Discovery of a potent and selective series of pyrazole bacterial methionyl-tRNA synthetase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 13, 2003, Pages 2231-2234

  Finn, John ^a   Mattia, Karen ^a   Morytko, Mike ^a   Ram, Siya ^a   Yang, Yingfei ^a   Wu, Ximao ^a   Mak, Elsa ^a   Gallant, Paul ^a   Keith, Dennis ^a  

^a Cubist Pharmaceutical Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

METHIONINE TRANSFER RNA LIGASE; PYRAZOLE DERIVATIVE;

ARTICLE; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY;

BACTERIA (MICROORGANISMS);

EID: 0037533953     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00298-1     Document Type: Article

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15. Treatment of lithium aroylpyruvates with aryl hydrazines is known to provide the 1,5-diarylpyrazole-3-carboxylate isomer with high regioselectivity. See: Murray W., Wachter M. J. Hetero. Chem. 26:1989;1389. When different pyridylmethylhydrazines were used the 1,3-disubstituted-pyrazole-5-carboxylate isomers were also isolated as the minor products with the 1,5-disubstituted-pyrazole-3-carboxylate isomer with ratios ranging between 3:2 and 3:1. The isomers are readily differentiated by the NMR signal of the methylene group with the methylene signal for the 5-carboxylate isomer is 0.5 ppm downfield of that for the 3-carboxylate isomer (e.g., 5.60 ppm for 10c and 6.10 ppm for 11c).
16. 50 was determined by fitting the results from a 10-point dose/response curve. All results are the average of at least two measurements.