Claims
- 1. A compound of the formula and the pharmaceutically acceptable salts thereof, whereinR1 and R2 form, together with the nitrogen to which they are attached, an azabicyclic ring containing from 6 to 14 ring members, from 1 to 3 of which are nitrogen and the rest of which are carbon; n is 0,1 or 2; and each carbon of said (CH2)n can optionally be substituted with a substituent R8; m is 0,1, or 2; and each carbon of said (CH2)m can optionally be substituted with a substituent R9; each R8 and each R9 is selected, independently, from (C1-C4)alkyl, aryl-(C1-C4)alkyl wherein said aryl is selected from phenyl and naphthyl; allyl and phenallyl; X and Y are selected, independently, from methyl, methoxy, hydroxy and hydrogen; and R10 is hydrogen or (C1-C6) alkyl; with the proviso that R8 is absent when n is zero and R9 is absent when m is zero; or a pharmaceutically acceptable salt of such compound.
- 2. A compound according to claim 1 wherein NR1R2 is a group of the formula wherein NR3R4 is NH2.
- 3. A compound according to claim 1 wherein NR1R2 is a group of the formula wherein R5 is aralkyl and R6 is (4-fluoro)phenylacetyl.
- 4. A pharmaceutical composition comprising a compound according to claim 1, and a pharmaceutically acceptable carrier.
- 5. A method of inhibiting NOS in a mammal, comprising administering to said mammal a NOS inhibiting effective amount of a compound according to claim 1.
- 6. A method according to claim 4, wherein the mammal is suffering from a condition selected from the group consisting of migraine, inflammatory diseases, stroke, acute and chronic pain, hypovolemic shock, traumatic shock, reperfusion injury, Crohn's disease, ulcerative colitis, septic shock, multiple sclerosis, AIDS associated dementia, neurodegenerative diseases, neuron toxicity, Alzheimer's disease, chemical dependencies and addictions, emesis, epilepsy, anxiety, psychosis, head trauma, adult respiratory distress syndrome (ARDS), morphine induced tolerance and withdrawal symptoms, inflammatory bowel disease, osteoarthritis, rheumatoid arthritis, ovulation, dilated cardiomyopathy, acute spinal cord injury, Huntington's disease, Parkinson's disease, glaucoma, macular degeneration, diabetic neuropathy, diabetic nephropathy and cancer in a mammal, comprising administering to said mammal a NOS inhibiting effective amount of a compound according to claim 1.
- 7. A compound selected from the following:6-((2-(6-(t-butoxycarbonylamino)-3-azabicyclo[3.1.0]hex-3-yl)ethyl)phenyl)-pyridin-2-ylamine; 3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-azabicyclo[3.1.0]hex-6-ylamine; 6-{4-[2-(3,4-Dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl}-pyridin-2-ylamine; 6-{4-[2-(5-Methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-ethyl]-phenyl}-pyridin-2-ylamine; 6-{4-[2-(8-Aza-spiro[4.5]dec-8-yl)-ethyl]-phenyl}-pyridin-2-ylamine; 6-{4-[2-(1,3-Dihydro-isoindol-2-yl)-ethyl]-phenyl}-pyridin-2-ylamine; 2-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid; 1-(3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hex-6-yl)-3-phenyl-urea; (3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hex-6-yl)-dimethyl-amine; N-(3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hex-6-yl)-2-(4-fluoro-phenyl)-acetamide; 8-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-benzyl-1,3,8-triaza-spiro[4.5]decane-2,4-dione; 3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.2.1]oct-8-ylamine; (3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hex-6-yl)-phenethyl-amine; (3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hex-6-yl)-(3-phenyl-propyl)-amine hydrochloride salt; 2-(3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hex-6-ylamino)-acetamide; 8-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-phenethyl-1,3,8-triaza-spiro[4.5]decane-2,4-dione; 8-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-8-aza-bicyclo[3.2.1]oct-3-ylamine; {2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-(8-benzyl-8-aza-bicyclo[3.2.1]oct-3-yl)-amine; {2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-(8-aza-bicyclo[3.2.1]oct-3-yl)-amine; 