90055-55-3Relevant articles and documents
Clopidogre and wherein the intermediate α-bromo-ortho-chlorophenyl acetic acid and α-thiophene substituted ethylamino- method for the preparation of acetic acid hydrochloride (by machine translation)
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Paragraph 0086-0088, (2017/04/29)
The invention discloses a preparation method of clopidogrel and intermediates thereof. The preparation method of the clopidogrel and intermediates thereof, provided by the invention, has the characteristics of being simple to operate, mild in reaction condition, little in pollution, low in energy consumption and the like and is suitable for industrial production, a high-purity intermediate can be provided for production of the clopidogrel, and the production cost of the clopidogrel is reduced.
Designing analogs of ticlopidine, a wall teichoic acid inhibitor, to avoid formation of its oxidative metabolites
Farha, Maya A.,Koteva, Kalinka,Gale, Robert T.,Sewell, Edward W.,Wright, Gerard D.,Brown, Eric D.
supporting information, p. 905 - 910 (2014/02/14)
The thienopyridine antiplatelet agent, ticlopidine and its analog, clopidogrel, have been shown to potentiate the action of β-lactam antibiotics, reversing the methicillin-resistance phenotype of methicillin-resistant Staphylococcus aureus (MRSA), in vitro. Interestingly, these thienopyridines inhibit the action of TarO, the first enzyme in the synthesis of wall teichoic acid, an important cell wall polymer in Gram-positive bacteria. In the human body, both ticlopidine and clopidogrel undergo a rapid P450-dependent oxidation into their respective antiplatelet-active metabolites, resulting in very low plasma concentrations of intact drug. Herein, a series of analogs of ticlopidine and clopidogrel that would avoid oxidative metabolism were designed, prepared and evaluated as inhibitors of TarO. Specifically, we replaced the P450-labile thiophene ring of ticlopidine and clopidogrel to a more stable phenyl group to generate 2-(2-chlorobenzyl)-1,2,3,4-tetrahydro- isoquinoline) (6) and (2-chloro-phenyl)-(3,4-dihydro-1H-isoquinolin-2-yl)-acetic acid methyl ester (22), respectively. The latter molecules displayed inhibitory activity against TarO and formed the basis of a library of analogs. Most synthesized compounds exhibited comparable efficacy to ticlopidine and clopidogrel. So far, it was introduction of a trifluoromethyl group to compound 6, to generate 2-(2-trifluoromethyl-benzyl)-1,2,3,4-tetrahydro-isoquinoline (13) that exhibited enhanced activity against TarO. Compound 13 represents a novel stable inhibitor of TarO with synergistic impact on β-lactam antibiotics against MRSA and low potential for P-450 metabolism.
PRODRUGS OF ANTI-PLATELET AGENTS
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Paragraph 00101; 00106; 00107, (2013/12/03)
Disclosed is the compounds of formula (I), formula (II), formula (la), formula (IIb) or its pharmaceutical acceptable salts, polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising and effective amount of formula (I), formula (II), formula (la), formula (lIb) and may be used to treatment or management of ischemia, stroke, cerebral thrombosis, arterial thrombosis, thrombotic cerebrovascular, cardiovasculard diseases and blood colts.
