- Discovery of novel N-benzylbenzamide derivatives as tubulin polymerization inhibitors with potent antitumor activities
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A series of novel N-benzylbenzamide derivatives were designed and synthesized as tubulin polymerization inhibitors. Among fifty-one target compounds, compound 20b exhibited significant antiproliferative activities with IC50 values ranging from 12 to 27 nM against several cancer cell lines, and possessed good plasma stability and satisfactory physicochemical properties. Mechanism studies demonstrated that 20b bound to the colchicine binding site and displayed potent anti-vascular activity. Notably, the corresponding disodium phosphate 20b-P exhibited an excellent safety profile with the LD50 value of 599.7 mg/kg (i.v. injection), meanwhile, it significantly inhibited tumor growth and decreased microvessel density in liver cancer cell H22 allograft mouse model without obvious toxicity. Collectively, 20b and 20b-P are novel promising anti-tubulin agents with more druggable properties and deserve to be further investigated for cancer therapy.
- Zhu, Huajian,Li, Wenlong,Shuai, Wen,Liu, Yang,Yang, Limei,Tan, Yuchen,Zheng, Tiandong,Yao, Hong,Xu, Jinyi,Zhu, Zheying,Yang, Dong-Hua,Chen, Zhe-Sheng,Xu, Shengtao
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- N-benzylbenzamide derivatives and preparation method and pharmaceutical application thereof
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The invention relates to the field of pharmaceutical chemistry, discloses N-benzylbenzamide derivatives with antitumor activity and a preparation method thereof, and further discloses pharmaceutical compositions containing the compounds and application of the compounds or pharmaceutical salts thereof or the compositions containing the compounds to preparation of medicines for treating tumors and inhibiting diseases or symptoms related to tubulin activity.
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- 2,3,4,5-tetrahydro-1H-(1,4)benzodiazepine-3-hydroxamic acids
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Compounds having the following formula: ? are useful in treating disease conditions mediated by matrix metalloproteinases and TACE, such as tumor growth, osteoarthritis, rheumatoid arthritis and degenerative cartilage loss.
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- Heteroarylcarboxylic acid amides, the preparation thereof and their use as pharmaceutical compositions
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A compound of formula wherein: Aa, Ra, X1 to X4, Het, and R5 to R7 are defined as in claim 1, the isomers and the salts thereof, particularly the physiologically acceptable salts thereof, which are valuable inhibitors of the microsomal triglyceride-transfer protein (MTP), medicaments containing these compounds and their use, as well as the preparation thereof.
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- Combination of MTP inhibitors or apoB-secretion inhibitors with fibrates for use as pharmaceuticals
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The invention relates to the use of fibrates for lowering the liver toxicity of MTP inhibitors as well as pharmaceutical compositions containing an MTP inhibitor and a fibrate.
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- Aromatization of enamines promoted by a catalytic amount of Pd/C. Synthesis of aromatic amines
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(Matrix presented) Aromatic amines were obtained efficiently from enamines by using a catalytic amount of Pd/C in the presence of nitrobenzene and 4 A molecular sieves in refluxing toluene.
- Cossy, Janine,Belotti, Damien
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p. 2557 - 2559
(2007/10/03)
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- 2,3,4,5-tetrahydro-1H-[1,4]-benzodiazepine-3-hydroxyamic acids
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Compounds are provided having the following formula: wherein R, R1, R2, R3, and R4 are defined in the specification, which have matrix metalloproteinase inhibiting activity.
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- High yields of meta-substituted amination products in the S(N)Ar substitution of benzenes
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Morpholine substitution in fluorobenzenes containing a meta-substituted electron withdrawing group proceeds in DMSO at 100 °C over 60 h to give meta-substitution products (by fluoride ion displacement) in pure isolated yields of 19-98%.
- Brown,Foubister,Ratcliffe
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p. 1219 - 1222
(2007/10/03)
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- Synthesis of meta-substituted aniline derivatives by nucleophilic substitution
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Substitution by amines of fluorobenzenes containing a meta- substituted electron withdrawing group (EWG), in DMSO at 100 °C over 60 h gave meta-substituted aniline derivatives in isolated yields of up to 98%. The scope of the reaction is explored in terms of reaction conditions and substrates. It is postulated that facile meta-substitutions are facilitated through field stabilisation of the intermediate anion by EWG substituents.
- Belfield, Andrew J.,Brown, George R.,Foubister, Alan J.,Ratcliffe, Paul D.
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p. 13285 - 13300
(2007/10/03)
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- Tandem Wolff rearrangement-'tert-amino effect' sequence: Synthesis of 2-oxoindolinium enolate derivatives
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The thermolysis of 1-diazo-2-oxo-(2-N,N-disubstituted aminophenyl)ethylphosphonates 1 gave rise to 2-oxoindolinium enolate derivatives 4 through Wolff rearrangement and interaction of the tert-amino moiety with the ketene functionality. Variable amounts of either ammonium ylides 5 or of products resulting from their transformations were also formed during the course of the reaction. If the amino moiety was substituted by a benzyl or an allyl group, indolinones, resulting from [1,3] or [1,2] benzylic or allylic shifts, were isolated in place of compounds 4 and 5.
- Leost, Francoise,Chantegrel, Bernard,Deshayes, Christian
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p. 7557 - 7576
(2007/10/03)
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