Crystal Structures of rac-Methyl- (3R*, 3aS*, 4R*, 7R*, 7aR*)-7-Acetoxymethyl)-3-benzyl-4,5-dimethyl-1-oxo-3a,4,7,7a-tetrahydroisoindoline-7a-carboxylate

The X-ray structures of the compounds 4 and 2 have been determined by direct methods and refined by least squares techniques. Crystals of C₂₂H₂₇NO₅ and C₂₇H₂₇NO₅ are triclinic, space groups Pī with lattice parameters a = 13.652 (5) Å, b = 10.926 (3) Å, c = 7.755 (2) Å, a = 111.554 (4) Å, β = 85.541 (3) Å, γ = 104.813 (4) Å, and a = 15.394 (4) Å, b = 9.674 (3) Å, c = 8.522 (3) Å, a = 111.04 (4) Å, ß = 93.65 (4) Å, γ = 95.01 (4) Å, respectively.     

Combinatorial solution-phase synthesis of alkyl (1S*,2S*,3R*,5R*,6R*)-1-alkyl-3-aryl-6-benzoylamino-1-hydroxy-7- oxo-5-phenylhexahydropyrazolo[1,2-a]pyrazole-2-carboxylates

Combinatorial solution-phase cycloadditions of (1Z,4R*,5R*)-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines 3 to beta-keto esters 4 afforded a library of 26 bicyclic pyrazolidinones 5 in 6-89% yields and in 14-100% de. All products were isolated in >90% purity according to 1H NMR, and 25 of them were analytically pure. The structures of cycloadducts were confirmed by NMR and X-ray diffraction. Most of the products were isolated as mixtures of the major (1S*,2S*,3R*,5R*,6R*)-epimers 5 and the minor (1R*,2S*,3R*,5R*,6R*)-epimers 6. Epimerization of cycloadducts 5/6 at the anomeric position 1 in solution was confirmed by 1H NMR.     

Synthesis and anxiolytic activity of N-substituted cyclic imides (1R*,2S*,3R*,4S*)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3- bicyclo[2.2.1]heptanedicarboximide (tandospirone) and related compounds.

A series of cyclic imides bearing a omega-(4-aryl and 4-heteroaryl-1-piperazinyl)alkyl moieties was synthesized and tested in vivo for anxiolytic activity. The in vitro binding affinities of these compounds were also examined for 5-HT1A receptor sites. Structure-activity relationships within these series are discussed. One of these compounds, (1R*,2S*,-3R*,4S*)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3- bicyclo[2.2.1]heptanedicarboximide (1: tandospirone), was found to be equipotent with buspirone in its anxiolytic activity and more anxio-selective than buspirone and diazepam. Tandospirone (1) is currently undergoing clinical evaluation as a selective anxiolytic agent.     

Effect of salts on the reaction direction of (2R*,3R*)-2-[(1R*)-1-iodoethyl)]-3-methyl(3,5-dimethyl)-1-(4-methylphenylsulfonyl)-2,3-dihydro-1H-indoles with dimethylformamide

Transformations of (2R*,3R*)-2-[(1R*)-1-iodoethyl)-3,5-dimethyl-1-(4-methylphenylsulfonyl-2,3-dihydro-1H-indole on heating in boiling dimethylformamide in the presence of various salts were studied.     

Diastereoselective synthesis of (R*,R*)-ethyl 2-[1H-indol-3-yl(phenyl)methyl]-3-oxobutanoate

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