- Method for preparing clopidogrel intermediate alpha-bromo (2-chloro) methyl phenylacetate by recycling aqueous solution method
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The invention provides a method for preparing clopidogrel intermediate alpha-bromo (2-chloro) methyl phenylacetate by recycling an aqueous solution method. According to the method, o-chlorophenylacetic acid is adopted as a main raw material, an organic solvent and water in an appropriate proportion are optimized to serve as a bromination mixed solvent, a two-phase reaction mode is adopted in the reaction process, a bromine-containing wastewater solution can be reused without complex treatment, a target product is prepared through bromination and esterification reactions, and the yield reaches78% or above; the method provided by the invention is based on a technical scheme of recycling an aqueous solution containing a bromination reagent. In the process production process, the input amountof a new bromination reagent is reduced to a great extent, the bromine atom utilization rate of the bromination reagent is increased, the problems of wastewater treatment and discharge are reduced, the pressure of environmental pollution is reduced, meanwhile, the reaction conditions are relatively mild, treatment is simple, and industrial production is facilitated.
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Paragraph 0021-0028
(2020/08/22)
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- New 4-aryl-1,3,2-oxathiazolylium-5-olates: Chemical synthesis and photochemical stability of a novel series of S-nitrosothiols
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S-nitrosothiols (RSNOs) remain one of the most popular classes of NO-donating compounds due to their ability to release nitric oxide (NO) under non-enzymatic means whilst producing an inert disulphide by-product. However, alligning these compounds to the different biological fields of NO research has proved to be problematic due to the inherent instability of such compounds under a variety of conditions including heat, light and the presence of copper ions. 1,3,2-Oxathiazolylium-5-olates (OZOs) represent an interesting subclass of S-nitrosothiols that lock the –SNO moiety into a five membered heterocyclic ring in an attempt to improve the compound's overall stability. The synthesis of a novel series of halogen-containing OZOs was comprehensively studied resulting in a seven-step route and overall yields ranging between 21 and 37%. The photochemical stability of these compounds was assessed to determine if S-nitrosothiols locked within these mesoionic ring systems can offer greater stability and thereby release NO in a more controllable fashion than their non-cyclic counterparts.
- Eilertsen, Monica,Allin, Steve M.,Pearson, Russell J.
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p. 1106 - 1110
(2018/02/28)
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- COMPOUNDS FOR OPTICALLY ACTIVE DEVICES
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The present invention relates to novel compounds, particularly to compounds comprising a photoactive unit, said novel compounds being particularly suitable for compositions and ophthalmic devices as well as tocompositions and ophthalmic devices comprising such compounds.
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Paragraph 93-94
(2018/09/12)
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- HYDROPHILIC COMPOUNDS FOR OPTICALLY ACTIVE DEVICES
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The present invention relates to novel compounds, particularly to compounds comprising a photoactive unit, said novel compounds being particularly suitable for compositions and ophthalmic devices as well as to compositions and ophthalmic devices comprising such compounds.
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Page/Page column 96
(2018/09/21)
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- Synthesis and Antibacterial Screening of 1,3,4-Thiadiazoles, 1,2,4-Triazoles, and 1,3,4-Oxadiazoles Containing Piperazine Nucleus
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A series of novel 1,3,4-thiadiazoles, 1,2,4-triazoles, and 1,3,4-oxadiazoles were synthesized by cyclization of substituted 1-(2-(2-chlorophenyl)-2-(4-(2,3-dichlorophenyl)piperazin-1-yl)acetyl)thiosemicarbazide. The structures of all newly synthesized compounds were elucidated on the basis of spectral studies. Some of them were screened for their antibacterial activity. The compounds 6b, 6c, 8e, 9a, and 9b have shown moderate activity towards Bacillus Subtilis and Escherichia Coli.
