Gilmore, John L’s team published research in Journal of Medicinal Chemistry in 2019-03-14 | 1003-21-0

Journal of Medicinal Chemistry published new progress about Anti-multiple sclerosis agents. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, HPLC of Formula: 1003-21-0.

Gilmore, John L.; Xiao, Hai-Yun; Dhar, T. G. Murali; Yang, Michael G.; Xiao, Zili; Xie, Jenny; Lehman-McKeeman, Lois D.; Gong, Lei; Sun, Huadong; Lecureux, Lloyd; Chen, Cliff; Wu, Dauh-Rurng; Dabros, Marta; Yang, Xiaoxia; Taylor, Tracy L.; Zhou, Xia D.; Heimrich, Elizabeth M.; Thomas, Rochelle; McIntyre, Kim W.; Borowski, Virna; Warrack, Bethanne M.; Li, Yuwen; Shi, Hong; Levesque, Paul C.; Yang, Zheng; Marino, Anthony M.; Cornelius, Georgia; D’Arienzo, Celia J.; Mathur, Arvind; Rampulla, Richard; Gupta, Anuradha; Pragalathan, Bala; Shen, Ding Ren; Cvijic, Mary Ellen; Salter-Cid, Luisa M.; Carter, Percy H.; Dyckman, Alaric J. published the artcile< Identification and preclinical pharmacology of ((1R,3S)-1-amino-3-((S)-6-(2-methoxyphenethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986166): a differentiated sphingosine-1-phosphate receptor 1 (S1P1) modulator advanced into clinical trials>, HPLC of Formula: 1003-21-0, the main research area is sphingosine 1 phosphate receptor pharmacokinetics arthritis antiarthritic multiple sclerosis; crystal structure.

Recently, our research group reported the identification of BMS-986104 (2) as a differentiated S1P1 receptor modulator. In comparison to fingolimod (1), a full agonist of S1P1 currently marketed for the treatment of relapse remitting multiple sclerosis (RRMS), 2 offers several potential advantages having demonstrated improved safety multiples in preclin. evaluations against undesired pulmonary and cardiovascular effects. In clin. trials, 2 was found to exhibit a pharmacokinetic half-life (T1/2) longer than that of 1, as well as a reduced formation of the phosphate metabolite that is required for activity against S1P1. Herein, we describe our efforts to discover highly potent, partial agonists of S1P1 with a shorter T1/2 and increased in vivo phosphate metabolite formation. These efforts culminated in the discovery of ((1R,3S)-1-amino-3-((S)-6-(2-methoxyphenethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol [1883345-06-9] (BMS-986166, 14a), which was advanced to human clin. evaluation. The pharmacokinetic/pharmacodynamic (PK/PD) relationship as well as pulmonary and cardiovascular safety assessments are discussed. Furthermore, efficacy of BMS-986166 in multiple preclin. models of autoimmune diseases are presented.

Journal of Medicinal Chemistry published new progress about Anti-multiple sclerosis agents. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, HPLC of Formula: 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem