701213-36-7 Usage
Description
BMS 626529 is an HIV-1 attachment inhibitor that binds to non-ligand bound HIV-1 gp120, preventing the interaction of HIV-1 with host CD4+ T cells and subsequent binding and cell entry. It effectively reduces the infectivity of both laboratory strains and clinical isolates of HIV-1 with a wide range of EC50 values and minimal cytotoxicity.
Uses
Used in Pharmaceutical Industry:
BMS 626529 is used as an antiviral agent for the treatment of HIV-1 infection. It serves as an HIV-1 attachment inhibitor, preventing the virus from binding to and entering host cells, thereby reducing viral infectivity and replication.
Used in Research and Development:
BMS 626529 is used as a research tool for studying the mechanisms of HIV-1 attachment and entry into host cells. It can help researchers understand the interactions between HIV-1 and host immune cells, potentially leading to the development of new therapeutic strategies and antiviral drugs.
Used in Drug Synthesis:
BMS 626529 is used as an intermediate in the synthesis of Fostemsavir (CAS# 864953-29-7), another HIV-1 attachment inhibitor. Its role in the synthesis process contributes to the production of Fostemsavir, which is used for the treatment of HIV-1 infection in adults.
in vitro
the activity of bms-626529 is virus dependent, due to heterogeneity within gp120. bms-626529 had half-maximal effective concentration values of6 log10, with half-maximal effective concentration values in the low pm range against the most susceptible viruses. measurement of the binding affinity of bms-626529 for purified gp120 suggests that a contributory factor to its inhibitory potency may be a relatively long dissociative half-life [1].
references
[1] nowicka-sans b, gong yf, mcauliffe b, dicker i, ho ht, zhou n, eggers b, lin pf, ray n, wind-rotolo m, zhu l, majumdar a, stock d, lataillade m, hanna gj, matiskella jd, ueda y, wang t, kadow jf, meanwell na, krystal m. in vitro antiviral characteristics of hiv-1 attachment inhibitor bms-626529, the active component of the prodrug bms-663068. antimicrob agents chemother. 2012;56(7):3498-507. [2] nettles re, schürmann d, zhu l, stonier m, huang sp, chang i, chien c, krystal m, wind-rotolo m, ray n, hanna gj, bertz r, grasela d. pharmacodynamics, safety, and pharmacokinetics of bms-663068, an oral hiv-1 attachment inhibitor in hiv-1-infected subjects. j infect dis. 2012;206(7):1002-11.
Check Digit Verification of cas no
The CAS Registry Mumber 701213-36-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 7,0,1,2,1 and 3 respectively; the second part has 2 digits, 3 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 701213-36:
(8*7)+(7*0)+(6*1)+(5*2)+(4*1)+(3*3)+(2*3)+(1*6)=97
97 % 10 = 7
So 701213-36-7 is a valid CAS Registry Number.
701213-36-7Relevant articles and documents
Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir
Wang, Tao,Ueda, Yasu,Zhang, Zhongxing,Yin, Zhiwei,Matiskella, John,Pearce, Bradley C.,Yang, Zheng,Zheng, Ming,Parker, Dawn D.,Yamanaka, Gregory A.,Gong, Yi-Fei,Ho, Hsu-Tso,Colonno, Richard J.,Langley, David R.,Lin, Pin-Fang,Meanwell, Nicholas A.,Kadow, John F.
, p. 6308 - 6327 (2018/06/27)
The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described. The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus. Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species. However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir). An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
Preparation of the HIV Attachment Inhibitor BMS-663068. Part 1. Evolution of Enabling Strategies
Fox, Richard J.,Tripp, Jonathan C.,Schultz, Mitchell J.,Payack, Joseph F.,Fanfair, Dayne D.,Mudryk, Boguslaw M.,Murugesan, Saravanababu,Chen, Chung-Pin H.,La Cruz, Thomas E.,Ivy, Sabrina E.,Broxer, Sévrine,Cullen, Ryan,Erdemir, Deniz,Geng, Peng,Xu, Zhongmin,Fritz, Alan,Doubleday, Wendel W.,Conlon, David A.
, p. 1095 - 1109 (2017/08/23)
The development of two enabling routes that led to the production of >1000 kg of BMS-663068 (3) is described. The route identified for the initial 100 kg delivery to support development activities and initial clinical trials involved the conversion of 2-amino-4-picoline to the parent active pharmaceutical ingredient (API), followed by pro-drug installation and deprotection. To eliminate the problematic isolation of the parent API and synthesis of di-t-butyl(chloromethyl)phosphate, a second-generation pro-drug installation route was developed which involved the conversion of a late-stage common intermediate to an N(1)-thioether derivative followed by chloromethylation, displacement with di-t-butylpotassium phosphate, and deprotection. This second strategy resulted in the multikilogram scale preparation of the API in 14 linear steps and ～7% overall yield.
