Abstract：
:SAH 51-641 (1) is a potent hypoglycemic agent, which acts by inhibiting hepatic gluconeogenesis. It is a prodrug of 4-(2, 2-dimethyl-1-oxopropyl)benzoic acid (2) and 4-(2, 2-dimethyl-1-hydroxypropyl)benzoic acid (3), which sequester coenzyme A (CoA) in the mitochondria, and inhibits medium-chain acyltransferase. 1-3 and 4-tert-butylbenzoic acid all cause testicular degeneration in rats at pharmacologically active doses. 14b (FOX 988) is a prodrug of 3, which is metabolized in the liver at a rate sufficient enough to have hypoglycemic potency (an ED50 of 65 micromol/kg, 28 mg/kg/day, for glucose lowering), yet by avoiding significant escape of the metabolite 3 to the systemic circulation, it avoids the testicular toxicity at doses up to 1500 micromol/kg/day. 14b was selected for clinical studies.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Aicher TD,Bebernitz GR,Bell PA,Brand LJ,Dain JG,Deems R,Fillers WS,Foley JE,Knorr DC,Nadelson J,Otero DA,Simpson R,Strohschein RJ,Young DAdoi
10.1021/jm980438ysubject
Has Abstractpub_date
1999-01-14 00:00:00pages
153-63issue
1eissn
0022-2623issn
1520-4804pii
jm980438yjournal_volume
42pub_type
杂志文章abstract：:Inhibition of the cell cycle kinase, cyclin-dependent kinase-4 (Cdk4), is expected to provide an effective method for the treatment of proliferative diseases such as cancer. The pyrido[2,3-d]pyrimidin-7-one template has been identified previously as a privileged structure for the inhibition of ATP-dependent kinases, a...
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pub_type： 杂志文章
doi：10.1021/jm00133a005
更新日期：1981-01-01 00:00:00
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doi：10.1021/acs.jmedchem.5b01249
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doi：10.1021/jm00391a043
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更新日期：1977-04-01 00:00:00
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更新日期：2014-03-13 00:00:00
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pub_type： 杂志文章
doi：10.1021/jm00400a020
更新日期：1988-05-01 00:00:00
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更新日期：2012-07-26 00:00:00
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更新日期：2008-07-24 00:00:00
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pub_type： 杂志文章
doi：10.1021/jm00392a025
更新日期：1987-09-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00163a061
更新日期：1990-01-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00038a020
更新日期：1994-06-10 00:00:00
abstract：:The discovery of the (acryloylaryloxy)acetic acids as a new class of potent diuretics prompted the investigation of related bicyclic compounds. Annelated analogues of the parent series, the (2-alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids, were the subjects of this study. Those compounds, unlike the monocycli...
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pub_type： 杂志文章
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更新日期：1977-11-01 00:00:00
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更新日期：1997-03-28 00:00:00
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更新日期：1990-02-01 00:00:00
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更新日期：2014-05-22 00:00:00
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更新日期：2012-08-09 00:00:00
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更新日期：2004-03-11 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2020-03-26 00:00:00
abstract：:Recently, the tryptophan-containing noncationizable opioid peptides emerged with atypical structure and unexpected in vivo activity. Herein, we describe analogs of the naturally occurring mixed κ/μ-ligand c[Phe-d-Pro-Phe-Trp] 1 (CJ-15,208). Receptor affinity, selectivity, and agonism/antagonism varied upon enlarging m...
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pub_type： 杂志文章
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更新日期：2016-10-13 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2016-09-08 00:00:00
