Claims
- 1. A compound of the formula: ##STR33## wherein: A is --(CR.sup.9 R.sup.10).sub.r R.sup.11 ;
- R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are each independently selected from:
- (1) hydrogen;
- (2) alkyl having 1 to 6 carbon atoms;
- (3) alkenyl having 2 to 6 carbon atoms;
- (4) --(CH.sub.2).sub.n M wherein n is 0 to 3 and M is
- (a) --C(O)R.sup.15 ;
- (b) --C(O)NR.sup.17 R.sup.17 ;
- (c) --CN;
- (d) --C(O)R.sup.16 ;
- (e) --C(O)CH.sub.2 OH (hydroxymethyl ketone);
- (f) --CF.sub.3 ;
- (g) --R.sup.14 ;
- (i) --OR.sup.12 ;
- (j) --OC(O)R.sup.16 ;
- (k) --OC(O)NR.sup.17 R.sup.17 ;
- (l) --OC(O)OR.sup.18 ;
- (m) --S(O).sub.2 NR.sup.17 R.sup.17 ;
- (n) --NR.sup.17 R.sup.17 ;
- (o) --NHC(O)R.sup.16 ;
- (p) --NHS(O).sub.2 R.sup.13 ;
- (q) --N.sub.3 ;
- (r) --NO.sub.2 ; or
- (s) -halogen;
- each R.sup.7 is independently H or C.sub.1 to C.sub.6 alkyl;
- each R.sup.8 is independently H or C.sub.1 to C.sub.6 alkyl;
- each R.sup.9 is independently H or C.sub.1 to C.sub.6 alkyl;
- each R.sup.10 is independently H, OH, C.sub.1 to C.sub.4 alkoxy, or C.sub.1 to C.sub.4 alkyl;
- R.sup.11 is --C(O)OR.sup.19 ;
- each R.sup.12 is independently H, C.sub.1 to C.sub.6 alkyl, benzyl, or R.sup.14 ;
- each R.sup.13 is independently C.sub.1 to C.sub.6 alkyl, CF.sub.3, or R.sup.14 ;
- each R.sup.14 is independently phenyl, mono-substituted phenyl, or di-substituted phenyl wherein the substituents are independently, C.sub.1 to C.sub.3 alkyl, C.sub.1 to C.sub.3 perfluoroalkyl, C.sub.1 to C.sub.3 alkoxy, halogen, CN, --C(O)OR.sup.15, or --CH.sub.2 --C(O)OR.sup.15 ;
- each R.sup.15 is independently H, phenyl, benzyl or C.sub.1 to C.sub.6 alkyl;
- each R.sup.16 independently is H, R.sup.13 or (CH.sub.2).sub.m C(O)OR.sup.15 ;
- each R.sup.17 is independently R.sup.12
- each R.sup.18 is independently C.sub.1 to C.sub.6 alkyl, benzyl or phenyl;
- each R.sup.19 is H, C.sub.1 to C.sub.6 alkyl, R.sup.14, R.sup.21, or R.sup.22 ;
- R.sup.21 is --CH.sub.2 --R.sup.14 ;
- R.sup.22 is --CH.sub.2 --CH.sub.2 --R.sup.14
- m is 0 to and
- r is 0 to 6.
- 2. A compound according to claim 1, wherein:
- R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are each independently selected from:
- (1) hydrogen;
- (2) alkyl having 1 to 6 carbon atoms;
- (3) alkenyl having 2 to 6 carbon atoms;
- (4) --(CH.sub.2).sub.n M wherein n is 0 or 1; and r is 1 to 6;
- 3. A compound according to claim 2, wherein:
- A is attached to the 6- or 7- position;
- n is 0;
- R.sup.11 is --CO.sub.2 H; and
- r is 1 or 2.
- 4. A compound according to claim 3, wherein:
- R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently selected from:
- (1) hydrogen;
- (2) alkyl having 1 to 6 carbon atoms;
- (3) M wherein M is
- (a) --C(O)OR.sup.15 ;
- (b) --C(O)NR.sup.17 R.sup.17 ;
- (c) --CN;
- (d) --C(O)R.sup.16 ;
- (f) --CF.sub.3 ;
- (g) --OR.sup.12 ;
- (h) --OC(O)R.sup.16 ;
- (i) --S(O).sub.2 NR.sup.17 R.sup.17 ;
- (j) --N.sub.3 ; or
- (k) -halogen;
- R.sup.5 and R.sup.6 are independently selected from:
- (1) hydrogen
- (2) alkyl having 1 to 6 carbon atoms
- (3) M wherein M is
- (a) --C(O)OR.sup.15 ;
- (b) --C(O)NR.sup.17 R.sup.17 ;
- (c) --CN;
- (d) --C(O)R.sup.16 ;
- (e) --CF.sub.3 ;
- (g) --S(O).sub.2 NR.sup.17 R.sup.17
- (h) --N.sub.3 ;
- (u) --NO.sub.2 ; or
- (j) -halogen;
- each R.sup.10 is independently H, or C.sub.1 to C.sub.4 alkyl; and
- r is 1.
- 5. A compound according to claim 2 which is:
- 2-Fluoro-5-(p-chlorobenzyl)-5,6,7,8,9,10-hexahydrocyclohept[b]indole-7-acetic acid;
- 2-Fluoro-5-(p-chlorobenzyl)-5,6,7,8,9,10-hexahydrocyclohept[b]indole-10-acetic acid;
- 2-Fluoro-5-(p-chlorobenzyl)-5,6,7,8,9,10-hexahydrocyclohept[b]indole-7-carboxylic acid;
- 2-Fluoro-5-(p-chlorobenzyl)-5,6,7,8,9,10-hexahydrocyclo-hept[b]indole-6-acetic acid;
- 2,4-Difluoro-5-(p-acetylbenzyl)-5,6,7,8,9,10-hexahydrocyclohept[b]indole-7-acetic acid; or
- 2,4-Difluoro-5-(p-dimethylsulfamoylbenzyl)-5,6,7,8,9,10-hexahydrocyclohept[b]indole-7-acetic acid.
- 6. A compound according to claim 1, which is a pure optical isomer.
- 7. A compound according to claim 6, which is the (+)-isomer.
- 8. A compound according to claim 6, which is the (-)-isomer.
- 9. A method of inhibiting leukotriene synthesis in a mammal, which comprises administering to a mammal an effective amount of a compound of claim 1.
- 10. A pharmaceutical composition which comprises a compound of claim 2 and a pharmaceutically acceptable carrier.
Parent Case Info
This is a continuation of application Ser. No. 076,096, filed July 21, 1987, now U.S. Pat. No. 4,775,680.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4009181 |
Berger et al. |
Feb 1977 |
|
4057559 |
Asselin et al. |
Nov 1977 |
|
Continuations (1)
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Number |
Date |
Country |
Parent |
76096 |
Jul 1987 |
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