BMS-688521

• CAT Number: I003068
• CAS Number: 893397-44-9
• Molecular Formula: C26H19Cl2N5O4
• Molecular Weight: 536.369
• Purity: ≥95%
• Synonyms: BMS-688521; BMS 688521; BMS688521; SCHEMBL5392413.;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
• Target: LFA-1 Antagonist
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4 °C for short term or -20 °C for long term
• IUPAC Name: 6-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl]pyridine-3-carboxylic acid
• InChI: InChI=1S/C26H19Cl2N5O4/c1-31-25(37)33(20-9-18(27)8-19(28)10-20)24(36)26(31)14-32(22-7-6-17(12-30-22)23(34)35)13-21(26)16-4-2-15(11-29)3-5-16/h2-10,12,21H,13-14H2,1H3,(H,34,35)/t21-,26+/m0/s1
• InChIKey: LILGMDXLRPEBNH-HFZDXXHNSA-N
• SMILES: CN1C(=O)N(C(=O)C12CN(CC2C3=CC=C(C=C3)C#N)C4=NC=C(C=C4)C(=O)O)C5=CC(=CC(=C5)Cl)Cl

BMS-688521 is a small molecule antagonist of leukocyte function associated antigen-1 (LFA-1). It has provided proof-of-concept for LFA-1 as an immunological target.

Reference

1:J Med Chem. 2010 May 13;53(9):3814-30. doi: 10.1021/jm100348u. 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).Watterson SH,Xiao Z,Dodd DS,Tortolani DR,Vaccaro W,Potin D,Launay M,Stetsko DK,Skala S,Davis PM,Lee D,Yang X,McIntyre KW,Balimane P,Patel K,Yang Z,Marathe P,Kadiyala P,Tebben AJ,Sheriff S,Chang CY,Ziemba T,Zhang H,Chen BC,DelMonte AJ,Aranibar N,McKinnon M,Barrish JC,Suchard SJ,Murali Dhar TG, PMID: 20405922 DOI: 10.1021/jm100348u Abstract: Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18 or alpha(L)beta(2), belongs to the beta(2) integrin subfamily and is constitutively expressed on all leukocytes. The major ligands of LFA-1 include three intercellular adhesion molecules 1, 2, and 3 (ICAM 1, 2, and 3). The interactions between LFA-1 and the ICAMs are critical for cell adhesion, and preclinical animal studies and clinical data from the humanized anti-LFA-1 antibody efalizumab have provided proof-of-concept for LFA-1 as an immunological 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 clinical compound (1), 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 clinical trials.