| 序号 | 专利名 | 申请号 | 申请日 | 公开（公告）号 | 公开（公告）日 | 发明人 |
|---|---|---|---|---|---|---|
| 141 | Novel diamines having a casr modulating activity | US10344146 | 2001-08-07 | US20050192317A1 | 2005-09-01 | Philippe Dauban; Robert Dodd; Helene Faure; Martial Ruat; Pierre Potier; Albane Kessler |
| The invention concerns diamines of general formula (I), wherein: A represents a group A1 or A2 of general formula (II); B represents a group B1 or B2 of general formula (III); X represents a SO2, CH2, C═O or COO; YZ represents a group of formula CH(R25)—CH(R26) or CH(R27)═(R28), and R1 to R28, identical or different, represent independently of one another, a hydrogen or halogen atom or an alkyl, cycloalkyl, CN, NO2, hydroxy, aryl, aralkyl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, cycloalkylamino, arylamino, arylalkylamino, diarylamino diarylalkylamino, trihalogenoalkyl or trihalogenoalkoxy group, provided that in the group A1, at least one of the radicals R1, R2, R3, R4 or R5 represents the hydrogen atom when the other four do not represent the hydrogen atom and in the group B1, at least one of the radicals R13, R14, R15, R16 or R17 represents the hydrogen atom when the other four do not represent the hydrogen atom, and their salts with a pharmaceutically acceptable acid, in the form of racemic mixture or their optically pore isomers. The invention also concerns their preparation, pharmaceutical compositions comprising them and their use as CaSR activity modulator and as medicine particularly designed for the treatment of psychological diseases and disorders involving CaSR activity modulation. | ||||||
| 142 | Synthesis of chiral 2-alkyl amino acids | US10439313 | 2003-05-15 | US06903220B2 | 2005-06-07 | Mukund S. Chorghade; Mukund K. Gurjar; Bhanu M. Chanda |
| Non-natural amino acids such as 2-alkylated amino acids allow for the synthesis of a wider variety of peptidal and non-peptidal pharmaceutically active agents. A method of preparing a 2-alkyl amino acid involves reacting cysteine (or a salt or an ester thereof) and an aryl carboxylic acid to form a thiazoline ring, stereospecifically alkylating the thiazoline ring, and hydrolyzing the thiazoline ring to obtain a 2-alkylcysteine (or related compound). The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. In this method, an aryl nitrile or imidate is condensed with cysteine, a 2-alkyl cysteine, or a cysteine ester. | ||||||
| 143 | Synthesis of benzonitriles from substituted benzoic acid | US10439341 | 2003-05-15 | US06875882B2 | 2005-04-05 | Mukund S. Chorghade; Mukund K. Gurjar; Joseph Cherian |
| There is a significant demand for organic nitriles, based on their versatility in reactions. Compounds prepared from nitriles have properties including superoxide inhibition, ferrielectric liquid crystal dopant, antipicornaviral agents, anti-inflammatory agents, anti-asthma agents, and fibringoen antagonists. The present invention discloses a facile synthesis for 2,4-dihydroxybenzonitrile, and ethers and diethers thereof, from 2,4-dihydroxybenzoic acid. The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. In this method, 2,4-dihydroxybenzonitrile is condensed with (S)-2-methylcysteine. | ||||||
| 144 | Synthesis of 2-alkylcysteine | US10438745 | 2003-05-15 | US06861532B2 | 2005-03-01 | Mukund S. Chorghade; Mukund K. Gurjar; Bhanu M. Chanda; Joseph Cherian |
| Non-natural amino acids such as 2-alkylated amino acids allow for the synthesis of a wider variety of peptidal and non-peptidal pharmaceutically active agents. A method of preparing a 2-alkylcysteine involves condensing cysteine with an aryl nitrile to form a 2-arylthiazoline-4-carboxylic acid, followed by alkylating the 2-arylthiazoline-4-carboxylic acid at the 4-position. The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. In this method, an aryl nitrile or imidate is condensed with cysteine or a 2-alkyl cysteine. | ||||||
