- Preparation method of glimepiride impurity
-
The invention belongs to the technical field of medicinal chemistry and particularly relates to a preparation method of a glimepiride impurity. The preparation method comprises the following steps: dropwise adding acetic anhydride into a solution of 2-phenethylamine and an organic solvent with a low boiling point to be subjected to reaction to generate N-acetyl phenethylamine; dropwise adding chlorosulfonic acid into the N-acetyl phenethylamine at the temperature of lower than 20 DEG C to be subjected to chlorosulfonation reaction, and performing hydrolysis after the reaction is completed to remove excess chlorosulfonic acid; performing filtration and washing to obtain an impurity J benzenesulfonyl chloride; performing ammonolysis on the impurity J benzenesulfonyl chloride to obtain an impurity J benzene sulfonamide; in acetone, enabling the impurity J benzene sulfonamide to firstly react with a catalyst and then react with trans-p-methylcyclohexyl isocyanate to obtain an impurity J acetyl substance; enabling the impurity J acetyl substance and ethanol to be subjected to alcoholysis under the condition of the catalyst to generate an impurity J and ethyl acetate; and performing refining to obtain a high-purity impurity J. The purity of the glimepiride impurity J prepared by the method is high, the liquid phase content of the glimepiride impurity J is greater than 98.5%, the rawmaterials used in the method are easily available, the process parameters are controllable, and the reaction is mild.
- -
-
Paragraph 0037; 0040-0041; 0048; 0051-0052; 0059; 0062-0063
(2020/04/02)
-
- Design and synthesis of sulfonamidophenylethylureas as novel cardiac myosin activator
-
To optimize the lead urea scaffold 1 and 2 as selective cardiac myosin ATPase activator, a series of urea derivatives have been synthesized to explore its structure activity relationship. Among them N,N-dimethyl-4-(2-(3-(3-phenylpropyl)ureido)ethyl)benzenesulfonamide (13, CMA = 91.6%, FS = 17.62%; EF = 11.55%), N,N-dimethyl-4-(2-(1-methyl-3-(3-phenylpropyl)ureido)ethyl)benzene sulfonamide (40, CMA = 52.3%, FS = 38.96%; EF = 24.19%) and N,N-dimethyl-4-(2-(3-methyl-3-(3-phenylpropyl)ureido)ethyl)benzenesulfonamide (41, CMA = 47.6%, FS = 23.19%; EF = 15.47%) proved to be efficient to activate the cardiac myosin in vitro and in vivo. Further the % change in ventricular cell contractility at 5 μM of 13 (47.9 ± 3.2), 40 (45.5 ± 2.4) and 41 (63.5 ± 2.2) showed positive inotropic effect in isolated rat ventricular myocytes. The potent compounds 13, 40, 41 were highly selective for cardiac myosin over skeletal and smooth muscle myosin, thus proving them these new urea derivatives is a novel scaffold for discovery of cardiac myosin activators for the treatment of systolic heart failure.
- Manickam, Manoj,Jalani, Hitesh B.,Pillaiyar, Thanigaimalai,Boggu, Pulla Reddy,Sharma, Niti,Venkateswararao, Eeda,Lee, You-Jung,Jeon, Eun-Seok,Son, Min-Jeong,Woo, Sun-Hee,Jung, Sang-Hun
-
p. 1869 - 1887
(2017/12/28)
-
- Synthesis process of glibenclamide intermediate 4-Acetamidobenzenesulfonamide
-
The invention aims at providing a synthesis process of glibenclamide intermediate 4-Acetamidobenzenesulfonamide. The synthesis process is characterized by comprising the following steps that 1, a crude acetyl phenethylamine acyl compound product is prepared, namely phenethylamine and acetic anhydride perform acylation reaction; 2, acetylamino-benzenesulfonyl chloride is prepared, namely an acetyl phenethylamine acyl compound and chlorosulfonic acid perform chlorosulfonation reaction; 3, the 4-Acetamidobenzenesulfonamide is prepared, namely the acetylamino-benzenesulfonyl chloride and ammonia water perform reaction; The synthesis process has the advantages that by changing the proportion of reactants and reaction conditions, the yield of the glibenclamide intermediate 4-Acetamidobenzenesulfonamide is improved, and further the glyburide yield is improved.
