2. Academic Validation
  3. Discovery of novel 4-aryl-thieno[1,4]diazepin-2-one derivatives targeting multiple protein kinases as anticancer agents

Discovery of novel 4-aryl-thieno[1,4]diazepin-2-one derivatives targeting multiple protein kinases as anticancer agents

  • Bioorg Med Chem. 2018 May 1;26(8):1628-1637. doi: 10.1016/j.bmc.2018.02.009.
Junghun Lee 1,  Hoyong Jung 1,  Minjung Kim 1,  Eunkyu Lee 1,  Daseul Im 1,  Waqar Aman 2,  Jung-Mi Hah 3
Affiliations

Affiliations

  • 1 Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea.
  • 2 Kohat University of Science & Technology, Kohat, Khyber Pukhtunkhwa, Pakistan.
  • 3 Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea. Electronic address: jhah@hanyang.ac.kr.
PMID: 29459144 DOI: 10.1016/j.bmc.2018.02.009
Abstract

A series of 4-aryl-thieno[1,4]diazepin-2-one were synthesized and evaluated for their antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Several compounds showed very potent antiproliferative activities toward both cell lines and the activities were better than that of sorafenib, the reference standard. Derivatives were made as amide (8a-8i, 9a-9m) and urea (10a-10d, 11a-11d) with diverse hydrophobic moieties. One of the most potent inhibitor 10d, 1-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(4-(2-oxo-2,3-dihydro-1H-thieno [3,4-b][1,4]diazepin-4-yl)phenyl)urea was found to be very potent inhibitor of multi-protein kinases including FMS kinase (IC50 = 3.73 nM) and is a promising candidate for further development in therapeutics for Cancer.

Keywords

4-Aryl-thieno[1,4]diazepin-2-one; Antiproliferative activity; Hematopoietic cell line; Kinase inhibitor; Multiple protein kinase inhibitor.

Figures