Abstract：
:The discovery and structure-activity relationship of first-generation small-molecule malonyl-CoA decarboxylase (MCD; CoA = coenzyme A) inhibitors are reported. We demonstrated that MCD inhibitors increased malonyl-CoA concentration in the isolated working rat hearts. Malonyl-CoA is a potent, endogenous, and allosteric inhibitor of carnitine palmitoyltransferase-I (CPT-I), a key enzyme for mitochondrial fatty acid oxidation. As a result of the increase in malonyl-CoA levels, fatty acid oxidation rates were decreased and the glucose oxidation rates were significantly increased. Demonstration of in vivo efficacy of methyl 5-(N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)morpholine-4-carboxamido)pentanoate (6u) in a pig ischemia model indicated that MCD inhibitors may be useful for treating ischemic heart diseases.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Cheng JF,Chen M,Wallace D,Tith S,Haramura M,Liu B,Mak CC,Arrhenius T,Reily S,Brown S,Thorn V,Harmon C,Barr R,Dyck JR,Lopaschuk GD,Nadzan AMdoi
10.1021/jm050109nkeywords:
subject
Has Abstractpub_date
2006-03-09 00:00:00pages
1517-25issue
5eissn
0022-2623issn
1520-4804journal_volume
49pub_type
杂志文章abstract：:Transient receptor potential canonical (TRPC) channels are highly homologous, nonselective cation channels that form many homo- and heterotetrameric channels. These channels are highly abundant in the brain and kidney and have been implicated in numerous diseases, such as depression, addiction, and chronic kidney dise...
journal_title：Journal of medicinal chemistry
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doi：10.1021/jm00142a028
更新日期：1981-10-01 00:00:00
abstract：:Using predictions from heme-quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure-function principles. We vary side chain length for both monoethyl and diethyl 4-N CQ derivatives. ...
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doi：10.1021/jm701478a
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abstract：:Analogues of 9-oxo-9H-xanthene-4-acetic acid (XAA) bearing small, lipophilic 5-substituents are among the most dose-potent compounds yet reported with the capability of causing hemorrhagic necrosis of implanted colon 38 tumors in mice. To further extend structure-activity relationships among this class of compound, a ...
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doi：10.1021/jm00369a019
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更新日期：2013-08-22 00:00:00
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更新日期：2011-10-27 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：2004-08-26 00:00:00
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doi：10.1021/jm701179m
更新日期：2008-03-27 00:00:00
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更新日期：2009-06-11 00:00:00
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abstract：:A novel series of 2- and 3-substituted 1,8-dihydroxy-9(10H)-anthracenones were synthesized and tested for their inhibitory activity against 5-lipoxygenase (5-LO) in bovine polymorphonuclear leukocytes and the growth of human keratinocytes. Structure-activity relationships are discussed with respect to the following re...
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abstract：:The synthesis and structure-activity relationships of C-terminal octapeptide analogues of anaphylatoxin C5a have been studied. The introduction of hydrophobic amino acids into the N-acetylated native octapeptide (N-Ac-His-Lys-Asp-Met-Gln-Leu-Gly-Arg-OH) (1) has led to an analogue with 100 times more activity than the ...
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：1993-03-19 00:00:00
