Design and Synthesis of ALK5 Inhibitors

Harun Patel

ISBN 10: 3659815438 / ISBN 13: 9783659815430

Published by LAP LAMBERT Academic Publishing Dez 2015, 2015

About this Item

Neuware -A new series of imidazo[2,1-b][1,3,4]thiadiazoles 5(a-g), 6(a-g), 9(a-i) and 12(a-h) were synthesized. Among them, 23 compounds 5a, 5b, 5e, 5d, 5f, 5g, 6a, 6b, 6c, 6d, 6e, 9b, 9d, 9f, 9g, 9h, 9i, 12b, 12c, 12d, 12e, 12g, and 12h were evaluated at National Cancer Institute for single dose in vitro primary cytotoxicity assay. Compound 5b, 5e, 6c, 6d, 6e, 12c, 12d and 12e were further screened for 5-log dose molar range as they have shown prominent cell growth inhibition at 10-5 M concentration against variety of cell lines. Compound 5e shows significant inhibition against Leukemia HL-60 cell line with GI50 of 0.0285 µM and highest selectivity towards the Leukemic Cancer cell line (selectivity ratio of 7.96) it also shows prominent ALK5 inhibition (IC50 = 0.0263 µM) and elective inhibition (91%) against KDR at10 µM. The binding mode of compound 5e by SP docking studies shows that it ¿ts well into the active site cavity of ALK5 by forming broad and tight interactions. Lipinski¿s rule and in silico ADME pharmacokinetic parameters are within the acceptable range defined for human use thereby indicating their potential as a drug-like molecules.Books on Demand GmbH, Überseering 33, 22297 Hamburg 100 pp. Englisch.

Seller Inventory # 9783659815430

Bibliographic Details

• Title: Design and Synthesis of ALK5 Inhibitors
• Publisher: LAP LAMBERT Academic Publishing Dez 2015
• Publication Date: 2015
• Language: English
• ISBN 10: 3659815438
• ISBN 13: 9783659815430
• Binding: Taschenbuch
• Condition: Neu
• Dimensions: 220W x 150H x 6D millimeters 220 millimeters width by 150 millimeters height by 6 millimeters depth
• Weight: 167 grams

About this title

Synopsis

A new series of imidazo[2,1-b][1,3,4]thiadiazoles 5(a-g), 6(a-g), 9(a-i) and 12(a-h) were synthesized. Among them, 23 compounds 5a, 5b, 5e, 5d, 5f, 5g, 6a, 6b, 6c, 6d, 6e, 9b, 9d, 9f, 9g, 9h, 9i, 12b, 12c, 12d, 12e, 12g, and 12h were evaluated at National Cancer Institute for single dose in vitro primary cytotoxicity assay. Compound 5b, 5e, 6c, 6d, 6e, 12c, 12d and 12e were further screened for 5-log dose molar range as they have shown prominent cell growth inhibition at 10-5 M concentration against variety of cell lines. Compound 5e shows significant inhibition against Leukemia HL-60 cell line with GI50 of 0.0285 µM and highest selectivity towards the Leukemic Cancer cell line (selectivity ratio of 7.96) it also shows prominent ALK5 inhibition (IC50 = 0.0263 µM) and elective inhibition (91%) against KDR at10 µM. The binding mode of compound 5e by SP docking studies shows that it fits well into the active site cavity of ALK5 by forming broad and tight interactions. Lipinski’s rule and in silico ADME pharmacokinetic parameters are within the acceptable range defined for human use thereby indicating their potential as a drug-like molecules.

About the Author

Dr. Harun M. Patel was born on 5th September 1983. He received Gold Medal in graduation and post graduation. Completed his doctoral study at Punjab Technical University-Jalndhar as Young Scientist (DST). Recently completed his post-doctoral study at University of KwaZulu Natal-Durban.