Claims
- 1. A compound of the formula ##STR23## where R is CH.sub.3 (CH.sub.2).sub.m --,
- A and B are each hydrogen or together are a bond or --(CH.sub.2).sub.n,
- X is ##STR24## m is 0,1,2 or 3 and n is 1,2 or 3, R.sub.1 is hydrogen or lower alkyl, and
- a)
- Y is --OH, or --OR.sub.2,
- where
- R.sub.2 is lower alkyl, phenyl, phenalkyl of 7 to 9 carbon atoms ,--(CH.sub.2).sub.n --CONR.sub.3 R.sub.4, --(CH.sub.2).sub.n --OCOR.sub.3, --(CH.sub.2).sub.n --NR.sub.3 R.sub.4 or ##STR25## and R.sub.3 and R.sub.4 are independently hydrogen or lower alkyl, with the proviso that when X is >CO and A and B are both hydrogen, Y is other than --OH or --OR.sub.2, where R.sub.2 is lower alkyl; or
- b)
- Y is --NR.sub.5 R.sub.6,
- where i) R.sub.5 is hydrogen or lower alkyl,
- R.sub.6 is hydrogen, lower alkyl, --(CH.sub.2).sub.m --SH, or --CHR.sub.7 --COOR.sub.3 and
- R.sub.7 is hydrogen, lower alkyl or ##STR26## where R.sub.8 and R.sub.9 are each independently hydrogen, hydroxy, halogen, lower alkyl or lower alkoxy, and m, n, and R.sub.3 are as defined above; or
- ii) R.sub.5 is hydrogen, lower alkyl, --COR.sub.10 or ##STR27## where R.sub.10 is lower alkyl or --OR.sub.3, and m, R.sub.3, R.sub.8 and R.sub.9 are as defined above, and ##STR28## where R.sub.11 and R.sub.12 are each independently hydrogen, halogen, lower alkyl, lower alkoxy, --CF.sub.3, --(CH.sub.2).sub.m COOR.sub.3, --CONR.sub.3 R.sub.4, --SO.sub.3 H or --PO.sub.3 H.sub.2, and m, R.sub.3 and R.sub.4 are as defined above or
- iii) R.sub.5 is hydrogen, lower alkyl, --OR.sub.3, ##STR29## where m, A, B, R, R.sub.3, R.sub.8 and R.sub.9 are as defined above and R.sub.6 is --COR.sub.13,
- where R.sub.13 is alkyl of 1 to 8 carbon atoms, phenalkenyl of 8 to 10 carbon atoms, ##STR30## where m, A, B, R, R.sub.8 and R.sub.9 are as define above, or a pharmaceutically acceptable metal salt or acid addition salt thereof.
- 2. A compound according to claim 1, in which X is >CO.
- 3. A compound according to claim 1, in which Y is as defined in group bi.
- 4. A compound according to claim 1 in which Y is as defined in group bii.
- 5. A compound according to claim 1 in which Y is as defined in group biii.
- 6. A compound according to claim 3, in which X is >CO.
- 7. A compound according to claim 4, in which X is >CO.
- 8. A compound according to claim 5, in which X is >CO.
- 9. A compound according to claim 1 of the formula ##STR31## where R, A and B and the proviso are as defined in claim 1.
- 10. A compound according to claim 9 which is 4-(1-methylcyclopropylcarbonyl)-benzoic acid or 4- ( 2,2-dimethyl-1-oxobutyl )-benzoic acid.
- 11. A compound according to claim 1 of the formula ##STR32## where R, A, B, R.sub.2 and the proviso are as defined in claim 1.
- 12. A compound according to claim 11, which is
- a) 4-(2,2-dimethyl-1-oxopropyl)-benzoic acid, (2-diethylamino)ethyl ester
- b) 4-(2,2-dimethyl-1-oxopropyl)-benzoic acid, (2,2-dimethyl-1-oxopropoxy)methyl ester
- c) 4-(2,2-dimethyl-1-oxopropyl)-benzoic acid, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester or
- d) 4-(2,2-dimethyl-1-oxoproyl)-benzoic acid, (2-diethylamino-2-oxo)ethyl ester.
- 13. A compound according to claim 1 of the formula ##STR33## where R, A, and B are as defined in claim 1 and R.sub.5 and R.sub.6 are as defined in group bi.