| 145 | Process for the preparation of enantiomerically enriched esters and alcohols | US10296840 | 2001-05-21 | US06841691B2 | 2005-01-11 | Gerardus Karel Maria Verzijl; Johannes Gerardus Vries De; Quirinus Bernardus Broxterman |
| Method for the preparation of an enantiomerically enriched ester, in which a mixture of the enantiomers of the corresponding secondary alcohol is subjected, in the presence of an acyl donor, to an enantioselective conversion in the presence of a racemisation catalyst upon which the ester is formed and an acyl donor residue is obtained, and in which the acyl donor residue is irreversibly removed from the phase in which the enantioselective conversion takes place. Preferably the enantioselective conversion is carried out enzymatically and a transfer hydrogenation catalyst is used as racemisation catalyst.The secondary alcohol can be formed in situ from the corresponding ketone, in the presence of a hydrogen donor. It is also possible to use a mixture of the secondary alcohol and the corresponding ketone as substrate.Preferably the acyl donor is chosen so that the acyl donor residue is converted in situ into another compound and/or the acyl donor residue is removed via distillation under reduced pressure.The enantiomerically enriched esters obtained can subsequently be converted into the corresponding enantiomerically enriched alcohols, which are desirable intermediate products in the preparation of liquid crystals, agro chemicals or pharmaceuticals. | ||||||
| 146 | Process for racemization of N-acetyl-(D)L-.alpha.-amino carboxylic acids | US95409 | 1998-06-10 | US06080887A | 2000-06-27 | Karlheinz Drauz; Michael Karrenbauer; Andreas Bommarius; Gunter Knaup |
| With known methods of racemizing N-acetyl-D(L)-.alpha.-amino carboxylic acids in the non-aqueous state by heating them to temperatures above room temperatures, significant quantities of by-products are formed, especially acetyl dipeptides. By converting at least a proportion of the N-acetyl-D(L)-.alpha.-amino carboxylic acids to corresponding N-acetyl-D(L)-.alpha.-amino carboxylic acid salts before or during the heating, it is possible to increase the sojourn time of the educt which is to be racemized at higher temperatures without any evident increase in the quantity of by-product formed (in particular acetylated dipeptides). Also disclosed is the production of optically active amino acids by enzymatic splitting of racemic compounds. | ||||||
| 147 | Optically active salts of 2-hydroxymethyl-3-phenylpropionic acid with cis-1-amino-2-indanol, .alpha.-methylbenzylamine, or 3-methyl-2-phenyl-1-butylamine | US166124 | 1998-10-05 | US6028217A | 2000-02-22 | Hiroyuki Nohira; Takayuki Suzuki; Takayuki Hamada; Kunisuke Izawa |
| A compound selected from the group consisting of(a) optically active 2-hydroxymethyl-3-phenylpropionic acid cis-1-amino-2-indanol salt,(b) optically active 2-hydroxymethyl-3-phenylpropionic acid .alpha.-methylbenzylamine salt,(c) optically active 2-hydroxymethyl-3-phenylpropionic acid 3-methyl-2-phenyl-1-butylamine salt,(d) a salt of (S)-2-hydroxymethyl-3-phenylpropionic acid with (1R, 2S)-(+)-cis-1-amino-2-indanol,(e) a salt of (R)-2-hydroxymethyl-3-phenylpropionic acid with (1S, 2R)-(-)-cis-1-amino-2-indanol,(f) a salt of (R)-2-hydroxymethyl-3-phenylpropionic acid with (S)-(-)-.alpha.-methylbenzylamine,(g) a salt of (S)-2-hydroxymethyl-3-phenylpropionic acid with (R)-(+)-.alpha.-methylbenzylamine,(h) a salt of (S)-2-hydroxymethyl-3-phenylpropionic acid with (S)-(-)-3-methyl-2-phenyl-1-butylamine, and(i) a salt of (R)-2-hydroxymethyl-3-phenylpropionic acid with (R)-(+)-3-methyl-2-phenyl-1-butylamine. | ||||||
| 148 | Racemization of optically active amines | US798336 | 1997-02-10 | US5847215A | 1998-12-08 | Klaus Ditrich |
