dihydrobenzoxazolyl, benzo[b]thienyl, 2,3-dihydrobenzothienyl, benzothiazolyl, 2,3-dihydrobenzothiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, chromenyl, chromenonyl, isochromenyl, chromanyl, chromanonyl, isochromanyl, acenaphthenyl, dihydroacenaphthenyl, fluorenyl, carbazolyl, dibenzofuranyl, dibenzothienyl, acridinyl, carbazinyl (acridanyl), phenazinyl, 9,10-dihydrophenazinyl, dibenzomorpholinyl (phenoxazinyl), dibenzothiomorpholinyl (phenothiazinyl), where the 44 last-mentioned radicals are bonded via the phenyl moiety of the fused system to the group X; or W is a saturated, partly unsaturated or aromatic 5- or 6-membered heterocyclic ring containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups as ring members or is a saturated, partly unsaturated or aromatic 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups as ring members which is fused to a phenyl ring and which is bonded via the heterocyclyl moiety of the fused system to the group X, where the above radicals may carry 1, 2, 3, 4 or 5 substituents R10 as defined above.
Suitable saturated, partly unsaturated or aromatic 5- or 6-membered heterocyclic ring containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups as ring members are the 5- or 6-membered saturated heterocyclic rings containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups, the 5- or 6-membered partly unsaturated heterocyclic rings containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups and the 5- or 6-membered heteroaromatic radicals listed above.
Suitable saturated, partly unsaturated or aromatic 5- or 6-membered heterocyclic rings containing 1 or 2 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups as ring members which are fused to a phenyl ring and which are bonded via the heterocyclyl moiety of the fused system to the group X are the above-listed fused systems which are however bound via the heterocyclic ring, in particular indol-1-yl, indol-2-yl, indol-3-yl, 2,3-dihydroindol-1-yl, 2,3-dihydroindol-2-yl, 2,3-dihydroindol-3-yl, indoxyl-1-yl, indoxyl-2-yl, oxindol-1-yl, oxindol-3-yl, indazol-1-yl, indazol-3-yl, 2,3-dihydroindazol-1-yl, 2,3-dihydroindazol-2-yl, 2,3-dihydroindazol-3-yl, benzimidazol-1-yl, benzimidazol-2-yl, 2,3-dihydrobenzimidazol-1-yl, 2,3-dihydrobenzimidazol-2-yl, 2,3-dihydrobenzimidazol-3-yl, cumaron-2-yl(benzo[b]furan-2-yl), cumaron-3-yl(benzo[b]furan-4-yl), 2,3-dihydrobenzofuran-2-yl, 2,3-dihydrobenzofuran-3-yl, benzo-1,3-diox-2-yl, benzo-1,4-dioxan-2-yl, benzoxazol-2-yl, 2,3-dihydrobenzoxazol-2-yl, 2,3-dihydrobenzoxazol-3-yl, benzo[b]thien-2-yl, benzo[b]thien-3-yl, 2,3-dihydrobenzothien-2-yl, 2,3-dihydrobenzothien-3-yl, benzothiazol-2-yl, 2,3-dihydrobenzothiazol-2-yl, 2,3-dihydrobenzothiazol-3-yl, [1,3,4]-(1H)-triazolo[α]pyrimidyl, quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, isoquinolin-1-yl, isoquinolin-3-yl, isoquinolin-4-yl, quinoxalin-2-yl, quinazolin-2-yl, quinazolin-4-yl, cinnolin-3-yl, cinnolin-4-yl, chromen-2-yl, chromen-3-yl, chromen-4-yl, chromen-4-on-2-yl, chromen-4-on-3-yl, isochromen-1-yl, isochromen-3-yl, isochromen-4-yl, chroman-2-yl, chroman-3-yl, chroman-4-yl, chroman-4-on-2-yl, chroman-4-on-3-yl, isochroman-1-yl, isochroman-3-yl or isochroman-4-yl.
Suitable saturated, partly unsaturated or aromatic 5- or 6-membered heterocyclic rings containing 1 or 2 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups as ring members which are fused to a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which contains as ring members 1, 2 or 3 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups are for example azolopyridine or azolopyrimidine radicals, such as pyrrolo-[2,3-a]-pyridyl, pyrrolo-[2,3-b]-pyridyl, imidazolo-[2,3-a]pyridyl, [1,3,4]-(1H)-triazolo[1,2-a]pyridyl and the like, the latter radical being preferred.
More preferably, W is selected from phenyl, naphthyl, anthracenyl, indanyl, tetralinyl, fluoren-1-yl, fluoren-2-yl, fluoren-3-yl, fluoren-4-yl, dihydroacenaphthen-1-yl, dihydroacenaphthen-2-yl, dihydroacenaphthen-3-yl, a 5- or 6-membered heteroaromatic ring containing 1, 2 or 3 heteroatoms selected from O, S and N as ring members and a saturated, partly unsaturated or aromatic 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups as ring members which is fused to a phenyl ring and which is bound via the heterocyclic moiety or via the phenyl moiety to the group X, where the heterocyclic ring for its part may be fused to a second phenyl ring. These radicals may carry 1, 2, 3, 4 or 5 substituents R10 as defined above.
Preferably, the fused system (=saturated, partly unsaturated or aromatic 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups as ring members which is fused to one or two phenyl rings and which is bound via the heterocyclic moiety or via a phenyl moiety to the group X) is selected from indol-1-yl, indol-2-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, 2,3-dihydroindol-1-yl, 2,3-dihydroindol-2-yl, 2,3-dihydroindol-3-yl, 2,3-dihydroindol-4-yl, 2,3-dihydroindol-5-yl, 2,3-dihydroindol-6-yl, 2,3-dihydroindol-7-yl, benzofuran-2-yl, benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl, benzofuran-7-yl, 2,3-dihydrobenzofuran-2-yl, 2,3-dihydrobenzofuran-3-yl, 2,3-dihydrobenzofuran-4-yl, 2,3-dihydrobenzofuran-5-yl, 2,3-dihydrobenzofuran-6-yl, 2,3-dihydrobenzofuran-7-yl, 1,3-benzodiox-2-yl, 1,3-benzodiox-4-yl, 1,3-benzodiox-5-yl, 1,4-benzodioxan-2-yl, 1,4-benzodioxan-5-yl, 1,4-benzodioxan-6-yl, benzothien-2-yl, benzothien-3-yl, benzothien-4-yl, benzothien-5-yl, benzothien-6-yl, benzothien-7-yl, 2,3-dihydrobenzothien-2-yl, 2,3-dihydrobenzothien-3-yl, 2,3-dihydrobenzothien-4-yl, 2,3-dihydrobenzothien-5-yl, 2,3-dihydrobenzothien-6-yl, 2,3-dihydrobenzothien-7-yl, benzimidazol-1-yl, benzimidazol-2-yl, benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl, benzimidazol-7-yl, 2,3-dihydrobenzimidazol-1-yl, 2,3-dihydrobenzimidazol-2-yl, 2,3-dihydrobenzimidazol-4-yl, 2,3-dihydrobenzimidazol-5-yl, 2,3-dihydrobenzimidazol-6-yl, 2,3-dihydrobenzimidazol-7-yl, benzoxazol-2-yl, benzoxazol-4-yl, benzoxazol-5-yl, benzoxazol-6-yl, benzoxazol-7-yl, benzothiazol-2-yl, benzothiazol-4-yl, benzothiazol-5-yl, benzothiazol-6-yl, benzothiazol-7-yl, carbazol-1-yl, carbazol-2-yl, carbazol-3-yl, carbazol-4-yl, dibenzofuran-1-yl, dibenzofuran-2-yl, dibenzofuran-3-yl, dibenzofuran-4-yl, phenothiazin-1-yl, phenothiazin-2-yl, phenothiazin-3-yl and phenothiazin-4-yl, where these radicals may carry 1, 2, 3, 4 or 5 substituents R10 as defined above.
Preferably, the 5- or 6-membered heteroaromatic ring containing 1, 2 or 3 heteroatoms selected from O, S and N as ring members is selected from pyrrolyl, such as pyrrol-1-yl, pyrrol-2-yl or pyrrol-3-yl, furanyl, such as furan-2-yl or furan-3-yl, thienyl, such as thien-2-yl or thien-3-yl, pyrazolyl, such as pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl or pyrazol-5-yl, imidazolyl, such as imidazol-1-yl, imidazol-2-yl, imidazol-4-yl or imidazol-5-yl, oxazolyl, such as oxazol-2-yl, oxazol-4-yl or oxazol-5-yl, isoxazolyl, such as isoxazol-3-yl, isoxazol-4-yl or isoxazol-5-yl, thiazolyl, such as thiazol-2-yl, thiazol-4-yl or thiazol-5-yl, isothiazolyl, such as isothiazol-3-yl, isothiazol-4-yl or isothiazol-5-yl, triazolyl, such as [1,2,3]-(1H)-triazol-1-yl, [1,2,3]-(1H)-triazol-4-yl, [1,2,3]-(1H)-triazol-5-yl, [1,2,3]-(2H)-triazol-2-yl, [1,2,3]-(2H)-triazol-4-yl, [1,2,3]-(2H)-triazol-5-yl, [1,2,4]-(1H)-triazol-1-yl, [1,2,4]-(1H)-triazol-3-yl, [1,2,4]-(1H)-triazol-5-yl, [1,2,4]-(4H)-triazol-3-yl, [1,2,4]-(4H)triazol-4-yl or [1,2,4]-(4H)-triazol-5-yl, oxadiazolyl, such as [1,3,4]oxadiazol-2-yl, [1,3,4]oxadiazol-5-yl, [1,2,3]oxadiazol-4-yl, [1,2,3]oxadiazol-5-yl, [1,2,4]oxadiazol-3-yl, [1,2,4]oxadiazol-5-yl, [2,1,5]-oxadiazol-3-yl or [2,1,5]-oxadiazol-4-yl, thiadiazolyl, such as [1,3,4]thiadiazol-2-yl, [1,3,4]thiadiazol-5-yl, [1,2,3]thiadiazol-4-yl, [1,2,3]thiadiazol-5-yl, [1,2,4]thiadiazol-3-yl, [1,2,4]thiadiazol-5-yl, [2,1,5]thiadiazol-3-yl or [2,1,5]thiadiazol-4-yl, pyridyl, such as pyrid-2-yl, pyrid-3-yl or pyrid-4-yl, pyrimidyl, such as pyrimid-2-yl, pyrimid-4-yl or pyrimid-5-yl, pyrazinyl and pyridazinyl, such as pyridazin-3-yl or pyridazin-4-yl. Among these, heteroaromatic rings which are not bound via a nitrogen atom are preferred.
More preferred are furanyl, such as furan-2-yl or furan-3-yl, thienyl, such as thien-2-yl or thien-3-yl, pyrazolyl, such as pyrazol-3-yl, pyrazol-4-yl or pyrazol-5-yl, imidazolyl, such as imidazol-2-yl, imidazol-4-yl or imidazol-5-yl, oxazolyl, such as oxazol-2-yl, oxazol-4-yl or oxazol-5-yl, isoxazolyl, such as isoxazol-3-yl, isoxazol-4-yl or isoxazol-5-yl, thiazolyl, such as thiazol-2-yl, thiazol-4-yl or thiazol-5-yl, isothiazolyl, such as isothiazol-3-yl, isothiazol-4-yl or isothiazol-5-yl, triazolyl, such as [1,2,3]-(1H)-triazol-4-yl, [1,2,3]-(1H)-triazol-5-yl, [1,2,3]-(2H)-triazol-4-yl, [1,2,3]-(2H)-triazol-5-yl, [1,2,4]-(1H)-triazol-3-yl, [1,2,4]-(1H)-triazol-5-yl, [1,2,4]-(4H)-triazol-3-yl or [1,2,4]-(4H)-triazol-5-yl, oxadiazolyl, such as [1,3,4]oxadiazol-2-yl, [1,3,4]oxadiazol-5-yl, [1,2,3]oxadiazol-4-yl, [1,2,3]oxad iazol-5-yl, [1,2,4]oxadiazol-3-yl, [1,2,4]oxadiazol-5-yl, [2,1,5]-oxadiazol-3-yl or [2,1,5]-oxadiazol-4-yl, pyridyl, such as pyrid-2-yl, pyrid-3-yl or pyrid-4-yl, and pyrimidyl, such as pyrimid-2-yl, pyrimid-4-yl or pyrimid-5-yl. Particularly preferred is pyridyl.
Thus, W is even more preferably selected from phenyl, naphthyl, anthracenyl, indanyl, tetralinyl, a 5- or 6-membered heteroaromatic ring containing 1, 2 or 3 heteroatoms selected from O, S and N as ring members (which is preferably selected from the heteroaromatic rings mentioned above (and which is in particular pyridyl), indol-1-yl, indol-2-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, 2,3-dihydroindol-1-yl, 2,3-dihydroindol-2-yl, 2,3-dihydroindol-3-yl, 2,3-dihydroindol-4-yl, 2,3-dihydroindol-5-yl, 2,3-dihydroindol-6-yl, 2,3-dihydroindol-7-yl, benzofuran-2-yl, benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl, benzofuran-7-yl, 2,3-dihydrobenzofuran-2-yl, 2,3-dihydrobenzofuran-3-yl, 2,3-dihydrobenzofuran-4-yl, 2,3-dihydrobenzofuran-5-yl, 2,3-dihydrobenzofuran-6-yl, 2,3-dihydrobenzofuran-7-yl, 1,3-benzodiox-2-yl, 1,3-benzodiox-4-yl, 1,3-benzodiox-5-yl, 1,4-benzodioxan-2-yl, 1,4-benzodioxan-5-yl, 1,4-benzodioxan-6-yl, benzothien-2-yl, benzothien-3-yl, benzothien-4-yl, benzothien-5-yl, benzofthien-6-yl, benzothien-7-yl, 2,3-dihydrobenzothien-2-yl, 2,3-dihydrobenzothien-3-yl, 2,3-dihydrobenzothien-4-yl, 2,3-dihydrobenzothien-5-yl, 2,3-dihydrobenzothien-6-yl, 2,3-dihydrobenzothien-7-yl, benzimidazol-1-yl, benzimidazol-2-yl, benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl, benzimidazol-7-yl, 2,3-dihydrobenzimidazol-1-yl, 2,3-dihydrobenzimidazol-2-yl, 2,3-dihydrobenzimidazol-4-yl, 2,3-dihydrobenzimidazol-5-yl, 2,3-dihydrobenzimidazol-6-yl, 2,3-dihydrobenzimidazol-7-yl, benzoxazol-2-yl, benzoxazol-4-yl, benzoxazol-5-yl, benzoxazol-6-yl, benzoxazol-7-yl, benzothiazol-2-yl, benzothiazol-4-yl, benzothiazol-5-yl, benzothiazol-6-yl, benzothiazol-7-yl, fluoren-1-yl, fluoren-2-yl, fluoren-3-yl, fluoren-4-yl, carbazol-1-yl, carbazol-2-yl, carbazol-3-yl, carbazol-4-yl, dibenzofuran-1-yl, dibenzofuran-2-yl, dibenzofuran-3-yl, dibenzofuran-4-yl, phenothiazin-1-yl, phenothiazin-2-yl, phenothiazin-3-yl, phenothiazin-4-yl, dihydroacenaphthen-1-yl, dihydroacenaphthen-2-yl and dihydroacenaphthen-3-yl, where these radicals may carry 1, 2, 3, 4 or 5 substituents R10 as defined above.
Particularly preferably, W is selected from phenyl, naphthyl, a 5- or 6-membered heteroaromatic ring containing 1, 2 or 3 heteroatoms selected from O, S and N as ring members (which is preferably selected from the heteroaromatic rings mentioned above) and a saturated, partly unsaturated or aromatic 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from O, S and N and optionally 1 or 2 carbony) groups as ring members which is fused to a phenyl ring and which is bonded via the heterocyclyl moiety or via the phenyl moiety of the fused system to the group X, where the above radicals may carry 1, 2, 3, 4 or 5 substituents R10 as defined above. Preferably, the heteroaromatic ring is pyridyl. Preferably, the heterocyclic ring fused to phenyl is selected from indol-1-yl, indol-2-yl, indol-3-yl, 2,3-dihydroindol-1-yl, 2,3-dihydroindol-2-yl, 2,3-dihydroindol-3-yl, benzofuran-2-yl, benzofuran-3-yl, 2,3-dihydrobenzofuran-2-yl, 2,3-dihydrobenzofuran-3-yl, 1,3-benzodiox-2-yl, 1,4-benzodioxan-2-yl, benzo-1,4-dioxan-5-yl, benzo-1,4-dioxan-6-yl, benzothien-2-yl, benzothien-3-yl, benzimidazol-2-yl and benzothiazol-2-yl and more preferably from indol-2-yl, indol-3-ylbenzo-1,4-dioxan-5-yl and benzo-1,4-dioxan-6-yl. These radicals W may carry 1, 2, 3, 4 or 5 substituents R10 as defined above.
R10 as optional substituent of the cyclic radical in group W is preferably selected from halogen, hydroxyl, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C6-alkoxy where the alkyl moiety may carry a CN group, C1-C4haloalkoxy, C1-C4alkylthio, C1-C4-haloalkylthio, C1-C4-alkylsulfonyl, C1-C4-haloalkylsulfonyl, C1-C4-alkylcarbonyl, C1-C4-haloalkylcarbonyl, C1-C4-alkylcarbonyloxy, C1-C4-haloalkylcarbonyloxy, C1-C4-alkoxycarbonyl, C1-C4-haloalkoxycarbonyl, C2-C6-alkenyl, C2-C6-alkenyloxy, C3-C6-cycloalkyl, phenyl, benzyl, phenoxy, benzoxy, phenoxymethyl, phenylthio, phenylsulfonyl, where the phenyl moiety in the 7 last-mentioned radicals may carry 1, 2, 3, 4 or 5 substituents independently selected from halogen, OH, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkylthio, phenyl, benzyl, phenoxy and benzoxy; 5- or 6-membered heteroaryl containing 1, 2, 3 or 4 heteroatoms selected from O, S and N as ring members, where the heteroaryl ring may carry 1, 2, 3 or 4 substituents independently selected from halogen, OH, C1-C4alkyl, C1-C4haloalkyl, C1-C4-alkoxy, C1-C4-alkoxy, C1-C4-alkylthio and C1-C4-haloalkylthio; aminocarbonyl and NRaRb, where Ra and Rb are independently selected from H, C1-C6-alkyl, formyl and C1-C4-alkylcarbonyl.
More preferably, R10 is selected from halogen, hydroxyl, C1-C6-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-C4-haloalkylthio, phenyl, benzyl, phenoxy and benzoxy (C6H5CH2O).
In the radical R9, Y is preferably CH2, CH(OH), CH(phenyl) or CH2CH2. More preferably, Y is CH2, CH(OH) or CH(phenyl) and even more preferably is CH2 or CH(OH). In particular, Y is CH2.
Z is preferably hydrogen, halogen, OR11, NR12R13 or phenyl which may carry 1, 2, 3 or 4 substituents R15 and more preferably hydrogen, OR11, NR12R13 or phenyl which may carry 1, 2, 3 or 4 substituents R15.
R11 is preferably H or C1-C4-alkyl, more preferably H, methyl or ethyl and in particular H or methyl.
In a preferred embodiment of the invention, R12 and R13 are independently of each other selected from hydrogen, C1-C4-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl, C1-C4-alkylcarbonyl, C1-C4-haloalkylcarbonyl, C1-C4-alkoxycarbonyl, C1-C4-haloalkoxycarbonyl, C1-C4-alkylsulfonyl, C1-C4-haloalkylsulfonyl, phenylcarbonyl, benzylcarbonyl, phenylsulfonyl and benzylsulfonyl, where the phenyl moiety in the six last-mentioned radicals may carry 1, 2 or 3, preferably 1 or 2 substituents, in particular 1 substituent selected from halogen, hydroxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, or R12 and R13, together with the nitrogen atom to which they are bound, form a 4-, 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which may contain as ring members 1 or 2 further heteroatoms selected from O, S and N and/or 1 or 2 carbonyl groups, and where the heterocyclic ring may carry 1, 2 or 3 substituents selected from halogen, hydroxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy.
Preferably, the above phenyl substituents are selected from halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, more preferably from C1-C4-alkyl and C1-C4-haloalkyl and in particular from methyl.