- -
-
Paragraph 0032; 0037; 0038
(2016/11/07)
-
- Compounds with cardiac myosin activating function and pharmaceutical composition containing the same for treating or preventing heart failure
-
The present invention relates to a compound having a cardiotonic activating function and a pharmaceutical composition containing the same. The composition comprising the compound according to the present invention is effective in preventing or treating heart failure. In addition, the compound is represented by chemical formula 2 or is pharmaceutically acceptable salt thereof.COPYRIGHT KIPO 2016
- -
-
Paragraph 0875-0878
(2017/02/02)
-
- SUBSTITUTED DIAMINOPYRIMIDYL COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
-
Provided herein are diaminopyrimidyl Compounds having the following structures: wherein X, L, R1, and R2 are as defined herein, compositions comprising an effective amount of a Diaminopyrimidyl Compound, and methods for treating or preventing PKC-theta-mediated disorders, or a condition treatable or preventable by inhibition of a kinase, for example, PKC-theta.
- -
-
Paragraph 0373
(2015/07/02)
-
- Compounds with cardiac myosin activating function and pharmaceutical composition containing the same for treating or preventing heart failure
-
Disclosed are a compound having cardiotonic activity and a pharmaceutical composition containing the same, and the composition containing the compound, according to the present invention, is useful for preventing and treating heart failure.COPYRIGHT KIPO 2016
- -
-
Paragraph 0876-0878
(2016/10/07)
-
- Synthesis and biological evaluation of sulfonylurea and thiourea derivatives substituted with benzenesulfonamide groups as potential hypoglycemic agents
-
A novel class of sulfonylurea and thiourea derivatives substituted with benzenesulfonamide groups were designed and synthesized. The target compounds were assayed for the effects on the insulin release of isolated rat pancreatic islets and the glucose transport in adipocytes of rats. Some of them exhibited high potency. Compound 10 also had potent antiplatelet activity and showed an excellent property to protect collagen-epinephrine-induced mice mortality as well as plasma glucose-lowering activity in vivo. The preliminary pharmacological profile of compound 10 showed that it might be useful in the treatment of diabetics with cardiovascular and nephropathy complications.
- Zhang, Hui-bin,Zhang, Ya-an,Wu, Guan-zhong,Zhou, Jin-pei,Huang, Wen-long,Hu, Xiao-wen
-
scheme or table
p. 1740 - 1744
(2009/12/03)
-
- Structural analysis of charge discrimination in the binding of inhibitors to human carbonic anhydrases I and II
-
Despite the similarity in the active site pockets of carbonic anhydrase (CA) isozymes I and II, the binding affinities of benzenesulfonamide inhibitors are invariably higher with CA II as compared to CA I. To explore the structural basis of this molecular recognition phenomenon, we have designed and synthesized simple benzenesulfonamide inhibitors substituted at the para position with positively charged, negatively charged, and neutral functional groups, and we have determined the affinities and X-ray crystal structures of their enzyme complexes. The para-substituents are designed-to bind in the midsection of the 15 A deep active site cleft, where interactions with enzyme residues and solvent molecules are possible. We find that a para-substituted positively charged amino group is more poorly tolerated in the active site of CA I compared with CA II. In contrast, a para-substituted negatively charged carboxylate substituent is tolerated equally well in the active sites of both CA isozymes. Notably, enzyme-inhibitor affinity increases upon neutralization of inhibitor charged groups by amidation or esterification. These results inform the design of short molecular linkers connecting the benzenesulfonamide group and a para-substituted tail group in "two-prong" CA inhibitors: an optimal linker segment will be electronically neutral, yet capable of engaging in at least some hydrogen bond interactions with protein residues and/or solvent. Microcalorimetric data reveal that inhibitor binding to CA I is enthalpically less favorable and entropically more favorable than inhibitor binding to CA II. This contrasting behavior may arise in part from differences in active site desolvation and the conformational entropy of inhibitor binding to each isozyme active site.
- Srivastava,Jude, Kevin M.,Banerjee, Abir L.,Haldar, Manas,Manokaran, Sumathra,Kooren, Joel,Mallik, Sanku,Christianson, David W.
-
p. 5528 - 5537
(2008/02/04)
-
