Claims
- 1. A compound, or all enatiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, said compound having the formula:
- 2. A compound according to claim 1 wherein R is selected from the group consisting of phenyl, benzyl, 3-fluorophenyl, 4-fluorophenyl, 3,5-difluorophenyl, 4-chlorophenyl, and 4-hydroxyphenyl.
- 3. A compound according to claim 1 wherein W has the formula:
- 4. A compound according to claim 3 wherein R2 is —NHC(O)CH3.
- 5. A compound according to claim 4 wherein R4 is a unit selected from the group consisting of benzyl, 2-imidazolylmethyl, 4-imidazolylmethyl, 4-fluorobenzyl, 4-hydroxybenzyl, and 4-acetoxybenzyl.
- 6. A compound according to claim 1 wherein W has the formula:
- 7. A compound according to claim 1 wherein W has the formula:
- 8. A compound according to claim 7 wherein R is selected from the group consisting of phenyl, benzyl, 3-fluorophenyl, 4-fluorophenyl, 3,5-difluorophenyl, 4-chlorophenyl, and 4-hydroxyphenyl.
- 9. A compound according to claim 1 wherein R15 is an ester or an amide.
- 10. A compound according to claim 9 wherein R15 is an ester selected from the group consisting of:
i) —C(O)OCH3; ii) —C(O)OCH2CH3; iii) —C(O)OCH2CH2CH3; iv) —C(O)OCH2CH2CH2CH3; v) —C(O)OCH(CH3)2; vi) —C(O)OCH2CH(CH3)2; vii) —C(O)OCH2CH═CHCH3; viii) —C(O)OCH2CH2CH(CH3)2; ix) —C(O)OCH2C(CH3)3; x) —OC(O)CH3; xi) —OC(O)CH2CH3; xii) —OC(O)CH2CH2CH3; xiii) —OC(O)CH(CH3)2; xiv) —OC(O)CH2CH2CH2CH3; xv) —OC(O)CH2CH(CH3)2; xvi) —OC(O)CH2CH═CHCH3; xvii) —OC(O)CH2C(CH3)3; and xviii) —OC(O)CH2CH2CH(CH3)2.
- 11. A compound according to claim 9 wherein R15 is an amide selected from the group consisting of:
i) —C(O)NHCH3; ii) —C(O)NHCH2CH3; iii) —C(O)NHCH2CH2CH3; iv) —C(O)NHCH2CH2CH2CH3; v) —C(O)NHCH(CH3)2; vi) —C(O)NHCH2CH(CH3)2; vii) —C(O)NHCH2CH═CHCH3; viii) —C(O)NHCH2CH2CH(CH3)2; ix) —C(O)NHCH2C(CH3)3; x) —NHC(O)CH3; xi) —NHC(O)CH2CH3; xii) —NHC(O)CH2CH2CH3; xiii) —NHC(O)CH(CH3)2; xiv) —NHC(O)CH2CH2CH2CH3; xv) —NHC(O)CH2CH(CH3)2; xvi) —NHC(O)CH2CH═CHCH3; xvii) —NHC(O)CH2C(CH3)3; and xviii) —NHC(O)CH2CH2CH(CH3)2.
- 12. A compound according to claim 1 wherein R15 is a unit selected from the group consisting of:
a) —C(X)N(R16)2; b) —C(X)NR16N(R16)2; c) —NR16C(X)N(R16)2; and d) —NHN(R16)2; wherein X is ═O, —S, or —NR16, R16 is hydrogen, methyl, cyano, hydroxy, and nitro; the index z is from 0 to 5.
- 13. A compound according to claim 12 wherein R15 has the formula:
- 14. A compound according to claim 13 wherein Y has the formula:
- 15. A compound according to claim 1 wherein R15 is a 5-member heterocyclic ring.