In a more preferred embodiment of the invention, R12 and R13 are independently of each other selected from hydrogen, C1-C4-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl, C1-C4-alkylsulfonyl and phenylsulfonyl, where the phenyl moiety in the last-mentioned radical may carry 1, 2 or 3, preferably 1 or 2 substituents, in particular 1 substituent as defined above, or R12 and R13, together with the nitrogen atom to which they are bound, form a 4-, 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which may contain as ring members 1 or 2 further heteroatoms selected from O, S and N and/or 1 or 2 carbonyl groups, and where the heterocyclic ring may carry 1, 2 or 3 substituents selected from halogen, hydroxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy.
If R12 and R13, together with the nitrogen atom to which they are bound, form a 4-, 5- or 6-membered ring, preferably a 5- or 6-membered ring, this is preferably saturated or aromatic. Preferably, the ring contains apart the nitrogen atom via which it is bound to the group Y no or one further heteroatom. The further heteroatom(s) is are preferably selected from O and N. If the ring is substituted, the substituent(s) may be bound at a C or at an N atom. Preferred ring substituents are selected from halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy, more preferably from C1-C4-alkyl and C1-C4-haloalkyl, more preferably from C1-C4-alkyl and in particular methyl.
In an alternatively preferred embodiment, R8 and R9, together with the CH group to which they are bonded, form a CH-bound saturated or partly unsaturated 5- or 6-membered carbocyclic ring which may contain 1 or 2 carbonyl groups as ring members or a saturated or partly unsaturated 5- or 6-membered heterocyclic ring, where the heterocyclic ring contains 1 or 2 heteroatoms selected from O, S and N and optionally 1 carbonyl group as ring members, where the carbocyclic ring and the heterocyclic ring are fused to a phenyl ring or to a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which contains as ring members 1, 2 or 3 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups, where the carbocyclic ring and the heterocyclic ring and/or the ring fused thereto may carry 1, 2 or 3 substituents R15, with the proviso that in case the carbocyclic ring is fused to a phenyl ring, the points of fusion are not in the 3,4-position, relative to the 1-position of the bond to the group NR7.
Suitable fused systems are those listed above. Examples are indanyl, such as indan-1-yl, indenyl, such as inden-3-yl, indanonyl, such as indan-2-on-1-yl or indan-3-on-1-yl, tetralinyl, such as tetralin-1-yl, dihydronaphthyl, such as 1,2-dihydronaphth-1-yl or 1,4-dihydronaphth-1-yl, 2,3-dihydroindolyl, indoxylyl, oxindolyl, 2,3-dihydrobenzimidazolyl, 2,3-dihydrobenzofuranyl, benzo-1,3-dioxyl, benzo-1,4-dioxanyl, 2,3-dihydrobenzoxazolyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothiazolyl, 1,3-benzoxazinyl, 1,4-benzoxazinyl, dihydro-1,3-benzoxazinyl, dihydro-1,4-benzoxazinyl, 1,2- and 3,4-dihydroquinolinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2- and 3,4-dihydroisoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2- and 3,4-dihydroquinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,2- and 3,4-dihydroquinazolinyl, 1,2,3,4-tetrahydroquinazolinyl, 1,2- and 3,4-dihydrocinnolinyl, 1,2,3,4-tetahydrocinnolinyl, chromenyl, chromonyl, isochromenyl, chromanyl, chromanonyl, isochromanyl, pyrrolidino-[2,3-a]-pyridyl, pyrrolidinoo-[2,3-b]-pyridyl, iidinomidazolo-[2,3-a]pyridyl, [1,3,4]-(1H)-triazolidino[1,2-a]pyridyl, 2,3-cyclopentenopyridyl, 2,3-cyclohexenopyridyl, 4,5,6,7-tetrahydroindolyl, 4,5,6,7-tetrahydrobenzimidazolyl and the like.
In this embodiment, it is preferred that R8 and R9, together with the CH group to which they are bonded, form a CH-bound saturated or partly unsaturated 5- or 6-membered carbocyclic ring which may contain 1 or 2 carbonyl groups as ring members or a saturated or partly unsaturated 5- or 6-membered heterocyclic ring, where the heterocyclic ring contains 1 or 2 heteroatoms selected from O, S and N and optionally 1 carbonyl group as ring members, where the carbocyclic ring and the heterocyclic ring are fused to a phenyl ring, where the carbocyclic ring and the heterocyclic ring and/or the phenyl ring fused thereto may carry 1, 2 or 3, preferably 1, substituents R15, with the proviso that in case it is the carbocyclic ring which is fused to a phenyl ring, the points of fusion are not in the 3,4-position, relative to the 1-position of the bond to the group NR7.
More preferably, R8 and R9, together with the CH group to which they are bonded, form a CH-bound saturated 5- or 6-membered carbocyclic ring which may contain 1 or 2 carbonyl groups as ring members or a saturated or partly unsaturated 5- or 6-membered heterocyclic ring, where the heterocyclic ring contains 1 or 2, preferably 1 heteroatoms selected from O, S and N, preferably O, and optionally 1 carbonyl group as ring members, where the carbocyclic ring and the heterocyclic ring are fused to a phenyl ring where the carbocyclic ring and the heterocyclic ring and/or the phenyl ring fused thereto may carry 1, 2 or 3, preferably 1, substituents R15, with the proviso that in case it is the carbocyclic ring which is fused to a phenyl ring, the points of fusion are not in the 3,4-position, relative to the 1-position of the bond to the group NR7.
In particular, this fused system is selected from indanyl, such as indan-1-yl, indenyl, such as inden-3-yl, indanonyl, such as indan-2-on-1-yl or indan-3-on-1-yl, tetralinyl, such as tetralin-1-yl, dihydronaphthyl, such as 1,2-dihydronaphth-1-yl or 1,4-dihydronaphth-1-yl, 2,3-dihydroindolyl, indoxylyl, oxindolyl, 2,3-dihydrobenzimidazolyl, 2,3-dihydrobenzofuranyl, benzo-1,3-dioxyl, benzo-1,4-dioxanyl, 2,3-dihydrobenzoxazolyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothiazolyl, 1,3-benzoxazinyl, 1,4-benzoxazinyl, dihydro-1,3-benzoxazinyl, dihydro-1,4-benzoxazinyl, 1,2- and 3,4-dihydroquinolinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2- and 3,4-dihydroisoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2- and 3,4-dihydroquinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,2- and 3,4-dihydroquinazolinyl, 1,2,3,4-tetrahydroquinazolinyl, 1,2- and 3,4-dihydrocinnolinyl, 1,2,3,4-tetahydrocinnolinyl, chromenyl, chromonyl, isochromenyl, chromanyl, chromanonyl and isochromanyl, more particularly from indanyl, such as indan-1-yl, indenyl, such as inden-3-yl, indanonyl, such as indan-2-on-1-yl or indan-3-on-1-yl, tetralinyl, such as tetralin-1-yl, dihydronaphthyl, such as 1,2-dihydronaphth-1-yl or 1,4-dihydronaphth-1-yl, 2,3-dihydrobenzofuranyl, benzo-1,3-dioxyl, benzo-1,4-dioxanyl, chromenyl, chromonyl, isochromenyl, chromanyl, chromanonyl and isochromanyl, and specifically from indanyl, such as indan-1-yl, and isochromanyl, such as isochroman-4-yl.
For these radicals, R15 is preferably selected from hydroxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy or C1-C4-haloalkoxy, more preferably from hydroxyl, C1-C4-alkoxy or C1-C4-haloalkoxy and specifically is hydroxyl.
Particularly preferred compounds I are those of formulae I.1.ab to I.58.ab and the racemates thereof where the variables have the above or, preferably, the below given meanings.
Examples of particularly preferred compounds of the general formula I are the compounds I compiled in Tables 1 to 3583094below. Moreover, the meanings mentioned for the individual variables in the tables are per se, independently of the combination in which they are mentioned, a particularly preferred embodiment of the substituents in question.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is H and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is OH and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is OCH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is OCH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is phenyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NH2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHCH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHCH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHCH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHCH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHCH2CH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHCH2CH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHCH(CH3)CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHC(CH3)3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is N(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is N(CH2CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is N(CH2CH2CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHC(O)OCH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHC(O)OCH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHC(O)OCH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHC(O)OCH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHC(O)OCH2CH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHC(O)OCH2CH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHC(O)OCH(CH3)CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHC(O)OC(CH3)3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHC(O)O-phenyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHC(O)O-4-tolyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHSO2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHSO2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHSO2CH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHSO2CH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHSO2CH2CH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHSO2CH2CH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHSO2CH(CH3)CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHSO2C(CH3)3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHSO2-phenyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is NHSO2-4-tolyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is 1-azetidinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is 1-pyrrolidinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is 1-piperidinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is 1-piperazinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is 4-methylpiperazin-1-yl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is 4-morpholinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is 4-thiomorpholinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is 1-pyrrolyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is 1-pyrazolyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH2, Z is 1-imidazolyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CHOH, Z is H and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CHOH, Z is phenyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is H and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is OH and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is OCH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is OCH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is phenyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NH2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHCH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHCH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHCH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHCH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHCH2CH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHCH2CH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHCH(CH3)CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHC(CH3)3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is N(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is N(CH2CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is N(CH2CH2CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHC(O)OCH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHC(O)OCH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHC(O)OCH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHC(O)OCH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHC(O)OCH2CH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHC(O)OCH2CH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHC(O)OCH(CH3)CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHC(O)OC(CH3)3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHC(O)O-phenyl and the combination (R10), for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHC(O)O-4-tolyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHSO2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHSO2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHSO2CH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHSO2CH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHSO2CH2CH2CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHSO2CH2CH(CH3)2 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHSO2CH(CH3)CH2CH3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHSO2C(CH3)3 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHSO2-phenyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is NHSO2-4-tolyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is 1-azetidinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is 1-pyrrolidinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is 1-piperidinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is 1-piperazinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is 4-methylpiperazin-1-yl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is 4-morpholinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is 4-thiomorpholinyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is 1-pyrrolyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is 1-pyrazolyl and the combination)(R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which R1 is H, R2 is H, R5 is H, R3 is H, R6 is H, Y is CH(phenyl), Z is 1-imidazolyl and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is CH3 and R6 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is H and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is H and R6 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is CH3 and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is CH3 and R6 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is H and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is CH3 and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is F and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is H and R6 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is CH3 and R6 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is H and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is H and R6 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is CH3 and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is CH3 and R6 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is H and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is CH3 and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is F and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is H and R6 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is CH3 and R6 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is H and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is H and R6 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is CH3 and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is CH3 and R6 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is H and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is CH3 and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is F and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is H and R6 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is CH3 and R6 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is H and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is H and R6 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is CH3 and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is CH3 and R6 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is H and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is CH3 and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is F and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is H and R6 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is CH3 and R6 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is H and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is H and R6 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is CH3 and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is CH3 and R6 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is H and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is CH3 and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is F and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is F, R5 is H, R3 is CH3 and R6 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is F, R5 is H, R3 is CH3 and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is CH3 and R6 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is F, R5 is H, R3 is CH3 and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is F, R5 is H, R3 is F and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R6 is H, R3 is H and R5 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R6 is H, R3 is H and R5 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R6 is H, R3 is CH3 and R5 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R6 is H, R3 is CH3 and R5 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R6 is H, R3 is H and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R6 is H, R3 is CH3 and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R6 is H, R3 is F and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R6 is H, R3 is CH3 and R5 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R6 is H, R3 is H and R5 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R6 is H, R3 is H and R5 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R6 is H, R3 is CH3 and R5 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R6 is H, R3 is CH3 and R5 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R6 is H, R3 is H and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R6 is H, R3 is CH3 and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R6 is H, R3 is F and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R6 is H, R3 is H and R5 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R6 is H, R3 is H and R5 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is CH3 and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R6 is H, R3 is CH3 and R5 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R6 is H, R3 is H and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R6 is H, R3 is CH3 and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is F and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is CH3 and R6 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R15)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R6 is H, R3 is H and R5 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R6 is H, R3 is H and R5 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R6 is H, R3 is CH3 and R5 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R6 is H, R3 is CH3 and R5 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R6 is H, R3 is H and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R15)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is CH3 and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R6 is H, R3 is F and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R6 is H, R3 is H and R5 is H.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R6 is H, R3 is H and R5 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R6 is H, R3 is H and R5 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is CH3 and R6 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R6 is H, R3 is CH3 and R5 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is H and R6 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R6 is H, R3 is CH3 and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R6 is H, R3 is F and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is F, R6 is H, R3 is CH3 and R5 is CH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R6 is H, R3 is CH3 and R5 is F.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is F, R6 is H, R3 is CH3 and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is F, R6 is H, R3 is F and R5 is OCH3.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R6 is H, R3 is H and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R6 is H, R3 is H and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R6 is H, R3 is H and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R6 is H, R3 is H and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R6 is H, R3 is H and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R6 is H, R3 is CH3 and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R6 is H, R3 is CH3 and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R6 is H, R3 is CH3 and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R6 is H, R3 is CH3 and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R6 is H, R3 is CH3 and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R6 is H, R3 is F and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R6 is H, R3 is F and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R6 is H, R3 is F and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R6 is H, R3 is F and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R6 is H, R3 is F and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is F, R6 is H, R3 is CH3 and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is H and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is H and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R5 is H, R3 is H and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is H and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is H and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is CH3 and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is CH3 and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R6 is H, R3 is CH3 and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is CH3 and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is CH3 and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is H, R5 is H, R3 is F and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is H, R5 is H, R3 is F and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is F, R2 is H, R6 is H, R3 is F and R5 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is Cl, R2 is H, R5 is H, R3 is F and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is CH3, R2 is CH3, R5 is H, R3 is F and R6 is Cl.
Compounds of the formula I.1.a, I.1.b and mixtures thereof, in which the combination of Y and Z is as defined in one of Tables 1 to 96, the combination (R10)n for a compound corresponds in each case to one row of Table A, R1 is H, R2 is F, R6 is H, R3 is CH3 and R5 is Cl.
Compounds of the formula I.2.a, I.2.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.3.a, I.3.b and mixtures thereof, in which the combination of Y, Z, R3 and R6 is as defined in one of Tables 1 to 576 and the combination (R10)n for a compound corresponds in each case to one row of Table A.
Compounds of the formula I.4.a, I.4.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table B (B.a).
Compounds of the formula I.5.a, I.5.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table B (B.b).
Compounds of the formula I.6.a, I.6.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table B (B.c).
Compounds of the formula I.7.a, I.7.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.8.a, I.8.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.9.a, I.9.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.10.a, I.10.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is H and the combination (R10)n for a compound corresponds in each case to one row of Table C (C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH3 and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH(CH3)2 and (R10)n for a compound corresponds in each case to one row of Table C (C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is —C(O)—O—C(CH3)3 and (R10)n for a compound corresponds in each case to one row of Table C (C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is phenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R3 and R6 is as defined in one of Tables 1 to 576, R101 is 2-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.11.a, I.11.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and (R10)n for a compound corresponds in each case to one row of Table C(C.a).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is H and the combination (R10)n for a compound corresponds in each case to one row of Table C (C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R3 and R6 is as defined in one of Tables 1 to 576, R101 is CH3 and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH(CH3)2 and (R10)n for a compound corresponds in each case to one row of Table C (C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R3 and R6 is as defined in one of Tables 1 to 576, R101 is —C(O)—O—C(CH3)3 and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is phenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R3 and R6 is as defined in one of Tables 1 to 576, R101 is 2-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R3 and R6 is as defined in one of Tables 1 to 576, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.12.a, I.12.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and (R10)n for a compound corresponds in each case to one row of Table C(C.b).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is H and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 6, R101 is CH2CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH(CH3)2 and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is —C(O)—O—C(CH3)3 and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is phenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.13.a, I.13.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is H and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R3 and R6 is as defined in one of Tables 1 to 576, R101 is CH(CH3)2 and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is —C(O)—O—C(CH3)3 and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is phenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.14.a, I.14.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is H and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.c)
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R3 and R6 is as defined in one of Tables 1 to 576 R101 is CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH(CH3)2 and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and (R10) for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is —C(O)—O—C(CH3)3 and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R3 and R6 is as defined in one of Tables 1 to 576, R101 is phenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, K R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.15.a, I.15.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and (R10)n for a compound corresponds in each case to one row of Table D (D.c).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is H and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH3 and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 R101 is CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH(CH3)2 and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and (R10) for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and (R10) for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is —C(O)—O—C(CH3)3 and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is phenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.16.a, I.16.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is H and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH3 and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 R101 is CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH(CH3)2 and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and (R10)n for a compound corresponds in each case to one row of Table C.
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table E (E.b)
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is —C(O)—O—C(CH3)3 and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is phenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.17.a, I.17.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and (R10)n for a compound corresponds in each case to one row of Table E (E.b)C.
Compounds of the formula I.18.a, I.18.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.19.a, I.19.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.20.a, I.20.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table E (E.c).
Compounds of the formula I.21.a, I.21.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table E (E.a).
Compounds of the formula I.22.a, I.22.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table E (E.b).
Compounds of the formula I.23.a, I.23.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table E (E.c).
Compounds of the formula I.24.a, I.24.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.25.a, I.25.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.26.a, I.26.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table D (D.a).
Compounds of the formula I.27.a, I.27.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table D (D.b).
Compounds of the formula I.28.a, I.28.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is H and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH3 and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 R101 is CH2CH3 and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH3 and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH(CH3)2 and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is —C(O)—O—C(CH3)3 and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is phenyl and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-methoxyphenyl and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.29.a, I.29.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and R10 for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.30.a, I.30.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and R101 for a compound corresponds in each case to one row of Table H.
Compounds of the formula I.31.a, I.31.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.32.a, I.32.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.33.a, I.33.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.34.a, I.34.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is H and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 R101 is CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH(CH3)2 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is —C(O)—O—C(CH3)3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is phenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.35.a, I.35.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination of R101 is H and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 R101 is CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH(CH3)2 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and (R10) for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is —C(O)—O—C(CH3)3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is phenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.36.a, I.36.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is H and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 R101 is CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH(CH3)2 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is —C(O)—O—C(CH3)3 and (R10)n for a compound corresponds in each case to one row of Table C.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is phenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.37.a, I.37.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is H and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 R101 is CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH(CH3)2 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CHF2 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is CH2CH2CH2OCH3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is cyclohexyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is —C(O)—O—C(CH3)3 and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is phenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-fluorophenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-methoxyphenyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 2-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 3-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.38.a, I.38.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, R101 is 4-pyridyl and (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.39.a, I.39.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.40.a, I.40.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.41.a, I.41.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table F.
Compounds of the formula I.42.a, I.42.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904.
Compounds of the formula I.43.a, I.43.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.44.a, I.44.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.45.a, I.45.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A is O, B, C and D are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.45.a, I.45.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, B is O, A, C and D are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.45.a, I.45.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, C is O, A, B and D are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.45.a, I.45.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, D is O, A, B and C are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.45.a, I.45.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A and D are O, B and C are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.45.a, I.45.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A, B, C and D are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.46.a, I.46.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A is O, B, C and D are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.46.a, I.46.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, B is O, A, C and D are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.46.a, I.46.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, C is O, A, B and D are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.46.a, I.46.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, D is O, A, B and C are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.46.a, I.46.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A and D are O, B and C are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.46.a, I.46.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A, B, C and D are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.47.a, I.47.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A is O, B is CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.47.a, I.47.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, B is O, A is CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.47.a, I.47.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A and B are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.47.a, I.47.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A and B are O and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.48.a, I.48.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A is O, B is CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.48.a, I.48.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, B is O, A is CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.48.a, I.48.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A and B are CH and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.48.a, I.48.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904, A and B are O and the combination (R10)n for a compound corresponds in each case to one row of Table G.
Compounds of the formula I.49.a, I.49.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and R101 for a compound corresponds in each case to one row of Table H.
Compounds of the formula I.50.a, I.50.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and R101 for a compound corresponds in each case to one row of Table H.
Compounds of the formula I.51.a, I.51.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and R101 for a compound corresponds in each case to one row of Table H.
Compounds of the formula I.52.a, I.52.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and R101 for a compound corresponds in each case to one row of Table H.
Compounds of the formula I.53.a, I.53.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904 and R101 for a compound corresponds in each case to one row of Table H.
Compounds of the formula I.54.a, I.54.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904.
Compounds of the formula I.55.a, I.55.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904.
Compounds of the formula I.56.a, I.56.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904.
Compounds of the formula I.57.a, I.57.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904.
Compounds of the formula I.58.a, I.58.b and mixtures thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is as defined in one of Tables 1 to 11904.
Compounds I of the present invention can be synthesized as outlined in the synthetic routes shown below.