| A process for the racemization of optically active amines of the formula (I), where Ar is an unsubstituted or substituted aryl and R is alkyl, in which a) (I) is reacted with the ketone (II) in which Ar and R have the same meanings as for (I), to give the condensation product (III), ##STR1## b) (III) is racemized by treatment with base, ##STR2## c) the arylalkylamine (I) is liberated as racemate from racemic (III) by reaction with optically active (I). ##STR3## | ||||||
| 149 | Racemisation process | US797524 | 1997-02-07 | US5821369A | 1998-10-13 | Raymond McCague |
| A process for the racemization of an enantiomerically-enriched compound of formula (3), comprises treatment of enantiomerically-enriched (3) with a base to obtain anion (4), optionally in protonated form, which is then combined with CH.sub.2 =CH--Y.sup.1 to form racemic (3), ##STR1## wherein Ar=aryl or heteroaryl; Ak=C.sub.1-20 alkyl; X=CN, CO.sub.2 R, CONR.sup.1 R.sup.2, and COR; Y and Y.sup.1 are independently selected from CN, CO.sub.2 R, CONR.sup.1 R.sup.2 and R, R.sub.1 and R.sub.2 are independently selected from H and C.sub.1-20 alkyl; optionally as a salt thereof. This racemization process can be used as part of an efficient synthesis of enantiomerically-enriched verapamil or aminoglutethimide. | ||||||
| 150 | Phenylserine amides and the preparation of phenylserines/phenylserine amides | US662797 | 1996-06-12 | US5773284A | 1998-06-30 | Bernardus Kaptein |
| Process for the preparation of a threo-phenylserine amide of the general formula 2 in which glycine amide is contacted with the corresponding substituted benzaldehyde of formula 3 in an excess relative to the amount of glycine amide, this taking place at a pH between 9 and 14 in the presence of a suitable solvent. The resulting phenylserine amide can subsequently be hydrolyzed to a phenylserine amide of the general formula 1, which is subsequently hydrolyzed to a phenylserine amide of the general formula 1, which is subsequently subjected to a stereoselective enzymatic hydrolysis yielding a (2S,3R) phenylserine. The non-hydrolyzed (2R,3S) phenylserine amide can be isolated as a Schiff base and be recirculated and simply racemized. The (2S,3R) phenylserine obtained can be used in the preparation of thiamphenicol or florfenicol. The threo-phenylserine amides of the general formula 1 or 2 are new intermediates in this commercially attractive process for the preparation of thiamphenicol and florfenicol. | ||||||
| 151 | Processes for preparing �L!- or �D!-homoalanin-4-yl-(methyl)phosphinic acid and salts thereof by racemate resolution | US398216 | 1995-03-02 | US5767309A | 1998-06-16 | Harald Knorr; Gunter Schlegel; Herbert Stark |
| Processes for preparing �L!- or �D!-homoalanin-4-yl-(methyl)phosphinic acid and salts thereof by racemate resolution The title compounds are obtained by racemate resolution of D,L-homoalanin-4-yl (methyl)phosphinic acid via precipitation of one of the diastereomeric salts using chiral bases such as quinine or cinchonine. It is possible to increase the yield of desired enantiomer by transformed racemate resolution when the precipitation of the diastereomeric salt takes place with the racemization of the undesired enantiomer in the presence of (hetero)aromatic aldehydes. The racemization method is also suitable for structurally different optically active amino acids. | ||||||
| 152 | Process for racemization of optically active 1-phenylethylamine derivative | US759633 | 1996-12-05 | US5723672A | 1998-03-03 | Shinichiro Nagata; Yoshimi Yamada; Koji Hagiya; Hideyuki Goto |