- 14. A compound according to claim 13 which is
- a) 4-(2,2-dimethyl-1-oxopropyl)-N,N-dimethylbenzamide
- b) 4-(2,2-dimethyl-1-oxopropyl)-N-methylbenzamide
- c) 4-(2,2-dimethyl-1-oxopropyl)-N-(1,1-dimethylethyl ) benzamide
- e) 4-(2,2-dimethyl-1-oxopropyl)-N-(2-mercaptoethyl) benzamide
- f) 4-(1-methylcyclopropylcarbonyl)benzamide
- g) 4-(2,2-dimethyl-1-oxobutyl)benzamide
- h) 4-(2,2-dimethyl-1-oxopropyl)benzamide
- i) 4-(2,2-dimethyl-1-oxopropyl)benzoyl-(L)phenylal aninamide
- j) 4-(2,2-dimethyl-1-oxopropyl)benzoyl-(D)-phenylalaninamide or
- k) 4-(2,2-dimethyl-1-oxopropyl)benzoyl-glycinamide.
- 15. A compound according to claim 1 of the formula ##STR34## where R, A, B, m, n and Y are as defined in claim 1.
- 16. A compound according to claim 15, which is
- a) 2-(4-carboxyphenyl) -2- (1-methylcyclopropyl)-1,3-dioxolane
- b) 2-(4-carboxyphenyl)-2-(1,1-dimethylpropyl)-1,3-dioxolane
- c) 2-(1,1-dimethylethyl)-2-(4-ethoxycarbonylphenyl)-1,3-dioxolane
- d) 2-[[4-[2-(diethlaminocarbonyl)ethoxy]carbonyl]phenyl]-2-(1,1-dimethylethyl)-1,3-dioxolane
- e) 2-(1,1-dimethylethyl)-2-[[4-[(2,2-dimethyl-1-oxopropoxy)methoxy]carbonyl]phenyl]-1,3 dioxolane
- f) 2-[4-[2-(diethylamino)ethoxy]carbonylphenyl]-2-(1,1-dimethylethyl)-1,3-dioxolane
- g) 2-(1,1-dimethylethyl)-2-[4-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methoxycarbonyl]phenyl]-1,3-dioxolane
- h) 2-[(4-carbamoyl)phenyl]-2-(1,1-dimethylethyl)-1,3-dioxolane
- i) 2-[(4-dimethylaminocarbonyl)phenyl]-2-(1,1-dimethylethyl)-1,3-dioxolane
- j) 2-(1,1-dimethylethyl )-2-[(4-phenylaminocarbonyl)phenyl]1,3-dioxolane
- k) 2-[(4-carbamoyl )phenyl]-2-(1-methylcyclopropyl )-1,3-dioxolane
- l) 2-[(4-carbamoyl)phenyl]-2-(1,1-dimethylpropyl )-1,3-dioxolane
- n) 2-(1,1-dimethylethyl)-2-[4-[(2-mercaptoethyl)aminocarbonyl]phenyl)-1,3-dioxolane
- o) 2-(1,1-dimethylethyl )-2- (4-carboxyphenyl)-1,3-dioxolane
- p) 4-(2-[1,1-dimethylethyl]-1,3-dioxolan-2-yl)benzoyl glycinamide or
- q) 4-(2-[1,1-dimethylethyl]-1,3-dioxalan-2-yl)benzoyl glycinamide, methyl ester.
- 17. A compound according to claim 1 of the formula ##STR35## where R, A, B, R.sub.1 and Y are as defined in claim 1.
- 18. A compound according to claim 17 which is
- a) 4-carboxy-.alpha.-(1,1-dimethylpropyl)-benzenemethanol
- b) 4-[(2-diethylamino-2-oxoethoxy)carbonyl]-.alpha.-(1,1-dimethylethyl)-benzenemethanol
- c) 4-carbamoyl-.alpha.-(1,1-dimethylpropyl)-benzenemethanol
- d) .alpha.-(1,1-dimethylethyl)-4-[(2-mercaptoethyl)aminocarbonyl]-benzenemethanol
- e) 4-carboxy-.alpha.-(1,1-dimethylethyl)-benzenemethanol
- f) 4-carboxy-.alpha.-(1,1-dimethylethyl)-.alpha.-methyl-benzenemethanol or
- g) 4-(2,2-dimethyl-1-hydroxypropyl)-N-(3-phenylpropionyl)-benzamide.
