This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

Provided herein are novel heterocyclic compounds, for example, compounds having Formula I, I-P, II, II-P, III, or IV. Also provided herein are pharmaceutical compositions comprising the compounds and methods of using the same, for example, in inhibiting aldehyde dehydrogenases, retinoid pathway activation, and/or for treating various cancers, cancer metastasis, type 2 diabetes, pulmonary arterial hypertension (PAH) or neointimal hyperplasia (NIH) or as a male contraceptive.

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Provided herein are novel heterocyclic compounds, for example, compounds having Formula I, I-P, II, II-P, III, or IV. Also provided herein are pharmaceutical compositions comprising the compounds and methods of using the same, for example, in inhibiting aldehyde dehydrogenases, retinoid pathway activation, and/or for treating various cancers, cancer metastasis, type 2 diabetes, pulmonary arterial hypertension (PAH) or neointimal hyperplasia (NIH) or as a male contraceptive.

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Provided are a therapeutic agent and a pharmaceutical composition exerting an excellent prophylactic or therapeutic effect on fibrosis and symptoms associated with fibrosis. The therapeutic agent for fibrosis comprises 4-[2-fluoro-4-[[[(2-phenylacetyl)amino]thioxomethyl]amino]-phenoxy]-7-methoxy-N-methyl-6-quinolinecarboxamide or a salt thereof as an active ingredient.

In one aspect, compounds modulating sirtuin activity are described herein. Sirtuin modulation by compounds described herein includes sirtuin activation and sirtuin inhibition. Modulation of sirtuin activity includes sirtuin activation and/or sirtuin inhibition. In some embodiments, a sirtuin modulating compound and/or salt thereof is of Formula I described herein.

In one aspect, compounds modulating sirtuin activity are described herein. Sirtuin modulation by compounds described herein includes sirtuin activation and sirtuin inhibition. Modulation of sirtuin activity includes sirtuin activation and/or sirtuin inhibition. In some embodiments, a sirtuin modulating compound and/or salt thereof is of Formula I described herein.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

Compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein G.sup.1, G.sup.2, G.sup.3, L.sup.1, L.sup.2, and L.sup.3 are as defined in the specification, are useful in treating conditions or disorders prevented by or ameliorated by the modulation of lysophosphatidic acid receptor 1. Methods for making the compounds are described. Also described are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.

##STR00001##

Compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein G.sup.1, G.sup.2, G.sup.3, L.sup.1, L.sup.2, and L.sup.3 are as defined in the specification, are useful in treating conditions or disorders prevented by or ameliorated by the modulation of lysophosphatidic acid receptor 1. Methods for making the compounds are described. Also described are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.

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