Patent EA-001427-B1 (EA)
Title: Thienoazepine derivatives as vasopressin antagonists
Inventor: ALBRIGHT JAY DONALD
IPC: A61P9/08
Filed: 1996-01-16
Abstract: 1.Thienozepine derivatives of general formula I:    wherein E-Y is selected from the moieties -CH=CH-, -CH2-CH2- and   R<1> is selected from hydrogen and halo; R<3> is -COAr, wherein Ar is a moiety selected from the group consisting of:   R<5> is selected from hydrogen, (C1-C3) alkyl, (C1-C3) alkoxy and halogen; R<6> is selected from (a) moieties of the formulas:   wherein J is   Ar` is selected from the moieties of formulas:    wherein W' is selected from O and S; (b) moiety of the formula -M-Rd wherein Rd is alkyl(C3-C8) or -(CH2)p-cycloalkyl(C3-C6), when M is O, and Rd is    when M is a bond; R<7> is selected from hydrogen and halogen; R<8> and R<9> are independently selected from hydrogen, alkyl(C1-C3), -S-alkyl(C1-C3), halogen, -NH-alkyl(C1-C3), -N-[alkyl(C1-C3)]2, -OCF3, -NO2, -NH2, -O-alkyl(C1-C3), R<10> is selected from hydrogen, halogen and -O-alkyl(C1-C3) and the pharmaceutically acceptable salts thereof. 2. .The compound according to claim 1 which is N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-3,4-dichlorobenzamide.  3. The compound according to claim 1 which is N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2-chlorobenzeneacetamide.  4. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2-methylbenzamide.  5. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2-furanecarboxamide.  6. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-4-tert-butylbenzamide.  7. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-4-(n-butyl)benzamide.  8. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-3-methyl-2-thiophenecarboxamide.  9. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2,5-dimethylbenzamide.  10. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2,5-dichlorobenzamide.  11. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2,3-dimethylbenzamide.  12. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2,4-dimethylbenzamide.  13. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]benzeneacetamide.  14. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2-methylbenzeneacetamide.  15. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2,4-dichlorobenzamide.  16. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-3-cyclohexenecarboxamide.  17. The compound according to claim 1, is 2,4-dichloro-N-[4-[(2-chloro-5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]benzamide. 18. The compound according to claim 1 N-[4-[(2-chloro-5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-3-fluoro-2-methylbenzamide.  19. The compound according to claim 1 N-[4-[(2-chloro-5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2,6-dichlorobenzamide.  20. The compound according to claim 1 N-[4-[(2-chloro-5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2-methylbenzamide.  21. The compound according to claim 1 N-[4-[(2-chloro-5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2-chlorobenzeneacetamide.  22. The compound according to claim 1 N-[4-[(2-chloro-5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]-3-chlorophenyl]-5-fluoro-2-methylbenzamide.  23. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-8-oxo-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-3-fluoro-2-methylbenzamide.  24. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-8-oxo-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-2,4-dichlorobenzamide.  25. The compound according to claim 1 N-[4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]-3-chlorophenyl]-2-chloro-4-fluorobenzamide.  26. The compound according to claim 1 N-[4-[(5,6-dihydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]-3-chlorophenyl]-3-fluoro-2-methylbenzamide.  27. The compound according to claim 1 N-[5-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]-2-pyridinyl]-5-fluoro-2-methylbenzamide. 28. A method for preparing compounds of general formula I:   wherein E-Y is selected from the moieties -CH=CH-, -CH2-CH2- and   R<1> is selected from hydrogen and halo; R<3> is -COAr, wherein Ar is a moiety selected from the group consisting of:   R<5> is selected from hydrogen, (C1-C3) alkyl, (C1-C3) alkoxy and halogen; R<6> is selected from (a) moieties of the formulas:   wherein J is   Ar` is selected from the moieties of formulas:    wherein W' is selected from O and S; (b) moiety of the formula -M-Rd wherein Rd is alkyl(C3-C8) or -(CH2)p-cycloalkyl(C3-C6), when M is O, and Rd is    when M is a bond; R<7> is selected from hydrogen and halogen; R<8> and R<9> are independently selected from hydrogen, alkyl(C1-C3), -S-alkyl(C1-C3), halogen, -NH-alkyl(C1-C3), -N-[alkyl(C1-C3)]2, -OCF3, -NO2, -NH2, -O-alkyl(C1-C3), R<10> is selected from hydrogen, halogen and -O-alkyl(C1-C3) and the pharmaceutically acceptable salts thereof, which comprises reaction of compound of formula   wherein -E-Y- and R` are determined above, with compound of formula   wherein Q is a halogen or an activating group, which results from conversion of an arylcarboxylic acid to an acid chloride, mixed anhydride or from activation with a peptide-coupling reagent.