Abstract：
:A series of transition-state analogues having heterocyclythio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. Oxidation of the thioether to sulfone was also investigated. Several of the compounds, especially those derived from N1-substituted-5-mercaptotetrazoles or N4-substituted-3-mercapto-5-(trifluoromethyl)-1,2,4-triazoles, were moderately potent inhibitors of human plasma renin, having IC50 values of 30-40 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys at 0.3-1.2 mg/kg, they reduced plasma renin activity by 75-98%. However, this inhibition and the accompanying drop in blood pressure were of short duration.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Ashton WT,Cantone CL,Meurer LC,Tolman RL,Greenlee WJ,Patchett AA,Lynch RJ,Schorn TW,Strouse JF,Siegl PKdoi
10.1021/jm00089a023keywords:
subject
Has Abstractpub_date
1992-05-29 00:00:00pages
2103-12issue
11eissn
0022-2623issn
1520-4804journal_volume
35pub_type
杂志文章abstract：:Dicarba analogues of the cyclic opioid peptides H-Tyr-c[d-Cys-Gly-Phe-d(or l)-Cys]NH2 were synthesized on solid phase by substituting allylglycines for the cysteines and cyclization by ring-closing metathesis between the side chains of the allylglycine residues. Mixtures of cis and trans isomers of the resulting olefi...
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更新日期：2001-02-15 00:00:00
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更新日期：1993-04-30 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：1991-05-01 00:00:00
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更新日期：1996-01-05 00:00:00
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更新日期：2008-08-14 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00020a020
更新日期：1995-09-29 00:00:00
abstract：:The dopamine D(3) receptor is recognized as a potential therapeutic target for the treatment of various neurological and psychiatric disorders. Targetting high affinity and D(3) versus D(2) receptor-preferring ligands, the partial agonist BP 897 was taken as a lead structure. Variations in the spacer and the aryl moie...
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更新日期：1999-09-09 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：1990-06-01 00:00:00
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更新日期：2004-01-01 00:00:00
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更新日期：2015-01-08 00:00:00
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更新日期：2008-06-12 00:00:00
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更新日期：1985-01-01 00:00:00
abstract：:Most non-thiol CAAX-peptidomimetic farnesyltransferase inhibitors bear nitrogen-containing heterocycles in place of the terminal cysteine which are supposed to coordinate the enzyme-bound zinc. However, it has been shown that those nitrogen-containing heterocycles can be replaced by carbocyclic aromatic moieties which...
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更新日期：2001-09-13 00:00:00
abstract：:A novel series of ligands with substitutions at the 5-position on phenyl ring A and at the 4'-position on phenyl ring B of 2-(2'-((dimethylamino)methyl)-4'-(fluoroalkoxy)phenylthio)benzenamine (4'-2-fluoroethoxy derivatives 28-31 and 4'-3-fluoropropoxy derivatives 40-42) were prepared and tested as serotonin transport...
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更新日期：2007-12-27 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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