50734-07-1Relevant articles and documents
PHARMACEUTICAL COMPOSITIONS COMPRISING ANTICOAGULANT N-(5-CHLOROPYRIDINE-2-YL)-2-({4-[ETHANIMIDOIL(METHYL)AMINO]BENZOYL}AMINO)-5-METHYLBENZAMIDE
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Page/Page column 7, (2018/01/20)
The invention relates to area of medicine, in particular to pharmacology, namely to novel pharmaceutical compositions for oral use for treatment of diseases associated with increased thrombus formation. The compositions comprise the anticoagulant N-(5-chloropyridine-2-yl)-2-({4-[ethanimidoil(methyl)amino]benzoyl}amino)-5-methylbenzamide or a pharmaceutically acceptable salt thereof, being a factor Xa inhibitor and polyprenol, and are protected from the contact with acidic gastric juice by an enteric coating or capsule. The compositions are of high efficacy and bioavailability and can be used to treat and prevent conditions characterized by undesirable thrombosis.
URETHANES, UREAS, AMIDINES AND RELATED INHIBITORS OF FACTOR XA
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Page/Page column 24, (2011/10/03)
The invention relates to a new class of compounds, their pharmaceutically acceptable salts and pharmaceutically acceptable compositions that are effective as selective inhibitors of factor Xa, both in the isolated state and in a complex with other proteins. The compounds of the invention can be used for treating and preventing diseases, such as acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, thromboses caused by post-thrombolytic therapy or coronary angioplasty, acute ischemia mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, and other diseases in humans and other mammals associated with blood coagulation problems.
Synthesis and structure-activity relationships of 2- pyrazinylcarboxamidobenzoates and β-ionylideneacetamidobenzoates with retinoidal activity
Jones, Paul,Villeneuve, Gérald B.,Fei, Chengpei,DeMarte, Josie,Haggarty, Allison J.,Nwe, Khin Than,Martin, Deborah A.,Lebuis, Anne-Marie,Finkelstein, Joshua M.,Gour-Salin, Barbara J.,Chan, Tak Hang,Leyland-Jones, Brian R.
, p. 3062 - 3077 (2007/10/03)
The structure-activity relationships of two series of novel retinoids (2-pyrazinylcarboxamidobenzoates and β-ionylideneacetamidobenzoates) have been investigated by evaluating their ability to induce differentiation in both human promyelocytic leukemia (H
Methotrexate analogues. 25. Chemical and biological studies on the γ-tert-Butyl esters of methotrexate and aminopterin
Rosowsky,Freisheim,Bader,Forsch,Susten,Cucchi
, p. 660 - 667 (2007/10/02)
γ-tert-Butylaminopterin (γ-tBAMT), the first example of an aminopterin (AMT) γ-monoester, was synthesized, and new routes to the known N10-methyl analogue γ-tert-butyl methotrexate (γ-tBMTX were developed. The inhibitory effects of γ-tBAMT on the activity of purified dihydrofolate reductase (DHFR) from L1210 murine leukemia cells, the growth of L1210 cells and CEM human leukemic lymphoblasts in suspension culture, and the growth of several lines of human squamous cell carcinoma of the head and neck in monolayer culture were compared with the effects of γ-tBMTX and the parent acids AMT and methotrexate (MTX). Patterns of cross-resistance to γ-tBAMT, γ-tBMTX, and AMT among several MTX-resistant cell lines were examined. In vivo antitumor activities of γ-tBAMT and γ-tBMTX were compared in mice with L1210 leukemia. While the activity of γ-tBAMT was very close to that of γ-tBMTX in the DHFR inhibition assay, the AMT ester was more potent than the MTX ester against cells in culture and against L1210 leukemia in vivo. Only partial cross-resistance was shown against γ-tBMTX and γ-tBAMT in cultured cells that were resistant to MTX by virtue of a transport defect or a combination of defective transport and elevated DHFR activity.
Synthesis of Monoamides of Methotrexate from L-Glutamic Acid Monoamide t-Butyl Esters
Antonjuk, David J.,Boadle, Deborah K.,Cheung, H.T.Andrew,Tran, Trung Q.
, p. 1989 - 2004 (2007/10/02)
Analoques of methotrexate (amethopterin) (1) with α- or γ-monoamide functions were synthesized starting with t-butyl L-isoglutamine (12a), t-butyl L-glutamine (22a), or the appropriate N'-alkyl or N'N'-dialkyl analoques (12b-k), (22d), (22k), (22l), and (22m).The corresponding N-benzyloxycarbonyl compounds (11) and/or (21) from which the above L-glutamic acid derivatives were obtained were generally synthesized by mixed-anhydride coupling of N-benzyloxycarbonyl-L-glutamic acid (9) with the appropriate amine, conversion into the t-butyl ester, and chromatographic separation.The resulting α-monoamide γ-t-butyl ester (11) and γ-monoamide α-t-butyl ester (21) are unambiguously distinguished by mass spectrometry and 13C n.m.r. spectroscopy.Factors which affect the γ-amide/α-amide product ratio are discussed.The N-deprotected L-glutamic acid monoamide t-butyl esters (12) or (22) were individually coupled to N-trifluoroacetyl-p-methylaminobenzoic acid, and the resulting α- or γ-monoamide t-butyl esters (13) or (23) of N-(p-methyl(trifluoroacetyl)aminobenzoyl)-L-glutamic acid was hydrolysed.The N-deprotected product, viz. t-butyl N-(p-methylaminobenzoyl)-L-glutamate α- or γ-monoamide (14) or (24) was converted into the appropriate methotrexate-monoamide t-butyl ester (15) or (25), and thence the desired methotrexate-monoamide (16) or (26), by reaction with 2,4-diamino-6-bromomethylpteridine (17) or by the Taylor procedure.Features of the mass and 13C n.m.r. spectra of the intermediates are discussed.
