- Shape Similarity by Fractal Dimensionality: An Application in the de novo Design of (?)-Englerin A Mimetics
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Molecular shape and pharmacological function are interconnected. To capture shape, the fractal dimensionality concept was employed, providing a natural similarity measure for the virtual screening of de novo generated small molecules mimicking the structurally complex natural product (?)-englerin A. Two of the top-ranking designs were synthesized and tested for their ability to modulate transient receptor potential (TRP) cation channels which are cellular targets of (?)-englerin A. Intracellular calcium assays and electrophysiological whole-cell measurements of TRPC4 and TRPM8 channels revealed potent inhibitory effects of one of the computer-generated compounds. Four derivatives of this identified hit compound had comparable effects on TRPC4 and TRPM8. The results of this study corroborate the use of fractal dimensionality as an innovative shape-based molecular representation for molecular scaffold-hopping.
- Bauer, Christoph,Byrne, Ryan,Friedrich, Lukas,Gudermann, Thomas,Mederos y Schnitzler, Michael,Schneider, Gisbert,Singh, Inderjeet,Storch, Ursula,Treder, Aaron
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supporting information
(2020/03/24)
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- A METHOD FOR PREPARING RAMIPRIL
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Enantio-specific synthesis of optically pure (2S)-acetylamino-3-(2-oxo-cyclopentyl)- propionic acid (I) comprising converting enantiomeric mixture of (1 -4C alkyl)-2- acetylamino-3-(2-oxocyclopentyl) propionoate (II) (+ and -) under the influence of an Alkaline serine endopeptidase is disclosed. The invention further describes use of optically pure (2S)-acetylamino-3-(2-oxocyclopentyl)-propionic acid (I) formed by the process of present invention, in the preparation of Ramipril.
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- Asymmetric synthesis of (S,S,S)-2-Aza-bicyclo-[3.3.0]-octane-3-carboxylic acid benzyl ester: Formal synthesis of ramipril
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An asymmetric synthesis of (S,S,S)-2-aza-bicyclo-[3.3.0]-octane-3- carboxylic acid benzyl ester 2 as an intermediate of angiotensin converting enzyme (ACE) inhibitor, ramipril 1, is described.
- Kondaiah,Vivekanandareddy,Reddy, L. Amarnath,Anurkar, Smita V.,Gurav,Ravikumar,Bhattacharya, Apurba,Bandichhor, Rakeshwar
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p. 1186 - 1191
(2011/05/05)
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- A PROCESS FOR PREPARATION OF RAMIPRIL
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Disclosed herein is a process for preparation of Ramipril; which comprises; reacting salts of (S,S,S)-azabicyclo[3.3.0]-octane-3-carboxylate with N-[l-(S)-ethoxy carbonyl)-3- phenyl propyl] -L-alanine in presence of dicyclohexylcarbodimide (DCC) and 1- hydroxybenzotriazole (HOBT) in a suitable solvent medium.
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Page/Page column 12
(2009/10/30)
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- METHOD FOR THE PRODUCTION OF RAMIPRIL
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An improved method for preparing ramipril is disclosed, and also an intermediate for use in the method.
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Page/Page column 6
(2009/01/24)
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- PREPARATION OF RAMIPRIL AND STABLE PHARMACEUTICAL COMPOSITIONS
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A process for preparing ramipril, and stable pharmaceutical compositions containing ramipril.
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Page/Page column 11
(2010/11/28)
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- Derivatives of bicyclic aminoacids agents containing these compounds and their use
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Disclosed are cis, exo- and trans-compounds of the formula I STR1 in which n denotes 0, 1 or 2, R1 denotes hydrogen, (C1 -C6)-alkyl which can optionally be substituted by amino, (C1 -C4)-acyl- or bezoylamino, (C2 -C6)-alkenyl, (C5 -C9)-cycloalkyl, (C5 -C9)-cycloalkenyl, (C5 -C7)-cycloalkyl-(C1 -C4)-alkyl, aryl or partially hydrogenated aryl, which can, in each case, be substituted by (C1 -C2)-alkyl, (C1 -C2)-alkoxy or halogen, aryl-(C1 -C4)-alkyl, /which can be substituted as defined previously in the aryl radical/, a monocyclic or bicyclic sulfur or nitrogen and/or nitrogen heterocyclic radical, or a side chain of naturally occurring aminoacid, R2 denotes hydrogen, (C1 -C6)-alkyl, (C2 -C6)-alkenyl or aryl-(C1 -C4)-alkyl, Y denotes hydrogen or hydroxyl, Z denotes hydrogen or Y and Z together denote oxygen, X denotes (C1 -C6)-alkyl, (C2 -C6)-alkenyl, (C6 -C9)-cycloalkyl or aryl which can be mono-, di- or tri- substituted by (C1 -C4)-alkyl, (C1 -C4)-alkoxy, hydroxyl, halogen, nitro, amino, (C1 -C4)-alkylamino, di-(C1 -C4 -alkylamino or methylenedioxy, or indol-3-yl, or physiologically acceptable salts thereof, a process of the preparation thereof, agents containing them, their use as a medicine and intermediates for the preparation thereof.
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- SYNTHESIS OF UNNATURAL AMINO ACIDS: (S,S,S)-2-AZABICYCLOOCTANE-3-CARBOXYLIC ACID
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(S,S,S)-2-Azabicyclooctane-3-carboxylic acid 1, a structural element of the very potent ACE inhibitor HOE 498, is readily available via a diastereo selective synthesis starting from serine or cystine.
- Teetz, V.,Geiger, R.,Gaul, H.
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p. 4479 - 4482
(2007/10/02)
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- Synthesis of a highly active angiotensin converting enzyme inhibitor: 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabicyc lo[3.3.0]octane-3-carboxylic acid (Hoe 498)
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The convergent, diastereoselective synthesis of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabicyc lo[3.3.0]octane-3-carboxylic acid (Hoe 498), a new ACE-inhibitor with improved bioavailability and pharmacokinetics, is described.
- Teetz,Geiger,Henning,Urbach
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p. 1399 - 1401
(2007/10/02)
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