公开(公告)号：EP1282594A1

公开(公告)日：2003-02-12

申请号：EP01931851.8

申请日：2001-05-16

申请人： Medivir UK Ltd

发明人： JACKSON, Richard, Francis, William ,  GRABOWSKA, Urszula

IPC分类号： C07C229/08 ,  C07C229/30 ,  C07C271/22

CPC分类号： C07C271/22 ,  C07B2200/07 ,  C07C227/16 ,  C07C229/08 ,  C07C229/30 ,  C07C2603/18

摘要： The invention relates to novel branched amino acids and novel methods for their production. The amino acids are useful in the preparation of non-natural peptides and peptidomimetics, by efficient synthesis methodology allowing good enantiomeric specificity at the alpha carbon. Typically the stereochemistry at the alpha carbon is at least 85 %, preferably at least 95 %, such as in excess of 99 % enantiomerically pure. L-stereochemistry at this location is convenient as most biological interactions will favour this configuration, but the invention also extends to enantiomerically enriched and preferably at least 85 %, preferably at least 95 % such as at least 99 % enantiomerically pure D stereoconfiguration. Compounds of the invention will find utility in the preparation of non-natural peptides and peptidomimetics, such as those used in the exploration of receptor specificity and activity or in peptidomimetic inhibitors of enzyme function. The compounds of the invention are built into such peptides/peptidomimetics using standard peptide chemistry.

摘要翻译： 本发明涉及新型支链氨基酸及其生产方法。 氨基酸可用于制备非天然肽和肽模拟物，通过有效的合成方法，可在α碳上具有良好的对映体特异性。 通常，α碳的立体化学为至少85％，优选至少95％，例如超过99％对映体纯度。 在这个位置的L-立体化学是方便的，因为大多数生物相互作用将有利于这种构型，但是本发明还延伸到对映异构体富集，优选至少85％，优选至少95％，例如至少99％的对映体纯D立体构型。 本发明的化合物可用于制备非天然肽和肽模拟物，例如用于探索受体特异性和活性的那些，或用于酶功能的肽模拟抑制剂。 使用标准肽化学法将本发明的化合物构建成这些肽/肽模拟物。

公开(公告)号：EP1237846A1

公开(公告)日：2002-09-11

申请号：EP00984267.5

申请日：2000-12-13

申请人： EASTMAN CHEMICAL COMPANY

发明人： BAYSTON, Daniel John ,  FALQUE, Virginie ,  SCOTT, Ronal, Michael

IPC分类号： C07C227/04 ,  C07C229/08 ,  C07B57/00

CPC分类号： C07C229/28 ,  C07B2200/07 ,  C07C2601/02

摘要： Disclosed is a process for preparing substantially enantiomerically pure 3-amino-3-cyclopropylpropanoate esters, i.e., esters of 3-amino-3-cyclopropylpropanoic acid (3-cyclopropylalanine esters or 3-CPA esters) by a 5-step process wherein cyclopropanecarboxaldehyde (CPCA) is reacted with malonic acid and a source of ammonia to obtain 3-cyclopropylalanine (3-CPA); esterifying the 3-CPA; contacting the 3-CPA ester with a substantially enantiomerically pure acid selected from tartaric acid, dibenzoyltartaric acid and mandelic acid to obtain a diastereomeric salt of the 3-CPA ester and the acid; recrystallization of the salt to substantial diastereomeric purity; and neutralizing the salt to afford the substantially enantiomerically pure 3-CPA ester.

摘要翻译： 公开了通过5步方法制备基本对映体纯的3-氨基-3-环丙基丙酸酯，即3-氨基-3-环丙基丙酸（3-环丙基丙氨酸酯或3-CPA酯）的酯的方法，其中环丙烷甲醛（ CPCA）与丙二酸和氨源反应以获得3-环丙基丙氨酸（3-CPA）; 酯化3-CPA; 使3-CPA酯与选自酒石酸，二苯甲酰酒石酸和扁桃酸的基本上对映体纯的酸接触以获得3-CPA酯和酸的非对映异构体盐; 盐重结晶至基本非对映体纯度; 并中和盐以提供基本上对映体纯的3-CPA酯。

公开(公告)号：EP1197504A1

公开(公告)日：2002-04-17

申请号：EP00944326.8

申请日：2000-07-07

申请人： Mitsui Chemicals, Inc.