- Deshmukh, Rajendra,Karale, Bhausaheb,Akolkar, Hemantkumar,Randhavane, Pratibha
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p. 1355 - 1360
(2017/03/27)
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- Synthesis method of clopidogrel hydrogen sulfate
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The invention discloses a synthesis method of clopidogrel hydrogen sulfate. The synthesis method takes o-phenylphthalic chloroacetic acid and 4,5,6,7tetrahydrothiophene[3,2-c] as raw materials and comprises the following steps: (1) carrying out acylation reaction; (2) carrying out bromination reaction; (3) carrying out esterification reaction; (4) preparing a clopidogrel base crude product; (5) extracting clopidogrel base; (5) carrying out racemic racemate reductionresolution; (7) preparing the clopidogrel hydrogen sulfate. According to the synthesis method of the clopidogrel hydrogen sulfate, disclosed by the invention, reasonable raw material selection and process route design are carried out, so that on one hand, a process flow is simplified and synthesis operation is easy to realize; on the other hand, reaction conditions are reduced, the reaction conditions are moderate and the method is easily smoothly carried out; the obtained finished product clopidogrel hydrogen sulfate has high yield and good quality; industrial production is easy to realize and a market prospect is wide.
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- Synthesis of Quinolines by Visible-Light Induced Radical Reaction of Vinyl Azides and α-Carbonyl Benzyl Bromides
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A visible-light induced radical reaction of vinyl azides and α-carbonyl benzyl bromides was developed, which provides an efficient route to polysubstituted quinolines via a C-C and C-N bond formation sequence.
- Wang, Qile,Huang, Jun,Zhou, Lei
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p. 2479 - 2484
(2015/08/18)
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- Synthesis and characterization of impurity B of S-(+)-clopidogrel bisulfate: An antiplatelet
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S-(+)-Clopidogrel bisulfate [(S-(+)-methyl 2-(2-chlorophenyl)-2-(6, 7-dihydrothieno[3, 2-c]pyridin-5(4H)-yl)acetate bisulfate)] is a platelet aggregation inhibitor drug. S-(+)-Clopidogrel bisulfate is prepared by different synthetic approaches in the literature. In almost all the approaches the major impurities known in the literature (A, B, and C) are also listed in the U.S. pharmacopoeia. The control of these pharmaceutical impurities is currently a critical issue to the pharmaceutical industry. In this article, a description of these impurities and their origins in the S-(+)-clopidogrel bisulfate process are presented along with the preparation of impurity B.
- Reddy, K. Tatendra,Kumar, K. Suneel,Omprakash,Dubey
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p. 1387 - 1396
(2013/05/22)
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- Regio- and chemoselective C-H chlorination/bromination of electron-deficient arenes by weak coordination and study of relative directing-group abilities
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It's all relative: A practical and efficient PdII-catalyzed regio- and chemoselective chlorination/bromination has been developed for the facile synthesis of a broad range of aromatic chlorides. The reaction demonstrates excellent reactivity, good functional-group tolerance, and high yields. A preliminary study was conducted to evaluate relative directing-group abilities of various functionalities. Copyright
- Sun, Xiuyun,Shan, Gang,Sun, Yonghui,Rao, Yu
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p. 4440 - 4444
(2013/05/22)
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- COMPOUNDS, COMPOSITIONS AND METHODS USEFUL FOR CHOLESTEROL MOBILISATION
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The invention relates to classes of pharmaceutically-active heterocyclic compounds and pharmaceutically acceptable salts, and hydrates thereof, and compositions comprising the same. The invention also relates to methods for treating or preventing a disease or disorder, which comprises administering a therapeutically or prophylactically effective amount a compound described herein.
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Page/Page column 180
(2012/05/05)
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- Processes for the preparation of clopidogrel
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The invention relates to processes for the preparation of clopidogrel and salts thereof. The inventors have developed a process for preparing racemic clopidogrel by racemizing R(?) clopidogrel. The process includes the step of reacting R(?) clopidogrel with a powered anhydrous base in one or more solvents.
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Page/Page column 2
(2010/06/14)
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- PROCESS FOR THE PREPARATION OF CLOPIDOGREL BISULPHATE FORM I
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The invention relates to a process for the preparation of crystalline form-I of S- (+)-clopidogrel bisulphate.
