Pyridinylpyrimidines selectively inhibit human methionine aminopeptidase-1 was written by Zhang, Pengtao;Yang, Xinye;Zhang, Feiran;Gabelli, Sandra B.;Wang, Renxiao;Zhang, Yihua;Bhat, Shridhar;Chen, Xiaochun;Furlani, Manuel;Amzel, L. Mario;Liu, Jun O.;Ma, Dawei. And the article was included in Bioorganic & Medicinal Chemistry in 2013.Recommanded Product: 4-methoxypicolinonitrile This article mentions the following:
Cellular protein synthesis is initiated with methionine in eukaryotes with few exceptions. Methionine aminopeptidases (MetAPs) which catalyze the process of N-terminal methionine excision are essential for all organisms. In mammals, type 2 MetAP (MetAP2) is known to be important for angiogenesis, while type 1 MetAP (MetAP1) has been shown to play a pivotal role in cell proliferation. Authors’ previous high-throughput screening of a com. compound library uncovered a novel class of inhibitors for both human MetAP1 (HsMetAP1) and human MetAP2 (HsMetAP2). This class of inhibitors contains a pyridinylpyrimidine core. To understand the structure-activity relationship (SAR) and to search for analogs of 2 with greater potency and higher HsMetAP1-selectivity, a total of 58 analogs were acquired through either com. source or by inhouse synthesis and their inhibitory activities against HsMetAP1 and HsMetAP2 were determined Through this systematic medicinal chem. anal., the authors have identified: (1) 5-chloro-6-methyl-2-pyridin-2-ylpyrimidine as the min. element for the inhibition of HsMetAP1; (2) 5′-chloro as the favored substituent on the pyridine ring for the enhanced potency against HsMetAP1; and (3) long C4 side chains as the essentials for higher HsMetAP1-selectivity. As a result of the SAR campaign, six compounds were found to be among the most selective and potent inhibitors of purified HsMetAP1 reported to date. In addition, crystallog. anal. of one representative inhibitor (I) in complex with N-terminally truncated HsMetAP1 was also performed. Map gene. In the experiment, the researchers used many compounds, for example, 4-methoxypicolinonitrile (cas: 36057-44-0Recommanded Product: 4-methoxypicolinonitrile).
4-methoxypicolinonitrile (cas: 36057-44-0) belongs to nitriles. Nitrile carbon shifts are in the range of 115–125 ppm whereas in isonitriles the shifts are around 155–165 ppm. In conventional organic reductions, nitrile is reduced by treatment with lithium aluminium hydride to the amine. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis, which uses stannous chloride in acid.Recommanded Product: 4-methoxypicolinonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts