23159-59-3Relevant academic research and scientific papers
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.
supporting information, 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.
Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives
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, (2008/06/13)
This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives. These compounds possess unique antiv
Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives
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Page 224-225, (2008/06/13)
This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives. These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS.