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Page/Page column 10
(2009/07/25)
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- PROCESSES FOR THE PREPARATION OF CLOPIDOGREL HYDROCHLORIDE
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The invention relates to processes for the preparation of pure clopidogrel hydrochloride. More particularly, it relates to the preparation of clopidogrel hydrochloride having reduced methyl chloride content. The invention also relates to pharmaceutical compositions that include the pure clopidogrel hydrochloride.
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Page/Page column 5
(2008/12/06)
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- PROCESSES FOR THE PREPARATION OF CLOPIDOGREL
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The invention relates to processes for the preparation of clopidogrel and salts thereof. The inventors have developed a process for preparing racemic clopidogrel by racemizing R(-) clopidogrel. The process includes the step of reacting R(-) clopidogrel with a powered anhydrous base in one or more solvents.
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Page/Page column 5
(2009/01/20)
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- THE METHOD OF MAKING OPTICALLY ACTIVE 2-HALO-2-(N-SUBSTITUTED PHENYL)ACETIC ACID ESTERS AND 2-HALO-2-(N-SUBSTITUTED PHENYL)ACETIC ACIDS BY ENZYMATIC METHOD
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The present invention relates to the process for the preparation of optically active 2-halo-2-(n-substituted phenyl)acetic acid esters and optically active 2-halo-2-(n-substituted phenyl)acetic acids, which are used intensively as important chiral intermediates, represented by general formula 2 and 3 respectively from racemic 2-halo-2-(n-substituted phenyl)acetic acid ester represented by general formula 1. In more detail, this invention relates to the process for preparing optically active 2-halo-2-(n-substituted phenyl)acetic acid esters and optically active 2-halo-2-(n-substituted phenyl)acetic acids by stereospecific hydrolysis of racemic 2-halo-2-(n-substituted phenyl)acetic acid esters using hydrolases or hydrolase-producing microorganisms in the aqueous phase or organic phase including aqueous solvent. This method is useful in the practical process because the production and separation of compounds with high optical purity is easier.
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- Substituted phenyl compounds with a substituent having a thienyl ring
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This invention is directed to compounds of formula I wherein R1 is CN, CH2CN, CH=CHCN, CHO, or CH=CHCO2H; R2 is aryl lower alkoxy, heteroaryl lower alkoxy, aryl lower alkylthio or heteroaryl lower alkylthio wherein each of the aryl and heteroaryl moieties is optionally substituted; R3 is halogen; R4 is optionally substituted aryl or optionally substituted heteroaryl; R5 is carboxy or an acid isostere; X is oxygen or sulphur; and n is zero or 1; or an N-oxide thereof, prodrug thereof solvate thereof, or pharmaceutically acceptable salt thereof, which compounds have endothelin antagonist activity. The invention is also directed to methods for preparing the compounds of formula I and their pharmaceutical use.
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- Selective ET(A) antagonists. 5. Discovery and structure-activity relationships of phenoxyphenylacetic acid derivatives
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The fifth paper in this series describes the culmination of our investigations into the development of a potent and selective ETA receptor antagonist for the treatment of diseases mediated by ET-1. Receptor site mapping of several ETA antagonists prepared previously identified a common cationic binding site which prompted synthesis of phenoxyphenylacetic acid derivative 13a, which showed good in vitro activity (IC50 59 nM, rat aortic ET(A)). Optimization of 13a led to the identification of 27b, which exhibited an IC50 of 4 nM. Although this did not translate into the expected in vivo potency, a compound of comparable in vitro activity, 27a (RPR118031A), showed a far better pharmacokinetic profile and in vivo potency (75 μmol/kg) and was duly proposed and accepted as a development candidate.
- Astles, Peter C.,Brown, Thomas J.,Halley, Frank,Handscombe, Caroline M.,Harris, Neil V.,Majid, Tahir N.,McCarthy, Clive,McLay, Lain M.,Morley, Andrew,Porter, Barry,Roach, Alan G.,Sargent, Carol,Smith, Christopher,Walsh, Roger J. A.