| A process for racemization of an optically active 1-phenylethylamine derivative represented by formula (I): ##STR1## wherein R.sup.1 represents a phenyl group substituted at least at the ortho-position, which comprises reacting the optically active 1-phenylethylamine derivative (1) with an aldehyde compound represented by formula (2): R.sup.2 --CHO (2) where R.sup.2 represents an optionally substituted alkyl group or an optionally substituted phenyl group to form an optically active imine represented by formula (3): ##STR2## reacting the imine with an alkaline metal tert-alkoxide in an aprotic solvent, and then hydrolyzing the resultant racemic imine. | ||||||
| 153 | Process for the manufacture of (4,5)-trans-oxazolidines | US739565 | 1996-10-30 | US5670653A | 1997-09-23 | Hans Hilpert |
| Compounds containing a (4,5)-cis-2-oxo-oxazolidine ring are isomerized to the corresponding (4,5)-trans-2-oxo-oxazolidine by treating the cis compound with a strong base. | ||||||
| 154 | Continuous racemization of benzylic alcohols, ethers, and esters by solid acid catalyst | US342460 | 1994-11-21 | US5476964A | 1995-12-19 | David W. House |
| Benzyl alcohols having a chiral center at the benzylic carbon can be conveniently racemized by treatment with solid acids which are strongly acidic cation exchange materials. Racemization may be effected generally in the range from 20.degree.-150.degree. C. in aqueous or partly aqueous systems in combination with a water-miscible organic solvent to improve solubility of the alcohol. Similar racemizations may be effected for benzyl ethers and esters. This process is valuable for recycling of unwanted enantiomers obtained in the resolution of racemic mixtures. | ||||||
| 155 | Optical resolution method | US974826 | 1992-11-16 | US5395962A | 1995-03-07 | Masatoshi Kawashima |
| The present invention provides three optical resolution methods. The first aspect comprises the steps of adding an optically active bifunctional resolving reagent to a bifunctional compound to form a liquid material, precipitating crystals therefrom, and treating the crystals and the liquid material separately with an acidic material, a basic material, or a basic material and an acidic material, to obtain a pair of enantiomers of an optically active bifunctional compound. The second aspect comprises an optical resolution method by which one necessary enantiomer of a pair of enantiomers in an optically active bifunctional compound is exclusively obtained. The third aspect comprises a method for racemizing one unnecessary enantiomer of a pair of enantiomers in an optically active bifunctional compound which is formed by the optical resolution method of the present invention. | ||||||
| 156 | Isomerisation process | US995861 | 1992-12-23 | US5334744A | 1994-08-02 | Ernest S. Cleugh; David J. Milner |
| A process for obtaining an isomer of a compound of general formulaR--CH(CN)--R' (I)wherein each of R and R' may be any organic radical linked directly or through a heteroatom to the carbon atom bearing the cyano group provided that at least one of R and R' comprises at least one resolved chiral center which is stable under the conditions of the process, or a racemic modification comprising the isomer and its enantiomer, which comprises the step of treating the epimer of the isomer, or the racemate comprising the epimer and the enantiomer of the epimer, in solution in a polar organic solvent, or in slurry in a polar organic liquid diluent in which the epimer or the racemate is partially soluble, with a source of cyanide ions, in the absence of a base, the isomer, or the racemic modification comprising the isomer and its enantiomer, being less soluble in the solvent or diluent than the epimer of the isomer, or the racemate comprising the epimer of the isomer and the enantiomer of the epimer, respectively. | ||||||
| 157 | Process and intermediates for chiral epoxides | US12109 | 1993-02-01 | US5296615A | 1994-03-22 | Leland O. Weigel |
