Synthesis and evaluation of 4,5-dihydro-5-methylisoxazolin-5-carboxamide derivatives as VLA-4 antagonists

Ajay Soni; Abdul Rehman; Keshav Naik; Sunanda Dastidar; M S Alam; Abhijit Ray; Tridib Chaira; Vanya Shah; Venkata P Palle; Ian A Cliffe; Viswajanani J Sattigeri

doi:10.1016/j.bmcl.2012.12.043

Synthesis and evaluation of 4,5-dihydro-5-methylisoxazolin-5-carboxamide derivatives as VLA-4 antagonists

Bioorg Med Chem Lett. 2013 Mar 1;23(5):1482-5. doi: 10.1016/j.bmcl.2012.12.043. Epub 2012 Dec 21.

Authors

Ajay Soni¹, Abdul Rehman, Keshav Naik, Sunanda Dastidar, M S Alam, Abhijit Ray, Tridib Chaira, Vanya Shah, Venkata P Palle, Ian A Cliffe, Viswajanani J Sattigeri

Affiliation

¹ Department of Medicinal Chemistry, New Drug Discovery Research, Ranbaxy Research Laboratories, Plot 20, Sector 18, Gurgaon 122015, Haryana, India. ajay_soni_78@yahoo.com

PMID: 23312947
DOI: 10.1016/j.bmcl.2012.12.043

Abstract

A novel set of compounds containing a 4,5-dihydro-5-methylisoxazoline have been successfully designed as VLA-4 receptor antagonists. Compound (14p) had a high receptor binding affinity of 4 nM and also found to be metabolically stable in vitro.

MeSH terms

Amides / chemical synthesis
Amides / chemistry
Amides / pharmacology
Drug Stability
Humans
Integrin alpha4beta1 / antagonists & inhibitors*
Integrin alpha4beta1 / chemistry
Isoxazoles / chemical synthesis
Isoxazoles / chemistry*
Isoxazoles / pharmacology*
Protein Binding
Structure-Activity Relationship
U937 Cells

Substances

Amides
Integrin alpha4beta1
Isoxazoles