Allergan Sales, Inc.

Allergan, Inc.

Allergen Sales, Inc.

Jayasree Vasudevan

Roshantha A Chandraratna

Alan T Johnson

Liming Wang

Dehua Huang

Richard L Beard

Vidyasagar Pradeep Vuligonda

Xiaoxia Liu

Kwok Yin Tsang

Ling Li

Janet A Takeuchi

Smita S Bhat

Thong Huy Vu

Kwok-Yin Tsang

Haiqing Yuan

Yang-Dar Yuan

Tien T Duong

Santosh C Sinha

Rong Yang

Roshantha A Chandratratna

Roshanta S Chandraratna

Roshantha S Chandraratna

Compounds of formulas 1 through 17 provided in the specification specifically or selectively inhibit either the cytochrome P450RAI-1 enzyme or the cytochrome P450RAI-2 enzyme.

Compounds having selective cytochrome P450RAI-1 or selective cytochrome P450RAI-2 inhibitory activity and methods of obtaining the same

The invention provides methods for treating an individual having a retinoid responsive disorder. In one embodiment, a method involves administering to the individual an effective amount of a selective CYP26B inhibitor, the selective CYP26B inhibitor having at least 10-fold selectivity for CYP26B relative to CYP26A. In another embodiment, a method involves administering to the individual an effective amount of a selective CYP26A inhibitor, the selective CYP26A inhibitor having a chemical formula set forth in the specification. The invention further provides screening methods for identifying a selective CYP26A inhibitor or selective CYP26B inhibitor.

Methods for treating retinoid responsive disorders using selective inhibitors of CYP26A and CYP26B

Compounds of the formula where the variables are defined in the specification have cytochrome P450RAI-1 and P450RAI-2 inhibitory activity, and are suitable for treatment of mammals with conditions which are treatable with retinoids, or which are controlled by or responsive to the organism's native retinoic acid. Formulations containing the compounds of the invention can also be co-administered with retinoids and/or Vitamin A to enhance or prolong the effects of medications containing retinoids, Vitamin A, or of the organism's native retinoic acid.

4-[(8-substituted)-6-chromanoyl]-and 4-[8-substituted)-chroman-6-YL-ethynyl]-benzoic and phenylacetic acids, their esters and salts having cytochrome P450RAI inhibitory activity

Compounds of the formulawhere the variations have the meaning defined in the specification are capable of reducing serum glucose levels in diabetic mammals without the undesirable side effects of transiently increasing triglyceride levels and reducing serum thyroxine levels.

7-[(7-Alkoxy)-chrom-3-en-6-yl]-heptatrienoic acid and 7-[(3-alkoxy)-5,6-dihydronaphthalen-2-yl]-heptatrienoic acid derivatives having serum glucose reducing activity

A method of identifying a compound which is an inhibitor of the enzyme cytochrome P450RAI is performed by selecting a compound that has retinoid activity in an art recognized assay and includes a benzoic acid, benzoic acid ester, naphthoic acid ester or heteroaryl carboxylic acid or ester moiety, with a partial structure of &#x2014;A(R)&#x2014;(CH)where n is 0 and the remaining variables are as described in the specification and claims. Thereafter, a compound having the cytochrome P450RAI inhibitory activity is identified and selected where the compound has the &#x2014;A(R)&#x2014;(CH)&#x2014;COORpartial structure wherein the variable n is 1 or 2.

Methods for identifying inhibitors of cytochrome P450RAI

3,5-di-iso-propyl-heptatrienoic acid derivatives having serum glucose reducing activity

4-&lsqb;(8-ETHYNYL, 8-VINYL OR 8-ETHYNYL-METHYL)-6-CHROMANOYL&rsqb;-BENZOIC AND 2-&lsqb;4-&lsqb;(8-ETHYNYL, 8-VINYL OR 8-ETHYNYL-METHYL)-6-CHROMANOYL&rsqb;-PHENYL&rsqb;-ACETIC ACID, THEIR ESTERS AND SALTS HAVING CYTOCHROME P450RAI INHIBITORY ACTIVITY

Dihydrobenzofuran and dihydrobenzothiophene 2,4-pentadienoic acid derivatives having selective activity for retinoid X (RXR) receptors

Compounds having Formula 4 wherein the symbols have the meaning defined in the specification are inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids.

Compounds having activity as inhibitors of cytochrome P450RAI

Compounds having Formula 4 wherein the symbols have the meaning defined in the specification are inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids

1-imidazolyl substituted tetrahydronaphthalene derivatives as inhibitors of eytochrome P450RAI

Compounds having Formula 1 wherein the symbols have the meaning defined in the specification are inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids.

Novel compounds having the Formulas 1 through 8, wherein the symbols have the meaning defined in the specification, and certain previously known compounds have been discovered to act as inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids. The compound can also be used in co-treatment with retinoids.

Methods of providing and using compounds having activity as inhibitors of cytochrome P450RAI

Compounds having the formulas below, where R is H, lower alkyl, or a pharmaceutically acceptable salt, and where R represents i-propyl, t-butyl or n-butyl groups, have selective RXR retionoid agonist activity.

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Anaheim, CA, United States of America

Jayasree Vasudevan