Chemical and Pharmaceutical Bulletin p. 1504 - 1513 (2000)
Update date:2022-08-02
Topics:
Ohta, Kiminori
Kawachi, Emiko
Inoue, Noriko
Fukasawa, Hiroshi
Hashimoto, Yuichi
Itai, Akiko
Kagechika, Hiroyuki
Several pyridine- and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]pyridine- 3-carboxylic acid (2b) and 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]pyridin e-3-carboxylic acid (5b) are more potent than the corresponding benzoic acid-type retinoids, Am80 (2a) and Am580 (5a), the replacement of the benzene ring of Am580 (5a), Am555 (6a), or Am55 (7a) with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series, 10 and 11) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series, 8 and 9) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino] pyrimidine-5-carboxylic acid (PA013, 10e) is most active retinoid synergist in HL-60 assay.
View MoreContact:+86-(0)21-3770 9035
Address:Room 301, Building 2, Meijiabang Road 1508, Shanghai China
Nantong Advance Chemical Co., Ltd
Contact:86-13818730908
Address:Fine Chemical Industry Garden,Beixin Town,Qidong
Feis International Trade Co,. Ltd
Contact:13961823444-18235944442
Address:Wuxi jiangsu
Contact:+86 021-51698675
Address:1701, Jielong Plaza, No.618 Pingliang Rd, ShangHai,China
Dalian Synco Chemical Co., Ltd.
Contact:+86-411-83635150
Address:Rm 1004, 24, Tangshan Street, Dalian
Doi:10.1021/jm970766i
(1998)Doi:10.1016/S0040-4020(97)10431-8
(1998)Doi:10.1021/acs.orglett.1c02066
(2021)Doi:10.1021/jm980156y
(1998)Doi:10.1016/S0040-4039(98)01702-X
(1998)Doi:10.1002/cctc.201700726
(2017)