发明人： OTA, Seiji, Mitsui Chemicals, Inc. ,  MATSUNAGA, Shinya, Mitsui Chemicals, Inc. ,  MIYAZAKI, Kazuhisa, Mitsui Chemicals, Inc. ,  ISHITOKU, Takeshi, Mitsui Chemicals, Inc. ,  HATA, Eiichiro, Mitsui Chemicals, Inc.

IPC分类号： C08F291/00 ,  C08L101/00 ,  C08G81/02 ,  C08F12/22 ,  C07D211/26 ,  C07D303/22 ,  C07D307/89 ,  C07D405/12 ,  C07C309/15 ,  C07C305/04 ,  C07C233/38 ,  C07C233/44 ,  C07C235/10 ,  C07C255/37 ,  C07C255/42 ,  C07C255/29 ,  C07C265/04 ,  C07C265/10 ,  C07C265/12 ,  C07C217/08 ,  C07C229/08

CPC分类号： C07D405/12 ,  C07D211/26 ,  C07D303/22 ,  C07D307/89 ,  C08F291/00 ,  C08L59/00

摘要： The present invention is intended to provide a polar group-containing thermoplastic polymer having high adhesion to metals and polar polymers, uses thereof and a polar group-containing unsaturated compound. The polar group-containing thermoplastic polymer is one obtained by graft modifying a thermoplastic polymer with at least one kind of a polar group-containing unsaturated compound represented by the following formula (I):

        A-X-R 2 -(Y) p -R 1      (I)

wherein A is a group containing a double bond, X is -COO-, -OCO-, -CO-, -O- or the like, R 2 is a divalent group containing a carbon atom or a single bond, Y is -CO-, -COO-, -OCO-, -O- or the like, p is 0 or 1, R 1 is a polar group selected from a carboxylic anhydride group, an epoxy group and the like or an alkyl, cycloalkyl or aryl group containing a polar group, and the bond chain linking the double bond in A to the polar group in R 1 is constituted of 6 or more atoms.

摘要翻译： 本发明的目的是提供具有高粘合性的金属和极性聚合物含极性基团的热塑性聚合物，及其用途和含极性基团的不饱和化合物。 含极性基团的热塑性聚合物是一种由得到的接枝改性的热塑性聚合物与至少一种由下式（I）表示的含极性基团的不饱和化合物的：AXR <2> - （Y）P <1> worin A是含有双键的基团，X是， - OCO - ， - CO - ， - O-或类似物，R <2>是含有一个碳原子或一个单一的键的二价基团，Y是 - CO - ， - COO - ， - OCO - ， - O-或类似物，p是0或1，R <1>是由羧酸酐组中的极性基团，烷基环氧等，或者于 环烷基或含有极性基团的芳基，和键合链A中的双键链接到R中的极性基团<1>构成6个或更多原子的。

公开(公告)号：EP0828704B1

公开(公告)日：2002-03-13

申请号：EP96913186.1

申请日：1996-04-26

申请人： WARNER-LAMBERT COMPANY

发明人： HUCKABEE, Brian, Keith ,  SOBIERAY, Denis, Martin

IPC分类号： C07C227/32 ,  C07C229/08 ,  C07C233/05

CPC分类号： C07C227/32 ,  C07C211/27 ,  C07C229/08 ,  C07C233/05

摘要： The present invention provides a method of making (S)-(+)-3-(aminomethyl)-5-methylhexanoic acid which comprises condensing isovaleraldehyde with an alkyl cyanoacetate to form a 2-cyano-5-methylhex-2-enoic acid alkyl ester; reacting the 2-cyano-5-methylhex-2-enoic acid alkyl ester with a dialkyl malonate to form 3-isobutylglutaric acid; forming the anhydride of 3-isobutylglutaric acid; reacting the anhydride with ammonia to form (+/-)-3-(carbamoylmethyl)-5-methylhexanoic acid; reacting (+/-)-3-(carbamoylmethyl)-5-methylhexanoic acid with (R)-(+)- alpha -phenylethylamine to obtain the (R)-(+)- alpha -phenylethylamine salt of (R)-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid; combining the salt with an acid to obtain (R)-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid; and reacting the (R)-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid with a Hofmann reagent to obtain (S)-(+)-3-(aminomethyl)-5-methylhexanoic acid.

