Claims
- 1. A compound of the formula I ##STR51## or a pharmaceutically acceptable salt thereof, wherein: R.sub.1 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, phenyl-substituted-(C.sub.1 -C.sub.3 alkyl), phenyl, or phenyl substituted with halo, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkoxy;
- R.sub.2 is C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, benzyl, or 2-phenylethyl;
- R.sub.3 is hydrogen, bromo, or chloro;
- Z is ##STR52## m is 0-4; A is a bond, ##STR53## Q is a bond, ##STR54## and R.sub.4 is ##STR55## where each of R, R', and R" is independently hydrogen or C.sub.1 -C.sub.3 alkyl;
- each of R.sub.5 and R.sub.6 is independently hydrogen, C.sub.1 -C.sub.3 ; alkyl, phenyl, or benzyl;
- R.sub.9 is hydroxy, C.sub.1 -C.sub.4 alkoxy, --NHOH, or --NR.sub.14 R.sub.15 ;
- R.sub.10 is hydrogen, hydroxy, C.sub.1 -C.sub.4 alkoxy, halo, C.sub.1 -C.sub.4 alkyl, amino, mono-or di-(C.sub.1 -C.sub.3 alkyl) amino, or (C.sub.1 -C.sub.3 alkyl)CONH--;
- R.sub.11 is ##STR56## R.sub.12 is hydrogen or C.sub.1 -C.sub.3 alkyl; R.sub.13 is hydrogen or methyl;
- each of R.sub.14 and R.sub.15 is independently hydrogen, C.sub.1 -C.sub.3 alkyl, or when taken together with the nitrogen/atom form a morpholine or N-methyl piperazine ring;
- R is 0-4;
- s is 1-4;
- W is a bond, --O--, --NR'"--, or ##STR57## R'" is hydrogen or C.sub.1 -C.sub.3 alkyl; and p is 0, 1, or 2;
- provided that
- (a) when R.sub.4 is --COR.sub.9, hydroxy, --NR.sub.11 R.sub.12, or ##STR58## Q may only be a bond and n may not be 0. (b) when A is --O--, ##STR59## --NR'--, or --CHOH--, and Z is --O--, ##STR60## --NR--, m may not be 0; (c) when A is --O--, ##STR61## --NR'--, OR --CHOH--, and Q is --O--, ##STR62## or --NR"--, n may not be 0; (d) when Z is --O--, ##STR63## or --NR--, Q is --O--, ##STR64## or --NR"--, and A is a bond, m and n may not both be 0; and (e) if A is ##STR65## (1) when Z is ##STR66## m may not be 0, (2) when Q is ##STR67## n may not be 0; and (3) when Z is --O-- or --NR-- and Q is --O-- or --NR"--, m and n may not both be 0.
- 2. A compound of claim 1 wherein R.sub.1 is methyl.
- 3. A compound of claim 1 of the formula Ib ##STR68## or a pharmaceutically acceptable salt thereof wherein: R2' is C1-C6 alkyl;
- Z' is --O--, --NH-- or ##STR69## each of R16' and R17' are independently hydrogen or methyl; and r' is 0, 1, or 2.
- 4. A compound of the formula ##STR70## and pharmaceutically acceptable salts thereof wherein: R.sub.2 ' is C.sub.1 -C.sub.6 alkyl;
- Z' is --0--, ##STR71## or --NH--; each of R.sub.16 ' and R.sub.17 ' are independently hydrogen or methyl;
- r' is 0, 1, or 2; and
- R.sub.4 ' is --COOH, 5-tetrazolyl, or 5-thiotetrazolyl.
- 5. The compound of claim 4 which is 5-[4-(4-acetyl-3-hydroxy-2-propylbenzyloxy) phenyl]-tetrazole or a pharmaceutically acceptable salt thereof.
- 6. The compound of claim 4 which is 5-[4-(4-acetyl-3-hydroxy-2-propylbenzyloxy) benzyl]-tetrazole or a pharmaceutically acceptable salt thereof.
- 7. The compound of claim 4 which is 5-[2-(4-[4-acetyl-3-hydroxy-2-propylbenzyloxy]-phenyl) ethyl]-tetrazole or a pharmaceutically acceptable salt thereof.
- 8. The compound of claim 4 which is 5-[1-(4-[4-acetyl-3-hydroxy-2-propylbenzyloxy]-phenyl) ethyl]-tetrazole or a pharmaceutically acceptable salt thereof.
- 9. A compound of claim 1 of the formula ##STR72## and pharmaceutically acceptable salts thereof wherein: R.sub.2 ' is C.sub.1 -C.sub.6 alkyl;
- Z' is --0--, ##STR73## or --NH--; m' is 2-4; and
- R.sub.4 ' is --COOH, 5-tetrazolyl, or 5-thiotetrazolyl.
- 10. A compound of claim 1 wherein R.sub.2 ' is propyl.
- 11. The compound of claim 8 which is 4-(4-acetyl-3-hydroxy-2-propylbenzyloxy)butanoic acid or a pharmaceutically acceptable salt thereof.
- 12. The compound of claim 8 which is 5-[3-(4-acetyl-3-hydroxy-2-propylbenzyloxy)propyl]-tetrazole or a pharmaceutically acceptable salt thereof.
- 13. The compound of claim 9 which is 5-[2-(4-acetyl-3-hydroxy-2-propylbenzyloxy)ethylthio]-tetrazole or a pharmaceutically acceptable salt thereof.
- 14. 4-(4-acetyl-3-hydroxy-2-propylbenzyloxy)butanoic acid or a pharmaceutically acceptable salt thereof.
- 15. A method of treating a mammal suffering from or susceptible to any condition characterized by an excessive release of leukotrienes, which comprises administering to said mammal a leukotriene antagonizing amount of a compound of claim 1.
- 16. A method of treating a mammal suffering from or susceptible to any condition characterized by an excessive release of leukotrienes, which comprises administering to said mammal a leukotriene antagonizing amount of a compound of claim 1.
- 17. A method of treating a mammal suffering from or susceptible to an immediate hypersensitivity reaction of the type represented by asthma, which comprises administering to said mammal a therapeutically-effective amount of a compound of claim 1.
- 18. A pharmaceutical formulation comprising a compound of claim 1 in association with a pharmaceutically acceptable carrier.
Parent Case Info
This application is a continuation of application Ser. No. 07/761,136, filed Sep. 17, 1991, abandoned, which is a division of application Ser. No. 06/514,428, filed Jul. 18, 1983, U.S. Pat. No. 5,105,012.
Divisions (1)
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Number |
Date |
Country |
Parent |
514428 |
Jul 1983 |
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Continuations (1)
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Number |
Date |
Country |
Parent |
761136 |
Sep 1991 |
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