- A method for synthesizing pulls the handkerchief for the Nepali side chain
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The invention discloses a synthetic method of lapatinib side chain, belongs to the field of synthesis of medicines and solves problems that synthesis of the lapatinib side chain in the prior art is expensive in raw materials and long in a synthetic line so that a large-scale production of the lapatinib side chain is high in difficulty. The method particularly includes following steps: carrying out a reaction between methylsulfonyl ethanol and methylsulfonyl chloride or methylsulfonyl ethanol and 4-toluene sulfonyl chloride to generate a compound methanesulfonate methylsulfonyl ethyl ester, and enabling the methanesulfonate methylsulfonyl ethyl ester to react with ammonia to obtain the lapatinib side chain. The synthetic method is low in cost of raw materials, is short in synthesis line and is easy to carry out in large-scale production.
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Paragraph 0017; 0018
(2017/04/08)
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- Design, synthesis and biological evaluation of novel pyrimidine, 3-cyanopyridine and m-amino-N-phenylbenzamide based monocyclic EGFR tyrosine kinase inhibitors
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36 new compounds with the typical skeleton of 4-anilino-5-vinyl/ethynyl pyrimidine, 4-anilino-3-cyano-5-vinyl/ethynyl/phenyl pyridine, and m-amino-N-phenylbenzamide, are designed, synthesized and selectively tested on EGFR, ErbB-2 kinases, and A-549, HL60 cells growth inhibition. Results from the bioactivity and chemical structures yield preliminary structure-activity relationships (SARs). The most potent 5-ethynylpyrimidine derivative 20a has an IC50 value of 45 nM to EGFR kinase. Several compounds of other series also show IC50 values 1 μM for EGFR and 5 μM for A-549 and HL60 cells growth inhibition.
- Mao, Yongjun,Zhu, Wenxiu,Kong, Xiaoguang,Wang, Zhen,Xie, Hua,Ding, Jian,Terrett, Nicholas Kenneth,Shen, Jingkang
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p. 3090 - 3104
(2013/07/11)
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- SUBSTITUTED 6,5-FUSED BICYCLIC HETEROARYL COMPOUNDS
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The present invention relates to substituted 6,5 -fused bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof.
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Page/Page column 324
(2012/09/21)
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- THE NEW PREPARATION OF ALIPHATIC AMINES WITH SULPHONYL GROUP AND THEIR SALTS
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The present invention relates to a novel preparation method of sulfonyl alkylamine and salts thereof. The method of present invention comprises steps of: adopting sulfonates containing a sulfone moiety as starring material and ammonia oz amine as substituting agent which reacts with the starting material to prepare for the products. Furthermore, the present invention provides a new intermediate 2-(N,N- dibenzylamino) ethyl methyl sulfone and salts thereof obtained from the above novel preparation method and their use. In addition, the present invention also provides a novel salt of 2-(anuno) ethyl methyl sulfone prepared using 2-(amine) ethyl methyl sulfone hydrochloride and the use of novel salt. The present invention is not only advantageous for reducing environmental pollution, but also could be used for mass fabrication of 2-(amino) ethyl methyl sulfone and the salts thereof, in addition, the present invention is advantageous for preparing for the highly purified 2-(amine) ethyl methyl sulfone hydrochloride.
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Page/Page column 7
(2011/04/25)
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- PHARMACEUTICAL USE OF SUBSTITUTED AMIDES
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The use of substituted amides for modulating the activity of 11-hydroxysteroid dehydrogenase type 1 (11HSD1) and the use of these compounds as pharmaceutical compositions, are described. Also a novel class of substituted amides, their use in therapy, pharmaceutical compositions comprising the compounds, as well as their use in the manufacture of medicaments are described. The present compounds are modulators and more specifically inhibitors of the activity of 11HSD1 and may be useful in the treatment, prevention and/or prophylaxis of a range of medical disorders where a decreased intracellular concentration of active glucocorticoid is desirable.
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Page/Page column 40
(2009/05/28)
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- Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series
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Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Changes made to the 6-furanyl group had little impact on the enzyme activity, but appeared to dramatically affect the cellular efficacy. The discovery of lapatinib emerged from this work.
- Petrov, Kimberly G.,Zhang, Yue-Mei,Carter, Malcolm,Cockerill, G. Stuart,Dickerson, Scott,Gauthier, Cassandra A.,Guo, Yu,Mook Jr., Robert A.,Rusnak, David W.,Walker, Ann L.,Wood, Edgar R.,Lackey, Karen E.
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p. 4686 - 4691
(2007/10/03)
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- Synthesis and SAR of potent EGFR/erbB2 dual inhibitors
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A series of 6-alkoxy-4-anilinoquinazoline compounds was prepared and evaluated for in vitro inhibition of the erbB2 and EGFR kinase activity. The IC50 values of the best compounds were below 0.10 uM. Further, several of these compounds inhibit the growth of erbB2 and EGFR over-expressing tumor cell lines at concentrations below 1 uM.
- Zhang, Yue-Mei,Cockerill, Stuart,Guntrip, Stephen B.,Rusnak, David,Smith, Kathryn,Vanderwall, Dana,Wood, Edgar,Lackey, Karen
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p. 111 - 114
(2007/10/03)
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- Imidazo-substituted compounds as p38 kinase inhibitors
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The present invention discloses compounds corresponding to formula I: wherein A, Z, Z1, Y, R1 and R2 are as defined in the specification, as well as pharmaceutical formulations, methods of making and uses thereof.
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- Process for the reduction of cyano-substituted sulfones to aminoalkylene-substituted sulfones
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Disclosed is a process for selectively reducing a nitrile containing organic compound that also contains a sulfone moiety, the nitrile being reduced to a primary amine.
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- N-Substituted aziridine-2-carboxylic acid derivatives for immuno stimulation
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Aziridine-2-carboxylic acid derivatives of the formula STR1 wherein X is a carboxyl, nitrile, alkoxycarbonyl or carbamoyl group, and R and R1 are various organic radicals, or pharmacologically acceptable salts thereof, exhibit marked immunostimulant activity, especially in conjunction with added chemotherapeutic agents such as a penicillin, a cephalosporin, a nitrofuran or chloramphenicol. Those compounds are new where X is a cyano group or an alkoxycarbonyl radical and R1 is a hydrogen atom, but R' is not an unsubstituted alkyl radical or an alkyl radical substituted by hydroxyl, alkoxy, dialkylamino, phenyl, 4-chlorophenyl or 4-methoxyphenyl or a vinyl radical substituted by a phenyl or methyl radical, or a cycloalkyl radical, a phenyl a 4-chlorophenyl, a 4-methoxyphenyl, an s-triazinyl or a pyridinyl radical; or where X is a carbamoyl group and R1 is a hydrogen atom, R' is not an unsubstituted cyclohexyl, alkyl or benzyl radical; or where X is a cyano group or an alkoxycarbonyl radical and R1 is a phenyl radical, R' is not an isopropyl, cyclohexyl, phenyl, benzyl or p-chlorobenzyl radical; or where R1 is a methyl radical, R1 is not a benzyl, p-chloro- or p- methoxybenzyl radical.
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