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Discovery and SAR of a novel series of Natriuretic Peptide Receptor-A (NPR-A) agonists.

Abstract：

:Novel thienopyrimidine compounds 2 and 3 were discovered from high-throughput screening as Natriuretic Peptide Receptor A (NPR-A) agonists. Scaffold hopping of a thienopyrimidine ring to a quinazoline ring, introduction of the basic functional group and optimization of the substituent on the 6-position of the benzene ring of quinazoline led to improved agonistic activity. We discovered compound 48, which showed potent agonistic activity for NPR-A with an EC50 value of 0.073μM, indicating 350-fold potency compared to the hit compound 3.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Iwaki T,Nakamura Y,Tanaka T,Ogawa Y,Iwamoto O,Okamura Y,Kawase Y,Furuya M,Oyama Y,Nagayama T

doi

10.1016/j.bmcl.2017.09.028

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

4904-4907

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(17)30923-X

journal_volume

27

pub_type

杂志文章

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