(A=OH, O—C(O)—R, OR, 1-imidazolyl, 1-pyrazolyl or Cl; R7′, R8′ and R9′ are R7, R8 and R9 or precursors of these groups)
A precursor is a radical which can be easily removed and replaced by the desired group or which can be modified to give the desired group. The precursor can also be an N-protective group.
As shown in scheme 1, compounds of formula I or precursors thereof can be prepared from the acid (derivative) II and the amine III by standard amide bond forming reactions. In case A is Cl, the reaction needs no further activation.
When the carboxylic acid II (A=OH) itself is used as the reactant II, the reaction is advantageously carried out in the presence of a coupling reagent. Suitable coupling reagents (activators) are known to those skilled in the art and are selected, for example, from carbodiimides such as DCC (dicyclohexylcarbodiimide), EDC (1-ethyl-3-(dimethylamino)-propyl) carbodiimide), CDI (carbonyldiimidazole), carbonyldipyrazole and DCI (diisopropylcarbodiimide), benzotriazole derivatives such as 1-hydroxybenzotriazole, HBTU ((O-benzotriazol-1-yl)-N,N′,N′-tetramethyluronium hexafluorophosphate) and HCTU (1-[bis(dimethylamino)methylene]-5-chloro-1Hbenzotriazolium tetrafluoroborate), pyridinotriazole derivatives such HATU (2-(7-aza-1H-bentotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate), and phosphonium activators such as BOP ((benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate), Py-BOP ((benzotriazol-1-yloxy)tripyrrolidinephosphonium hexafluorophosphate) and Py-BrOP (bromotripyrrolidinephosphonium hexafluorophosphate). In general, the activator is used in excess. The benzotriazole and phosphonium coupling reagents are generally used in a basic medium, e.g. in the presence of an amine different from III, preferably a non-nucleophilic amine, such as tertiary aliphatic and alicyclic amines.
The acid anhydride II (A=—O—C(O)—R) is an asymmetric anhydride in which —O—C(O)—R is a group which can be displaced easily by the amine III used in the reaction. Suitable acid derivatives with which the carboxylic acid II (A=OH) forms suitable mixed anhydrides are, for example, the esters of chloroformic acid, for example isopropyl chloroformate and isobutyl chloroformate.
Suitable esters II (A=OR) derive preferably from C1-C4-alkanols ROH in which R is C1-C4-alkyl, such as methanol, ethanol, propanol, isopropanol, n-butanol, butan-2-ol, isobutanol and tert-butanol, preference being given to the methyl and ethyl esters (R=methyl or ethyl). Suitable esters may also derive from C2-C6-polyols such as glycol, glycerol, trimethylolpropane, erythritol, pentaerythritol and sorbitol, preference being given to the glycerol ester.
Alternatively, as ester II (A=OR) can be used a so-called active ester, which is obtained by the reaction of the acid II (A=OH) with an active ester-forming alcohol such as p-nitrophenol, N-hydroxysuccinimide or OPfp (pentafluorophenol).
In a further alternative, A is 1-imidazolyl, i.e. the compound II is an amide with imidazole as amine component, or A is 1-pyrazolyl, i.e. the compound II is an amide with pyrazole as amine component. This compound can be obtained by reacting the corresponding acid chloride (compound II wherein A=Cl) with imidazole or pyrazole, respectively or, more suitably, it is formed as an intermediate when the acid (compound II with A=OH) is reacted with CDI or with carbonyldipyrazole.
(R7′, R8′ and R9′ are R7, R8 and R9 or precursors of these groups)
Alternatively, the amide IV can be coupled to a pyridine through a variety of metalmediated coupling reactions well known to those skilled in the art. For example, the amide IV can be coupled with a 4-pyridyl tin reagent (Stille reaction) or with a 4-pyridyl boronic acid (Suzuki coupling) in the presence of a palladium catalyst. These reaction types and suitable reaction conditions are well known in the art.
4-(Pyrid-4-yl)-benzoic acids II (A=OH) are commercially available or can be prepared by known substitution reactions on aromaticsheteroaromatics from commercially available compounds. Acid derivatives (A=Cl; OR; OC(O)R) can be prepared ba standard derivatization reactions, for example by reaction of the acid with sulfonyl chloride to give the chloride (A=Cl), by reaction of the acid or the chloride with an alcohol ROH to give an ester (A=OR) or by reaction of the acid or the chloride with an acid RCOOH to give an anhydride (A=OC(O)R).
Amines III are commercially available or can be prepared by standard alkylation, arylation, acylation or sulfonation reactions of amines.
4-Bromobenzoic amides IV are commercially available or can be prepared by amide bond formation from the corresponding 4-bromobenzoic acid or an acid derivative thereof and an amine III in analogy to the method described with respect to scheme 1.
If R7′, R8′ and R9′ in compound I′ are not the desired final groups R7, R8 and R9, they can be converted into these by standard methods. For example, if R7′ represents H, this can be converted into a group R7 different from H by alkylating or arylating the amido nitrogen atom. R7′ can also be a protective group. The protective group may be removed to yield a compound I wherein R7′ is H. Suitable protective groups are known in the art and are, for example, selected from tert-butoxycarbonyl (boc), benzyloxycarbonyl (Cbz), 9-fluorenylmethoxycarbonyl (Fmoc), triphenylmethyl (Trt) and nitrobenzenesulfenyl (Nps). A preferred protective group is boc. The protective groups can be removed by known methods, such as treatment of the protected amine with an acid, e.g halogen acid, such as HCl or HBr, or trifluoroacetic acid, or by hydrogenation, optionally in the presence of a Pd catalyst. The resulting compound, wherein R7′ is H, can then be reacted, as already said, in the sense of an alkylation, with a compound R7—X. In this compound, R7 is C1-C8-alkyl, C1-C8-haloalkyl, C6-C14-aryl or C6-C14-aryl-C1-C4-alkyl and X is a nucleophilically displaceable leaving group, e.g. halogen, trifluoroacetate, alkylsulfonate, arylsulfonate, alkyl sulfate and the like. The reaction conditions which are required for the alkylation have been adequately disclosed, e.g. in Bioorganic and Medicinal Chemistry Lett. 2002, 12(7), pp. 2443-2446 and also 2002, 12(5), pp. 1917-1919.
If R8 is a group X—W′, where W′ does not carry the desired substituent R10, this can be converted into the desired radical by standard substitution reactions. In particular N-bound radicals R10 can be introduced into compounds of the formula I by reacting the corresponding halogen compound, i.e. a compound of the formula I, which instead of the desired group R10 carries a halogen atom, in particular a bromine or iodine atom, with a primary or secondary amine in the presence of a base, preferably also in the presence of a palladium catalyst in terms of a Buchwald-Hartwig reaction.
If R9 is a group Y′—CH2OH (Y′=single bond, CO, C1-C3-alkylene), this can for example be converted into a group Y′—CH2NR12R13 by first oxidizing the alcohol group to a carbonyl function (Y′—CHO) and the submitting the resulting aldehyde to a reductive amination with an amine NHR12R13. Suitable reductive agents are for example borohydrides such as sodium borohydride, sodium cyanoborohydride or sodium triacetoxyborohydride. The skilled person is familiar with the reaction conditions which are required for a reductive amination, e.g. from Bioorganic and Medicinal Chemistry Lett. 2002, 12(5), pp. 795-798 and 12(7) pp. 1269-1273.
By starting from enantiomerically pure (S)- or pure (R)-amines III, enantiomerically pure (S)- and (R)-enantiomers of compounds I (with respect to the configuration at the C(H)atom bound to NR7) can be obtained. Alternatively, racemates of compounds I, I′ or IV can be separated, e.g. by chromatography using a chiral stationary phase.
If not indicated otherwise, the above-described reactions are generally carried out in a solvent at temperatures between room temperature and the boiling temperature of the solvent employed. Alternatively, the activation energy which is required for the reaction can be introduced into the reaction mixture using microwaves, something which has proved to be of value, in particular, in the case of the reactions catalyzed by transition metals (with regard to reactions using microwaves, see Tetrahedron 2001, 57, p. 9199 ff. p. 9225 if. and also, in a general manner, “Microwaves in Organic Synthesis”, André Loupy (Ed.), Wiley-VCH 2002.
The acid addition salts of compounds I are prepared in a customary manner by mixing the free base with a corresponding acid, where appropriate in solution in an organic solvent, for example a lower alcohol, such as methanol, ethanol or propanol, an ether, such as methyl tert-butyl ether or diisopropyl ether, a ketone, such as acetone or methyl ethyl ketone, or an ester, such as ethyl acetate.
The compounds according to the invention of the formula I have a surprisingly high affinity for ROCK1 and ROCK2. Specifically, they have a ROCK antagonistic activity.
The high activity of the compounds according to the invention for ROCKs is reflected in very low in-vitro enzyme inhibition constants (Ki(ROCK) values) of as a rule less than 500 nM (nmol/l), preferably of less than 100 nM and, in particular of less than 50 nM. The modulation of phosphorylation of suitable peptide substrates can, for example, be used in studies for determining enzyme inhibition constants of ROCK.
Because of their profile, the compounds can be used for treating diseases which respond to the influencing of ROCK activity, i.e. they are effective for treating those medical disorders or diseases in which exerting an influence on (modulating) the ROCK activity leads to an improvement in the clinical picture or to the disease being cured. Examples of these diseases are given above.
The disorders which can be treated in accordance with the invention include the diseases listed in the introductory part, e.g. cardiovascular diseases such as hypertension, chronic and congestive heart failure, cardiac hypertrophy, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension and ocular hypertension, cancer and tumor metastasis, asthma, male erectile dysfunctions, female sexual dysfunctions, over-active bladder syndrome, preterm labor, ischemia reperfusion, myocardial infarction, restenosis, atherosclerosis, graft failure, CNS disorders, such acute neuronal injury, e.g. spinal chord injury, traumatic brain injury and stroke, Parkinson's disease and Alzheimer's disease, inflammatory and demyelating diseases such as multiple sclerosis, acute and chronic pain, rheumatoid arthritis, osteoarthritis, osteoporosis, irritable bowel syndrome and inflammatory bowel disease, amyotrophic lateral sclerosis, HIV-1 encephalitis, virus and bacterial infections, insulin resistance, diabetes, cognitive dysfunctions, such as the above-mentioned Alzheimer disease, vascular dementia and other dementia forms, glaucoma, psoriasis, retinopathy, and benign prostatic hypertrophy. In particular the disorders are cancer, pain, asthma, cognitive dysfunctions, in particular vascular dementia and Alzheimer's disease, multiple sclerosis, rheumatoid arthritis and spinal cord injuries.
Within the meaning of the invention, a treatment also includes a preventive treatment (prophylaxis), in particular as relapse prophylaxis or phase prophylaxis, as well as the treatment of acute or chronic signs, symptoms and/or malfunctions. The treatment can be orientated symptomatically, for example as the suppression of symptoms. It can be effected over a short period, be orientated over the medium term or can be a long-term treatment, for example within the context of a maintenance therapy.
Within the context of the treatment, the use according to the invention of the described compounds involves a method. In this method, an effective quantity of one or more compounds, as a rule formulated in accordance with pharmaceutical and veterinary practice, is administered to the individual to be treated, preferably a mammal, in particular a human being, productive animal or domestic animal. Whether such a treatment is indicated, and in which form it is to take place, depends on the individual case and is subject to medical assessment (diagnosis) which takes into consideration signs, symptoms and/or malfunctions which are present, the risks of developing particular signs, symptoms and/or malfunctions, and other factors.
As a rule, the treatment is effected by means of single or repeated daily administration, where appropriate together, or alternating, with other active compounds or active compound-containing preparations such that a daily dose of preferably from about 0.1 to 1000 mg/kg of bodyweight, in the case of oral administration, or of from about 0.1 to 100 mg/kg of bodyweight, in the case of parenteral administration, is supplied to an individual to be treated.
If desired, the effective daily dose can be divided into multiple doses for purposes of administration. Consequently, single dose compositions may contain such amounts or submultiples thereof to make up the daily dose.
The invention also relates to the production of pharmaceutical compositions for treating an individual, preferably a mammal, in particular a human being, productive animal or domestic animal. Thus, the ligands are customarily administered in the form of pharmaceutical compositions which comprise a pharmaceutically acceptable excipient together with at least one compound according to the invention and, where appropriate, other active compounds. These compositions can, for example, be administered orally, rectally, transdermally, subcutaneously, intravenously, intramuscularly or intranasally.
Examples of suitable pharmaceutical formulations are solid medicinal forms, such as powders, granules, tablets, in particular film tablets, lozenges, sachets, cachets, sugarcoated tablets, capsules, such as hard gelatin capsules and soft gelatin capsules, suppositories or vaginal medicinal forms, semisolid medicinal forms, such as ointments, creams, hydrogels, pastes or plasters, and also liquid medicinal forms, such as solutions, emulsions, in particular oil-in-water emulsions, suspensions, for example lotions, injection preparations and infusion preparations, and eyedrops and eardrops. Implanted release devices can also be used for administering inhibitors according to the invention. In addition, it is also possible to use liposomes or microspheres.
When producing the compositions, the compounds according to the invention are optionally mixed or diluted with one or more excipients. Excipients can be solid, semisolid or liquid materials which serve as vehicles, carriers or medium for the active compound.
Suitable excipients are listed in the specialist medicinal monographs. In addition, the formulations can comprise pharmaceutically acceptable carriers or customary auxiliary substances, such as glidants; wetting agents; emulsifying and suspending agents; preservatives; antioxidants; antiirritants; chelating agents; coating auxiliaries; emulsion stabilizers; film formers; gel formers; odor masking agents; taste corrigents; resin; hydrocolloids; solvents; solubilizers; neutralizing agents; diffusion accelerators; pigments; quaternary ammonium compounds; refatting and overfatting agents; raw materials for ointments, creams or oils; silicone derivatives; spreading auxiliaries; stabilizers; sterilants; suppository bases; tablet auxiliaries, such as binders, fillers, glidants, disintegrants or coatings; propellants; drying agents; opacifiers; thickeners; waxes; plasticizers and white mineral oils. A formulation in this regard is based on specialist knowledge as described, for example, in Fiedler, H. P., Lexikon der Hilfsstoffe für Pharmazie, Kosmetik and angrenzende Gebiete [Encyclopedia of auxiliary substances for pharmacy, cosmetics and related fields], 4th edition, Aulendorf: ECV-Editio-Kantor-Verlag, 1996.
The following examples serve to explain the invention without limiting it.
The compounds were either characterized via proton-NMR in d6-dimethylsulfoxid or dchloroform, if not stated otherwise, on a 400 MHz or 500 MHz NMR instrument (Bruker AVANCE), or by mass spectrometry, generally recorded via HPLC-MS in a fast gradient on C18-material (electrospray-ionisation (ESI) mode.
The magnetic nuclear resonance spectral properties (NMR) refer to the chemical shifts (δ) expressed in parts per million (ppm). The relative area of the shifts in the 1H NMR spectrum corresponds to the number of hydrogen atoms for a particular functional type in the molecule. The nature of the shift, as regards multiplicity, is indicated as singlet (s), broad singlet (s. br.), doublet (d), broad doublet (d br.), triplet (t), broad triplet (t br.), quartet (q), quintet (quint.) and multiplet (m).
LC/MS (Halo Purity QC method): The gradient was 5-60% B in 1.5 min then 60-95% B to 2.5 min with a hold at 95% B for 1.2 min (1.3 mL/min flow rate). Mobile phase A was 10 mM ammonium acetate, mobile phase B was HPLC grade acetonitrile. The column used for the chromatography is a 4.6×50 mm MAC-MOD Halo C8 column (2.7 μm particles). Detection methods are diode array (DAD) and evaporative light scattering (ELSD) detection as well as positive/negative electrospray ionization.
4-Pyridin-4-ylbenzoic acid (5.86 g, 29.4 mmol) was dissolved in 300 ml of THF. Subsequently, N-methylmorpholine (4.04 g, 29.5 mmol), (2S)-2-amino-2-phenylethanol (3.96 g, 29.3 mmol) and 1-hydroxybenzotriazol (3.96 g, 29.3 mmol) were added. Finally EDC (5.63 g, 29.4 mmol) was added over a period of 5 min and the heterogenic reaction mixture was stirred for 24 h, whereupon an oily precipitation occurred. After evaporation of the solvent under reduced pressure the residue was dissolved in DCM (500 ml), washed twice with aqueous NaOH (50 ml of a 2 M solution) and subsequently with water. After drying the organic phase over sodium sulfate and evaporating the solvent under reduced pressure the raw title compound was obtained as an oily residue (8.4 g). Column chromatography (silica gel; eluent: EtOAc with an increasing amount of MeOH (0 up to 5%)) yielded the pure title compound (5.2 g, yield: 56%) as a white crystalline product.
1H NMR (400 MHz, DMSO-d6): 8.83 (d, 1H), 8.67 (d, 2H), 8.06 (d, 2H), 7.93 (d, 2H), 7.77 (d, 2H), 7.41 (d, 2H), 7.32 (dd, 2H), 7.23 (dd, 1H), 5.14-5.07 (m, 1H), 4.98 (t, 1H), 3.79-3.63 (m, 2H).
Formula: C20H18N2O2
Calc MW: 318.37
MS: m/z: 319.1 (M+H).
The title compound was prepared according to the procedure outlined in Example 1, however substituting, (2S)-2-amino-2-phenylethanol with (3R)-3-amino-3-phenylpropan-1-ol.
1H NMR (400 MHz, DMSO-d6): 8.88 (d, 1H), 8.66 (d, 2H), 8.01 (d, 2H), 7.91 (d, 2H), 7.75 (d, 2h), 7.39 (d 2H), 7.32 (dd, 2H), 7.21 (dd, 1H), 5.18 (dd, 1H), 4.59 (t, 1H), 3.51-3.39 (m, 2H), 2.12-2.02 (m, 1H), 1.97-1.88 (m, 1H).
Formula: C21H20N2O2
Calc MW: 332.41
MS: m/z: 333.1 (M+H).
The title compound was prepared according to the procedure outlined in Example 1, however substituting, (2S)-2-amino-2-phenylethanol with tert-butyl (2-amino-2-phenylethyl)carbamate.
Formula: C25H27N3O3
Calc MW: 417.51
MS: m/z: 418.1 (M+H).
The title compound was prepared by BOC cleavage of the compound obtained in Example 3 with HCl in 2-propanol/DCM at room temperature.
Formula: C20H19N3O
Calc MW: 317.39
MS: m/z: 318.1 (M+H).
The title compounds were prepared by subjecting the compound of Example 4 to a column chromatography with a chiral stationary phase (Prep HPLC; column: Whelk O 2.5 cm ID×25 cm; mobile phase: hexane/EtOH/MeOH/DEA=5025250.1; flow rate: 40 ml/min; detector: UV 270 nm; column temp: RT; sample preparation: 10 mg/ml; load: 10 ml (100 mg))
1H NMR (400 MHz, DMSO-d6): 9.48 (d, 1H), 8.66 (d, 2H), 8.58-8.23 (broad signal, 2H), 8.21 (d, 2H), 7.91 (d 2H), 7.77 (d 2H), 7.47 (d, 2H), 7.36 (dd, 2H), 7.27 (dd, 1H), 5.43-5.36 (m, 1H), 3.47 (dd, 1H), 3.14 (dd, 1H).
Formula: C20H19N3O
Calc MW: 317.39
MS: m/z 318.1 (M+H).
1H NMR (400 MHz, DMSO-d6): 9.61 (d, 1H), 8.89 (d, 2H), 8.59-8.46 (broad signal, 2H), 8.25 (d, 4H), 8.07 (d, 2H), 7.48 (d 2H), 7.36 (dd, 2H), 7.28 (dd, 1H), 5.43-5.36 (m, 1H), 3.47 (dd, 1H), 3.14 (dd, 1H).
Formula: C20H19N3O.
Calc MW: 317.39
MS: m/z 318.1 (M+H).
In a microwave vial containing 3 eq. of PS-DCC, 4-(pyridin-4-yl)benzoic acid (20 mg, 0.1 mmol) was added dissolved in DMA (1.0 ml). Then a solution of HOBT (14 mg, 0.1 mmol) dissolved in DMA (0.3 ml) was added followed by the addition of DIEA (36 μl, 0.2 mmol) dissolved in DMA (0.3 ml) and the addition of (S)-2-amino-3-phenylpropan-1-ol (17 mg, 0.11 mmol) dissolved in DMA (0.6 ml). The mixture was heated in the microwave to 100° C. for 600 seconds. The reaction was filtered through Si-Carbonate, 6 ml-1 g supplied by Silicycle chemical Division and transferred to 20 ml vials. The reaction was checked by LC/MS and concentrated to dryness. The residues were dissolved in 1:1 DMSO/MeOH and purified by reverse phase HPLC (TFA method). Product was characterized by 1H NMR, MS and LC/MS.
