Bioorganic and Medicinal Chemistry p. 4298 - 4311 (2014)
Update date:2022-08-02
Topics:
Miah, Afjal H.
Abas, Hossay
Begg, Malcolm
Marsh, Benjamin J.
O'Flynn, Daniel E.
Ford, Alison J.
Percy, Jonathan M.
Procopiou, Panayiotis A.
Richards, Steve A.
Rumley, Sally-Anne
A knowledge-based library of 2,3-dichlorophenylsulfonyl derivatives of commercially available aryl amines was synthesised and screened as human CCR4 antagonists, in order to identify a suitable hit for the start of a lead-optimisation programme. Hits were required to be more potent than an existing indazole series, have better physicochemical properties (c log P <3.5, chrom log D7.4 <5.3 and CLND solubility >116 μg/mL), and be stable to acid and light. The benzimidazol-2-one core was identified as a hit suitable for further investigation. Substitution at N1 with small alkyl groups was tolerated; however, these analogues were inactive in the whole blood assay (pA2 <5). Azabenzimidazolone analogues were all found to be active, with compound 38 exhibiting whole blood activity of 6.1, low molecular weight (389) and chrom log D7.4 (2.4), high LE (0.43), and solubility (152 μg/mL). In addition, 38 had human serum albumin binding of around 93% and met all the criteria for progression to lead optimisation.
View MoreRudong Zhenfeng Yiyang Chemical Co., Ltd.
Contact:0513-84573047
Address:South Fengli Town, Rudong County, Jiangsu Province, China
Jiangsu Wanlong Chemical Co., Ltd.
website:http://www.wanlongchem.com
Contact:+86-511-86810993 0086-511-8681 0888;
Address:Quanzhou Town, Danyang City, Jiangsu
Sichuan WeiKeqi Biological Technology Co., Ltd.
Contact:86-028-81700200
Address:sichuan Chengdu Qingjiang Zhonglu 63号
Contact:+86-25-85281586
Address:13F,Bld2#,South of Longpan Road
Changzhou BaoKang Pharmaceutical & Chemical Co., Ltd
Contact:(86) 519-88782201 88784080 88785278
Address:Henglin town, changzhou,Jiangsu
Doi:10.1002/anie.200603070
(2006)Doi:10.1021/jo01044a018
(1963)Doi:10.1021/ja00527a055
(1980)Doi:10.1055/s-2006-950200
(2006)Doi:10.1021/jm00181a010
(1980)Doi:10.3184/030823408X314482
(2008)