Synthesis of potent and selective inhibitors of Candida albicans N-myristoyltransferase based on the benzothiazole structure.
Two parallel synthetic methods using solid-supported reagents were established to examine the rapid optimization of weak hit compound 1. Several compounds showed high potency in the low nanomolar range against N-myristoyltransferase. The structure-activity relationship (SAR) and antifungal activities of a series of novel 2-aminobenzothiazole N-myristoyltransferase inhibitors are presented.
Yamazaki
Kazuo
K
Central Research Laboratories, SSP Co., Ltd, 1143 Nanpeidai, Narita, Chiba 286-8511, Japan. kazuo.yamazaki@ssp.co.jp <kazuo.yamazaki@ssp.co.jp>
Kaneko
Yasushi
Y
Suwa
Kie
K
Ebara
Shinji
S
Nakazawa
Kyoko
K
Yasuno
Kazuhiro
K
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D052160:Benzothiazoles; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000935:Antifungal Agents; D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D013844:Thiazoles; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase; C005465:benzothiazole