1H NMR (500 MHz, DMSO-D6/D2O) δ=2.71-2.86 (m, 1H) 2.94-3.02 (m, 1H) 3.42-3.59 (m, 2H) 4.15-4.27 (m, 1H) 7.14-7.22 (m, 1H) 7.23-7.33 (m, 4H) 7.73-7.82 (m, 2H) 7.84-7.97 (m, 4H) 8.61-8.68 (m, 2H);
Formula: C21H20N2O2
Calc MW: 332.40
MS (ESI) positive ion 333 (M+H); negative ion 331 (M−H).
The following compounds were prepared in an analogous method:
Formula: C21H19F N2O2
Calc MW: 350.39
ESI-MS: 351 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 3.38-3.47 (m, 1H) 3.59-3.67 (m, 1H) 4.19-4.27 (m, 1H) 4.95 (d, 1H) 7.17-7.25 (m, 1H) 7.31 (t, 2H) 7.34-7.41 (m, 2H) 7.73-7.81 (m, 2H) 7.81-7.98 (m, 4H) 8.58-8.72 (m, 2H);
Formula: C21H20N2O3
Calc MW: 348.40
MS (ESI) negative ion 347 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.73-2.85 (m, 1H) 2.97 (dd, 1H) 3.43-3.60 (m, 2H) 4.09-4.29 (m, 1H) 7.24-7.36 (m, 4H) 7.71-7.83 (m, 2H) 7.85-7.98 (m, 4H) 8.59-8.73 (m, 2H);
Formula: C21H19ClN2O2
Calc MW: 366.85
MS (ESI) negative ion 365 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 3.54-3.72 (m, 2H) 5.00-5.21 (m, 1H) 7.24-7.29 (m, 1H) 7.32-7.37 (m, 2H) 7.38-7.45 (m, 2H) 7.76-7.81 (m, 2H) 7.89-7.99 (m, 2H) 8.00-8.09 (m, 2H) 8.60-8.75 (m, 2H);
Formula: C20H18N2O2
Calc MW: 318.37
MS (ESI) positive ion 319 (M+H); negative ion 317 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.20 (d, 3H) 1.72-1.98 (m, 2H) 2.58-2.70 (m, 2H) 3.97-4.12 (m, 1H) 7.13-7.24 (m, 3H) 7.25-7.35 (m, 2H) 7.74-7.82 (m, 2H) 7.89-7.93 (m, 2H) 7.96-8.03 (m, 2H) 8.56-8.75 (m, 2H);
Formula: C22H22N2O
Calc MW: 330.43
MS (ESI) positive ion 331 (M+H); negative ion 329 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 3.24-3.29 (m, 3H) 3.31-3.39 (m, 1H) 3.50-3.60 (m, 1H) 4.34-4.41 (m, 1H) 4.89 (d, 1H) 7.15-7.28 (m, 1H) 7.26-7.42 (m, 4H) 7.72-7.79 (m, 2H) 7.84-7.98 (m, 4H) 8.63-8.69 (m, 2H);
Formula: C22H22N2O3
Calc MW: 362.43
MS (ESI) positive ion 363 (M+H); negative ion 361 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.90-2.99 (m, 1H) 3.02-3.10 (m, 1H) 3.47-3.63 (m, 2H) 4.25-4.33 (m, 1H) 7.00 (t, 1H) 7.08 (t, 1H) 7.15-7.18 (m, 1H) 7.34 (d, 1H) 7.65 (d, 1H) 7.73-7.82 (m, 2H) 7.85-8.16 (m, 4H) 8.61-8.68 (m, 2H);
Calc MW: 371.44
MS (ESI) positive ion 372 (M+H); negative ion 370 (M−H)+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.63-2.70 (m, 1H) 2.80-2.88 (m, 1H) 3.36-3.59 (m, 2H) 3.99-4.24 (m, 1H) 6.56-6.72 (m, 2H) 6.98-7.13 (m, 2H) 7.71-7.80 (m, 2H) 7.84-7.96 (m, 4H) 8.51-8.82 (m, 2H);
Formula: C21H22N2O3
Calc MW: 348.40
MS (ESI) negative ion 347 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.70-2.97 (m, 2H) 3.25-3.32 (m, 3H) 3.37-3.59 (m, 2H) 4.21-4.46 (m, 1H) 7.10-7.22 (m, 1H) 7.23-7.34 (m, 4H) 7.70-7.83 (m, 2H) 7.85-8.02 (m, 4H) 8.54-8.71 (m, 2H);
Formula: C22H22N2O2
Calc MW: 346.43
MS (ESI) positive ion 347 (M+H); negative ion 345 (M−H)
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.73-2.83 (m, 1H) 2.91-3.05 (m, 1H) 3.37-3.58 (m, 2H) 4.11-4.27 (m, 1H) 7.08-7.22 (m, 1H) 7.22-7.34 (m, 4H) 7.67-7.83 (m, 2H) 7.84-8.02 (m, 4H) 8.52-8.73 (m, 2H);
Formula: C21H20N2O2
Calc MW: 332.40
MS (ESI) positive ion 333 (M+H); negative ion 331 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.51 (d, 3H) 5.00-5.26 (m, 1H) 7.16-7.27 (m, 1H) 7.29-7.44 (m, 4H) 7.68-7.83 (m, 2H) 7.86-7.94 (m, 2H) 7.98-8.10 (m, 2 H) 8.50-8.78 (m, 2H);
Formula: C20H18N2O
Calc MW: 302.38
MS (ESI) positive ion 303 (M+H); negative ion 301 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.51 (d, 3H) 5.05-5.26 (m, 1H) 7.18-7.30 (m, 1H) 7.31-7.46 (m, 4H) 7.70-7.80 (m, 2H) 7.88-7.95 (m, 2H) 7.98-8.05 (m, 2H) 8.63-8.68 (m, 2H);
Formula: C20H18N2O
Calc MW: 302.38
MS (ESI) positive ion 303 (M+H); negative ion 301 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.41-2.45 (m, 3H) 3.37-3.45 (m, 1H) 3.58-3.66 (m, 1H) 4.14-4.25 (m, 1H) 4.86-4.94 (m, 1H) 7.13-7.23 (m, 2H) 7.25-7.35 (m, 2H) 7.74-7.83 (m, 2H) 7.86-7.94 (m, 4H) 8.61-8.72 (m, 2H);
Formula: C22H22N2O3S
Calc MW: 394.49
MS (ESI) positive ion 395 (M+H); negative ion 393 (M−H)
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.89-2.95 (m, 1H) 3.10-3.18 (m, 1H) 4.52-4.59 (m, 1H) 5.47 (d, 1H) 7.15-7.32 (m, 4H) 7.73-7.86 (m, 2H) 7.90-7.96 (m, 2H) 8.02-8.14 (m, 2H) 8.53-8.78 (m, 2H);
Formula: C21H18N2O2
Calc MW: 330.39
MS (ESI) positive ion 331 (M+H); negative ion 329 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.85-2.97 (m, 1H) 3.07-3.20 (m, 1H) 4.53-4.59 (m, 1H) 5.47 (d, 1H) 7.20-7.35 (m, 4H) 7.74-7.87 (m, 2H) 7.88-7.96 (m, 2H) 8.02-8.11 (m, 2H) 8.61-8.70 (m, 2H));
Formula: C21H18N2O2
Calc MW: 330.39
MS (ESI) positive ion 331 (M+H); negative ion 329 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.86-3.10 (m, 2H) 3.46-3.63 (m, 2H) 4.19-4.32 (m, 1H) 6.95-7.02 (m, 1H) 7.05-7.10 (m, 1H) 7.13-7.18 (m, 1H) 7.33 (d, 1H) 7.64 (d, 1H) 7.74-7.82 (m, 2H) 7.85-7.98 (m, 4H) 8.61-8.71 (m, 2H);
Formula: C23H21N3O2
Calc MW: 371.44
MS (ESI) positive ion 372 (M+H); negative ion 370 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.61-2.73 (m, 1H) 2.78-2.93 (m, 1H) 3.37-3.54 (m, 2H) 3.98-4.18 (m, 1H) 6.57-6.72 (m, 2H) 6.93-7.23 (m, 2H) 7.69-7.81 (m, 2H) 7.83-8.01 (m, 4H) 8.56-8.76 (m, 2H);
Formula: C21H20N2O3
Calc MW: 348.40
MS (ESI) negative ion 347 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.17-2.26 (m, 3H) 4.81-4.92 (m, 1H) 5.35-5.45 (m, 1H) 6.96-7.32 (m, 14H) 7.77-7.83 (m, 2H) 7.88-7.95 (m, 4H) 8.60-8.72 (m, 2H) 8.83 (d, 1H);
Formula: C33H29N3O3S
Calc MW: 547.68
MS (ESI) negative ion 546 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.67-2.77 (m, 1H) 2.86-2.96 (m, 1H) 3.39-3.53 (m, 2H) 4.09-4.24 (m, 1H) 4.97-5.06 (m, 2H) 6.86-6.93 (m, 2H) 7.14-7.23 (m, 2H) 7.25-7.49 (m, 5H) 7.73-7.79 (m, 2H) 7.85-7.96 (m, 4H) 8.53-8.74 (m, 2H);
Formula: C28H26N2O3
Calc MW: 438.52
MS (ESI) negative ion 437 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 3.62-3.71 (m, 2H) 4.96-5.13 (m, 1H) 7.42-7.52 (m, 3H) 7.73-7.84 (m, 2H) 7.89-8.07 (m, 4H) 8.61-8.72 (m, 2H);
Formula: C20H16Cl2N2O2
Calc MW: 387.26
MS (ESI) negative ion 385 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.47-2.17 (m, 4H) 2.67-3.54 (m, 8H) 4.28-4.75 (m, 1H) 7.15-7.21 (m, 1H) 7.23-7.29 (m, 4H) 7.74-7.80 (m, 2H) 7.84-7.96 (m, 4H) 8.46-8.79 (m, 2H);
Formula: C25H27N3O
Calc MW: 385.51
MS (ESI) positive ion 386 (M+H); negative ion 384 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 4.94 (d, 1H) 5.18 (d, 1H) 7.19-7.37 (m, 6H) 7.44-7.51 (m, 4H) 7.68-7.86 (m, 6H) 8.60-8.69 (m, 2H);
Formula: C26H22N2O2
Calc MW: 394.47
MS (ESI) positive ion 395 (M+H); negative ion 393 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.21-2.26 (m, 6H) 2.39-2.47 (m, 1H) 2.79-2.88 (m, 1H) 5.17-5.25 (m, 1H) 7.22-7.49 (m, 5H) 7.75-7.82 (m, 2H) 7.89-7.95 (m, 2H) 8.01-8.08 (m, 2H) 8.62-8.71 (m, 2H);
Formula: C22H23N3O
Calc MW: 345.44
MS (ESI) positive ion 346 (M+H); negative ion 344 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.57-1.81 (m, 4H) 2.53-2.58 (m, 4H) 2.61-2.69 (m, 1H) 2.92-3.14 (m, 1H) 5.10-5.26 (m, 1H) 7.21-7.29 (m, 1H) 7.32-7.38 (m, 2H) 7.40-7.48 (m, 2H) 7.72-7.83 (m, 2H) 7.87-7.98 (m, 2H) 7.99-8.10 (m, 2H) 8.54-8.71 (m, 2H);
Formula: C24H25N3O
Calc MW: 371.48
MS (ESI) positive ion 372 (M+H); negative ion 370 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.32-2.52 (m, 5H) 2.81-2.93 (m, 1H) 3.47-3.63 (m, 4H) 5.09-5.42 (m, 1H) 7.20-7.31 (m, 1H) 7.33-7.40 (m, 2H) 7.39-7.50 (m, 2H) 7.74-7.81 (m, 2H) 7.88-8.00 (m, 2H) 7.96-8.09 (m, 2H) 8.56-8.75 (m, 2H);
Formula: C24H25N3O2
Calc MW: 387.48MS (ESI) positive ion 388 (M+H); negative ion 386 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.04-2.16 (m, 3H) 2.20-2.41 (m, 4H) 2.40-2.53 (m, 5H) 2.82-2.91 (m, 1H) 5.10-5.43 (m, 1H) 7.19-7.30 (m, 1H) 7.32-7.38 (m, 2H) 7.39-7.46 (m, 2H) 7.75-7.84 (m, 2H) 7.89-7.97 (m, 2H) 7.99-8.09 (m, 2H) 8.54-8.74 (m, 2H);
Formula: C25H28N4O
Calc MW: 400.52
MS (ESI) positive ion 401 M+H); negative ion 399M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 4.94 (d, 1H) 5.17 (d, 1H) 7.11-7.38 (m, 6H) 7.43-7.56 (m, 4H) 7.68-7.90 (m, 6H) 8.55-8.67 (m, 2H);
Formula: C26H22N2O2
Calc MW: 394.47
MS (ESI) positive ion 395 (M+H); negative ion 393 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 4.41 (d, 2H) 5.44 (t, 1H) 6.83-6.90 (m, 1 H) 7.27-7.36 (m, 2H) 7.38-7.44 (m, 2H) 7.50-7.58 (m, 2H) 7.69-7.74 (m, 1H) 7.75-7.81 (m, 2H) 7.84-7.99 (m, 4H) 8.52-8.70 (m, 2H);
Formula: C23H20N4O
Calc MW: 368.44
MS (ESI) positive ion 369 (M+H); negative ion 367 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.28-1.52 (m, 6H) 2.29-2.52 (m, 4H) 2.81-2.90 (m, 1H) 2.99-3.09 (m, 1H) 5.18-5.33 (m, 1H) 7.21-7.29 (m, 1H) 7.31-7.38 (m, 2H) 7.39-7.44 (m, 2H) 7.74-7.82 (m, 2H) 7.90-7.96 (m, 2H) 7.99-8.06 (m, 2H) 8.61-8.70 (m, 2H);
Formula: C25H27N3O
Calc MW: 385.51
MS (ESI) positive ion 386 (M+H); negative ion 384 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.29 (t, 3H) 3.61-3.67 (m, 1H) 3.69-3.73 (m, 1H) 3.99 (q, 2H) 4.93-5.11 (m, 1H) 6.85-6.90 (m, 2H) 7.25-7.36 (m, 2H) 7.67-7.81 (m, 2H) 7.88-7.97 (m, 2H) 8.00-8.06 (m, 2H) 8.53-8.74 (m, 2H);
Formula: C22H22N2O3
Calc MW: 362.43
MS (ESI) positive ion 363 (M+H); negative ion 361 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.20-1.34 (m, 9H) 3.60-3.74 (m, 2H) 4.94-5.18 (m, 1H) 7.29-7.35 (m, 4H) 7.73-7.83 (m, 2H) 7.89-7.94 (m, 2H) 8.00-8.09 (m, 2H) 8.60-8.68 (m, 2H);
Formula: C24H26N2O2
Calc MW: 374.48
MS (ESI) positive ion 375 (M+H); negative ion 373 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 3.76-3.86 (m, 2H) 5.13 (t, 1H) 7.36-7.47 (m, 1H) 7.75-7.81 (m, 2H) 7.84-7.89 (m, 1H) 7.91-7.97 (m, 2H) 8.03-8.08 (m, 2 H) 8.41-8.50 (m, 1H) 8.57-8.64 (m, 1H) 8.65-8.71 (m, 2H);
Formula: C19H17N3O2
Calc MW: 319.36
MS (ESI) positive ion 320 (M+H); negative ion 318 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.17-2.27 (m, 3H) 2.37-2.44 (m, 3H) 3.47-3.72 (m, 2H) 5.20-5.36 (m, 1H) 6.93-7.04 (m, 2H) 7.25-7.34 (m, 1H) 7.73-7.82 (m, 2H) 7.89-7.95 (m, 2H) 7.99-8.06 (m, 2H) 8.60-8.72 (m, 2H);
Formula: C22H22N2O2
Calc MW: 346.43
MS (ESI) positive ion 347 (M+H); negative ion 345 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.25-2.29 (m, 3H) 2.29-2.33 (m, 3H) 3.50-3.69 (m, 2H) 5.26-5.45 (m, 1H) 7.03-7.05 (m, 2H) 7.23-7.30 (m, 1H) 7.73-7.86 (m, 2H) 7.88-7.97 (m, 2H) 7.97-8.10 (m, 2H) 8.54-8.70 (m, 2H);
Formula: C22H22N2O2
Calc MW: 346.43
MS (ESI) positive ion 347 (M+H); negative ion 345 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.18 (d, 6H) 2.80-2.91 (m, 1H) 3.59-3.71 (m, 2H) 5.00-5.10 (m, 1H) 7.16-7.23 (m, 2H) 7.26-7.35 (m, 2H) 7.74-7.81 (m, 2H) 7.86-7.95 (m, 2H) 7.94-8.10 (m, 2H) 8.54-8.72 (m, 2H); MS (ESI) positive ion 361 (M+H); negative ion 359 (M−H).
Formula: C23H24N2O2
Calc MW: 360.45
MS (ESI) positive ion 361 (M+H); negative ion 359 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.41-2.48 (m, 3H) 3.57-3.71 (m, 2H) 4.97-5.16 (m, 1H) 7.20-7.26 (m, 2H) 7.33-7.40 (m, 2H) 7.73-7.81 (m, 2H) 7.87-7.99 (m, 2H) 7.99-8.10 (m, 2H) 8.56-8.74 (m, 2H);
Formula: C21H20N2O2S
Calc MW: 364.47
MS (ESI) positive ion 365 (M+H); negative ion 363 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 3.14-3.25 (m, 1H) 3.28-3.37 (m, 1H) 3.73-3.76 (m, 3H) 5.27-5.38 (m, 1H) 6.97 (d, 2H) 7.38 (d, 2H) 8.07-8.14 (m, 4H) 8.32 (d, 2H) 8.90 (d, 2H);
Formula: C21H21N3O2
Calc MW: 347.42
MS (ESI) positive ion 348 (M+H)
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 3.17-3.29 (m, 1H) 3.30-3.43 (m, 1H) 3.73-3.79 (m, 3H) 5.31-5.41 (m, 1H) 6.86-6.94 (m, 1H) 7.00-7.08 (m, 2H) 7.27-7.38 (m, 1H) 8.05-8.18 (m, 4H) 8.30 (d, 2H) 8.89 (d, 2H);
Formula: C21H21N3O2
Calc MW: 347.42
MS (ESI) positive ion 348 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 2.24-2.35 (m, 3H) 3.15-3.24 (m, 1H) 3.29-3.41 (m, 1H) 5.30-5.38 (m, 1H) 7.19 (d, 2H) 7.36 (d, 2H) 8.07-8.16 (m, 4H) 8.33 (d, 2H) 8.91 (d, 2H);
Formula: C21H21N3O
Calc MW: 331.42
MS (ESI) positive ion 332 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.65 (d, 3H) 5.91-6.05 (m, 1H) 7.48-7.69 (m, 4H) 7.86 (d, 1H) 7.97 (d, 1H) 8.04-8.15 (m, 4H) 8.22 (d, 1H) 8.27-8.33 (m, 2H) 8.81-8.95 (m, 2H);
Formula: C24H20N2O
Calc MW: 352.44
MS (ESI) positive ion 353 (M+H); negative ion 351 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 3.01-3.28 (m, 2H) 5.16-5.42 (m, 1H) 7.14-7.54 (m, 10H) 7.90-8.07 (m, 4H) 8.15-8.29 (m, 2H) 8.74-8.96 (m, 2H);
Formula: C26H22N2O
Calc MW: 378.48
MS (ESI) positive ion 379 (M+H); negative ion 377 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 6.39-6.45 (m, 1H) 7.27-7.35 (m, 1H) 7.35-7.53 (m, 8H) 8.01-8.15 (m, 4H) 8.15-8.23 (m, 2H) 8.78-8.88 (m, 2H);
Formula: C25H19ClN2O
Calc MW: 398.90
MS (ESI) positive ion 399 (M+H); negative ion 397 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.20 (d, 3H) 1.69-1.96 (m, 2H) 2.58-2.67 (m, 2H) 3.97-4.14 (m, 1H) 7.14-7.33 (m, 5H) 8.01-8.09 (m, 4H) 8.19-8.33 (m, 2H) 8.81-8.91 (m, 2H);
Formula: C22H22N2O
Calc MW: 330.43
MS (ESI) positive ion 331 (M+H); negative ion 329 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.66 (d, 3H) 5.95-6.03 (m, 1H) 7.49-7.70 (m, 4H) 7.85 (d, 1H) 7.97 (d, 1H) 8.05-8.14 (m, 4H) 8.20-8.25 (m, 1H) 8.29-8.36 (m, 2H) 8.80-8.96 (m, 2H);
Formula: C24H20N2O
Calc MW: 352.44
MS (ESI) positive ion 353 (M+H); negative ion 351 (M−H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.65 (d, 3H) 5.45 (q, 1H) 6.77-6.87 (m, 1H) 7.30 (d, 1H) 7.57 (d, 1H) 7.65-7.74 (m, 1H) 8.07-8.16 (m, 4H) 8.35 (d, 2H) 8.91 (d, 2H);
Formula: C22H17ClN2O2
Calc MW: 376.85
MS (ESI) positive ion 377 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.52 (d, 3H) 5.30 (q, 1H) 6.28-6.35 (m, 1H) 6.39-6.48 (m, 1H) 7.53-7.60 (m, 1H) 8.05-8.13 (m, 4H) 8.34 (d, 2H) 8.90 (d, 2H);
Formula: C18H16N2O2
Calc MW: 292.34
MS (ESI) positive ion 293 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.48 (d, 3H) 2.19-2.29 (m, 3H) 3.65-3.74 (m, 3H) 5.12 (q, 1H) 7.40-7.49 (m, 1H) 7.99-8.14 (m, 4H) 8.42 (d, 2H) 8.94 (d, 2H);
Formula: C19H20N4O
Calc MW: 320.4
MS (ESI) positive ion 321 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.46-1.64 (m, 3H) 5.30 (q, 1H) 7.26-7.58 (m, 3H) 7.67-7.91 (m, 2H) 7.96-8.20 (m, 5H) 8.25-8.43 (m, 2H) 8.77-9.03 (m, 2 H);
Formula: C23H19FN4O
Calc MW: 386.43
MS (ESI) positive ion 387 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.57 (d, 3H) 5.27 (q, 1H) 7.27-7.43 (m, 2H) 7.72-7.77 (m, 1H) 7.81-7.87 (m, 2H) 8.07-8.14 (m, 4H) 8.34-8.42 (m, 3H) 8.92 (d, 2H);
Formula: C23H19F N4O
Calc MW: 386.43
MS (ESI) positive ion 387 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.57 (d, 3H) 3.78-3.82 (m, 3H) 5.25 (q, 1H) 7.05 (d, 2H) 7.66-7.72 (m, 3H) 8.05-8.12 (m, 4H) 8.26-8.30 (m, 1H) 8.36 (d, 2H) 8.91 (d, 2H);
Formula: C24H22N4O2
Calc MW: 398.47
MS (ESI) positive ion 399 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.57 (d, 3H) 3.86-3.88 (m, 3H) 5.27 (q, 1 H) 7.05-7.12 (m, 1H) 7.23 (d, 1H) 7.34-7.42 (m, 1H) 7.59 (d, 1H) 7.68-7.74 (m, 1H) 8.08-8.14 (m, 5H) 8.40 (d, 2H) 8.93 (d, 2H);
Formula: C24H22N4O2
Calc MW: 398.47
MS (ESI) positive ion 399 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 0.91 (t, 3H) 1.64 (d, 3H) 1.66-1.72 (m, 2H) 2.67 (t, 2H) 5.39 (q, 1H) 8.08-8.13 (m, 4H) 8.31 (d, 2H) 8.88 (d, 2H);
Formula: C19H2O N4O2
Calc MW: 336.4
MS (ESI) positive ion 337 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.73 (d, 3H) 5.49 (q, 1H) 7.55-7.64 (m, 3H) 7.99-8.04 (m, 2H) 8.11-8.18 (m, 4H) 8.39 (d, 2H) 8.93 (d, 2H);
Formula: C22H18N4O2
Calc MW: 370.41
MS (ESI) positive ion 371 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.75 (d, 3H) 5.52 (q, 1H) 8.08 (d, 2H) 8.11-8.18 (m, 4H) 8.39 (d, 2H) 8.86 (d, 2H) 8.93 (d, 2H);
Formula: C21H17N5O2
Calc MW: 371.4
MS (ESI) positive ion 372 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 0.84 (t, 3H) 1.66 (d, 3H) 1.70-1.82 (m, 2 H) 4.01-4.15 (m, 2H) 5.48 (q, 1H) 8.05-8.11 (m, 4H) 8.30 (d, 2H) 8.88 (d, 2H) 8.94-9.02 (m, 1H);
Formula: C19H21N5O
Calc MW: 335.41
MS (ESI) positive ion 336 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.68 (d, 3H) 3.21-3.31 (m, 3H) 3.58-3.73 (m, 2H) 4.29-4.44 (m, 2H) 5.48 (q, 1H) 8.04-8.21 (m, 4H) 8.39 (d, 2H) 8.91 (d, 2 H) 8.99-9.05 (m, 1H);
Formula: C19H21N5O2
Calc MW: 351.41
MS (ESI) positive ion 352 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.56-1.67 (m, 2H) 1.71 (d, 3H) 1.76-1.84 (m, 2H) 1.85-1.96 (m, 2H) 1.99-2.10 (m, 1H) 2.20-2.31 (m, 1H) 4.73-4.88 (m, 1H) 5.56 (q, 1H) 8.06-8.14 (m, 4H) 8.39 (d, 2H) 8.93 (d, 2H) 9.38-9.44 (m, 1H);
Formula: C21H23N5O
Calc MW: 361.45
MS (ESI) positive ion 362 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.70 (d, 3H) 1.95-2.12 (m, 2H) 3.14-3.21 (m, 3H) 3.26-3.45 (m, 2H) 4.13-4.31 (m, 2H) 5.51 (q, 1H) 8.05-8.17 (m, 4H) 8.39 (d, 2H) 8.91 (d, 2H) 9.18-9.27 (m, 1H);
Formula: C20H23N5O2
Calc MW: 365.44
MS (ESI) positive ion 366 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.27 (t, 3H) 1.50 (d, 3H) 2.27 (s, 3H) 2.33 (s, 3H) 4.02 (q, 2H) 5.04 (q, 1H) 8.00-8.14 (m, 4H) 8.39 (d, 2H) 8.92 (d, 2H);
Formula: C21H24N4O
Calc MW: 348.45
MS (ESI) positive ion 349 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.73 (d, 3H) 5.49 (q, 1H) 7.66 (d, 2H) 8.03 (d, 2H) 8.09-8.16 (m, 4H) 8.34 (d, 2H) 8.90 (d, 2H);
Formula: C22H17ClN4O2
Calc MW: 404.86
MS (ESI) positive ion 405 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.73 (d, 3H) 2.38 (s, 3H) 5.48 (q, 1H) 7.38 (d, 2H) 7.89 (d, 2H) 8.07-8.16 (m, 4H) 8.32 (d, 2H) 8.89 (d, 2H);
Formula: C23H20N4O2
Calc MW: 384.44
MS (ESI) positive ion 385 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.74 (d, 3H) 2.40 (s, 3H) 5.48 (q, 1H) 7.39-7.51 (m, 2H) 7.76-7.85 (m, 2H) 8.09-8.17 (m, 4H) 8.39 (d, 2H) 8.93 (d, 2H);
Formula: C23H20N4O2
Calc MW: 384.44
MS (ESI) positive ion 385 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.51 (d, 3H) 2.28 (s, 3H) 2.35 (s, 3H) 3.70 (s, 3H) 5.03 (q, 1H) 8.03-8.17 (m, 4H) 8.42 (d, 2H) 8.94 (d, 2H);
Formula: C20H22N4O
Calc MW: 334.42
MS (ESI) positive ion 335 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.49 (d, 3H) 2.26 (s, 3H) 5.15-5.30 (m, 1H) 5.99 (s, 1H) 6.20 (s, 1H) 7.97-8.18 (m, 4H) 8.38 (d, 2H) 8.90 (d, 2H);
Formula: C13H18N2O2
Calc MW: 306.37
MS (ESI) positive ion 307 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.62 (d, 3H) 5.41-5.51 (m, 1H) 6.97-7.03 (m, 1H) 7.03-7.12 (m, 1H) 7.36-7.42 (m, 1H) 8.04-8.15 (m, 4H) 8.37 (d, 2H) 8.90 (d, 2H);
Formula: C18H16N2O S
Calc MW: 308.41
MS (ESI) positive ion 309 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.75 (d, 3H) 5.51 (q, 1H) 7.68-7.77 (m, 1H) 8.10-8.22 (m, 4H) 8.38-8.54 (m, 3H) 8.79-8.86 (m, 1H) 8.96 (d, 2H) 9.15-9.24 (m, 1H);
Formula: C21H17N5O2
Calc MW: 371.4
MS (ESI) positive ion 372 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.74 (d, 3H) 5.52 (q, 1H) 7.52-7.59 (m, 1 H) 7.59-7.64 (m, 1H) 7.67-7.74 (m, 1H) 7.88-7.94 (m, 1H) 8.07-8.15 (m, 4H) 8.29 (d, 2H) 8.89 (d, 2H);
Formula: C22H17ClN4O2
Calc MW: 404.86
MS (ESI) positive ion 405 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 0.93 (t, 3H) 1.78-1.94 (m, 2H) 4.88-4.99 (m, 1H) 7.21-7.29 (m, 1H) 7.33-7.39 (m, 2H) 7.39-7.45 (m, 2H) 8.05-8.16 (m, 4H) 8.39 (d, 2H) 8.92 (d, 2H);
Formula: C21H20N2O
Calc MW: 316.41
MS (ESI) positive ion 317 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.65 (d, 3H) 5.35 (q, 1H) 7.75-7.84 (m, 1H) 7.89-8.00 (m, 1H) 8.10-8.18 (m, 4H) 8.36-8.43 (m, 3H) 8.73-8.79 (m, 1H) 8.95 (d, 2H);
Formula: C13H17N3O
Calc MW: 303.37
MS (ESI) positive ion 304 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.54-1.69 (d, 3H) 2.70 (s, 3H) 5.32 (q, 1 H) 7.72 (d, 1H) 7.79 (d, 1H) 8.07-8.16 (m, 4H) 8.30-8.40 (m, 3H) 8.84-8.99 (m, 2 H);
Formula: C20H19N3O
Calc MW: 317.39
MS (ESI) positive ion 318 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.64 (d, 3H) 2.46 (s, 3H) 5.32 (q, 1H) 7.93 (d, 1H) 8.09-8.17 (m, 4H) 8.34 (d, 1H) 8.42 (d, 2H) 8.60-8.68 (m, 1H) 8.90-9.00 (m, 2H);
Formula: C20H19N3O
Calc MW: 317.39
MS (ESI) positive ion 318 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.62 (d, 3H) 5.35 (q, 1H) 8.01-8.09 (m, 1H) 8.10-8.17 (m, 4H) 8.37-8.43 (m, 2H) 8.57-8.68 (m, 1H) 8.77-8.84 (m, 1H) 8.91-9.01 (m, 3H);
Formula: C19H17N3O
Calc MW: 303.37
MS (ESI) positive ion 304 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.65 (d, 3H) 5.34 (q, 1H) 7.74-7.85 (m, 1H) 7.92-7.99 (m, 1H) 8.10-8.21 (m, 4H) 8.37-8.45 (m, 3H) 8.73-8.79 (m, 1H) 8.95 (d, 2H);
Formula: C19H17N3O
Calc MW: 303.37
MS (ESI) positive ion 304 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.51 (d, 3H) 5.15 (q, 1H) 7.38 (d, 2H) 7.54 (d, 2H) 8.06-8.11 (m, 4H) 8.35 (d, 2H) 8.91 (d, 2H);
Formula: C20H17BrN2O
Calc MW: 381.28
MS (ESI) positive ion 381 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.49 (d, 3H) 2.28 (s, 3H) 5.16 (q, 1H) 7.15 (d, 2H) 7.30 (d, 2H) 8.05-8.11 (m, 4H) 8.34 (d, 2H) 8.90 (d, 2H);
Formula: C21H20N2O
Calc MW: 316.41
MS (ESI) positive ion 317 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.49 (d, 3H) 3.72 (s, 3H) 5.15 (q, 1H) 6.92 (d, 2H) 7.34 (d, 2H) 8.04-8.13 (m, 4H) 8.34-8.41 (m, 2H) 8.88-8.96 (m, 2H);
Formula: C21H20N2O2
Calc MW: 332.41
MS (ESI) positive ion 333 (M+H).
1H NMR (300 MHz, DMSO-D6) δ ppm: 8.89 (d, J=8.1 Hz, 1H), 8.67 (d, J=6.1 Hz, 2 H), 8.03 (d, J=8.8 Hz, 2H), 7.92 (d, J=8.8 Hz, 2H), 7.77 (d, J=6.1 Hz, 2H), 7.24 (t, J=7.8 Hz, 1H), 6.95-7.00 (m, 2H), 6.80 (ddd, J=1.0, 2.4, 8.1 Hz, 1H), 5.16 (quin, J=7.1 Hz, 1H), 3.74 (s, 3H), 1.48 (d, J=7.1 Hz, 3H)
Formula: C21H20N2O2
Calc MW: 332.40
MS (ESI) positive ion 333 (M+H)
αD20=−20.7 (c 1.0, methanol).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.51 (d, 3H) 5.20 (q, 1H) 7.11-7.22 (m, 2 H) 7.42-7.50 (m, 2H) 8.05-8.12 (m, 4H) 8.35 (d, 2H) 8.91 (d, 2H);
Formula: C20H17FN2O
Calc MW: 320.37
MS (ESI) positive ion 321 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.51 (d, 3H) 5.48 (q, 1H) 7.43-7.52 (m, 1H) 7.65-7.75 (m, 2H) 7.80-7.87 (m, 1H) 8.07-8.11 (m, 4H) 8.34 (d, 2H) 8.91 (d, 2 H);
Formula: C21H17F3N2O
Calc MW: 370.38
MS (ESI) positive ion 371 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.55 (d, 3H) 5.28 (q, 1H) 7.58-7.65 (m, 2 H) 7.71-7.79 (m, 2H) 8.06-8.12 (m, 4H) 8.35 (d, 2H) 8.92 (d, 2H);
Formula: C21H17F3N2O
Calc MW: 370.38
MS (ESI) positive ion 371 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.51 (d, 3H) 5.42 (q, 1H) 7.14-7.23 (m, 2H) 7.27-7.35 (m, 1H) 7.45-7.53 (m, 1H) 8.05-8.13 (m, 4H) 8.33 (d, 2H) 8.89 (d, 2H);
Formula: C20H17FN2O
Calc MW: 320.37
MS (ESI) positive ion 321 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.58 (d, 3H) 5.35 (q, 1H) 7.97-8.03 (m, 1H) 8.05-8.10 (m, 4H) 8.10-8.13 (m, 2H) 8.19-8.24 (m, 2H) 8.84-8.89 (m, 2H);
Formula: C22H16F6N2O
Calc MW: 438.38
MS (ESI) positive ion 439 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.50 (d, 3H) 5.17 (q, 1H) 7.37-7.47 (m, 4H) 8.06-8.11 (m, 4H) 8.33 (d, 2H) 8.90 (d, 2H);
Formula: C20H17ClN2O
Calc MW: 336.82
MS (ESI) positive ion 337 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.62 (d, 3H) 5.36 (q, 1H) 7.46-7.55 (m, 2 H) 7.59-7.65 (m, 1H) 7.87-7.94 (m, 4H) 8.04-8.14 (m, 4H) 8.27 (d, 2H) 8.87 (d, 2 H);
Formula: C24H20N2O
Calc MW: 352.44
MS (ESI) positive ion 353 (M+H).
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm 1.13 (d, 3H) 3.57-3.69 (m, 2H) 3.79-3.88 (m, 1H) 4.05-4.19 (m, 1H) 4.35-4.66 (m, 2H) 7.16-7.52 (m, 5H) 7.72-7.81 (m, 2H) 7.86-8.06 (m, 4H) 8.47-8.78 (m, 2H);
Formula: C23H24N2O3
Calc MW: 376.46
MS (ESI) positive ion 377 (M+H); negative ion 375 (M−H).
Formula: C21H18N2O2
Calc MW: 330.39
1H NMR (400 MHz, DMSO-D6) δ ppm: 8.88 (d, J=8.0, 1H), 8.68 (d, J=5.6, 2H), 7.80 (dd, J=1.6, 4.5, 2H), 7.78 (d, J=8.0, 1H), 7.50 (d, J=1.6, 1H), 7.45 (dd, J=1.6, 8.0, 1H), 7.40-7.29 (m, 4H), 7.26-7.20 (m, 1H), 5.19 (dd, J=7.3, 13.9, 1H), 4.69 (s, 1H), 4.03 (s, 3H), 3.45 (dd, J=5.5, 10.3, 2H), 2.04-1.85 (m, 2H).
Formula: C22H22N2O3
Calc MW: 362.43
MS m/z: 363.18 [M+H]+, Rt=1.84 min.
A mixture of 4-(pyridin-4-yl)benzoic acid (0.970 g, 4.87 mmol), (S)-1-(3-methoxyphenyl)ethanamine (0.884 g, 5.84 mmol), DIEA (1.7 ml, 9.8 mmol), and O(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1.87 g, 5.82 mmol) in DMF (10 ml) was stirred overnight, diluted with EtOAc, washed with 1N NaOH, sat NaHCO3, and brine, dried (Na2SO4), and chromatographed (20-85% EtOAc/dichloromethane) and triturated (Et2O) to give the title compound (1.075 g, 3.23 mmol) as a white solid.
1H NMR (300 MHz, DMSO-D6) δ ppm: 8.89 (d, J=8.1 Hz, 1H), 8.67 (d, J=6.1 Hz, 2H), 8.03 (d, J=8.8 Hz, 2H), 7.92 (d, J=8.8 Hz, 2H), 7.77 (d, J=6.1 Hz, 2H), 7.24 (t, J=7.8 Hz, 1H), 6.95-7.00 (m, 2H), 6.80 (ddd, J=1.0, 2.4, 8.1 Hz, 1H), 5.16 (quin, J=7.1 Hz, 1H), 3.74 (s, 3H), 1.48 (d, J=7.1 Hz, 3H.
Formula: C21H20N2O2
Calc MW: 332.40
MS (ESI) m/z: 333.0 [M+H]+
αD20=+22.4 (c 1.0, methanol).
Formula: C22H22N2O2
Calc MW: 346.43
Formula: C22H22N2O3
Calc MW: 362.43
Formula: C22H22N2O2
Calc MW: 346.43
Formula: C21H19FN2O2
Calc MW: 350.39
Formula: C23H24N2O2
Calc MW: 360.45
The synthesis of the title compound was performed as described for example 7.
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.45-1.56 (m, 3H), 2.37-2.45 (s, 3H), 3.74-3.76 (s, 3H), 5.13-5.18 (m, 1H), 6.81-6.85 (m, 1H), 6.96-7.01 (m, 2H), 7.25-7.30 (m, 1H), 7.61-7.69 (m, 2H), 7.85-7.94 (m, 1H), 8.03-8.07 (m, 2H), 8.72-8.90 (m, 2H)
Formula: C22H22N2O2
Calc MW: 346.43
MS (ESI) m/z: 347 [M+H]+
The following compounds of Examples 102 to 104 were prepared in an analogous method as described above
Formula: C22H22N2O2
Calc MW: 346.43
Formula: C22H22N2O3
1H NMR (400 MHz, DMSO) δ 8.67 (d, J=5.5, 2H), 8.53 (d, J=8.0, 1H), 7.79 (d, J=5.8, 2H), 7.73 (d, J=7.9, 1H), 7.50 (s, 1H), 7.45 (d, J=8.0, 1H), 7.26 (t, J=7.6, 1H), 6.98 (d, J=7.1, 1H), 6.84-6.78 (m, 1H), 5.12 (p, J=7.1, 1H), 4.01 (s, 3H), 3.75 (d, J=10.8, 3H), 1.45 (d, J=7.0, 3H).
Formula: C25H27N3O2
Calc MW: 401.51
To a solution of 2-methoxy-4-(pyridin-4-yl)benzoic acid (34 mg, 0.15 mmol), dissolved in DMA (0.5 ml) was added a solution of HATU (68 mg, 0.18 mmol) dissolved in DMA (0.5 ml). Then a solution of TEA (55 mg, 0.5 mmol), dissolved in DMA (0.4 ml) was added, followed by a solution of 2,3-dihydro-1H-inden-1-amine (27 mg, 0.2 mmol) dissolved in DMA (0.7 ml). The resulting mixture was shaken for 4 hours at room temperature. The reaction was checked by LC/MS and concentrated to dryness. The residue was dissolved in 1:1 DMSO/methanol and purified by reverse phase HPLC (TFA method) to afford the title compound.
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.88-2.00 (m, 1H), 2.46-2.52 (m, 1H), 2.82-3.02 (m, 2H), 3.98-4.03 (s, 3H), 5.53 (t, 1H), 7.23-7.34 (m, 4H), 7.62-7.68 (m, 2H), 7.85-7.89 (m, 1H), 8.37-8.43 (m, 2H), 8.90-8.94 (m, 2H)
Formula: C22H20N2O2
Calc MW: 344.41
MS (ESI) m/z: 345 [M+H]+
The following compounds of the examples 106 to 147 were prepared as described for example 105.
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.57-1.67 (m, 3H), 3.99-4.05 (s, 3H), 5.88-5.99 (m, 1H), 7.52-7.70 (m, 6H), 7.76-7.80 (m, 1H), 7.84-7.89 (m, 1H), 7.95-8.01 (m, 1H), 8.20-8.24 (m, 1H), 8.33-8.37 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C25H22N2O2
Calc MW: 382.46
MS (ESI) m/z: 383 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.54-1.61 (m, 3H), 4.04-4.09 (s, 3H), 5.28-5.33 (m, 1H), 7.47-7.67 (m, 5H), 7.77-7.82 (m, 1H), 7.87-7.95 (m, 4H), 8.34-8.39 (m, 2H), 8.87-8.91 (m, 2H)
Formula: C25H22N2O2
Calc MW: 382.46
MS (ESI) m/z: 383 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 4.00-4.08 (s, 3H), 4.98-5.03 (m, 1H), 5.22-5.36 (m, 1H), 7.19-7.32 (m, 10H), 7.58-7.68 (m, 2H), 7.81-7.88 (m, 1H), 8.32-8.40 (m, 2H), 8.88-8.95 (m, 2H)
Formula: C27H24N2O3
Calc MW: 424.50
MS (ESI) m/z: 425 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.85-2.93 (m, 1H), 3.13-3.23 (m, 1H), 4.01-4.07 (s, 3H), 4.51-4.59 (m, 1H), 5.40-5.46 (m, 1H), 7.18-7.30 (m, 4H), 7.66-7.73 (m, 2H), 8.21-8.27 (m, 1H), 8.33-8.41 (m, 2H), 8.87-8.94 (m, 2H)
Formula: C22H20N2O3
Calc MW: 360.41
MS (ESI) m/z: 361 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.59-1.64 (m, 3H), 3.99-4.03 (s, 3H), 5.89-5.98 (m, 1H), 7.52-7.68 (m, 6H), 7.76-7.80 (m, 1H), 7.84-7.89 (m, 1H), 7.94-8.00 (m, 1H), 8.20-8.26 (m, 1H), 8.32-8.37 (m, 2H), 8.83-8.98 (m, 2H)
Formula: C25H22N2O2
Calc MW: 382.46
MS (ESI) m/z: 383 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.77-2.06 (m, 4H), 2.72-2.85 (m, 2H), 3.93-4.02 (m, 3H), 5.13-5.31 (m, 1H), 7.12-7.23 (m, 3H), 7.30-7.36 (m, 1H), 7.58-7.66 (m, 2H), 7.81-7.95 (m, 1H), 8.26-8.43 (m, 2H), 8.83-8.92 (m, 2H)
Formula: C23H22N2O2
Calc MW: 358.44
MS (ESI) m/z: 359 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.45-1.50 (m, 3H), 4.00-4.06 (s, 3H), 5.11-5.18 (m, 1H), 7.25-7.44 (m, 5H), 7.58-7.65 (m, 2H), 7.77-7.83 (m, 1H), 8.26-8.38 (m, 2H), 8.81-8.97 (m, 2H)
Formula: C21H20N2O2
Calc MW: 332.40
MS (ESI) m/z: 333 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.83-2.95 (m, 1H), 3.11-3.23 (m, 1H), 4.02-4.07 (s, 3H), 4.51-4.61 (m, 1H), 5.39-5.50 (m, 1H), 7.16-7.35 (m, 4H), 7.66-7.74 (m, 2H), 8.21-8.27 (m, 1H), 8.35-8.41 (m, 2H), 8.87-8.97 (m, 2H)
Formula: C22H20N2O3
Calc MW: 360.41
MS (ESI) m/z: 361 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.44-1.50 (m, 3H), 3.99-4.09 (s, 3H), 5.10-5.26 (m, 1H), 7.22-7.47 (m, 5H), 7.58-7.63 (m, 2H), 7.74-7.83 (m, 1H), 8.26-8.39 (m, 2H), 8.83-8.94 (m, 2H)
Formula: C21H20N2O2
Calc MW: 332.40
MS (ESI) m/z: 333 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 4.01-4.07 (m, 3H), 4.99-5.03 (m, 1H), 5.25-5.31 (m, 1H), 7.17-7.32 (m, 10H), 7.58-7.67 (m, 2H), 7.81-7.87 (m, 1H), 8.31-8.39 (m, 2H), 8.85-8.95 (m, 2H)
Formula: C27H24N2O3
Calc MW: 424.50
MS (ESI) m/z: 425 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.40-1.49 (m, 3H), 2.27-2.31 (s, 3H), 4.00-4.05 (s, 3H), 5.04-5.17 (m, 1H), 7.15-7.21 (m, 2H), 7.27-7.34 (m, 2H), 7.59-7.63 (m, 2H), 7.74-7.84 (m, 1H), 8.30-8.35 (m, 2H), 8.85-8.91 (m, 2H)
Formula: C22H22N2O2
Calc MW: 346.43
MS (ESI) m/z: 347 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.42-1.47 (m, 3H), 2.25-2.32 (s, 3H), 4.00-4.06 (s, 3H), 5.06-5.13 (m, 1H), 7.15-7.20 (m, 2H), 7.27-7.33 (m, 2H), 7.59-7.65 (m, 2H), 7.77-7.80 (m, 1H), 8.31-8.36 (m, 2H), 8.85-8.93 (m, 2H)
Formula: C22H22N2O2
Calc MW: 346.43
MS (ESI) m/z: 347 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.73-2.85 (m, 1H), 3.12-3.25 (m, 1H), 3.98-4.03 (s, 3H), 4.34-4.47 (m, 1H), 5.24-5.32 (m, 1H), 7.19-7.27 (m, 4H), 7.62-7.67 (m, 2H), 7.87-7.93 (m, 1H), 8.30-8.42 (m, 2H), 8.87-8.93 (m, 2H)
Formula: C22H20N2O3
Calc MW: 360.41
MS (ESI) m/z: 361 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.42-1.52 (m, 3H), 3.98-4.05 (s, 3H), 5.01-5.19 (m, 1H), 7.35-7.50 (m, 4H), 7.59-7.67 (m, 2H), 7.73-7.81 (m, 1H), 8.31-8.43 (m, 2H), 8.85-9.00 (m, 2H)
Formula: C21H19ClN2O2
Calc MW: 366.85
MS (ESI) m/z: 367 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.41-1.51 (m, 3H), 4.01-4.05 (s, 3H), 5.08-5.16 (m, 1H), 7.39-7.47 (m, 4H), 7.59-7.67 (m, 2H), 7.73-7.80 (m, 1H), 8.30-8.40 (m, 2H), 8.84-8.95 (m, 2H)
Formula: C21H19ClN2O2
Calc MW: 366.85
MS (ESI) m/z: 367 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.52-1.61 (m, 3H), 4.03-4.08 (s, 3H), 5.28-5.37 (m, 1H), 7.47-7.67 (m, 5H), 7.77-7.82 (m, 1H), 7.88-7.97 (m, 4H), 8.33-8.38 (m, 2H), 8.86-8.94 (m, 2H)
Formula: C25H22N2O2
Calc MW: 382.46
MS (ESI) m/z: 383 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 3.66-3.71 (m, 2H), 3.84-3.86 (s, 3H), 4.05-4.10 (s, 3H), 4.94-5.06 (m, 1H), 7.07-7.18 (m, 1H), 7.29-7.37 (m, 1H), 7.44-7.47 (m, 1H), 7.62-7.71 (m, 2H), 7.85-7.89 (m, 1H), 8.32-8.42 (m, 2H), 8.88-8.94 (m, 2H)
Formula: C22H21ClN2O4
Calc MW: 412.87
MS (ESI) m/z: 413 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.24-2.32 (m, 6H), 3.55-3.69 (m, 2H), 4.05-4.11 (s, 3H), 5.28-5.41 (m, 1H), 7.05-7.10 (m, 2H), 7.18-7.23 (m, 1H), 7.59-7.69 (m, 2H), 7.84-7.91 (m, 1H), 8.32-8.42 (m, 2H), 8.84-8.94 (m, 2H)
Formula: C23H24N2O3
Calc MW: 376.45
MS (ESI) m/z: 377 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.16-1.21 (m, 6H), 2.82-2.91 (m, 1H), 3.64-3.75 (m, 2H), 4.05-4.12 (s, 3H), 5.02-5.08 (m, 1H), 7.20-7.33 (m, 4H), 7.62-7.69 (m, 2H), 7.90-7.95 (m, 1H), 8.34-8.41 (m, 2H), 8.82-8.96 (m, 2H)
Formula: C24H26N2O3
Calc MW: 390.48
MS (ESI) m/z: 391 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.34-1.47 (m, 3H), 3.87-3.92 (s, 3H), 4.05-4.10 (s, 3H), 5.33-5.43 (m, 1H), 6.89-7.07 (m, 2H), 7.23-7.40 (m, 2H), 7.62-7.70 (m, 2H), 7.88-7.97 (m, 1H), 8.35-8.44 (m, 2H), 8.87-8.98 (m, 2H)
Formula: C22H22N2O3
Calc MW: 362.43
MS (ESI) m/z: 363 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.44-1.47 (m, 3H), 4.01-4.05 (s, 3H), 5.09-5.17 (m, 1H), 7.23-7.30 (m, 1H), 7.37-7.52 (m, 2H), 7.58-7.66 (m, 2H), 7.71-7.80 (m, 1H), 8.27-8.39 (m, 2H), 8.79-9.05 (m, 2H)
Formula: C21H18F2N2O2
Calc MW: 368.38
MS (ESI) m/z: 369 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.44-1.50 (m, 3H), 3.99-4.04 (s, 3H), 5.08-5.21 (m, 1H), 7.14-7.25 (m, 2H), 7.43-7.50 (m, 2H), 7.59-7.65 (m, 2H), 7.74-7.80 (m, 1H), 8.31-8.38 (m, 2H), 8.86-8.93 (m, 2H)
Formula: C21H19FN2O2
Calc MW: 350.39
MS (ESI) m/z: 351 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.42-1.48 (m, 3H), 3.73-3.75 (s, 3H), 3.99-4.06 (s, 3H), 5.05-5.15 (m, 1H), 6.90-6.96 (m, 2H), 7.31-7.38 (m, 2H), 7.59-7.65 (m, 2H), 7.75-7.85 (m, 1H), 8.28-8.38 (m, 2H), 8.81-8.95 (m, 2H)
Formula: C22H22N2O3
Calc MW: 362.43
MS (ESI) m/z: 363 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.40-1.47 (m, 3H), 3.74-3.76 (s, 3H), 3.99-4.04 (s, 3H), 5.08-5.14 (m, 1H), 6.90-6.98 (m, 2H), 7.31-7.36 (m, 2H), 7.58-7.64 (m, 2H), 7.75-7.82 (m, 1H), 8.32-8.39 (m, 2H), 8.85-8.96 (m, 2H)
Formula: C22H22N2O3
Calc MW: 362.43
MS (ESI) m/z: 363 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.40-1.52 (m, 3H), 3.76-3.78 (s, 3H), 4.01-4.06 (s, 3H), 5.06-5.16 (m, 1H), 6.78-6.87 (m, 1H), 6.94-7.04 (m, 2H), 7.24-7.37 (m, 1H), 7.62-7.66 (m, 2H), 7.74-7.81 (m, 1H), 8.36-8.44 (m, 2H), 8.88-8.97 (m, 2H)
Formula: C22H22N2O3
Calc MW: 362.43
MS (ESI) m/z: 363 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.42-1.49 (m, 3H), 4.00-4.05 (m, 3H), 5.08-5.18 (m, 1H), 7.15-7.23 (m, 2H), 7.42-7.48 (m, 2H), 7.57-7.63 (m, 2H), 7.74-7.82 (m, 1H), 8.24-8.37 (m, 2H), 8.82-8.92 (m, 2H)
Formula: C21H19FN2O2
Calc MW: 350.39
MS (ESI) m/z: 349 [M−H]−
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.42-1.54 (m, 3H), 4.00-4.09 (s, 3H), 5.16-5.35 (m, 1H), 7.59-7.87 (m, 7H), 8.30-8.45 (m, 2H), 8.86-9.07 (m, 2H)
Formula: C22H19F3N2O2
Calc MW: 400.40
MS (ESI) m/z: 401 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.25-1.41 (m, 6H), 1.41-1.48 (m, 3H), 3.93-4.11 (m, 7H), 5.04-5.14 (m, 1H), 6.86-6.95 (m, 2H), 6.98-7.11 (m, 1H), 7.56-7.66 (m, 2H), 7.71-7.85 (m, 1H), 8.24-8.42 (m, 2H), 8.79-8.98 (m, 2H)
Formula: C25H28N2O4
Calc MW: 420.51
MS (ESI) m/z: 421 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.36-1.50 (m, 3H), 3.99-4.08 (s, 3H), 4.15-4.28 (m, 4H), 4.96-5.14 (m, 1H), 6.78-6.99 (m, 3H), 7.58-7.68 (m, 2H), 7.72-7.82 (m, 1H), 8.31-8.42 (m, 2H), 8.84-8.95 (m, 2H)
Formula: C23H22N2O4
Calc MW: 390.44
MS (ESI) m/z: 391 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 3.68-3.75 (m, 2H), 4.07-4.12 (s, 3H), 5.02-5.09 (m, 1H), 7.44-7.51 (m, 3H), 7.60-7.70 (m, 2H), 7.80-7.90 (m, 1H), 8.28-8.42 (m, 2H), 8.86-8.95 (m, 2H)
Formula: C21H18Cl2N2O3
Calc MW: 417.29
MS (ESI) m/z: 417 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.43-2.48 (s, 3H), 3.62-3.75 (m, 2H), 4.05-4.11 (s, 3H), 5.00-5.07 (m, 1H), 7.23-7.39 (m, 4H), 7.63-7.72 (m, 2H), 7.89-7.94 (m, 1H), 8.38-8.45 (m, 2H), 8.90-8.97 (m, 2H)
Formula: C22H22N2O3S
Calc MW: 394.49
MS (ESI) m/z: 395 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.22-1.28 (m, 6H), 3.62-3.72 (m, 2H), 4.05-4.10 (s, 3H), 4.54-4.59 (m, 1H), 4.97-5.04 (m, 1H), 6.86-6.94 (m, 2H), 7.26-7.31 (m, 2H), 7.61-7.68 (m, 2H), 7.88-7.96 (m, 1H), 8.29-8.39 (m, 2H), 8.85-8.93 (m, 2H)
Formula: C24H26N2O4
Calc MW: 406.48
MS (ESI) m/z: 407 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.37-1.44 (m, 3H), 3.86-3.98 (s, 3H), 4.06-4.10 (s, 3H), 5.36-5.42 (m, 1H), 6.90-7.12 (m, 2H), 7.23-7.37 (m, 2H), 7.57-7.69 (m, 2H), 7.88-7.94 (m, 1H), 8.27-8.38 (m, 2H), 8.84-8.93 (m, 2H)
Formula: C22H22N2O3
Calc MW: 362.43
MS (ESI) m/z: 363 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.25-2.33 (s, 3H), 3.61-3.72 (m, 2H), 4.03-4.12 (s, 3H), 4.96-5.07 (m, 1H), 7.12-7.34 (m, 4H), 7.58-7.72 (m, 2H), 7.87-7.96 (m, 1H), 8.30-8.40 (m, 2H), 8.80-8.98 (m, 2H)
Formula: C22H22N2O3
Calc MW: 362.43
MS (ESI) m/z: 363 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 3.74-3.80 (m, 1H), 3.86-3.93 (m, 1H), 4.08-4.13 (s, 3H), 5.88-5.96 (m, 1H), 7.50-7.71 (m, 6H), 7.85-8.02 (m, 3H), 8.25-8.30 (m, 1H), 8.35-8.41 (m, 2H), 8.87-8.95 (m, 2H)
Formula: C25H22N2O3
Calc MW: 398.46
MS (ESI) m/z: 399 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.22-2.27 (m, 3H), 2.36-2.40 (s, 3H), 3.55-3.67 (m, 2H), 4.04-4.11 (s, 3H), 5.18-5.28 (m, 1H), 6.92-7.05 (m, 2H), 7.16-7.28 (m, 1H), 7.58-7.71 (m, 2H), 7.85-7.92 (m, 1H), 8.33-8.39 (m, 2H), 8.78-9.02 (m, 2H)
Formula: C23H24N2O3
Calc MW: 376.45
MS (ESI) m/z: 377 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 3.58-3.71 (m, 2H), 3.87-3.89 (s, 3H), 4.10-4.13 (s, 3H), 5.32-5.42 (m, 1H), 6.91-7.08 (m, 2H), 7.19-7.33 (m, 2H), 7.61-7.74 (m, 2H), 7.95-8.04 (m, 1H), 8.35-8.44 (m, 2H), 8.80-9.01 (m, 2H)
Formula: C22H22N2O4
Calc MW: 378.43
MS (ESI) m/z: 379 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 3.70-3.78 (m, 1H), 3.83-3.90 (m, 1H), 3.95-3.98 (s, 3H), 4.07-4.11 (s, 3H), 5.79-5.89 (m, 1H), 6.94-7.05 (m, 1H), 7.49-7.71 (m, 5H), 7.88-7.97 (m, 1H), 8.18-8.27 (m, 2H), 8.34-8.43 (m, 2H), 8.87-8.96 (m, 2H)
Formula: C26H24N2O4
Calc MW: 428.49
MS (ESI) m/z: 429 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 3.59-3.73 (m, 2H), 4.04-4.09 (s, 3H), 4.98-5.04 (m, 1H), 5.07-5.11 (s, 2H), 6.90-7.04 (m, 2H), 7.27-7.50 (m, 7H), 7.60-7.68 (m, 2H), 7.89-7.95 (m, 1H), 8.28-8.40 (m, 2H), 8.85-8.94 (m, 2H)
Calc MW: 454.52
MS (ESI) m/z: 455 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.38-1.51 (m, 3H), 3.99-4.05 (s, 3H), 5.02-5.23 (m, 1H), 7.34-7.81 (m, 7H), 8.30-8.39 (m, 2H), 8.85-8.98 (m, 2H)
Formula: C21H19BrN2O2
Calc MW: 411.30
MS (ESI) m/z: 409 [M−H]−
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.40-1.49 (m, 3H), 4.00-4.04 (s, 3H), 5.06-5.15 (m, 1H), 7.36-7.43 (m, 2H), 7.52-7.66 (m, 4H), 7.74-7.78 (m, 1H), 8.32-8.38 (m, 2H), 8.85-8.98 (m, 2H)
Formula: C21H19BrN2O2
Calc MW: 411.30
MS (ESI) m/z: 411 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 4.01-4.10 (s, 3H), 4.96-5.06 (m, 1H), 5.23-5.34 (m, 1H), 7.16-7.38 (m, 10H), 7.57-7.65 (m, 2H), 7.82-7.87 (m, 1H), 8.26-8.32 (m, 2H), 8.81-8.94 (m, 2H)
Formula: C27H24N2O3
Calc MW: 424.50
MS (ESI) m/z: 425 [M+H]+
The synthesis of the title compound was performed as described for example 1.
1H NMR (400 MHz, DMSO-d6): 8.84 (d, 1H), 8.66 (d, 2H), 8.01 (d, 2H), 7.90 (d, 2H), 7.75 (d, 2h), 7.40 (d 2H), 7.31 (dd, 2H), 7.21 (dd, 1H), 5.22-5.14 (m, 1H), 4.55 (t, 1H), 3.52-3.39 (m, 2H), 2.12-2.02 (m, 1H), 1.97-1.88 (m, 1H).
Formula: C21H20N2O2
Calc MW: 332.40
MS (ESI) m/z: 333.1 [M+H]+
The synthesis of the title compound was performed as described for example 1.
