Watterson, Scott H.; Xiao, Zili; Dodd, Dharmpal S.; Tortolani, David R.; Vaccaro, Wayne; Potin, Dominique; Launay, Michele; Stetsko, Dawn K.; Skala, Stacey; Davis, Patric M.; Lee, Deborah; Yang, Xiaoxia; McIntyre, Kim W.; Balimane, Praveen; Patel, Karishma; Yang, Zheng; Marathe, Punit; Kadiyala, Pathanjali; Tebben, Andrew J.; Sheriff, Steven; Chang, Chieh Ying Y.; Ziemba, Theresa; Zhang, Huiping; Chen, Bang-Chi; DelMonte, Albert J.; Aranibar, Nelly; McKinnon, Murray; Barrish, Joel C.; Suchard, Suzanne J.; Murali Dhar, T. G. published the artcile< Small Molecule Antagonist of Leukocyte Function Associated Antigen-1 (LFA-1): Structure-Activity Relationships Leading to the Identification of 6-((5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl)nicotinic Acid (BMS-688521)>, Safety of Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is spirocyclic hydantoin derivative preparation LFA1 antagonist SAR.
Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18 or αLβ2, belongs to the β2 integrin subfamily and is constitutively expressed on all leukocytes. The major ligands of LFA-1 include three intercellular adhesion mols. 1, 2, and 3 (ICAM 1, 2, and 3). The interactions between LFA-1 and the ICAMs are critical for cell adhesion, and preclin. animal studies and clin. data from the humanized anti-LFA-1 antibody efalizumab have provided proof-of-concept for LFA-1 as an immunol. target. This article will detail the structure-activity relationships (SAR) leading to a novel second generation series of highly potent spirocyclic hydantoin antagonists of LFA-1. With significantly enhanced in vitro and ex vivo potency relative to our first clin. compound (1, I), as well as demonstrated in vivo activity and an acceptable pharmacokinetic and safety profile, 6-((5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro-[4.4]nonan-7-yl)nicotinic acid (2e) was selected to advance into clin. trials.
Journal of Medicinal Chemistry published new progress about Homo sapiens. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Safety of Ethyl 2-chloropyrimidine-5-carboxylate.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia