- [6+5] FUSED BICYCLES AS A THROMBIN ANTAGONIST, PROCESS FOR PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE BICYCLES
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The present invention relates to the new [6+5] fused bicycle derivatives, pharmaceutically acceptable salts or isomers thereof, processes for preparing the same, and pharmaceutical compositions comprising the same. The [6+5] fused bicycle derivatives can antagonize the thrombin receptor and thus may be effectively used for the treatment and prevention of thrombus, platelet aggregation, atherosclerosis, restenosis, blood coagulation, hypertension, arrhythmia, angina pectoris, heart failure, inflammation and cancer when used alone or with other cardiovascular agents.
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Page/Page column 43-44
(2012/01/14)
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- Complete relative stereochemistry of maitotoxin
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By addressing the relative stereochemistry of the four acyclic portions via organic synthesis, the complete relative stereochemistry of maitotoxin (MTX) has been established as 1B. The relative stereochemistry of the C.1-C.15 portion was elucidated via a two-phase approach: (1) the synthesis of the eight diastereomers possible for model C, representing the C.1-C.11 portion, and the eight diastereomers possible for model D, representing the C.11-C.15 portion, and the comparison of their proton and carbon NMR characteristics with those of MTX, concluding that 9 and 35 represent the relative stereochemistry of the corresponding portions of MTX; (2) the synthesis of the two remote diastereomers 51 and 52, and comparison of their proton and carbon NMR characteristics with those of MTX, concluding that 51 represents the relative stereochemistry of the C.1-C.15 portion of MTX. The relative stereochemistry of the C.35-C.39, C.63-C.68, and C.134-C.142 acyclic portions was established via (1) the synthesis of the 8, 8, and 16 diastereomers possible for models E, F, and G, respectively, and (2) the comparison of their proton and carbon NMR characteristics with those of MTX, concluding that 81, 117, and 187, respectively, represent the relative stereochemistry of the corresponding portions of MTX. Some biogenetic considerations have been given to speculate on the absolute configuration of MTX. The vicinal proton coupling constants observed for models 51, 81, 117, and 187 were used to elucidate their preferred solution conformation. Assembling the preferred solution conformations found for the four acyclic portions allows one to suggest that the approximate global conformation of MTX is represented by the shape of a hook, with the C.35-C.39 portion being its curvature. MTX appears to be conformationally relatively rigid, except for conformational flexibility around the C.7-C.9 and C.12-C.14 portions. On the basis of the experimental results gained in the current work, coupled with those in the AAL-toxin/fumonisin area, it has been pointed out that the structural properties of 51, 81, 117, 187 and their diastereomers are inherent to the specific stereochemical arrangement of the small substituents on the carbon backbone and are independent from the rest of the molecule. Thus, it has been suggested that each of these diastereomers has the capacity to install a unique structural characteristic through a specific stereochemical arrangement of substituents on the carbon backbone, and that fatty acids and related classes of compounds may be able to carry specific information and serve as functional materials in addition to structural materials.
- Zheng,DeMattei,Wu,Duan,Cook,Oinuma,Kishi
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p. 7946 - 7968
(2007/10/03)
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- Total synthesis of Taxol. 2. Construction of A and C ring intermediates and initial attempts to construct the ABC ring system
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A method for the formation of Taxol's ABC ring system has been developed. General methods for the synthesis of versatile synthons for Taxol's A ring (8) and C ring (55) are presented. A model study using a simplified C ring synthon (17) confirmed the viability of the sequential Shapiro-McMurry strategy for formation of Taxol's B ring. Careful exploration of the chemistry of various A-B ring conjugates allowed the development of a successful method for formation of the B ring in a more functionalized system.
- Nicolaou,Liu,Yang,Ueno,Sorensen,Claiborne,Guy,Hwang,Nakada,Nantermet
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p. 634 - 644
(2007/10/02)
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- Cyclisation concertee d'homologues cyclohexaniques et cyclohexeniques du chloro-4 butanol: enthalpies et entropies d'activation; modelisation du chemin reactionel; evolutions d'etats de transition
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The relative stabilities of cis and trans stereoisomers of 1-chloromethyl-2-hydroxymethyl cyclohexane and of 4-chloromethyl-5-hydroxymethyl cyclohexene, and of their related bicyclic ethers, have been calculated using the MM2 molecular mechanics program.T
- Kechayan, Josette,Lauricella, Robert,Davidovics, Gisele,Bodot, Hubert
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p. 559 - 565
(2007/10/02)
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- Enantioselectivity of the Microsomal Epoxide Hydrolase Catalyzed Hydrolysis of trans-4,5-Dimethyl-1,2-epoxycyclohexane
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The hydrolysis of the racemic and enantiomeric forms of trans-4,5-dimethyl-1,2-epoxycyclohexane, catalyzed by rabbit liver microsomal epoxide hydrolase (EH), has been investigated to clarify further the mechanism of enantioselection by this enzyme.Both ac
- Bellucci, Giuseppe,Berti, Giancarlo,Ferretti, Maria,Mastrorilli, Ettore,Silvestri, Luca
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p. 1471 - 1474
(2007/10/02)
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