Patent Evaluation: Indole leukotriene biosynthesis antagonists

Summary

Novelty: Novel indole derivatives are disclosed as leukotriene antagonists in these four related patents. These are: azaarylmethoxy (AG7604 and AG7610), bicyclic-heteroarylmethoxy (AG7612) and heteroarylmethoxy (AG7913) indoles. All are potentially useful as anti-inflammatory, anti-allergic and anti-asthmatic agents. They are also stated to be cytoprotective and to be useful for the treatment of a variety of disorders including hypertension, angina, cerebral spasm and migraine.

Biology: Protocols for an LTB₄ inhibitory assay and an asthmatic rat assay are given. However, no specific biological data are disclosed.

Chemistry: In AG7604 a total of sixteen final compounds are disclosed. Syntheses are given in four examples. All are specifically claimed including 3-1-(4-chlorobenzyl)-3-(t-butylthio)-5-(isoquinolin-3-yl-methoxy)indol-2-yl]-2,2-dimethylpropanoic acid.

In AG7610 eighteen final compounds are described. Syntheses are given in five examples. Preparation of intermediates is also given. All eighteen compounds are specifically claimed including 3-1-(4-chlorobenzyl)-3-(t-butylthio)-5-(pyridin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoic acid.

Twenty-seven final compounds are disclosed in AG7612. Syntheses are given in three examples. The twenty-seven compounds are specifically claimed including 3-1-(4-chlorobenzyl)-3-methyl-5-(benzothiazol-2-ylmethoxy)indol-2-yl]2,2-dimethyl propanoic acid.

Finally, in AG7613 a total of twenty-one final compounds are disclosed. Syntheses are given in three examples. Twenty-one compounds are specifically claimed including 3-1-(4-chlorobenzyl)-3-methyl-5-(4-prop-2-ylthiazol-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoic acid.