- 16. A compound according to claim 15 wherein R15 is selected from the group consisting of:
i) triazolyl having the formula: 179ii) tetrazolyl having the formula: 180iii) thiazolyl, 2-methylthiazolyl, 4-mentylthiazolyl, 5-methylthiazolyl having the formula: 181iv) 1,3,4-thiadiazolyl, 2-methyl-1,3,4-thiadiazolyl having the formula: 182v) 1,2,5-thiadiazolyl, 3-methyl-1,2,5-thiadiazolyl having the formula: 183vi) oxazolyl, 2-methyloxazolyl, 4-methyloxazolyl, 5-methyloxazolyl having the formula: 184vii) imidazolyl, 2-methylimidazolyl, 5-methylimidazolyl having the formula: 185viii) 5-methyl-1,2,4-oxadiazolyl, 2-methyl-1,3,4-oxadiazolyl, 5-amino-1,2,4-oxadiazolyl, having the formula: 186ix) 1,2-dihydro[1,2,4]triazol-3-one-1-yl, 2-methyl-1,2-dihydro[1,2,4]triazol-3-one-5-yl, having the formula: 187x) oxazolidin-2-one-3-yl; 4,4-dimethyloxazolidin-2-one-3-yl; imidazolidin-2-one-1-yl; 1-methylimidazolidin-2-one-1-yl, having the formula: 188xi) 2-methyl-1,3,4-oxadiazolyl, 2-amino-1,3,4-oxadiazolyl, 2-(N,N-dimethylamino)-1,3,4-oxadiazolyl, having the formula: 189
- 17. A compound according to claim 16 wherein Y has the formula:
- 18. A compound according to claim 1 wherein R15 is a 6-member heterocyclic ring.
- 19. A compound according to claim 18 wherein R15 is selected from the group consisting of:
i) pyridinyl units having the formula: 191ii) pyrimidinyl units having the formula: 192ii) piperidinyl units having the formula: 193
- 20. A compound according to claim 1 wherein R15 is selected from the group consisting of amino, guanidino, guanyl, amidino, pyrrolyl, 2H-pyrrolyl, 3H-pyrrolyl, pyrazolyl, 2H-imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, isoxazolyl, oxazoyl, 1,2,3-isoxazolyl, 1,2,4-oxadiazolyl, 2H-pyranyl, 4H-pyranyl, 2H-pyran-2-one-yl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, piperazinyl, s-triazinyl, 4H-1,2-oxazinyl, 2H-1,3-oxazinyl, 1,4-oxazinyl, morpholinyl, azepinyl, oxepinyl, 4H-1,2-diazepinyl, indenyl, 2H-indenyl, benzofuranyl, isobenzofuranyl, indolyl, 3H-indolyl, 1H-inolyl, benzoxazolyl, 2H-1-benzopyranyl, quinolinyl, isoquinolinyl, quinazolinyl, 2H-1,4-benzoxazinyl, pyrrolidinyl, pyrrolidonyl, pyrrolinyl, quinoxalinyl, pyrrolyl, and benzimidazolyl.
- 21. A compound according to claim 1 wherein R10 is —CO2H, —CO2CH3, —CONHCH3, and —CONH2,
- 22. A compound according to claim 21 wherein R9 is benzyl or 2-naphthylmethyl.
- 23. A compound according to claim 22 wherein R9 is phenyl or 2-naphthyl.
- 24. A compound according to claim 1 consisting of a scaffold selected from the group consisting of:
- 25. A compound according to claim 1 wherein units which substitute for hydrogen atoms are units selected from the group consisting of:
i) —NHCOR30; ii) —COR30; iii) —COOR30; iv) —COCH═CH2; v) —C(═NH)NH2; vi) —NHC(═NH)NH2; vii) —N(R30)2; viii) —NHC6H5; ix) ═CHC6H5; x) —CON(R30)2; xi) —CONHNH2; xii) —NHCN; xiii) —OCN; xiv) —CN; xv) F, Cl, Br, I, and mixtures thereof, xvi) ═O; xvii) —OR30; xviii) —NHCHO; xix) —OH; xx) —NHN(R30)2; xxi) ═NR30; xxii) ═NOR30; xxiii) —NHOR30; xxiv) —CNO; xxv) —NCS; xxvi) ═C(R30)2; xxvii) —SO3M; xxviii) —OSO3M; xxix) —SCN; xxx) —P(O)H2; xxxi) —PO2; xxxii) —P(O)(OH)2; xxxiii) —SO2NH2; xxxiv) —SO2R30; xxxv) —NO2; xxxvi) —CF3, —CCl3, —CBr3; xxxvii) and mixtures thereof; wherein R30 is hydrogen, C1-C20 linear or branched alkyl, C6-C20 aryl, and C7-C20 alkylenearyl; M is hydrogen, or a salt forming cation.
- 26. A pharmaceutical composition comprising:
A) an effective amount of a compound, or all enatiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, said compound having the formula: 195wherein A is a conformationally restricted ring system selected from the group consisting of: 196wherein the carbon atoms marked with an asterisk can have any stereo-chemical configuration; W has the formula: 197R is phenyl or substituted phenyl; wherein R2, R3, and R4 units are independently selected from the group: a) rings consisting of:
i) substituted or unsubstituted aromatic carbocyclic rings, said rings selected from phenyl, benzyl, α-naphthyl, or β-naphthyl; ii) substituted or unsubstituted aromatic heterocyclic rings, said rings selected from 1-quinolinyl, 2-quinolinyl, 3-quinolinyl, 4-quinolinyl, 5-quinolinyl, 6-quinolinyl, 7-quinolinyl, 8-quinolinyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 1-imidazolylmethyl, 2-imidazolylmethyl, 4-imidazolylmethyl, 1-pyridinyl, 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl; iii) and mixtures thereof; b) hydrogen; c) a unit selected from the group consisting of —CH2C(O)CH3, —NHC(O)CH3, —NHC(O)CH2CH3, and —NHC(O)CH2CH2CH3; d) two of R2, R3, or R4 can be taken together to form a ring consisting of:
i) substituted or unsubstituted aromatic carbocyclic rings, said rings selected from phenyl, α-naphthyl, or β-naphthyl; ii) substituted or unsubstituted aromatic heterocyclic rings, said rings selected from 1-quinolinyl, 2-quinolinyl, 3-quinolinyl, 4-quinolinyl, 5-quinolinyl, 6-quinolinyl, 7-quinolinyl, 8-quinolinyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 1-pyridinyl, 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl; and e) mixtures thereof; Y is a pendant unit containing at least one heteroatom having the formula:—(CH2)b—R15wherein R15 contains a heteroatom selected from nitrogen, oxygen, or mixtures thereof; the index b is from 1 to 4; Z is a pendant unit, which contains an aromatic carbocyclic ring; said unit having the formula: 198wherein R8 is hydrogen; R9 is phenyl, benzyl, 1-naphthyl, 2-naphthyl, 1-naphthylmethyl, 2-naphthylmethyl; R10 is hydrogen, —C(X)2R17, —C(X)N(R16)2, —N(R16)2—N+(R16)3D−, —C(X)N+(R16)3D−, and —NR16C(X)R17; R16 is hydrogen, or C1-C10 alkyl; R17 is C1-C16 linear or branched, substituted or unsubstituted alkyl, C7-C16 linear or branched, substituted or unsubstituted alkylenearyl; X is oxygen, sulfur, and ═NR16; D is a salt forming anion; and B) the balance carriers, excipients, and adjunct ingredients.
- 27. A method for treating a body weight disorder selected from the group consisting of obesity, anorexia and cachexia in a subject needing treatment, the method comprising administering to said subject a compound, or all enatiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, said compound having the formula:
- 28. A method according to claim 27, wherein the disease is obesity.
- 29. A method of treating a disorder selected from the group consisting of insulin resistance, glucose intolerance, Type-2 diabetes mellitus, coronary artery disease, elevated blood pressure, hypertension, dyslipidaemia, cancer (e.g., endometrial, cervical, ovarian, breast, prostate, gallbladder, colon), menstrual irregularities, hirsutism, infertility, gallbladder disease, restrictive lung disease, sleep apnea, gout, osteoarthritis, and thromboembolic disease, in an animal subject in need thereof, the method comprising administering to said subject a compound according to claim 1.
- 30. A method of treating a disorder selected from the group consisting of a body weight disorder, CNS depression, behavior-related disorders, memory related disorders, cardiovascular function, inflammation, sepsis, septic shock, cardiogenic shock, hypovolemic shock, sexual dysfunction, erectile dysfunction, muscle atrophy, diseases associated with nerve growth and repair, and intrauterine fetal growth, in an animal subject in need thereof, the method comprising administering to said subject the compound of claim 1.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Divisional Application of application Ser. No. 10/121,874 filed Apr. 12, 2002 which claims priority under Title 35, United States Code 119(e) from Provisional Application Serial No. 60/286,610 filed Apr. 25, 2001.
Provisional Applications (1)
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Number |
Date |
Country |
|
60286610 |
Apr 2001 |
US |
Divisions (1)
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Number |
Date |
Country |
Parent |
10121874 |
Apr 2002 |
US |
Child |
10856983 |
May 2004 |
US |