Journal of Medicinal Chemistry p. 5702 - 5713 (2014)
Update date:2022-08-29
Topics:
Hameed P, Shahul
Chinnapattu, Murugan
Shanbag, Gajanan
Manjrekar, Praveena
Koushik, Krishna
Raichurkar, Anandkumar
Patil, Vikas
Jatheendranath, Sandesh
Rudrapatna, Suresh S.
Barde, Shubhada P.
Rautela, Nikhil
Awasthy, Disha
Morayya, Sapna
Narayan, Chandan
Kavanagh, Stefan
Saralaya, Ramanatha
Bharath, Sowmya
Viswanath, Pavithra
Mukherjee, Kakoli
Bandodkar, Balachandra
Srivastava, Abhishek
Panduga, Vijender
Reddy, Jitender
Prabhakar
Sinha, Achyut
Jiménez-Díaz, María Belén
Martínez, María Santos
Angulo-Barturen, I?igo
Ferrer, Santiago
Sanz, Laura María
Gamo, Francisco Javier
Duffy, Sandra
Avery, Vicky M.
Magistrado, Pamela A.
Lukens, Amanda K.
Wirth, Dyann F.
Waterson, David
Balasubramanian
Iyer, Pravin S.
Narayanan, Shridhar
Hosagrahara, Vinayak
Sambandamurthy, Vasan K.
Ramachandran, Sreekanth
Whole-cell high-throughput screening of the AstraZeneca compound library against the asexual blood stage of Plasmodium falciparum (Pf) led to the identification of amino imidazoles, a robust starting point for initiating a hit-to-lead medicinal chemistry effort. Structure-activity relationship studies followed by pharmacokinetics optimization resulted in the identification of 23 as an attractive lead with good oral bioavailability. Compound 23 was found to be efficacious (ED90 of 28.6 mg·kg-1) in the humanized P. falciparum mouse model of malaria (Pf/SCID model). Representative compounds displayed a moderate to fast killing profile that is comparable to that of chloroquine. This series demonstrates no cross-resistance against a panel of Pf strains with mutations to known antimalarial drugs, thereby suggesting a novel mechanism of action for this chemical class.
View MoreBeijing Stable Chemcial Co.ltd
Contact:86-10-63785052
Address:A1301 Technological Edifice. No.4 FuFeng Road,FengTai District, Beijing. China
Contact:+86-531-58668191 58668193 58668196 58661173
Address:No 55,Beixiaoxinzhuang West Street,Jinan City, Shandong Province
Heliosense Biotechnologies, Inc.
Contact:+86-592-5667290
Address:Xiamen Torch Hi-tech Zone Venture Weiye Building S506
CHANGYI CITY FENGRUN FINE CHEMICAL CO.,LTD
website:http://www.fengrunhuagong.com
Contact:+86-536-7869976
Address:Changyi Coastal Economic Development Zone
Contact:732.938.2777
Address:5012 Industrial Road Farmingdale, NJ 07727
Doi:10.1016/j.poly.2020.114561
(2020)Doi:10.1016/S0040-4039(02)02273-6
(2002)Doi:10.1007/BF01430301
(1863)Doi:10.1039/c4ra11961d
(2014)Doi:10.1002/ejoc.202100827
(2021)Doi:10.1016/j.electacta.2009.07.057
(2009)