Design and synthesis of heterocyclic malonyl-CoA decarboxylase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 3, 2006, Pages 695-700

  Cheng, Jie Fei ^a,b   Chen, Mi ^a   Liu, Bin ^a   Hou, Zheng ^a   Arrhenius, Thomas ^a   Nadzan, Alex M ^a  

^a LLC   (United States)

^b Tanabe Research Laboratories   (United States)

Author keywords

Acetyl CoA; Malonyl CoA; Malonyl CoA decarboxylase; MCD

Indexed keywords

DECARBOXYLASE INHIBITOR; IMIDAZOLE DERIVATIVE; ISOXAZOLE DERIVATIVE; MALONYL COENZYME A DECARBOXYLASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG DESIGN; DRUG SYNTHESIS;

ANIMALS; CARBOXY-LYASES; CARDIOTONIC AGENTS; DRUG DESIGN; ENERGY METABOLISM; ENZYME INHIBITORS; FATTY ACIDS; GLUCOSE; IMIDAZOLES; MODELS, CHEMICAL; MYOCARDIAL ISCHEMIA; OXIDATION-REDUCTION; RATS; SWINE;

SUS SCROFA;

EID: 29544439396     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.10.020     Document Type: Article

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23. 4 (Sigma), 2 mM malate (Sigma), 2 mM NAD (Boehringer Mannheim), 0.786 units MD (Roche Chemicals), 0.028 unit CS (Roche Chemicals), 5-10 nM MBP-hMCD, and varying amounts of malonyl-CoA substrate. Assays were initiated by the addition of malonyl-CoA, and the rates were corrected for the background rate determined in the absence of hMCD.
24. Two products could be detected and purified for all O-substituted oximes. The predominant isomers were tested and are reported in Table 2. They are presumably the trans products. The minor isomers (<10% yield) showed a slightly lower activity as compared to the major products.