1H NMR (400 MHz, DMSO-D6) δ ppm: 1.65 (t, 4H), 2.49-2.53 (m, 4H, overly with DMSO signal), 2.61 (dd, 1H), 2.98 (dd, 1H), 3.74 (s, 3H), 5.13-5.19 (m, 1H), 6.80 (dd, 1H), 6.98 (d, 1H), 6.99-7.05 (m, 1H), 7.23 (dd, 1H), 7.75 (d, 2H), 7.91 (d, 2H), 8.01 (d, 2H), 8.66 (d, 2H), 8.81 (d, 1H);
Formula: C25H27N3O2
Calc MW: 401.51
MS (ESI) m/z: 425 [M+H]+
The synthesis of the title compound was performed as described for example 1.
1H NMR (400 MHz, DMSO-D6) δ ppm: 0.97 (t, 3H),1.48 (d, 3H), 1.71 (sext, 2H), 3.90 (t, 2H), 5.16 (quint, 1H), 6.77 (dd, 1H), 6.95 (d, 1H), 6.96 (s, 1H), 7.21 (t, 1H) 7.76 (d, 2H) 7.91 (d, 2H) 8.02 (d, 2H) 8.66 (d, 2H) 8.88 (d, 1H)
Formula: C23H24N2O2
Calc MW: 360.45
MS (ESI) m/z: 361.2 [M+H]+
The synthesis of the title compound was performed as described for example 1.
1H NMR (400 MHz, DMSO-D6) δ ppm: 1.48 (d, 3H), 5.08 (s, 2H), 5.17 (quint, 1H), 6.87 (dd, 1H), 6.97 (d, 1H), 7.06 (s, 1H), 7.24 (t, 1H), 7.31 (dd, 1H), 7.36 (t, 2H), 7.44 (d, 2H) 7.76 (d, 2H) 7.91 (d, 2H) 8.02 (d, 2H) 8.66 (d, 2H) 8.88 (d, 1H)
Formula: C27H24N2O2
Calc MW: 408.50
MS (ESI) m/z: 409 [M+H]+
The synthesis of the title compound was performed as described for example 1.
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.24 (d, 3H), 1.26 (d, 3H), 1.48 (d, 3H), 4.58 (sept, 1H), 5.15 (quint, 1H), 6.76 (dd, 1H), 6.92 (d, 1H), 6.93 (s, 1H), 7.20 (t, 1H), 7.76 (d, 2H), 7.91 (d, 2H), 8.02 (d, 2H), 8.66 (d, 2H) 8.88 (d, 1H)
Formula: C23H24N2O2
Calc MW: 360.45
MS (ESI) m/z: 361.2 [M+H]+
The synthesis of the title compound was performed as described for example 1.
1H NMR (400 MHz, DMSO-D6) ppm: ppm 0.97 (d, 6H), 1.48 (d, 3H), 2.00 (sept, 1H), 3.72 (d, 2H), 5.15 (quint, 1H), 6.77 (dd, 1H), 6.95 (d, 1H), 6.96 (s, 1H), 7.21 (t, 1H), 7.75 (d, 2H), 7.91 (d, 2H), 8.02 (d, 2H), 8.66 (d, 2H) 8.88 (d, 1H)
Formula: C24H26N2O2
Calc MW: 374.48
MS (ESI) m/z: 375 [M+H]++
The synthesis of the title compound was performed as described for example 7.
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.95-2.12 (m, 1H), 2.45-2.52 (m, 1H), 2.82-3.06 (m, 2H), 5.47-5.69 (m, 1H), 7.07-7.45 (m, 4H), 8.05-8.17 (m, 4H), 8.28-8.41 (m, 2H), 8.85-8.95 (m, 2H)
Formula: C21H18N2O
Calc MW: 314.39
MS (ESI) m/z: 315 [M+H]+
The compounds of Example 155 and 156 were prepared in an analogous method as described above.
1H NMR (400 MHz, DMSO-D6) δ ppm: 1.48 (d, 3H) 3.7 (s, 3H) 5.16 (m, 1H) 6.8 (ddd, 1H) 6.97 (dd, 2H) 7.24 (t, 1H) 7.62 (s, 1H) 7.77 (m, 1H) 8.0 (m, 4H) 8.34 (d, 1H) 8.9 (d, 1H).
Formula: C21H19FN2O2
Calc MW: 350.39
MS (ESI) positive ion: 351 [M+H]+
Formula: C21H19ClN2O2
Calc MW: 366.85
The following compounds of the Examples 157 to 186 were prepared as described for example 7.
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.48-1.56 (m, 3H), 2.37-2.44 (s, 3H), 5.10-5.34 (m, 1H), 7.21-7.48 (m, 5H), 7.61-7.69 (m, 2H), 7.86-7.93 (m, 1H), 7.99-8.09 (m, 2H), 8.75-8.81 (m, 1H), 8.83-8.89 (m, 1H)
Formula: C21H20N2O
Calc MW: 316.40
MS (ESI) m/z: 317 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) ppm: 1.49-1.54 (m, 3H), 2.41-2.44 (s, 3H), 5.15-5.23 (m, 1H), 7.22-7.50 (m, 5H), 7.61-7.70 (m, 2H), 7.88-7.94 (m, 1H), 8.02-8.10 (m, 2H), 8.75-8.81 (m, 1H), 8.83-8.88 (m, 1H)
Formula: C21H20N2O
Calc MW: 316.40
MS (ESI) m/z: 317 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.61-1.69 (m, 3H), 2.37-2.46 (s, 3H), 5.95-6.02 (m, 1H), 7.47-7.71 (m, 6H), 7.82-8.10 (m, 5H), 8.19-8.28 (m, 1H), 8.74-8.81 (m, 1H), 8.82-8.89 (m, 1H)
Formula: C25H22N2O
Calc MW: 366.46
MS (ESI) m/z: 367 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.71-2.06 (m, 4H), 2.39-2.46 (s, 3H), 2.67-2.90 (m, 2H), 5.13-5.42 (m, 1H), 7.12-7.23 (m, 4H), 7.62-7.68 (m, 2H), 7.85-7.91 (m, 1H), 8.04-8.10 (m, 2H), 8.74-8.81 (m, 1H), 8.82-8.88 (m, 1H)
Formula: C23H22N2O
Calc MW: 342.44
MS (ESI) m/z: 343 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.34-2.38 (s, 3H), 4.92-4.97 (m, 1H), 5.15-5.23 (m, 1H), 7.17-7.40 (m, 6H), 7.44-7.59 (m, 6H), 7.76-7.82 (m, 3H), 8.66-8.85 (m, 2H)
Formula: C27H24N2O2
Calc MW: 408.50
MS (ESI) m/z: 409 [M+H]+
The synthesis of the title compound was performed as described for example 7.
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.33-2.39 (s, 3H), 4.91-4.98 (m, 1H), 5.15-5.25 (m, 1H), 7.18-7.38 (m, 6H), 7.44-7.60 (m, 6H), 7.71-7.89 (m, 3H), 8.61-8.90 (m, 2H)
Formula: C27H24N2O2
Calc MW: 408.50
MS (ESI) m/z: 409 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.46-1.52 (m, 3H), 2.24-2.30 (s, 3H), 2.40-2.44 (s, 3H), 5.10-5.23 (m, 1H), 7.12-7.18 (m, 2H), 7.27-7.33 (m, 2H), 7.63-7.67 (m, 2H), 7.89-7.95 (m, 1H), 8.02-8.08 (m, 2H), 8.72-8.89 (m, 2H)
Formula: C22H22N2O
Calc MW: 330.43
MS (ESI) m/z: 331 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.47-1.51 (m, 3H), 2.26-2.29 (s, 3H), 2.41-2.45 (s, 3H), 5.08-5.25 (m, 1H), 7.10-7.19 (m, 2H), 7.25-7.35 (m, 2H), 7.60-7.72 (m, 2H), 7.87-7.96 (m, 1H), 8.01-8.08 (m, 2H), 8.69-8.84 (m, 1H), 8.82-8.98 (m, 1H)
Formula: C22H22N2O
Calc MW: 330.43
MS (ESI) m/z: 331 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.98-2.08 (m, 1H), 2.40-2.44 (s, 3H), 2.46-2.51 (m, 1H), 2.84-3.09 (m, 2H), 5.52-5.65 (m, 1H), 7.17-7.33 (m, 4H), 7.62-7.69 (m, 2H), 7.85-7.91 (m, 1H), 8.05-8.11 (m, 2H), 8.74-8.77 (m, 1H), 8.81-8.85 (m, 1H)
Formula: C22H20N2O
Calc MW: 328.41
MS (ESI) m/z: 329 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.48-1.52 (m, 3H), 2.39-2.44 (s, 3H), 5.10-5.18 (m, 1H), 7.32-7.43 (m, 2H), 7.51-7.55 (m, 2H), 7.62-7.72 (m, 2H), 7.85-7.94 (m, 1H), 8.02-8.07 (m, 2H), 8.57-9.27 (m, 2H)
Formula: C21H19BrN2O
Calc MW: 395.30
MS (ESI) m/z: 396 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.47-1.55 (m, 3H), 2.38-2.45 (s, 3H), 5.10-5.21 (m, 1H), 7.37-7.40 (m, 2H), 7.52-7.56 (m, 2H), 7.63-7.71 (m, 2H), 7.86-7.94 (m, 1H), 8.03-8.07 (m, 2H), 8.74-8.88 (m, 2H)
Formula: C21H19BrN2O
Calc MW: 395.30
MS (ESI) m/z: 396 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.49-1.52 (m, 3H), 2.38-2.46 (s, 3H), 5.12-5.22 (m, 1H), 7.39-7.48 (m, 4H), 7.63-7.67 (m, 2H), 7.86-7.94 (m, 1H), 8.02-8.09 (m, 2H), 8.69-9.00 (m, 2H)
Formula: C21H19ClN2O
Calc MW: 350.85
MS (ESI) m/z: 351 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.41-1.60 (m, 3H), 2.30-2.48 (s, 3H), 5.04-5.30 (m, 1H), 7.33-7.50 (m, 4H), 7.59-7.72 (m, 2H), 7.85-7.94 (m, 1H), 8.01-8.13 (m, 2H), 8.66-8.89 (m, 2H)
Formula: C21H19ClN2O
Calc MW: 350.85
MS (ESI) m/z: 351 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.58-1.64 (m, 3H), 2.37-2.44 (s, 3H), 5.33-5.41 (m, 1H), 7.46-7.70 (m, 5H), 7.85-7.94 (m, 5H), 8.06-8.12 (m, 2H), 8.76-8.91 (m, 2H)
Formula: C25H22N2O
Calc MW: 366.46
MS (ESI) m/z: 367 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.39-2.44 (s, 3H), 3.53-3.68 (m, 2H), 3.84-3.87 (s, 3H), 5.43-5.51 (m, 1H), 6.91-6.98 (m, 1H), 6.99-7.03 (m, 1H), 7.22-7.29 (m, 1H), 7.33-7.38 (m, 1H), 7.63-7.69 (m, 2H), 7.84-7.92 (m, 1H), 8.05-8.12 (m, 2H), 8.70-8.87 (m, 2H)
Formula: C22H22N2O3
Calc MW: 362.43
MS (ESI) m/z: 363 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.38-2.43 (m, 3H), 3.81-3.91 (m, 2H), 5.90-6.02 (m, 1H), 7.49-7.69 (m, 6H), 7.83-7.91 (m, 2H), 7.95-8.01 (m, 1H), 8.06-8.14 (m, 2H), 8.26-8.34 (m, 1H), 8.70-8.85 (m, 2H);
Formula: C25H22N2O2
Calc MW: 382.46
MS (ESI) m/z: 383 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.27-2.29 (s, 3H), 2.40-2.43 (s, 3H), 3.58-3.74 (m, 2H), 5.02-5.12 (m, 1H), 7.12-7.20 (m, 2H), 7.26-7.33 (m, 2H), 7.62-7.69 (m, 2H), 7.85-7.91 (m, 1H), 8.03-8.09 (m, 2H), 8.73-8.87 (m, 2H)
Formula: C22H22N2O2
Calc MW: 346.43
MS (ESI) m/z: 347 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.39-2.42 (s, 3H), 3.61-3.73 (m, 2H), 3.81-3.85 (m, 3H), 4.98-5.14 (m, 1H), 7.09-7.15 (m, 1H), 7.31-7.38 (m, 1H), 7.46-7.49 (m, 1H), 7.64-7.70 (m, 2H), 7.86-7.92 (m, 1H), 7.99-8.12 (m, 2H), 8.66-8.87 (m, 2H)
Formula: C22H21ClN2O3
Calc MW: 396.87
MS (ESI) m/z: 397 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.40-1.47 (m, 3H), 2.38-2.45 (s, 3H), 3.83-3.88 (s, 3H), 5.40-5.50 (m, 1H), 6.88-7.05 (m, 2H), 7.20-7.28 (m, 1H), 7.34-7.40 (m, 1H), 7.62-7.70 (m, 2H), 7.87-7.92 (m, 1H), 8.04-8.09 (m, 2H), 8.75-8.87 (m, 2H)
Formula: C22H22N2O2
Calc MW: 346.43
MS (ESI) m/z: 347 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.48-1.53 (m, 3H), 2.37-2.44 (s, 3H), 5.15-5.21 (m, 1H), 7.22-7.30 (m, 1H), 7.35-7.50 (m, 2H), 7.63-7.67 (m, 2H), 7.86-7.91 (m, 1H), 8.03-8.07 (m, 2H), 8.75-8.86 (m, 2H)
Formula: C21H18F2N2O
Calc MW: 352.38
MS (ESI) m/z: 353 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.48-1.55 (m, 3H), 2.38-2.44 (s, 3H), 5.16-5.23 (m, 1H), 7.13-7.20 (m, 2H), 7.43-7.47 (m, 2H), 7.63-7.67 (m, 2H), 7.86-7.90 (m, 1H), 8.03-8.06 (m, 2H), 8.73-8.87 (m, 2H)
Formula: C21H19FN2O
Calc MW: 334.39
MS (ESI) m/z: 335 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.46-1.53 (m, 3H), 2.39-2.45 (s, 3H), 3.71-3.75 (s, 3H), 5.09-5.19 (m, 1H), 6.87-6.94 (m, 2H), 7.31-7.38 (m, 2H), 7.62-7.68 (m, 2H), 7.87-7.92 (m, 1H), 8.00-8.07 (m, 2H), 8.73-8.90 (m, 2H)
Formula: C22H22N2O2
Calc MW: 346.43
MS (ESI) m/z: 347 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.47-1.53 (m, 3H), 2.40-2.44 (s, 3H), 3.74-3.76 (s, 3H), 5.10-5.24 (m, 1H), 6.79-6.85 (m, 1H), 6.95-7.03 (m, 2H), 7.24-7.31 (m, 1H), 7.61-7.68 (m, 2H), 7.82-7.92 (m, 1H), 8.01-8.08 (m, 2H), 8.73-8.88 (m, 2H)
Formula: C22H22N2O2
Calc MW: 346.43
MS (ESI) m/z: 347 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.48-1.54 (m, 3H), 2.38-2.44 (s, 3H), 5.12-5.31 (m, 1H), 7.11-7.24 (m, 2H), 7.38-7.50 (m, 2H), 7.61-7.69 (m, 2H), 7.83-7.94 (m, 1H), 7.99-8.14 (m, 2H), 8.69-8.91 (m, 2H)
Formula: C21H19FN2O
Calc MW: 334.39
MS (ESI) m/z: 335 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.52-1.57 (m, 3H), 2.37-2.42 (s, 3H), 5.23-5.30 (m, 1H), 7.58-7.69 (m, 4H), 7.71-7.79 (m, 2H), 7.85-7.89 (m, 1H), 7.99-8.11 (m, 2H), 8.73-8.87 (m, 2H)
Formula: C22H19F3N2O
Calc MW: 384.40
MS (ESI) m/z: 385 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.52-1.58 (m, 3H), 2.39-2.44 (s, 3H), 5.21-5.28 (m, 1H), 7.63-7.75 (m, 6H), 7.86-7.90 (m, 1H), 8.04-8.09 (m, 2H), 8.75-8.86 (m, 2H)
Formula: C22H19F3N2O
Calc MW: 384.40
MS (ESI) m/z: 385 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.34-2.38 (s, 3H), 4.93-5.00 (m, 1H), 5.16-5.23 (m, 1H), 7.20-7.36 (m, 6H), 7.46-7.51 (m, 4H), 7.54-7.58 (m, 2H), 7.75-7.81 (m, 3H), 8.69-8.81 (m, 2H)
Formula: C27H24N2O2
Calc MW: 408.50
MS (ESI) m/z: 409 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.62-1.69 (m, 3H), 2.39-2.43 (s, 3H), 5.96-6.03 (m, 1H), 7.50-7.71 (m, 6H), 7.84-7.90 (m, 2H), 7.95-7.99 (m, 1H), 8.05-8.10 (m, 2H), 8.20-8.25 (m, 1H), 8.74-8.87 (m, 2H)
Formula: C25H22N2O
Calc MW: 366.46
MS (ESI) m/z: 367 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.41-2.45 (m, 3H), 3.67-3.77 (m, 2H), 5.03-5.13 (m, 1H), 7.45-7.52 (m, 3H), 7.65-7.71 (m, 2H), 7.86-7.93 (m, 1H), 8.05-8.10 (m, 2H), 8.74-8.89 (m, 2H)
Formula: C21H18Cl2N2O2
Calc MW: 401.29
MS (ESI) m/z: 402 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.71-2.07 (m, 4H), 2.66-2.88 (m, 2H), 5.21-5.33 (m, 1H), 7.07-7.34 (m, 4H), 8.04-8.16 (m, 4H), 8.24-8.34 (m, 2H), 8.77-8.96 (m, 2H)
Formula: C22H20N2O
Calc MW: 328.41
MS (ESI) m/z: 329 [M+H]+
The following compounds of Examples 187 to 190 were prepared in an analogous method as described before:
1H NMR (300 MHz, DMSO-D6) δ ppm: 3.8 (m, 3H) 5.98 (m, 1H) 7.4-7.8 (m, 4H) 7.9 (m, 1H) 8.00 (m, 5H) 8.2 (m, 2H) 8.4 (m, 1H) 8.8 (m, 2H) 9.02 (d, 1H)
Formula: C24H20N2O2
Calc MW: 368.43
MS (ESI) positive ion: 369 [M+H]+
1H NMR (300 MHz, DMSO-D6) δ ppm: 3.3 (s, 3H) 3.6 (m, 1H) 3.8 (m, 1H) 5.3 (m, 1H) 7.3-7.5 (m, 5H) 8.2 (m, 4H) 8.4 (m, 2H) 8.8 (d, 2H) 9.00 (d, 1H)
Formula: C21H20N2O2
Calc MW: 332.40
MS (ESI) positive ion: 333 [M+H]+
1H NMR (300 MHz, DMSO-D6) δ ppm: 1.6 (d, 3H) 3.9 (s, 3H) 5.8 (m, 1H), 7.0 (d, 1H) 7.5 (m, 3H) 8.0-8.3 (m, 8H) 8.8 (d, 2H), 9.0 (d, 1H)
Formula: C25H22N2O2
Calc MW: 382.46
MS (ESI) positive ion: 393 [M+H]+
1H NMR (400 MHz, DMSO-D6) δ ppm: 8.91 (d, J=8.1, 1H), 8.51 (dd, J=0.6, 5.2, 1H), 8.04 (d, J=8.6, 2H), 7.97 (d, J=8.7, 2H), 7.93 (dd, J=0.6, 1.6, 1H), 7.82 (dd, J=1.6, 5.3, 1H), 7.24 (t, J=8.1, 1H), 6.97 (dd, J=1.6, 3.9, 2H), 6.80 (ddd, J=0.9, 2.5, 8.2, 1H), 5.16 (p, J=7.1, 1H), 3.74 (s, 3H), 1.48 (d, J=7.1, 3H).
Formula: C21H19ClN2O2
Calc MW: 366.85
MS m/z: 367.18 [M+H]+, Rt=2.34 min.
