181227-46-3Relevant articles and documents
Method for preparing D-indanyl glycine
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Paragraph 0116-0117; 0119; 0129, (2018/04/01)
The invention discloses a method for preparing D-indanyl glycine. The method specifically comprises the following steps: dissolving 2-indan aldehyde, R-2-hydroxylamino-2-phenylethanol in a mixed solution of ethanol and water or an organic solvent A, and stirring at the temperature of 10-40 DEG C to be completely reacted so as to obtain a compound I; dissolving the obtained compound I and trimethylsilyl cyanide in an organic solvent B, reacting at the temperature of 0-70 DEG C in the presence of a catalyst A for 1-8 hours so as to obtain a compound II; mixing the obtained compound II and an acid, and carrying out a hydrolysis reaction at the temperature of 30-120 DEG C for 1-10 hours so as to obtain a compound III; and dissolving the obtained compound III in an organic solvent C, adding a catalyst B, carrying out an atmospheric hydrogenation reaction at the temperature of 40-60 DEG C for 4-12 hours, and filtering the obtained product to remove the catalyst B, thereby obtaining the D-indanyl glycine. The method disclosed by the invention has the advantages of mild reaction conditions, easy and convenient operation, high atom utilization rate, environmental friendliness, low production cost and the like, and is a novel method for preparing the D-indanyl glycine.
Pyridyl-2,5-diketopiperazines as potent, selective, and orally bioavailable oxytocin antagonists: Synthesis, pharmacokinetics, and in vivo potency
Borthwick, Alan D.,Liddle, John,Davies, Dave E.,Exall, Anne M.,Hamlett, Christopher,Hickey, Deirdre M.,Mason, Andrew M.,Smith, Ian E. D.,Nerozzi, Fabrizio,Peace, Simon,Pollard, Derek,Sollis, Steve L.,Allen, Michael J.,Woollard, Patrick M.,Pullen, Mark A.,Westfall, Timothy D.,Stanislaus, Dinesh J.
experimental part, p. 783 - 796 (2012/03/11)
A six-stage stereoselective synthesis of indanyl-7-(3′-pyridyl)-(3R, 6R,7R)-2,5-diketopiperazines oxytocin antagonists from indene is described. SAR studies involving mono- and disubstitution in the 3′-pyridyl ring and variation of the 3-isobutyl group gave potent compounds (pKi > 9.0) with good aqueous solubility. Evaluation of the pharmacokinetic profile in the rat, dog, and cynomolgus monkey of those derivatives with low cynomolgus monkey and human intrinsic clearance gave 2′,6′-dimethyl-3′- pyridyl R-sec-butyl morpholine amide Epelsiban (69), a highly potent oxytocin antagonist (pKi = 9.9) with >31000-fold selectivity over all three human vasopressin receptors hV1aR, hV2R, and hV1bR, with no significant P450 inhibition. Epelsiban has low levels of intrinsic clearance against the microsomes of four species, good bioavailability (55%) and comparable potency to atosiban in the rat, but is 100-fold more potent than the latter in vitro and was negative in the genotoxicity screens with a satisfactory oral safety profile in female rats.
Crystallization-induced asymmetric transformation (CIAT) with simultaneous epimerization at two stereocenters. A short synthesis of conformationally constrained homophenylalanines
Kolarovi?, Andrej,Berke?, Du?an,Baran, Peter,Pova?anec, Franti?ek
, p. 975 - 978 (2007/10/03)
CIAT of aza-Michael adducts allows simultaneous build up of two stereocenters. A consequent short and efficient synthesis affords simple access to the both antipodes of various conformationally restricted homophenylalanines.