Benzofuran 2-carbox amides useful as inhibitors of leukoriene biosynthesis

Abstract

Compounds of the Formula I: ##STR1## and pharmaceutically acceptable salts thereof are inhibitors of leukotriene biosynthesis. These compounds inhibit the mammalian 5-lipoxygenase enzyme, thus preventing the metabolism of arachidonic acid to the leukotrienes. These compounds are thus useful in the treatment of asthma, allergic disorders, inflammation, skin diseases and certain cardiovascular disorders.

Description

Claims

1. A compound of the Formula: ##STR9## wherein the substituents for compound are selected from the following groups:

______________________________________Compound R.sub.1 R.sub.2______________________________________162 CH.sub.3 ##STR10##163 CH.sub.3 NHPh164 CH.sub.3 NHPh-p-NO.sub.2165 CH.sub.3 NHPh-p-OMe166 CH.sub.3 NHPh-p-OMe167 CH.sub.3 NHPh-p-NO.sub.2168 CH.sub.3 NHPh-p-OMe169 CH.sub.3 NHPh-p-NO.sub.2170 CH.sub.3 ##STR11##171 CH.sub.3 NHPh173 CH.sub.3 NHCH.sub.2 Ph174 CH.sub.3 NHPh-p-Cl175 CH.sub.3 ##STR12##176 CH.sub.3 ##STR13##177 Pr NHPh-p-Cl178 Ph NHPh-p-Cl181 CH.sub.3 ##STR14##182 Ph NHPh-p-Cl183 CH.sub.3 NMePh184 CH.sub.3 ##STR15##185 CH.sub.3 NMePh186 CH.sub.3 NHPh-p-OMe187 CH.sub.3 ##STR16##188 Pr NHPh-p-Cl189 CH.sub.3 NHPh-p-Cl190 CH.sub.3 NHPh-p-Cl191 CH.sub.3 NHPh-p-OMe192 CH.sub.3 NHPh-p-Cl193 Pr NHPh-p-Cl278 CH.sub.3 ##STR17##______________________________________Compound R.sub.3 R.sub.4______________________________________162 4-OH H163 4-OH H164 6-OH H165 6-OH H166 4-OH H167 4-OAc H168 4-OAc H169 4-OH H170 4-OH H171 4-OAc H173 4-OAc H174 4-OAc H175 4-OAc H176 4-OH H177 6-OH H178 6-OAc H181 5-OH H182 6-OH H183 4-OAc H184 4-OH H185 4-OH H186 4-OH 5-Pr187 4-OAc H188 6-OAc H189 4-OH H190 ##STR18## 5-CH.sub.2 CHCH.sub.2191 ##STR19## 5-Pr192 5-OH H193 ##STR20## H278 4-OH H______________________________________

2. A method of inhibiting mammalian leukotriene biosynthesis or action which comprises administering to a mammal in need of such treatment a pharmaceutically effective amount of a compound of claim 1.

3. A method of claim 2 wherein the mammal is a human.

4. A method of treating pulmonary conditions, inflammation, allergies, pain, cardiovascular conditions, or skin conditions which comprises administering to a human in need of such treatment a pharmaceutically effective amount of a compound of claim 1.

5. A pharmaceutical composiiton useful for inhibiting the ibosynthesis of mammalian leukotrienes comprising a pharmaceuticlaly acceptable carrier and an effective amount of a compound of claim 1.