| Chiral epoxybutyrates are prepared in high yield from novel dihydro-3R-substituted sulfonyloxy-4R-hydroxy-2-(3H)furanones via based catalyzed alcoholysis. The product chiral epoxy butyrates are useful intermediates for the synthesis of 1-carba-1-dethia cephem antibiotics. | ||||||
| 158 | L-buthionine-S-sulfoximine and methods of making | US56464 | 1993-05-05 | US5294736A | 1994-03-15 | Owen W. Griffith |
| The pure isomers L-buthionine-S-sulfoximine and L-buthionine-R-sulfoximine are provided. The L-S-isomer has utility, for example, in causing the depletion of glutathione, a major protectant molecule in tumors and certain parasites. The L-R-isomer has utility as a compound decreasing further uptake and thus effect of the L-S-isomer and for causing glutathione depletion specific to the kidney. The isolation of pure isomers from L-buthionine-SR-sulfoximine enables treatment at lower dosages without cross effects.The pure L-buthionine-S-sulfoximine isomer is obtained from L-buthionine-SR-sulfoximine by recrystallization preferably by forming a solution of L-buthionine-SR-sulfoximine in water at a concentration of 0.8 M and cooling to form crystals enriched in the L-R-isomer and a filtrate enriched in L-S-isomer, drying the filtrate to obtain a solid, dissolving the solid in ethanol, adding trifluoroacetic acid to form acid salt and provide solvent, then adding hexane to cause crystal formation, then converting the crystals to the free zwitterion using ion exchange resin.Both isomers can be separated concurrently by reverse phase chromotography in Cu.sup.++ /D-proline buffers. | ||||||
| 159 | Process for preparation of enantiomerically pure polysubstituted 1,4-dihydropyridines | US743415 | 1991-08-14 | US5245039A | 1993-09-14 | Carmelo A. Gandolfi; Marco Frigerio; Carlo Riva; Andrea Zaliani; Giorgio Long; Roberto D. Domenico |
| A process for the optical resolution of racemic 1,4-dihydropyridines, containing isothioureido groups. Salification of racemic isothioureas with optically active acids produces diasteroisomeric mixtures of isothiouronium salts, that, using conventional techniques, are separated in the individual components to give optically pure isothioureides of 1,4-dihydropyridines and salts thereof with conventional acids. Said optically pure 1,4-dihydropyridines can then be subjected to desulphuration and to different transformations to give to other enantiomerically pure and therapeutically useful 1,4-dihydropyridines. | ||||||
| 160 | Racemization process for an optically active carboxylic acid or ester thereof | US825150 | 1992-01-24 | US5221765A | 1993-06-22 | Deepak R. Patil; Azfar A. Choudhury; Abbas Kadkhodayan |
| A method for racemizing an optically active carboxylic acid, or ester thereof, of the formula: ##STR1## where R.sub.1 is hydrogen or C.sub.1 to C.sub.6 linear or branched alkyl; R.sub.2, R.sub.3 and R.sub.4 are different and are hydrogen or C.sub.1 to C.sub.6 linear or branched alkyl, C.sub.1 to C.sub.6 linear or branched haloalkyl, aralkyl, cycloalkyl, alkyl substituted cycloalkyl, C.sub.6 to C.sub.10 aryl, C.sub.1 to C.sub.6 linear or branched alkoxy, C.sub.6 to C.sub.10 aryloxy, C.sub.1 to C.sub.6 alkylthio, C.sub.2 to C.sub.8 cycloalkylthio, C.sub.6 to C.sub.10 arylthio, C.sub.6 to C.sub.10 arylcarbonyl, C.sub.4 to C.sub.8 cycloalkenyl, trifluoromethyl, halo, C.sub.4 to C.sub.5 heteroaryl, C.sub.10 to C.sub.14 aryl, or biphenyl unsubstituted or substituted with methyl or halo, comprising heating said optically active carboxylic acid or ester thereof in the presence of water at a temperature of from about 75.degree. C. to about 200.degree. C. in the presence of a catalytically effective amount of an aliphatic, aromatic or mixed aliphatic and aromatic tertiary amine for a time sufficient to racemize said carboxylic acid or ester thereof. | ||||||
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