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p. 900 - 910
(2007/10/03)
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- SUBSTITUTED PHENYL COMPOUNDS WITH A SUBSTITUENT HAVING A 1,3-BENZODIOXOLE RING
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This invention is directed to compounds of formula I STR1 wherein R 1 is CN, CH 2 CN, CH=CHCN, CHO, or CH=CHCO. sub. 2 H;R 2 is aryl lower alkoxy, heteroaryl lower alkoxy, aryl lower alkylthio or heteroaryl lower alkylthio wherein each of the aryl and heteroaryl moieties is optionally substituted;R 3 is halogen;R 4 is optionally substituted aryl or optionally substituted heteroaryl;R. sup.5 is carboxy or an acid isostere; X is oxygen or sulphur; and n is zero or 1; or an N-oxide thereof, prodrug thereof solvate thereof, or pharmaceutically acceptable salt thereof, which compounds have endothelin antagonist activity. The invention is also directed to methods for preparing the compounds of formula I and their pharmaceutical use.
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- 2-silyloxy-tetrahydrothienopyridine, salt thereof and process for preparing the same
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A 2-silyloxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine represented by the formula (I): STR1 wherein R 1, R 2 and R 3 each independently represent an alkyl group having 1 to 10 carbon atoms or an aryl group,and a salt thereof and a process for preparing the same, and a 5-alkyl-2-silyloxy-4,5,6,7-tetrahydrothieno[3,2-c]-pyridine represented by the formula (IV): STR2 wherein R 1, R 2 and R 3 represent the same meanings as described above; R 4 represents a hydrogen atom, an alkoxycarbonyl group having 2 to 10 carbon atoms, an acyl group having 2 to 10 carbon atoms or a cyclo-alkylcarbonyl group having 4 to 10 carbon atoms; andR 5 represents a halogen atom, an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms,which is useful as a synthetic intermediate of an antiplatelet medicine and an elastase inhibitor, etc., and a process for preparing the same.
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- Imidazole angiotensin II antagonists incorporating a substituted benzyl element
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Substituted imidazoles attached through a methylene bridge to novel substituted phenyl derivatives of the Formula I, are useful as angiotensin II antagonists. STR1
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- QUINOLINE ANGIOTENSIN II ANTAGONISTS INCORPORATING A SUBSTITUTED BENZYL ELEMENT
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Substituted quinolines and azaquinolines (1,5-naphthridines) attached through an oxymethylene bridge to novel substituted phenyl derivatives of the Formula I, are useful as angiotensin II antagonists. STR1
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- TRIAZOLE ANGIOTENSIN II ANTAGONISTS INCORPORATING A SUBSTITUTED BENZYL ELEMENT
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Substituted triazoles attached through a methylene bridge to novel substituted phenyl derivatives of the Formula I, are useful as angiotensin II antagonists. STR1
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- ANGIOTENSIN II ANTAGONISTS INCORPORATING A SUBSTITUTED PYRIDOIMIDAZOLYL RING
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Substituted heterocycles attached through a methylene bridge to novel substituted phenyl derivatives of the Formula I are useful as angiotensin II antagonists. STR1
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- QUINAZOLINONE, TRIAZOLINONE AND PYRIMIDINONE ANGIOTENSIN II ANTAGONISTS INCORPORATING A SUBSTITUTED BENZYL ELEMENT
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Substituted heterocycles attached through a methylene bridge to novel substituted phenyl derivatives of the Formula I are useful as angiotensin II antagonists. STR1
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- Method of treating depression using azabicyclohexanes
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The present invention concerns certain novel substituted 3-azabicyclo[3.1.0]hexanes and a method of treating depression and stress in a warm-blooded animal, comprising the administration of substituted 3-azabicyclo[3.1.0]hexanes.
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- Azabicyclohexanes
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Substituted 3-azabicyclo[3.1.0]hexanes, acid addition salts, method of use and method of preparation are described. The compounds have anxiolytic and analgesic activity.
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