1-(3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethylamino}-8-aza-bicyclo[3.2.1]oct-8-yl)-2-(4-fluoro-phenyl)-ethanone; {2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-amine; {2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-(3-benzyl-3-aza-bicyclo[3.1.0]hex-6-yl)-amine; {2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-[8-(4-fluoro-benzyl)-8-aza-bicyclo[3.2.1]oct-3-yl]-amine; {2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-[8-(4-chloro-benzyl)-8-aza-bicyclo[3.2.1]oct-3-yl]-amine; N-(8-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-8-aza-bicyclo[3.2.1]oct-3-yl)-benzamide; {2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-(3-benzyl-3-aza-bicyclo[3.3.1]non-9-yl)-amine; N-(8-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-8-aza-bicyclo[3.2.1]oct-3-yl)-2-(4-fluoro-phenyl)-acetamide; N-(3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.3.1]non-9-yl)-benzamide (anti-isomer); N-(3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.3.1]non-9-yl)-benzamide (syn-isomer); 3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.3.1]non-9-yl)-ylamine; 3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hexane-6-carboxylic acid ethyl ester; 3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hexane-6-carboxylic acid; 3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hex-6-ylamine (anti-isomer); (3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hex-6-yl)-(4-methyl-piperazin-1-yl)-methanone; {2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-(9-benzyl-3-oxa-9-benzyl-3-oxa-9-aza-bicyclo[3.3.1]non-7-yl)-amine (more polar diastereomer); {2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-(9-benzyl-3-oxa-9-aza-bicyclo[3.3.1]non-7-yl)-amine (less polar diastereomer); {2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-(3-oxa-9-aza-bicyclo[3.3.1]non-7-yl)-amine; 9-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-oxa-9-aza-bicyclo[3.3.1]non-7-ylamine; {2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-(3-oxa-9-aza-bicyclo[3.3.1]non-7-yl)-amine; and 6-{4-[2-(4-(Isoquinolin-1-yl)-piperazin-1-yl)-ethyl]-phenyl}-pyridin-2-ylamine; or a pharmaceutically acceptable salt thereof.
- 8. A compound according to claim 1, wherein R1 and R2, together with the nitrogen to which they are attached, form an azabicyclic ring selected from the following: wherein R3 and R4 are selected from hydrogen, (C1-C6)alkyl, phenyl, naphthyl, (C1-C6)alkyl-C(═O)—, HC(═O)—, (C1-C6)alkoxy-(C═O)—, phenyl-C(═O)—, naphthyl-C(═O)—, and (R7)2NC(═O)— wherein each R7 is selected, independently, from hydrogen and (C1-C6)alkyl; and R5 is selected from hydrogen, (C1-C6)alkyl, phenyl, naphthyl, phenyl-(C1-C6)alkyl- and naphthyl(C1-C6)alkyl-.
- 9. A compound according to claim 1, wherein such compound is selected from:3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hex-6-ylamine; {2-[4-(6-Amino-pyridin-2-yl)-plenyl]-ethyl}-(3-oxa-9-aza-bicyclo[3.3.1]non-7-yl)-amine; (3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.1.0]hex-6-yl)-dimethyl-amine; 8-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-benzyl-1,3,8-triaza-spiro[4.5]decane-2,4-dione; 8-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-8-aza-bicyclo[3.2.1]oct-3-ylamine; 3-{2-[4-(6-Amino-pyridin-2-yl)-phenyl]-ethyl}-3-aza-bicyclo[3.2.1]oct-8-ylamine; and 6-{4-[2-(8-Aza-spiro[4.5]dec-8-yl)-ethyl]-phenyl}-pyridin-2-ylamine; and the pharmaceutically acceptable salts of these compounds.
Parent Case Info
This application claims the benefit of provisional application No. 60/014,343, filed on Mar. 29, 1996.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5629322 |
Guthikonda |
May 1997 |
|
Non-Patent Literature Citations (2)
Entry |
Parkash L et al. Curr. Sci. 58(17), 967-70, 1989.* |
Verma SS et al. J. Indian Chem. Soc. 65(11), 789-9, 1988. |
Provisional Applications (1)
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Number |
Date |
Country |
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60/014343 |
Mar 1996 |
US |