72679-01-7Relevant articles and documents
AMINO ACID DERIVATIVE HAVING N,N-DIALKYIAMINOPHENYL GROUP
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, (2008/06/13)
A compound of the formula wherein R1 is hydrogen, lower alkyl, phenyl-lower alkyl, lower alkanoyl or benzoyl, and each phenyl in the phenyl lower alkyl and the benzoyl is unsubstituted or substituted by halogen, lower alkyl or alkoxy; R2 represents a carb
Angiotensin-Converting Enzyme Inhibitors. New Orally Active Antihypertensive (Mercaptoalkanoyl)- and glycine Derivatives
Suh, John T.,Skiles, Jerry W.,Williams, Bruce E.,Youssefyeh, Raymond D.,Jones, Howard,et al.
, p. 57 - 66 (2007/10/02)
A variety of N-substituted (mercaptoalkanoyl)- and glycine derivatives was synthesized and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) was examined in vitro and in vivo.The acylthio derivatives prepared are assumed to act as prodrugs since they are much less active than the corresponding free SH compounds in vitro and can be expected to act in vivo only after conversion to the free sulfhydryl compounds.A number of this compounds are potent ACE inhibitors that lowered blood pressure in Na-deficient, conscious spontaneously hypertensive rats (SHR), a high renin model.One of the most active members of the series was (S)-N-cyclopentyl-N--2-methyl-1-oxopropyl>glycine (REV 3659-(S), pivopril).Structure-activity relationships are discussed.
Studies on angiotensin-converting enzyme inhibitors. I. Syntheses and angiotensin-converting enzyme inhibitory activity of 2-(3-merecaptopropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives
Hayashi,Ozaki,Nunami,Uchida,Kato,Kinashi,Yoneda
, p. 570 - 576 (2007/10/02)
(3S)-2-[(2S)-mercapto-2-methylpropionyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid [(3S), (2S)-6a] was prepared by the reaction of (3S)-1,2,3,4-tetrahydreoisoquinoline-3-carboxylic acid test-butyl ester [(3S)-2a) or benzyl ester [(3S)-2b] with 3-benzoylthio-2-methylpropionyl chloride (3a), followed by fractional crystallization and removal of the protective group. The absolute configuration of (3S), (2S)-6a was confirmed by X-ray diffraction analysis of the thiazepinol[4,3-b]isoquinoline compound (7) derived from 6a. Resolution of 3-benzoylthio-2-methylpropionic acid (8) was completed by using optically active phenylalanine amide as a resolving agent. The other optical isomers of (3S),(2S)-6a were prepared by the reaction of (3S)- or (3R)-2b with optically active 3a. The in vitro ACE inhibitory activity of each isomer of 6a was evaluated. Among them, (3S),(2S)-6a was found to be the most potent inhibitor with an IC50 value of 8.6X10-9M. Compound (3S),(2S)-6a induced a dose-dependent inhibition of the pressor response to angiotensin 1 after oral administration to normotensive anesthetized rats. Moreover, (3S),(2S)-6a markedly reduced the systolic blood pressure in renal hypertensive rats (RHR) and spontaneously hypertensive rats (SHR). The in vivo ACE inhibitory activity and the hypotensive effects of (3S),(2S)-6a were comparable to those of captopril.
