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Synthesis of 4‐(3,4‐dicarboxamido‐1 H ‐pyrrole)pyrimidines as Anaplastic Lymphoma Kinase Inhibitors
Author(s) -
Latif Muhammad,
Byun Byung Jin,
Lee Kwangho
Publication year - 2015
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.10097
Subject(s) - pyrrole , anaplastic lymphoma kinase , pyrimidine , chemistry , aniline , stereochemistry , organic chemistry , lung cancer , medicine , malignant pleural effusion
To explore non‐aniline aromatic substitution on the pyrimidine C4 position, novel 4‐( N , N ′‐di‐ n ‐propyl‐3,4‐dicarboxamido‐1 H ‐pyrrole)pyrimidines are designed and synthesized as anaplastic lymphoma kinase inhibitors for non‐small cell lung cancer treatment. To overcome the unexpected cleavage between the C‐N linkage of pyrrole nitrogen and C4‐pyrimidine during hydrolysis and inaccessibility of the desired diamide formation through coupling agent‐mediated conditions, the 4‐( N,N ′‐di‐n‐propyl‐3,4‐dicarboxamido‐1H‐pyrrole)pyrimidine was assembled through direct nucleophilic substitution under microwave irradiation. Thus prepared 4‐( N,N ′‐di‐n‐propyl‐3,4‐dicarboxamido‐1 H ‐pyrrole)pyrimidines were measured both ALK binding and H3122 cell proliferation assay. Their weak ALK activities are explained with molecular modeling study.