Synthesis of pyrazoles and isoxazoles as potent alpha(v)beta3 receptor antagonists

Bioorganic & Medicinal Chemistry Letters
Thomas D PenningWilliam Westlin

Abstract

We describe a series of pyrazole and isoxazole analogs as antagonists of the alpha(v)beta3 receptor. Compounds showed low to sub-nanomolar potency against alpha(v)beta3, as well as good selectivity against alpha(IIb)beta3. In HT29 cells, most analogs also demonstrated significant selectivity against alpha(v)beta6. Several compounds showed good pharmacokinetic properties in rats, in addition to anti-angiogenic activity in a mouse corneal micropocket model. Compounds were synthesized in a straightforward manner from readily available glutarate precursors.

References

Apr 22, 1994·Science·P C BrooksD A Cheresh
Oct 1, 1995·The Journal of Clinical Investigation·P C BrooksD A Cheresh
Oct 1, 1993·Current Opinion in Cell Biology·B Felding-Habermann, D A Cheresh
May 1, 1997·The International Journal of Biochemistry & Cell Biology·M A Horton
Jan 14, 2000·Journal of Medicinal Chemistry·W J PittsP K Jadhav
Nov 4, 2000·Expert Opinion on Investigational Drugs·J S KerrS A Mousa
Nov 4, 2000·Expert Opinion on Investigational Drugs·G D Hartman, M E Duggan
Feb 24, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·M W LarkM Gowen
Apr 2, 2003·Bioorganic & Medicinal Chemistry Letters·William H MillerWilliam F Huffman
Mar 10, 2004·Bioorganic & Medicinal Chemistry Letters·Thomas D PenningG Allen Nickols

❮ Previous
Next ❯

Citations

Feb 13, 2017·Journal of Photochemistry and Photobiology. B, Biology·K Indrasena ReddyR Siva
Sep 26, 2017·Angewandte Chemie·Richard J D HatleyPauline T Lukey
Mar 23, 2010·Expert Opinion on Therapeutic Patents·Keiichi Masuya, Naoki Teno
Mar 24, 2016·Acta Crystallographica. Section E, Crystallographic Communications·Md Lutfor RahmanChing Kheng Quah
Oct 14, 2011·The Journal of Organic Chemistry·Metin Zora, Arif Kivrak
Jul 12, 2011·The Journal of Organic Chemistry·Metin ZoraCeyda Yazici

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.