- 19. A compound according to claim 1 of the formula ##STR36## where R, A, B, and Y are as defined in claim 1.
- 20. A compound according to claim 19, which is
- a) 4-(1,1-difluoro-2,2-dimethylpropyl)benzoic acid or
- b) 4-(1,1-difluoro-2,2-dimethylpropyl)benzamide.
- 21. A compound according to claim 1 of the formula ##STR37## where R, A, and B are as defined in claim 1, and R.sub.5 and R.sub.6 are as defined in group bii.
- 22. A compound according to claim 21, which is
- a) 4-(2,2-dimethyl-1-oxopropyl)-N-(3-ethoxycarbonylphenyl)-benzamide;
- b) 4-(2,2-dimethyl-1-oxopropyl)-N-(2-ethoxycarbonyiphenyl)-benzamide;
- c) 4-(2,2-dimethyl-1-oxopropyl)-N-(4-tolyl)-benzamide;
- d) 4-(2,2-dimethyl-1-oxopropyl)-N-(4-trifluromethylphenyl)-benzamide;
- e) 4-(2,2-dimethyl-1-oxopropyl)-N-(4-ethoxycarbonylmethylphenyl)-benzamide;
- f) 4-(2,2-dimethyl-1-oxopropyl)-N-(4-sulfophenyl)-benzamide;
- g) 4-(2,2-dimethyl-1-oxopropyl)-N-(4-phosphonophenyl)-benzamide;
- h) 4-(2,2-dimethyl-1-oxopropyl)-N-(4-carbamoylphenyl)-benzamide;
- i) 4-(2,2-dimethyl-1-oxopropyl)-N-(2-methoxy-4-ethoxycarbonylphenyl)-benzamide;
- j) 4-(2,2-dimethyl-1-oxopropyl)-N-(2-chloro-4-ethoxycarbonylphenyl)-benzamide;
- k) 4-(2,2-dimethyl-1-oxopropyl)-N-(3-bromo-4-ethoxycarbonylphenyl)-benzamide;
- l) 4-(2,2-dimethyl-1-oxopropyl)-N-(2-trifluoromethy-4-methoxycarbonylphenyl)-benzamide;
- m) 4-(2,2-dimethyl-1-oxopropyl)-N-methyl-N-(4-ethoxycarbonyl-phenyl)-benzamide;
- n) 4-(2,2-dimethyl-1-oxopropyl)-N-benzyl-N-(4-ethoxycarbonylphenyl)-benzamide;
- o) 4-(2,2-dimethyl-1-oxopropyl)-N-acetyl-N-(4-ethoxycarbonylphenyl)-benzamide;
- p) 4-(2,2-dimethyl-1-oxopropyl)-N-ethoxycarbonyl-N-(4-ethoxycarboxylphenyl)-benzamide;
- q) 4-(2,2-dimethyl-1-oxopropyl)-N-(4-fluoroplenyl)-benzamide;
- r) 4-(2,2-dimethyl-1-oxopropyl)-N-phenylbenzamide;
- s) 4-(2,2-dimethyl-1-oxopropyl)-N-(4-carboxyphenyl)-benzamide;
- t) 4-(2,2-dimethyl-1-oxopropyl)-N-(4-ethoxycarbonylphenyl)-benzamide;
- u) 4-(2,2-dimethyl-1-oxopropyl)-N-benzylbenzamide;
- v) 4-(2,2-dimethyl-1-oxopropyl)-N-methyl-N-phenylbenzamide; or
- w) 4-(2,2-d imethyl-1-oxopropyl)-N-phenethylbenzamide.
- 23. A compound according to claim 1 of the formula ##STR38## where R, A and B are as defined in claim 1, and R.sub.5 and R.sub.6 are as defined in group biii.
- 24. A compound according to claim 23 in which R is methyl and A and B are both hydrogen.
- 25. The compound according to claim 23 which is 4-(2,2-dimethyl-1-oxopropyl)-N-[4-(2,2-dimethyl-1-oxopropyl)benzoyl]-benzamide.
