Patent EA-003992-B1 (EA)
Title: Substituted tricyclics
Inventor: BACH NICHOLAS J
IPC: C07D409/04
Filed: 1997-10-23
Abstract: 1. A compound of the formula (III): wherein R<20> is -CO2H, where R4 is phenyl; R<21> is hydrogen, methyl, ethyl (non-interfering substituents); R1' is -NHNH2 or -NH2; R2' is -OH, -O(CH2)tR<5>, where R<5> is CN or phenyl and t equal to 1-5 or -(OCH2)-acid group; or a pharmaceutically acceptable salt, racemate, solvate, tautomer, optical isomer or prodrug derivative thereof; for inhibiting a mediated sPLA2 release of fatty acids. 2. A compound of the formula (I): wherein R<1> is NHNH2 or -NH2; R<2> is -OH or -O(CH2)mR<5>, where R<5> is phenyl and m equal to 1-3; and R<4> is phenyl; or a pharmaceutically acceptable salt, racemate, solvate, tautomer, optical isomer or prodrug derivative thereof; for inhibiting a mediated sPLA2 release of fatty acids. 3. A method according to claim 2, where a compound is 4-[(9-benzyl-4-carbamoyl-1,2,3,4-tetrahydrocarbazol-6-yl)oxy]butyric acid; 3-[(9-benzyl-4-carbamoyl-1,2,3,4-tetrahydrocarbazol-6-yl)oxy]propyl phosphonic acid; 2-[(9-benzyl-4-carbamoyl-1,2,3,4-tetrahydrocarbazol-6-yl)oxy]methyl benzoic acid; 3-[(9-benzyl-4-carbamoyl-7-n-oktyl-1,2,3,4-6-tetrahydrocarbazol-6-yl)oxy]propyl phosphonic acid; 4-[(9-benzyl-4-carbamoyl-7-ethyl-1,2,3,4-tetrahydrocarbazol-6-yl)oxy]butyric acid; 3-[(9-benzyl-4-carbamoyl-7-ethyl-1,2,3,4-6-tetrahydrocarbazol-6-yl)oxy]propyl phosphonic acid; 3-[(9-benzyl-4-carbamoyl-7-ethyl-1,2,3,4-6-tetrahydrocarbazol-6-yl)oxy]propyl phosphonic acid; (S)-(+)-4-[(9-benzyl-4-carbamoyl-7-ethyl-1,2,3,4-tetrahydrocarbazol-6-yl)oxy]butyric acid; 4-[9-benzyl-4-carbamoyl-6-(2-cyanoethyl)-1,2,3,4-tetrahydrocarbazol-6-yl]oxy butyric acid; 4-[9-benzyl-4-carboxamido-7-(2-phenylethyl)-1,2,3,4-tetrahydrocarbazol-6-yl]oxy butyric acid; 4-[9-benzyl-4-carboxamidocarbazol-6-yl]oxy butyric acid; methyl 2-[(9-benzyl-4-carbamoyl-1,2,3,4-tetrahydrocarbazol-6-yl)oxy]methyl benzoate; hydrazide 9-benzyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazol-4-carbonic acid; 9-benzyl-5,7-dimethoxy-1,2,3,4- tetrahydrocarbazol-4-carboxamide; natrium salt[9-benzyl-4-carbamoyl-7-methoxy-1,2,3,4-tetrahydrocarbazol-5-yl]oxy acetic acid; 4-[9-benzyl-4-carbomoyl-7-(2-cyanolethyl)-1,2,3,4-tetrahydrocarbazol-6-yl]oxy butyric acid; [9-benzyl-4-carbamoyl-7-methoxycarbazol-5-yl]oxy acetic acid; methyl [9-benzyl-4-carbamoyl-7-methoxycarbazol-5-yl)oxy acetic acid; 9-benzyl-7-methoxy-5-cyanomethoxy-1,2,3,4- tetrahydrocarbazol-4-carboxamide; 9-benzyl-7-methoxy-5-(1H-tetrazol-5-ylmethyl)oxy)-1,2,3,4-tetrahydrocarbazol-4-carboxamide; 9-benzyl-4-carbamoyl-8-methyl-1,2,3,4- tetrahydrocarbazol-5-yl]oxy acetic acid; 9-benzyl-4-carbamoyl-8-methylcarbazol-5-yl]oxy acetic acid; 9-benzyl-4-carbamoyl-1,2,3,4-tetrahydrocarbazol-5-yl]oxy acetic acid and 9-benzyl-4-carbamoylcarbazol-5-yl]oxy acetic acid and pharmaceutically acceptable salt, racemate, solvate, tautomer, optical isomer or prodrug derivative thereof. 4. A method of selectively inhibiting sPLA2 in a mammal in need of such treatment comprising administering to said mammal a therapeutically effective amount of a compound of formula (III) As claimed in claim 1. 5. A method of claim 4, wherein the mammal is a human. 6. A method of selectively inhibiting sPLA2 in a mammal in need of such treatment comprising administering to said mammal a therapeutically effective amount of a compound of formula (II): wherein R<1> is -NHNH2 or -NH2; R<2> is -OH or -O(CH2)mR<5>, wherein m equal to 1-3 and R<5> is -CN or phenyl; R<4> is phenyl; or a pharmaceutically acceptable salt, racemate, solvate, optical isomer or prodrug derivative. 7. A method of claim 6, wherein the mammal is a human. 8. A method of selectively inhibiting sPLA2 in a mammal in need of such treatment, which comprises administering to a mammal a therapeutically effective amount of a compound of formula III, sufficient to inhibit sPLA2 mediated release of fatty acid and to thereby inhibit or prevent the arachidonic acid metabolism and its deleterious products. 9. A method of claim 8, wherein the mammal is a human. 10. A compound of the formula (III): wherein R<20> is -CH2-R<4>, wherein R<4> is phenyl; R<21> is hydrogen, methyl, ethyl (non-interfering substituents); R1' is -NHNH2 or -NH2; R2' is -OH, -O(CH2)tR<5>, wherein -(OCH2)-(acid group); or a pharmaceutically acceptable salt, racemate, solvate, optical isomer or prodrug derivative thereof; for selectively inhibiting sPLA2 in a mammal in need of such treatment. 11. A compound of the formula (I): wherein R<1> is -NHNH2 or -NH2; R<2> is -OH, -O(CH2)tR<5>, wherein R<5> is phenyl and m equal to 1-3; and R<4> is phenyl; or a pharmaceutically acceptable salt, racemate, solvate, optical isomer or prodrug derivative thereof; for selectively inhibiting sPLA2 in a mammal in need of such treatment. 12. A compound of the formula (III): wherein R<20> is -CH2-R<4>, wherein R<4> is phenyl; R<21> is hydrogen, methyl, ethyl (non-interfering substituents); R1' is -NHNH2 or -NH2; R2' is -OH, -O(CH2)tR<5>, wherein R<5> is CN or phenyl and t equal to 1-5, or -(OCH2)-(acid group); or a pharmaceutically acceptable salt, racemate, solvate, optical isomer or prodrug derivative thereof; for producing a medicine for selectively inhibiting sPLA2 in a mammal in need of such treatment. 13. A compound of the formula (I): wherein R<1> is -NHNH2 or -NH2; R<2> is -OH, -O(CH2)tR<5>, wherein R<5> is phenyl and m equal to 1-3; and R<4> is phenyl; or a pharmaceutically acceptable salt, racemate, solvate, optical isomer or prodrug derivative thereof; for producing a medicine for selectively inhibiting sPLA2 in a mammal in need of such treatment.