Continuous Flow Synthesis of ACE Inhibitors From N-Substituted l-Alanine Derivatives
A strategy for the continuous flow synthesis of angiotensin converting enzyme (ACE) inhibitors is described. An optimization effort guided by in situ IR analysis resulted in a general amide coupling approach facilitated by N-carboxyanhydride (NCA) activation that was further characterized by reaction kinetics analysis in batch. The three-step continuous process was demonstrated by synthesizing 8 different ACE inhibitors in up to 88 % yield with throughputs in the range of ≈0.5 g h?1, all while avoiding both isolation of reactive intermediates and process intensive reaction conditions. The process was further developed by preparing enalapril, a World Health Organization (WHO) essential medicine, in an industrially relevant flow platform that scaled throughput to ≈1 g h?1.
Breen, Christopher P.,Jamison, Timothy F.
supporting information
p. 14527 - 14531
(2019/11/03)
Inhibitors of interleukin-1βconverting enzyme
-
-
(2008/06/13)
Design and synthesis of N-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-N-(indan-2-y l)glycine (CV-3317), a new, potent angiotensin converting enzyme inhibitor
We report a series of novel dipeptides, which exhibit potent in vitro angiotensin-converting enzyme (ACE) inhibition. These dipeptides embody N-substituted glycine as the COOH terminus amino acid. The dipeptide L-lysyl-N-(2,3-dihydro-1Hinden-5-yl)glycine,
Suh,Regan,Skiles,et al.
p. 563 - 570
(2007/10/02)
Angiotensin-Converting Enzyme Inhibitors. New Orally Active Antihypertensive (Mercaptoalkanoyl)- and glycine Derivatives
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.
Suh, John T.,Skiles, Jerry W.,Williams, Bruce E.,Youssefyeh, Raymond D.,Jones, Howard,et al.
p. 57 - 66
(2007/10/02)
More Articles about upstream products of 83402-63-5