Journal of Medicinal Chemistry p. 2006 - 2011 (1990)
Update date:2022-08-05
Topics:
McNamara, Dennis J.
Cook, P. Dan
Allen, Lois B.
Kehoe, Mary J.
Holland, Carolyn S.
Teepe, Annette G.
Novel 3-substituted analogues of 4-amino-1-β-D-ribofuranosyl-2(1H)-pyridinone (3-deazacytidine, 3) and 4-hydroxy-1-β-D-ribofuranosyl-2(1H)-pyridinone (3-deazauridine, 4) have been synthesized and tested for antitumor and antiviral activity.Thus the 3-chloro (9a), 3-bromo (9b), and 3-nitro (9c) analogues of 3 and the 3-chloro (9d), 3-bromo (9e), and 3-nitro (9f) analogues of 4 were prepared by standard glycosylating procedures.Novel requisite heterocycles 4-amino-3-chloro-2(1H)-pyridinone (7a) and 4-amino-3-bromo-2(1H)-pyridinone (7b) were prepared by halogenating4-amino-2(1H)-pyridinone (5).Requisite heterocycles 4-amino-3-nitro-2(1H)-pyridinone (7c), 3-chloro-4-hydroxy-2(1H)-pyridinone (7d), 3-bromo-4-hydroxy-2(1H)-pyridinone (7e), and 4-hydroxy-3-nitro-2(1H)-pyridinone (7f) were synthesized by known procedures from 4-hydroxy-2(1H)-pyridinone (6).Structure proof of target nucleosides was provided by independent synthesis, 1H NMR, and UV.Compounds 9a-f were devoid of activity against intraperitoneally implanted L1210 leukemia in mice.Compound 9f displayed significant activity against rhinovirus type 34 grown in WISH cells. 4-Amino-3-fluoro-1-β-D-ribofuranosyl-2(1H)-pyridinone (1) displayed good activity against intraperitoneally implanted P388 leukemia in mice, but it was devoid of activity against M5076 sarcoma, amelanotic (LOX) melanoma xenograft, and subrenal capsule human mammary carcinoma MX-1 xenograft in mice.Compound 1 also displayed significant activity against rhinovirus type 34.
View MoreZhejiang Newfine Industry Co.,Ltd.
Contact:+86-573-82262042
Address:No.225,Dongqing Road, garoms@163.com
Shaanxi Lighte Optoelectronics Material Co., Ltd.
Contact:+86-29-88320728-622/619/620
Address:No.55 INDUSTRY ROAD 2,XI'AN NATIONAL CIVIL AEROSPACE INDUSTRIAL PARK.XI'AN China 710065.
Beijing Hope Pharmaceutical Co., Ltd.
Contact:86-10-67886402
Address:309,Block 1 District B,No.12 Hongda North Road , Beijing Economic-Technological Development Area, Beijing, China
Zhenjiang Haitong Chemical Industry Co., Ltd.
Contact:+86 (511) 8448-0369
Address:Baoyan Town, Dantu District, Zhenjiang City, Jiangsu, China
Contact:86-516-66656369
Address:The west road of Huaihai, Xuzhou, China
Doi:10.1007/BF00764881
(1987)Doi:10.1021/ja960263m
(1996)Doi:10.1021/jo01067a054
(1961)Doi:10.1002/ejoc.201601043
(2016)Doi:10.1016/0006-3002(57)90433-X
(1957)Doi:10.1246/cl.1986.1639
(1986)