188812-40-0Relevant articles and documents
1-(3-AMINOPROPYL) SUBSTITUTED CYCLIC AMINE COMPOUNDS, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Paragraph 0086; 0093, (2017/04/11)
Provided are 1-(3-aminopropyl) substituted cyclic amine compounds as represented by formula (I), pharmaceutically acceptable salts, enantiomers, diastereoisomers, racemates and mixtures thereof, and a method of synthesizing said 1-(3-aminopropyl) substituted cyclic amine compounds by using aromatic heterocyclic formaldehyde as raw material. Said compounds can be used as CCR 5 antagonist for the treatment of HIV infection.
Practical, catalytic enantioselective hydrogenation to synthesize N -unprotected β-amino esters
Matsumura, Kazuhiko,Zhang, Xiaoyong,Hori, Kiyoto,Murayama, Toshiyuki,Ohmiya, Tadamasa,Shimizu, Hideo,Saito, Takao,Sayo, Noboru
experimental part, p. 1130 - 1137 (2012/01/03)
Practical and simple catalytic enantioselective hydrogenation reactions to synthesize N-unprotected β-amino esters have been developed: (1) asymmetric hydrogenation of N-unprotected β-enamine ester and (2) asymmetric direct reductive amination of β-keto esters using ammonium salts. A Ru-DM-SEGPHOS complex was used as the catalyst in both cases and gave high enantioselectivity, high reactivity, and wide substrate applicability. These protocols greatly reduced reaction time and waste compared to conventional synthetic routes. The direct reductive amination route was demonstrated on a >100 kg scale.
PLATELET ADP RECEPTOR INHIBITORS
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Page/Page column 42-43, (2008/06/13)
Compounds are provided which are useful as platelet ADP receptor inhibitors, for treating thrombosis and for reducing the likelihood and/or severity of a secondary ischemic event in a patient.
PROCESS FOR PRODUCING AMINO ACID DERIVATIVES
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Page/Page column 57-58, (2008/06/13)
The present invention relates to a process for producing amino acid derivatives such as optically active β-amino acid in short steps with good yield and high optical purity, which comprises reacting a keto acid of the formula (1): wherein R1 is hydrogen, an optionally substituted hydrocarbon, etc.; R2 is a spacer; and R3 is an optionally substituted alkoxy, etc., or a salt thereof, with ammonia or an amine or a salt thereof in the presence of a chiral catalyst and in the presence or absence of an acid and/or a fluorine-containing alcohol, to give an amino acid derivative of the formula (2): wherein Q is a group formed by removing one hydrogen atom from ammonia or an amine; X' is an acid and/or a fluorine-containing alcohol; and b is 0 or 1.
Method for producing an optically active beta-amino acid
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Page 18, (2010/02/06)
To provide a producing method of an optically active β-amino acid useful as intermediate for the production of medicines, agricultural chemicals and physiologically active substances, by means of a catalytic and asymmetric synthesis method of high performance and a high enantiomeric excess, without requiring additional procedures such as introduction and removal of protecting group and so on. A producing method of an optically active β-amino acids which comprises subjecting an enamine to an asymmetric hydrogenation.
Potent, orally active GPIIb/IIIa antagonists containing a nipecotic acid subunit. Structure-activity studies leading to the discovery of RWJ-53308
Hoekstra, William J.,Maryanoff, Bruce E.,Damiano, Bruce P.,Andrade-Gordon, Patricia,Cohen, Judith H.,Costanzo, Michael J.,Haertlein, Barbara J.,Hecker, Leonard R.,Hulshizer, Becky L.,Kauffman, Jack A.,Keane, Patricia,McComsey, David F.,Mitchell, John A.,Scott, Lorraine,Shah, Rekha D.,Yabut, Stephen C.
, p. 5254 - 5265 (2007/10/03)
Although intravenously administered antiplatelet fibrinogen receptor (GPIIb/IIIa) antagonists have become established in the acute-care clinical setting for the prevention of thrombosis, orally administered drugs for chronic use are still under development. Herein, we present details from our exploration of structure-activity surrounding the prototype fibrinogen receptor antagonist RWJ-50042 (racemate of 1), which was derived from a unique approach involving the γ-chain of fibrinogen (Hoekstra et al. J. Med. Chem. 1995, 38, 1582). Our analogue studies culminated in the discovery of RWJ-53308 (2), a potent, orally active GPIIb/IIIa antagonist. To progress from RWJ-50042 to a suitable candidate for clinical development, we conducted a series of optimization cycles that employed solid-phase parallel synthesis for the rapid, efficient preparation of nearly 250 analogues, which were assayed for fibrinogen receptor affinity and inhibition of platelet aggregation induced by four different activators. This strategy produced several promising analogues for advanced study, including 3-(3,4- methylenedioxybenzene)-β-amino acid analogue 3 (significant improved in vivo potency) and 3-(3-pyridyl)-β-amino acid 2 (significantly improved potency, oral absorption, and duration of action). In dogs, 2 displayed significant ex vivo antiplatelet activity on oral administration at 1.0 mg/kg, 16% systemic oral bioavailability, minimal metabolic transformation, and an excellent safety profile. Additionally, 2 was found to be efficacious in three in vivo thrombosis models: canine arteriovenous (AV) shunt (0.01-0.1 mg/kg, iv), guinea pig photoactivation-induced injury (0.3-3 mg/kg, iv), and guinea pig ferric chloride-induced injury (0.3-1 mg/kg, iv). On the basis of its noteworthy preclinical data, RWJ-53308 (2) was selected for clinical evaluation.