A 20-ml scintillation vial was charged with a solution of 2-chloro-4-(pyridin-4-yl)benzoic acid in DMA (20.0 mg, 0.085 mmol, 1.0 eq), a solution of HATU in DMA (39.06 mg, 0.103 mmol, 1.20 eq), and triethylamine (28.83 μL, 0.205 mmol, 2.40 eq). The mixture was briefly shaken and a solution of (R)-1-phenylethanamine (14.52 mg, 0.1198 mmol, 1.40 eq) in DMA was added. The mixture was left to shake at room temperature overnight. The mixture was then concentrated in vacuo and dissolved in 1.4 ml of DMSO/methanol (1:1 v/v) and submitted for reverse phase purification to afford (R)-2-chloro-N-(1-phenylethyl)-4-(pyridin-4-yl)benzamide (27.30 mg, 70.74% yield). 1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.44-1.48 (d, 3H), 5.11-5.17 (q, 1H), 7.25-7.30 (t, 1H), 7.35-7.40 (t, 2H), 7.41-7.45 (d, 2H), 7.62-7.66 (d, 1H), 7.98-8.01 (dd, 1H), 8.13-8.15 (d, 1H), 8.32-8.35 (d, 2H), 8.89-8.93 (d, 2H)
Formula: C20H17ClN2O
Calc MW: 336.82
MS (ESI) m/z: 337.0 [M+H]+
The following compounds of the Examples 192 to 213 were prepared as described for example 191.
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.59-1.65 (d, 3H), 5.89-5.96 (q, 1H), 7.51-7.60 (m, 2H), 7.60-7.69 (m, 3H), 7.86-7.89 (d, 1H), 7.94-8.00 (t, 2H), 8.09-8.13 (s, 1H), 8.21-8.26 (d, 3H), 8.84-8.89 (d, 2H)
Formula: C24H19ClN2O
Calc MW: 386.88
MS (ESI) m/z: 385.3 [M−H]−
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.62 (d, 3H), 5.93 (q, 1H), 7.52-7.60 (m, 2H), 7.65 (dd, 3H), 7.88 (d, 1H), 7.97 (t, 2H), 8.09-8.12 (s, 1H), 8.24 (d, 3H), 8.87 (d, 2H)
Formula: C22H19ClN2O
Calc MW: 362.86
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 4.79 (d, 1H), 5.19 (d, 1H), 7.05 (d, 1H), 7.24-7.38 (m, 7H), 7.43 (q, 4H), 7.87 (dd, 1H), 8.00 (d, 1H), 8.20 (d, 2H), 8.85 (d, 2H)
Formula: C26H21ClN2O2
Calc MW: 428.92
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.43 (d, 3H), 2.27-2.31 (s, 3H), 5.09 (q, 1H), 7.17 (d, 2H), 7.30 (d, 2H), 7.58 (d, 1H), 7.91 (d, 1H), 8.05 (t, 3H), 8.79 (d, 2H)
Formula: C21H19ClN2O
Calc MW: 350.85
MS (ESI) m/z: 351.0 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.44 (d, 3H), 2.27-2.32 (m, 3H), 5.10 (q, 1H), 7.17 (d, 2H), 7.30 (d, 2H), 7.62 (d, 1H), 7.98 (dd, 1H), 8.11-8.15 (m, 1H), 8.31 (d, 2H), 8.89 (d, 2H)
Formula: C21H19ClN2O
Calc MW: 350.85
MS (ESI) m/z: 351.0 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.89 (dd, 1H), 3.13 (dd, 1H), 4.57 (ddd, 1H), 5.43 (d, 1H), 7.26 (tt, 3H), 7.34 (t, 1H), 7.78 (d, 1H), 7.98 (dd, 1H), 8.12 (d, 1H), 8.24 (d, 2H), 8.86 (d, 2H)
Formula: C21H17ClN2O2
Calc MW: 364.83
MS (ESI) m/z: 365.0 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.88 (dd, 1H), 3.13 (dd, 1H), 4.57 (ddd, 1H), 5.42 (d, 1H), 7.26 (tt, 3H), 7.33 (t, 1H), 7.77 (d, 1H), 7.96 (dd, 1H), 8.09 (d, 1H), 8.16 (d, 2H), 8.83 (d, 2H)
Formula: C21H17ClN2O2
Calc MW: 364.83
MS (ESI) m/z: 365.0 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.88-1.99 (m, 1H), 2.46-2.52 (m, 1H), 2.82-2.91 (m, 1H), 2.94-3.02 (m, 1H), 5.51 (t, 1H), 7.26 (tt, 3H), 7.38 (t, 1H), 7.68 (d, 1H), 7.97 (dd, 1H), 8.12 (d, 1H), 8.24 (d, 2H), 8.86 (d, 2H)
Formula: C21H17ClN2O
Calc MW: 348.83
MS (ESI) m/z: 349.0 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.88-1.99 (m, 1H), 2.46-2.52 (m, 1H), 2.82-2.91 (m, 1H), 2.94-3.02 (m, 1H), 5.51 (t, 1H), 7.26 (tt, 3H), 7.38 (t, 1H), 7.68 (d, 1H), 7.97 (dd, 1H), 8.12 (d, 1H), 8.24 (d, 2H), 8.86 (d, 2H)
Formula: C20H16BrClN2O
Calc MW: 415.72
MS (ESI) m/z: 416.8 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.45 (d, 3H), 5.12 (q, 1H), 7.44 (q, 4H), 7.66 (d, 1H), 8.00 (dd, 1H), 8.14 (d, 1H), 8.34 (d, 2H), 8.92 (d, 2H)
Formula: C20H16Cl2N2O
Calc MW: 371.27
MS (ESI) m/z: 371.0 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.45 (d, 3H), 5.12 (q, 1H), 7.44 (q, 4H), 7.64 (d, 1H), 7.99 (dd, 1H), 8.12 (d, 1H), 8.28 (d, 2H), 8.89 (d, 2H)
Formula: C20H16Cl2N2O
Calc MW: 371.27
MS (ESI) m/z: 369.0 [M−H]−
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.56 (d, 3H), 5.30 (q, 1H), 7.49-7.57 (m, 2H), 7.61 (dd, 1H), 7.66 (d, 1H), 7.91 (t, 4H), 7.98 (dd, 1H) 8.11 (d, 1H) 8.22 (d, 2H) 8.86 (d, 2H)
Formula: C24H19ClN2O
Calc MW: 386.88
MS (ESI) m/z: 384.9 [M−H]−
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.56 (d, 3H), 5.30 (q, 1H), 7.49-7.57 (m, 2H), 7.61 (dd, 1H), 7.67 (d, 1H), 7.91 (t, 4H), 7.98 (dd, 1H), 8.11 (d, 1H), 8.23 (d, 2H), 8.87 (d, 2H)
Formula: C24H19ClN2O
Calc MW: 386.88
MS (ESI) m/z: 387.0 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 3.50 (dd, 1H), 3.63 (dd, 1H), 3.84-3.86 (m, 3H), 5.43 (q, 1H), 6.95 (t, 1H), 7.02 (d, 1H), 7.28 (t, 1H), 7.37 (dd, 1H), 7.70 (d, 1H), 8.01 (dd, 1H), 8.14 (d, 1H), 8.31 (d, 2H), 8.90 (d, 2H)
Formula: C21H19ClN2O3
Calc MW: 382.85
MS (ESI) m/z: 381.0 [M−H]−
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 3.16-3.19 (s, 1H), 3.86 (dd, 1H), 5.90 (q, 1H), 7.51-7.60 (m, 2H), 7.62-7.71 (m, 3H), 7.88 (d, 1H), 7.99 (t, 2H), 8.12 (d, 1H), 8.28 (t, 3H), 8.88 (d, 2H)
Formula: C24H19ClN2O2
Calc MW: 402.88
MS (ESI) m/z: 403.0 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 2.28-2.31 (m, 3H), 3.62 (d, 2H), 5.01 (t, 1H), 7.17 (d, 2H), 7.30 (d, 2H), 7.67 (d, 1H), 7.99 (dd, 1H), 8.12 (d, 1H), 8.30 (d, 2H), 8.89 (d, 2H)
Formula: O21H19ClN2O2
Calc MW: 366.85
MS (ESI) m/z: 365.1 [M−H]−
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 3.59-3.66 (m, 2H), 3.83-3.86 (s, 3H), 4.99 (t, 1H), 7.14 (d, 1H), 7.35 (dd, 1H), 7.47 (d, 1H), 7.67 (d, 1H), 7.99 (dd, 1H), 8.12 (d, 1H), 8.27 (d, 2H), 8.88 (d, 2H)
Formula: C21H18Cl2 N2O3
Calc MW: 417.29
MS (ESI) m/z: 415.0 [M−H]−
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 3.59-3.64 (m, 2H), 5.00 (t, 1H), 5.08-5.12 (m, 2H), 7.00 (d, 2H), 7.34 (t, 3H), 7.40 (t, 2H), 7.45 (d, 2H), 7.65 (d, 1H), 7.97 (dd, 1H), 8.09 (d, 1H), 8.20 (d, 2H), 8.85 (d, 2H)
Formula: O27H23ClN2O3
Calc MW: 458.94
MS (ESI) m/z: 457.1 [M−H]−
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.38 (d, 3H), 3.84-3.86 (s, 3H), 5.42 (q, 1H), 6.96 (t, 1H), 7.02 (d, 1H), 7.26 (t, 1H), 7.39 (dd, 1H), 7.64 (d, 1H), 7.99 (dd, 1H), 8.13 (d, 1H), 8.29 (d, 2H), 8.89 (d, 2H)
Formula: O21H19ClN2O2
Calc MW: 366.85
MS (ESI) m/z: 367.0 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.45 (d, 3H), 5.12 (q, 1H), 7.25-7.30 (m, 1H), 7.38-7.49 (m, 2H), 7.66 (d, 1H), 7.98 (dd, 1H), 8.12 (d, 1H), 8.27 (d, 2H), 8.88 (d, 2H)
Formula: C20H15ClF2N2O
Calc MW: 372.80
MS (ESI) m/z: 373.0 [M+H]+
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.44 (d, 3H), 3.75-3.75 (s, 3H), 5.09 (q, 1H), 6.93 (d, 2H), 7.35 (d, 2H), 7.62 (d, 1H), 7.97 (dd, 1H), 8.11 (d, 1H), 8.27 (d, 2H), 8.88 (d, 2H)
Formula: C21H19ClN2O2
Calc MW: 366.85
MS (ESI) m/z: 365.1 [M−H]−
1H NMR (500 MHz, DMSO-D6/D2O) δ ppm: 1.48 (d, 3H), 3.74-3.76 (s, 3H), 5.19 (q, 1H), 7.65 (t, 3H), 7.74 (d, 2H), 7.93 (dd, 1H), 8.08 (dd, 3H), 8.81 (d, 2H).
Formula: C21H19ClN2O2
Calc MW: 366.85
The synthesis of the title compound was performed as described for Example 104
Formula: C25H27N3O2
Calc MW: 401.51
The following compounds of Examples 215 to 242 were prepared as described for example 105.
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 7.52-7.70 (m, 2H), 7.76-7.80 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C20H17FN2O
Calc MW: 320.37
MS (ESI) m/z: 321 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 7.52-7.70 (m, 2H), 7.76-7.80 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C20H17FN2O
Calc MW: 320.37
MS (ESI) m/z: 3210 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.88-5.99 (m, 1H), 7.52-7.70 (m, 4H), 7.76-7.80 (m, 1H), 7.84-7.89 (m, 5H), 8.20-8.24 (m, 2H), 8.33-8.37 (m, 1H), 8.86-8.91 (m, 2H)
Formula: C24H19FN2O
Calc MW: 370.43
MS (ESI) m/z: 371 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 5.31-5.34 (s, 1H), 5.45-5.51 (m, 1H), 7.52-7.70 (m, 7H), 7.76-7.80 (m, 4H), 7.84-7.89 (m, 2H), 7.95-8.01 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C26H21FN2O2
Calc MW: 412.46
MS (ESI) m/z: 413 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 5.31-5.34 (s, 1H), 5.45-5.51 (m, 1H), 7.52-7.70 (m, 7H), 7.76-7.80 (m, 4H), 7.84-7.89 (m, 2H), 7.95-8.01 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C26H21FN2O2
Calc MW: 412.46
MS (ESI) m/z: 413 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 2.1 (s, 3H), 5.88-5.99 (m, 1H), 7.52-7.70 (m, 2H), 7.84-7.89 (m, 3H), 7.95-8.01 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H19FN2O
Calc MW: 334.39
MS (ESI) m/z: 335 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 2.1 (s, 3H), 5.88-5.99 (m, 1H), 7.52-7.70 (m, 2H), 7.84-7.89 (m, 3H), 7.95-8.01 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H19FN2O
Calc MW: 334.39
MS (ESI) m/z: 335 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.5 (m, 2H), 2.0 (m, 1H) 3.2 (s, 1H) 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H17FN2O2
Calc MW: 348.38
MS (ESI) m/z: 349 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.5 (m, 2H), 2.0 (m, 1H) 3.2 (s, 1H) 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H17FN2O2
Calc MW: 348.38
MS (ESI) m/z: 349 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.5 (m, 2H), 2.0 (m, 1H) 3.2 (s, 1H) 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H17FN2O2
Calc MW: 348.38
MS (ESI) m/z: 349 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 0.9 (m, 2H), 2.0 (m, 2H) 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H17FN2O
Calc MW: 332.38
MS (ESI) m/z: 333 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C20H16BrFN2O
Calc MW: 399.26
MS (ESI) m/z: 399 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C20H16ClFN2O
Calc MW: 354.81
MS (ESI) m/z: 355 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C20H16ClFN2O
Calc MW: 354.81
MS (ESI) m/z: 355 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.35-5.39 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 1H), 7.84-7.89 (m, 7H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C24H19FN2O
Calc MW: 370.43
MS (ESI) m/z: 371 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.35-5.39 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 1H), 7.84-7.89 (m, 7H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C24H19FN2O
Calc MW: 370.43
MS (ESI) m/z: 371 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 3.99-4.05 (s, 3H), 5.19-5.22 (m, 1H), 6.87-6.91 (m, 1H), 6.95-7.1 (m, 1H), 7.19-7.22 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H19FN2O2
Calc MW: 350.39
MS (ESI) m/z: 351 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2 H)
Formula: C20H15F3N2O
Calc MW: 356.35
MS (ESI) m/z: 357 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C20H16F2N2O
Calc MW: 338.36
MS (ESI) m/z: 338 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 6.95-7.1 (m, 2H), 7.19-7.22 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H19FN2O2
Calc MW: 350.39
MS (ESI) m/z: 351 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H19FN2O2
Calc MW: 350.39
MS (ESI) m/z: 351 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 6.87-6.91 (m, 1H), 6.95-7.1 (m, 2H), 7.19-7.22 (m, 1H), 7.52-7.70 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H19FN2O2
Calc MW: 350.39
MS (ESI) m/z: 351 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C20H16F2N2O
Calc MW: 338.36
MS (ESI) m/z: 338 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 7.52-7.70 (m, 2H), 7.76-7.80 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H16F4N2O
Calc MW: 388.36
MS (ESI) m/z: 389 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.19-5.22 (m, 1H), 7.52-7.70 (m, 2H), 7.76-7.80 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C21H16F4N2O
Calc MW: 388.36
MS (ESI) m/z: 389 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 5.31-5.34 (s, 1H), 5.45-5.51 (m, 1H), 7.52-7.70 (m, 7H), 7.76-7.80 (m, 4H), 7.84-7.89 (m, 2H), 7.95-8.01 (m, 2H), 8.86-8.91 (m, 2H)
Formula: C26H21FN2O2
Calc MW: 412.46
MS (ESI) m/z: 412 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 5.88-5.99 (m, 1H), 7.52-7.70 (m, 4H), 7.76-7.80 (m, 1H), 7.84-7.89 (m, 5H), 8.20-8.24 (m, 2H), 8.33-8.37 (m, 1H), 8.86-8.91 (m, 2H)
Formula: C24H19FN2O
Calc MW: 370.43
MS (ESI) m/z: 371 [M+H]+
1H NMR (500 MHz, D2O) δ ppm: 1.57-1.67 (m, 3H), 3.99-4.05 (s, 3H), 5.88-5.99 (m, 1H), 7.52-7.70 (m, 4H), 7.76-7.80 (m, 1H), 7.84-7.89 (m, 1H), 7.95-8.01 (m, 5H), 8.86-8.91 (m, 2H)
Formula: C21H19FN2O2
Calc MW: 350.39
MS (ESI) m/z: 351.1 [M+H]+
The following compounds of Examples 243 to 249 were prepared in analogous manner as described above.
1H NMR (400 MHz, DMSO-D6) δ ppm: 8.97 (d, J=8.2, 1H), 8.68 (d, J=6.0, 2H), 7.96 (d, J=1.6, 1H), 7.84 (dd, J=1.6, 7.9, 1H), 7.80-7.75 (m, 2H), 7.26 (t, J=8.1, 1H), 7.01-6.96 (m, 2H), 6.84-6.79 (m, 1H), 5.11 (p, J=7.3, 1H), 3.76 (s, 3H), 1.43 (d, J=7.0, 3H).
Formula: C21H19ClN2O2
Calc MW: 366.85
MS m/z: 366.92 [M+H]+, Rt=2.11 min
1H NMR (400 MHz, DMSO-D6) δ ppm: 8.96 (d, J=8.0, 1H), 8.71 (d, J=6.0, 2H), 7.89 (s, 1H), 7.88-7.85 (m, 1H), 7.77 (t, J=8.0, 1H), 7.63 (d, J=4.7, 2H), 7.25 (t, J=8.1, 1H), 6.97 (dd, J=1.9, 4.5, 2H), 6.81 (dd, J=2.5, 8.2, 1H), 5.15 (p, J=7.2, 1H), 3.75 (s, 3H), 1.49 (d, J=7.1, 3H).
Formula: C21H19FN2O2
Calc MW: 350.39
MS m/z: 350.95 [M+H]+, Rt=2.16 min
Formula: C21H19FN2O2
Calc MW: 350.39
Formula: C22H21FN2O2
Calc MW: 364.42
Formula: C22H21FN2O3
Calc MW: 380.42
Formula: C22H21FN2O2
Calc MW: 364.42
Formula: C23H24N2O3
Calc MW: 376.45
II.1 Activity studies:
In 50 μl final assay volume hROCK-2 (Upstate) (0.8 nM) is incubated with 20 mM HEPES pH 7.5, 10 mM MgCl2, 0.01% Triton X-100, 100 μM Na3VO4, 1.5 μM biotinylated S6 peptide (biotin-RRRLSSLRA-NH2, Anaspec), 1 mM DTT, 5 μM ATP, 5 μCi/ml [33P]-ATP, test compound and 1% DMSO in 96-well microplates at room temperature for 60 min. The reaction is stopped by addition of 150 μl of 0.1 M EDTA in Dulbecco's PBS. 170 μl from each well are loaded onto a FlashPlate (PerkinElmer) and incubated at room temperature for 30 min. After 3× washing with 250 μl PBS containing 0.05% Tween80 the FlashPlate is sealed and read on a Microbeta (PerkinElmer) and the data is analyzed using GraphPad Prism to determine the IC50 and K, values.
As previously described in detail by Kim and Chung (Kim S. H., Chung J. M., An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992, 50, 355-363), in anesthesized rats, a 1.5 cm incision was made dorsal to the lumbosacral plexus. The paraspinal muscles (left side) were separated from the spinous processes, the L5 and L6 spinal nerves isolated and tightly ligated with 3-0 silk threads. Following hemostasis, the wound was sutured and coated with antibiotic ointment. The rats were allowed to recover and then placed in a cage with soft bedding for 7-14 days before behavioral testing for mechanical allodynia (Chaplan S.R., Bach, F. W., Pogrel J. W., Chung J.M. and Yaksh T.L., Quantitative assessment of tactile allodynia in the rat paw. Journal of Neuroscience Methods, 1994, 53(1), 55-63.
As previously described in detail by Bennett and Xie (Bennett G. J.; Xie Y-K., A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988, 33, 87-107), in anesthetized rats, a 1.5 cm incision was made 0.5 cm below the pelvis and the biceps femoris and the gluteous superficialis (right side) were separated. The sciatic nerve was exposed, isolated, and four loose ligatures (5-0 chromic catgut) with 1 mm spacing were placed around it. The rats were allowed to recover and then placed in a cage with soft bedding for 14-21 days before behavioral testing for mechanical allodynia. Selected analogs of compounds of the invention, dosed either i.p. or p.o. demonstrated >30% decrease in tactile allodynia in the spinal nerve or sciatic nerve injury models of neuropathic pain at doses ranging from 1-150 mg/kg.
| Number | Date | Country | |
|---|---|---|---|
| 60966278 | Aug 2007 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 13868765 | Apr 2013 | US |
| Child | 14523296 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 12675430 | Jul 2010 | US |
| Child | 13868765 | US |
