Design, synthesis and biological evaluation of some tetrazole acetamide derivatives as novel non-carboxylic PTP1B inhibitors

被引：22

作者：

Maheshwari, Neelesh ^{[1
]}

Karthikeyan, Chandrabose ^{[1
,2
]}

Bhadada, Shraddha, V ^{[3
]}

Verma, Amit K. ^{[4
]}

Sahi, Chandan ^{[4
]}

Moorthy, N. S. Hari Narayana ^{[1
,2
]}

Trivedi, Piyush ^{[1
]}

机构：

[1] Rajiv Gandhi Proudyogiki Vishwavidyalaya, Sch Pharmaceut Sci, Airport Bypass Rd, Bhopal 462036, MP, India

[2] Indira Gandhi Natl Tribal Univ, Dept Pharm, Amarkantak 484887, MP, India

[3] Nirma Univ, Inst Pharm, Dept Pharmacol, Ahmadabad 382481, Gujarat, India

[4] Indian Inst Sci Educ & Res, Dept Biol Sci, Bhopal 462066, Madhya Pradesh, India

来源：

BIOORGANIC CHEMISTRY | 2019年 / 92卷

关键词：

PTP1B; Diabetes; tetrazoles; TYROSINE-PHOSPHATASE; 1B; ACID-DERIVATIVES; POTENT; DISCOVERY; IDENTIFICATION;

D O I：

10.1016/j.bioorg.2019.103221

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of ten N-(3-(1H-tetrazole-5-yl)phenyl)acetamide derivatives (NM-07 to NM-16) designed from a lead molecule identified previously in our laboratory were synthesized and evaluated for protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Among the synthesized molecules, NM-14, a 5-Cl substituted benzothiazole analogue elicited significant PTP1B inhibition with an IC50 of 1.88 mu M against reference standard suramin (IC50 >= 10 mu M). Furthermore, this molecule also showed good in vivo antidiabetic activity which was comparable to that of standard antidiabetic drugs metformin and glimepiride. Overall, the results of the study clearly reveal that the reported tetrazole derivatives especially NM-14 are valuable prototypes for the development of novel non-carboxylic inhibitors of PTP1B with antidiabetic potential.

引用

页数：6

共 23 条

[21] The therapeutic potential of phosphatase inhibitors [J].