For research use only. Not for therapeutic Use.
BMS-688521 (Cat No.: I003068) is an investigational small molecule inhibitor targeting the hepatitis C virus (HCV) NS5B polymerase, an essential enzyme for viral replication. As a non-nucleoside inhibitor, BMS-688521 binds to an allosteric site on NS5B, disrupting RNA synthesis and inhibiting viral replication. It has been studied for its potential in treating chronic HCV infections, particularly in combination with other antiviral agents. Preclinical and early clinical studies have explored its efficacy, safety, and resistance profile in combating HCV-related liver diseases.
| CAS Number | 893397-44-9 |
| 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 |
| Molecular Formula | C26H19Cl2N5O4 |
| Purity | ≥95% |
| Target | Integrin |
| 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 |
| 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 </br><span>Abstract:</span> 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. |