- 26. A compound according to claim 23, which is:
- a) 4-(2,2-dimethyl-1-oxopropyl)-N-acetylbenzamide;
- b) 4-(2,2-dimethyl-1-oxopropyl)-N-octanoylbenzamide;
- c) 4-(2,2-dimethyl-1-oxopropyl)-N-(3-phenylacrlyl)benzamide;
- d) 4-(2,2-dimethyl-1-oxopropyl)-N-(3-phenylpropionyl)benzamide;
- e) 4-(2,2-dimethyl-1-oxopropyl)-N-methyl-N-[4-(2,2-dimethyl-1-oxopropyl)-benzoyl]-benzamide;
- g) 4-(2,2-dimethyl-1-oxopropyl)-N,N-di-[4-(2,2-dimethyl-1-oxopropyl)-benzoyl]-benzamide;
- h) 4-(2,2-dimethyl-1-oxopropyl)-N-benzoyl-benzamide; or
- i) 4-(2,2-dimethyl-1-oxopropyl)-N-(p-fluorobenzoyl)-benzamide.
- 27. The compound of claim 17 which is 4-carboxy-.alpha.-(1,1-dimethylethyl)-benzenemethanol.
- 28. A pharmaceutical composition useful in treating diabetes comprising an antidiabetic effective amount of a compound of the formula ##STR39## where R is CH.sub.3 (CH.sub.2).sub.m --, A and B are each hydrogen or together are a bond or --(CH.sub.2).sub.n --, ##STR40## m is 0, 1, 2 or 3 and n is 1, 2 or 3, R.sub.1 is hydrogen or lower alkyl, and
- a)
- Y is --OH or --OR.sub.2 ,
- where R.sub.2 is lower alkyl, phenyl, phenalkyl of 7 to 9 carbon atoms, --(CH.sub.2).sub.n --CONR.sub.3 R.sub.4, --(CH.sub.2).sub.n --OCOR.sub.3, --(CH.sub.2).sub.n --NR.sub.3 R.sub.4 or ##STR41## and R.sub.3 and R.sub.4 are independently hydrogen or lower alkyl, with the proviso that when X is >CO and A and B are both hydrogen, Y is other than --OH or OR.sub.2, where R.sub.2 is lower alkyl; or
- b)
- Y is --NR.sub.5 R.sub.6
- where i)
- R.sub.5 is hydrogen or lower alkyl,
- R.sub.6 is hydrogen, lower alkyl, --(CH.sub.2).sub.m SH or --CHR.sub.7 --COOR.sub.3 and
- R.sub.7 is hydrogen, lower alkyl or ##STR42## where R.sub.8 and R.sub.9 are each independently hydrogen, hydroxy, halogen, lower alkyl or lower alkoxy and
- m, n, and R.sub.3 are as defined above; or
- ii) R.sub.5 is hydrogen, lower alkyl, --COR.sub.10 or ##STR43## where R.sub.10 is lower alkyl or OR.sub.3 and m, R.sub.3, R.sub.8 and R.sub.9 are as defined above, and ##STR44## where R.sub.11 and R.sub.12 are each independently hydrogen, halogen, lower alkyl, lower alkoxy, --CF.sub.3, --(CH.sub.2).sub.m COOR.sub.3, --CONR.sub.3 R.sub.4, --SO.sub.3 H or --PO.sub.3 H.sub.2 and m, R.sub.3 and R.sub.4 are as defined above or
- iii) R.sub.5 is hydrogen, lower alkyl, --OR.sub.3, ##STR45## where m, A, B, R, R.sub.3, R.sub.8 and R.sub.9 are as defined above and R.sub.6 is --COR.sub.13,
- where R.sub.13 is alkyl of 1 to 8 carbon atoms, phenalkenyl of 8 to 10 carbon atoms, ##STR46## where m, A, B, R, R.sub.8 and R.sub.9 are as defined above, or a pharmaceutically acceptable metal salt or acid addition salt thereof and a pharmaceutically acceptable carrier therefor.
Parent Case Info
This is a continuation application of Ser. No. 07/970,754, filed Nov. 3, 1992, now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4623662 |
De Vries |
Nov 1986 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
0900178 |
Jan 1985 |
BEX |
0463989 |
Jan 1992 |
EPX |
Non-Patent Literature Citations (3)
Entry |
De Vries et al., J. Med. Chem. (1986), vol. 29, pp. 1131-1133. |
Chem. Abs., 109:93863r, Takahashi et al., 1988. |
Brinkhaus et al., Tetrahedron (1986), vol. 42, pp. 553-560. |
Continuations (1)
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Number |
Date |
Country |
Parent |
970754 |
Nov 1992 |
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