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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)5666-5673
Number of pages8
JournalTetrahedron
Volume70
Issue number35
DOIs
StatePublished - Sep 2 2014
Externally publishedYes

Fingerprint

Bearings (structural)
Structural optimization
Palladium
Inhibitory Concentration 50
Catalytic Domain
Crystal structure
X-Rays
X rays

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Palladium-catalyzed N-arylation of 2-aminobenzothiazole-4-carboxylates/carboxamides : Facile synthesis of PARP14 inhibitors. / Wang, Pingyuan; Li, Jian; Jiang, Xue; Liu, Zhiqing; Ye, Na; Xu, Youjun; Yang, Guangfu; Xu, Yechun; Zhang, Ao.

In: Tetrahedron, Vol. 70, No. 35, 02.09.2014, p. 5666-5673.

Research output: Contribution to journalArticle

Wang, Pingyuan ; Li, Jian ; Jiang, Xue ; Liu, Zhiqing ; Ye, Na ; Xu, Youjun ; Yang, Guangfu ; Xu, Yechun ; Zhang, Ao. / Palladium-catalyzed N-arylation of 2-aminobenzothiazole-4-carboxylates/carboxamides : Facile synthesis of PARP14 inhibitors. In: Tetrahedron. 2014 ; Vol. 70, No. 35. pp. 5666-5673.
@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",
year = "2014",
month = "9",
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

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

VL - 70

SP - 5666

EP - 5673

JO - Tetrahedron

JF - Tetrahedron

SN - 0040-4020

IS - 35

ER -