Palladium-catalyzed N-arylation of 2-aminobenzothiazole-4-carboxylates/carboxamides: Facile synthesis of PARP14 inhibitors

Pingyuan Wang; Jian Li; Xue Jiang; Zhiqing Liu; Na Ye; Youjun Xu; Guangfu Yang; Yechun Xu; Ao Zhang

doi:10.1016/j.tet.2014.06.064

Palladium-catalyzed N-arylation of 2-aminobenzothiazole-4-carboxylates/carboxamides: Facile synthesis of PARP14 inhibitors

Pingyuan Wang, Jian Li, Xue Jiang, Zhiqing Liu, Na Ye, Youjun Xu, Guangfu Yang, Yechun Xu, Ao Zhang

Pharmacology & Toxicology

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

We have developed a palladium-catalyzed N-arylation of the biologically interesting, but synthetically rather challenging 2-arylaminobenzothiazoles bearing multiple functionalities. This protocol was successfully used to readily synthesize our initial PARP14 inhibitor followed by a limited structural optimization. A more potent PARP14 inhibitor with an IC₅₀ value of 1.69 μM was identified, and the interaction was ascertained by the X-ray co-crystal structure of the catalytic domain of PARP14 in complex with compound 8.

Original language	English (US)
Pages (from-to)	5666-5673
Number of pages	8
Journal	Tetrahedron
Volume	70
Issue number	35
DOIs	https://doi.org/10.1016/j.tet.2014.06.064
State	Published - Sep 2 2014

Keywords

2-Arylaminobenzothiazoles
C-N coupling
N-arylation
PARP14
Pd(dba)

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

Access to Document

10.1016/j.tet.2014.06.064

Fingerprint Dive into the research topics of 'Palladium-catalyzed N-arylation of 2-aminobenzothiazole-4-carboxylates/carboxamides: Facile synthesis of PARP14 inhibitors'. Together they form a unique fingerprint.

Cite this

@article{cc425432002e486bb22ef2f5e425ff22,

title = "Palladium-catalyzed N-arylation of 2-aminobenzothiazole-4-carboxylates/carboxamides: Facile synthesis of PARP14 inhibitors",

abstract = "We have developed a palladium-catalyzed N-arylation of the biologically interesting, but synthetically rather challenging 2-arylaminobenzothiazoles bearing multiple functionalities. This protocol was successfully used to readily synthesize our initial PARP14 inhibitor followed by a limited structural optimization. A more potent PARP14 inhibitor with an IC50 value of 1.69 μM was identified, and the interaction was ascertained by the X-ray co-crystal structure of the catalytic domain of PARP14 in complex with compound 8.",

keywords = "2-Arylaminobenzothiazoles, C-N coupling, N-arylation, PARP14, Pd(dba)",

author = "Pingyuan Wang and Jian Li and Xue Jiang and Zhiqing Liu and Na Ye and Youjun Xu and Guangfu Yang and Yechun Xu and Ao Zhang",

note = "Funding Information: This work was supported by grants of Chinese National Sciences Foundation ( 81125021 , 81373277 ), National Science & Technology Major Project on {\textquoteleft}Key New Drug Creation and Manufacturing Program{\textquoteright}, China (Numbers: 2012ZX09103-101-035 , 2012ZX09301001-001 ). Supporting grants from the 'Interdisciplinary Cooperation Team' Program for Science and Technology Innovation (CAS) , and grant from the State Key Laboratory of Drug Research ( SIMM1302KF-08 , SIMM1302KF-02 ), Shanghai Institute of Materia Medica were also appreciated. ",

year = "2014",

month = sep,

day = "2",

doi = "10.1016/j.tet.2014.06.064",

language = "English (US)",

volume = "70",

pages = "5666--5673",

journal = "Tetrahedron",

issn = "0040-4020",

publisher = "Elsevier Limited",

number = "35",

}

TY - JOUR

T1 - Palladium-catalyzed N-arylation of 2-aminobenzothiazole-4-carboxylates/carboxamides

T2 - Facile synthesis of PARP14 inhibitors

AU - Wang, Pingyuan

AU - Li, Jian

AU - Jiang, Xue

AU - Liu, Zhiqing

AU - Ye, Na

AU - Xu, Youjun

AU - Yang, Guangfu

AU - Xu, Yechun

AU - Zhang, Ao

N1 - Funding Information: This work was supported by grants of Chinese National Sciences Foundation ( 81125021 , 81373277 ), National Science & Technology Major Project on ‘Key New Drug Creation and Manufacturing Program’, China (Numbers: 2012ZX09103-101-035 , 2012ZX09301001-001 ). Supporting grants from the 'Interdisciplinary Cooperation Team' Program for Science and Technology Innovation (CAS) , and grant from the State Key Laboratory of Drug Research ( SIMM1302KF-08 , SIMM1302KF-02 ), Shanghai Institute of Materia Medica were also appreciated.

PY - 2014/9/2

Y1 - 2014/9/2

N2 - We have developed a palladium-catalyzed N-arylation of the biologically interesting, but synthetically rather challenging 2-arylaminobenzothiazoles bearing multiple functionalities. This protocol was successfully used to readily synthesize our initial PARP14 inhibitor followed by a limited structural optimization. A more potent PARP14 inhibitor with an IC50 value of 1.69 μM was identified, and the interaction was ascertained by the X-ray co-crystal structure of the catalytic domain of PARP14 in complex with compound 8.

AB - We have developed a palladium-catalyzed N-arylation of the biologically interesting, but synthetically rather challenging 2-arylaminobenzothiazoles bearing multiple functionalities. This protocol was successfully used to readily synthesize our initial PARP14 inhibitor followed by a limited structural optimization. A more potent PARP14 inhibitor with an IC50 value of 1.69 μM was identified, and the interaction was ascertained by the X-ray co-crystal structure of the catalytic domain of PARP14 in complex with compound 8.

KW - 2-Arylaminobenzothiazoles

KW - C-N coupling

KW - N-arylation

KW - PARP14

KW - Pd(dba)

UR - http://www.scopus.com/inward/record.url?scp=84949133420&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949133420&partnerID=8YFLogxK

U2 - 10.1016/j.tet.2014.06.064

DO - 10.1016/j.tet.2014.06.064

M3 - Article

AN - SCOPUS:84949133420

VL - 70

SP - 5666

EP - 5673

JO - Tetrahedron

JF - Tetrahedron

SN - 0040-4020

IS - 35

ER -