Journal of Medicinal Chemistry p. 3303 - 3312 (1994)
Update date:2022-08-04
Topics:
Damewood Jr.
Edwards
Feeney
Gomes
Steelman
Tuthill
Williams
Warner
Woolson
Wolanin
Veale
A series of potent nonpeptidic inhibitors of the enzyme human leukocyte elastase (HLE) is reported. These inhibitors contain a 3-amino-2-pyridone ring as a central template in which the pyridone carbonyl and 3-position NH group are thought to form important hydrogen bonding interactions with the Val-216 residue of HLE. Substitution of the 6-position of the pyridone ring by various alkyl and aryl groups was found to afford increases in the in vitro potency of these inhibitors. A 6-position phenyl group, compound 10f, was found to result in a large increase in binding affinity, which was not obtained when the phenyl group was placed in either the 4- or 5-position of the molecule. Compound 10f was found to have good selectivity for HLE over other proteolytic enzymes, with the exception of bovine pancreatic chymotrypsin (BPC). Substitution of the 6-phenyl group in these molecules was found to decrease binding affinity for BPC without adversely affecting affinity for HLE.
View MoreDaicel Chiral Technologies (China)CO.,LTD
Contact:021-5046-0086*8
Address:Part C, FL 5, the 16th Building, No. 69, XiYa Road, WaiGaoQiao Free Trade Zone, Shanghai, 200131, P.R.China
Chuzhou Baiao Biologhy S&T Co., Ltd.
Contact:+86-25-83212599;+86-25-83212699 13705185959
Address:Room 905, Tianzheng International Platza, No.399, Zhongyang Road ,Nanjing, Jiangsu Province, China
Hangzhou Yanshan Chemical Co.,Ltd.
Contact:86-571- 87698076
Address:Room 1001, #1 Building, Zhongtian MCC, No.2 Youzhinong, Wenyi West Road, Xihu District, Hangzhou, China
Contact:+86-25-85281586
Address:13F,Bld2#,South of Longpan Road
website:http://www.angchenchem.com
Contact:+86-510-88302099 82327577
Address:Rm. 404/405, Floor 4th, No. 983 FengXiang Road, Wuxi, China
Doi:10.1055/s-0040-1706421
(2020)Doi:10.1016/S0040-4020(01)86351-1
(1993)Doi:10.1002/hlca.19930760218
(1993)Doi:10.1002/hlca.200890242
(2008)Doi:10.1016/S0040-4039(00)77629-5
(1993)Doi:10.1016/S0968-0896(99)00129-7
(1999)