169532-12-1Relevant articles and documents
PLASMA KALLIKREIN INHIBITORS
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, (2022/01/05)
The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.
Application of polymer-supported enzymes and reagents in the synthesis of γ-aminobutyric acid (GABA) analogues
Baxendale, Ian R.,Ernst, Martin,Krahnert, Wolf-Rüdiger,Ley, Steven V.
, p. 1641 - 1644 (2007/10/03)
Polymer-supported pig liver esterase was used for the resolution of meso-diesters. The enzyme can be recovered quantitatively from the reaction mixture by filtration and reused without significant loss of activity. Further transformation of the resulting enantiomerically enriched carboxylic acids through the application of polymer-supported reagents and scavengers provides a number of GABA-analogues.
Enantioselective intramolecular cyclopropanations of allylic and homoallylic diazoacetates and diazoacetamides using chiral dirhodium(II) carboxamide catalysts
Doyle, Michael P.,Austin, Richard E.,Bailey, A. Scott,Dwyer, Michael P.,Dyatkin, Alexey B.,Kalinin, Alexey V.,Kwan, Michelle M. Y.,Liras, Spiros,Oalmann, Christopher J.,Pieters, Roland J.,Protopopova, Marina N.,Raab, Conrad E.,Roos, Gregory H. P.,Zhou, Qi-Lin,Martin, Stephen F.
, p. 5763 - 5775 (2007/10/02)
Diazo decomposition of allylic and homoallylic diazoacetates 10a-p and 22a-j catalyzed by chiral dirhodium(II) tetrakis[methyl 2-pyrrolidone-5(S)-carboxylate], Rh2(SS-MEPY)4 (7), and its enantiomer, Rh2(5R-MEPY)4 (8), produces the corresponding intramolecular cyclopropanation products 11a-p and 23a-j in good to excellent yields and with exceptional enantioselectivity. Higher enantiocontrol is observed with allylic diazoacetates than with their homoallylic counterparts, but allylic diazoacetates are subject to greater variations in enantioselectivities with changes in substitution patterns on the carbon-carbon double bond. For example, the enantioselectivities in the intramolecular cyclopropanations of 3-alkyl/aryl-2(Z)-alken-1-yl diazoacetates are generally ≥94%, whereas the cyclizations of the homologous 4-alkyl/aryl-3(Z)-alken-1-yl diazoacetates are typically in the range of 70-90% ee. The corresponding 3-alkyl/aryl-2(E)-alken-1-yl and 4-alkyl/aryl-3(E)-alken-1-yl diazoacetates undergo cyclization with slightly lower ee's (54-85%). Although the Rh2(5S-MEPY)4-catalyzed cyclization of the 2-methallyl diazoacetate 10c proceeds with only 7% ee, alternative chiral dirhodium(II) catalysts, including those with methyl N-acylimidazolidin-2-one-4(5)-carboxylate ligands such as Rh2(4S-MACIM)4 (14) and Rh2(4S-MPAIM)4 (15), may be employed to increase the level of enantiocontrol to 78 and 65%, respectively. Some allylic diazoacetamides also undergo highly enantioselective cyclization to form cyclopropyl lactams as illustrated by the diazo decomposition of N-allyl diazoacetamide (19) in the presence of dirhodium(II) tetrakis[methyl 2-oxazolidinone-4(S)-carboxylate], Rh2(4S-MEOX)4, to give the 3-azabicyclo[3.1.0]hexan-2-one 20 in 98% ee. The absolute configuration and the level of enantiocontrol in these intramolecular cyclopropanations have been interpreted by a transition state model in which the important determinants are (i) the preferred conformation about the rhodium-carbon bond; (ii) the trajectory of approach of the double bond to the metallocarbene center; and (iii) the orientation of the double bond with respect to the chiral face of the catalyst.
