Syntheses and structure-activity relationships of 5,6,7, 8-tetrahydro-5,5,8,8-tetramethyl-2-quinoxaline derivatives with retinoic acid receptor alpha agonistic activity

K Kikuchi; S Hibi; H Yoshimura; N Tokuhara; K Tai; T Hida; T Yamauchi; M Nagai

doi:10.1021/jm990063w

Syntheses and structure-activity relationships of 5,6,7, 8-tetrahydro-5,5,8,8-tetramethyl-2-quinoxaline derivatives with retinoic acid receptor alpha agonistic activity

J Med Chem. 2000 Feb 10;43(3):409-19. doi: 10.1021/jm990063w.

Authors

K Kikuchi¹, S Hibi, H Yoshimura, N Tokuhara, K Tai, T Hida, T Yamauchi, M Nagai

Affiliation

¹ Tsukuba Basic Research Laboratories for Drug Discovery, Eisai Co., Ltd., 1-3, Tokodai 5-chome, Tsukuba-shi, Ibaraki, 300-2635, Japan.

PMID: 10669568
DOI: 10.1021/jm990063w

Abstract

In the course of our studies on retinoic acid receptor (RAR) agonists, we have designed and synthesized a series of quinoxaline derivatives. One of them, 4-[5-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethyl-2-quinoxalinyl)-1H-2-pyrrolyl]benzoic acid (3a), which possesses a 2,5-disubstituted pyrrole moiety, showed selectivity for the RARalpha receptor and exerted highly potent cell-differentiating activity on HL-60 cells.

MeSH terms

Benzoates / chemical synthesis*
Benzoates / chemistry
Benzoates / metabolism
Benzoates / pharmacology
Binding, Competitive
Cell Differentiation / drug effects
Cell Line
Humans
Quinoxalines / chemical synthesis*
Quinoxalines / chemistry
Quinoxalines / metabolism
Quinoxalines / pharmacology
Receptors, Retinoic Acid / agonists*
Receptors, Retinoic Acid / metabolism
Retinoic Acid Receptor alpha
Retinoids / chemical synthesis*
Retinoids / chemistry
Retinoids / metabolism
Retinoids / pharmacology
Structure-Activity Relationship

Substances

Benzoates
Quinoxalines
RARA protein, human
Receptors, Retinoic Acid
Retinoic Acid Receptor alpha
Retinoids
ER 34617