公开(公告)号：EP1179529A1

公开(公告)日：2002-02-13

申请号：EP00927793.0

申请日：2000-05-17

申请人： Daiichi Fine Chemical Co., Ltd.

发明人： FUJISAWA, Tetsunori Daiichi Fine Chemical Co.,Ltd. ,  ODAKE, Shinjiro Daiichi Fine Chemical Co.,Ltd. ,  ITO, Hajime Daiichi Fine Chemical Co., Ltd. ,  YASUDA, Junko Daiichi Fine Chemical Co., Ltd. ,  OHTANI, Miwa Daiichi Fine Chemical Co., Ltd. ,  MORIKAWA, Tadanori Daiichi Fine Chemical Co., Ltd.

IPC分类号： C07C259/06 ,  C07C229/08 ,  C07C231/02 ,  C07C233/47 ,  A61K31/198 ,  A61K31/216 ,  A61P43/00

CPC分类号： C07C233/47 ,  C07C229/08 ,  C07C259/06 ,  C07C279/14 ,  Y02P20/55

摘要： Disclosed are compounds which have not only potent metalloproteinase-inhibiting activity but also amazingly excellent bioavailability and biological activity in vivo, including the property of being well absorbed via oral routes, thereby serving as useful pharmaceuticals, intermediates and processes for the production thereof. The disclosed compounds of the formula (I):
wherein R 1 is hydrogen, or a hydroxy-protecting group; R 2 is hydrogen, or an amino-protecting group; R 3 , R 7 , and R 8 , which may be identical or different, are each independently hydrogen, hydroxy, unsubstituted or optionally substituted (C 1 -C 6 ) alkyl, or unsubstituted or optionally substituted aryl-(C 1 -C 6 ) alkyl; R 4 is unsubstituted or optionally substituted (C 1 -C 6 ) alkyl, or unsubstituted or optionally substituted aryl-(C 1 -C 6 ) alkyl; R 5 is hydrogen, unsubstituted or optionally substituted alkyl, unsubstituted or optionally substituted aralkyl, or a carboxy-protecting group; R 6 is hydrogen, hydroxy, amino, and a group of the formula: -X-Y wherein X is oxygen, (C 1 -C 6 ) alkylene or phenylene, Y is a group of the formula: -A-B or -B, wherein A is (C 1 -C 6 ) alkylene, imino, and (C 1 -C 6 ) alkyleneimino, and B is hydrogen, amino, amidino, sulfonyl, acylimidoyl, unsubstituted or optionally substituted imidazolyl, unprotected or optionally protected bis(phosphono)methyl or unprotected or optionally protected bis(phosphono)hydroxymethyl; or salts thereof are useful for pharmaceutical and/or veterinary compositions, particularly as metalloproteinase inhibitors which inhibit matrix metalloproteinases or tumor necrosis factor-α-converting enzymes (TNF-α convertases).

摘要翻译： 公开了不仅具有有效的金属蛋白酶抑制活性，而且在体内具有惊人优异的生物利用度和生物活性的化合物，包括通过口服途径良好吸收的性质，从而作为有用的药物，中间体及其制备方法。 所公开的式（I）化合物：其中R 1是氢或羟基保护基的 R 2是氢或氨基保护基; R 3，R 7和R 8可以相同或不同，各自独立地为氢，羟基，未取代或任选取代的（C 1 -C 6）烷基，或未取代或任选取代的芳基 - （C 1 -C 6） -C 6）烷基; R 4是未取代的或任选取代的（C 1 -C 6）烷基，或未取代或任选取代的芳基 - （C 1 -C 6）烷基; R 5是氢，未取代或任选取代的烷基，未取代或任选取代的芳烷基或羧基保护基; R 6是氢，羟基，氨基和下式基团-XY，其中X是氧，（C1-C6）亚烷基或亚苯基，Y是下式的基团：-AB或-B，其中A 是（C 1 -C 6）亚烷基亚氨基，亚氨基和（C 1 -C 6）亚烷基亚氨基，B是氢，氨基，脒基，磺酰基，酰亚胺基，未取代的或任选取代的咪唑基，未被保护或任选被保护的双（膦酰基）甲基或未被保护或任选地 保护的双（膦酰基）羟甲基; 或其盐可用于药物和/或兽医组合物，特别是作为抑制基质金属蛋白酶或肿瘤坏死因子-α转化酶（TNF-α转化酶）的金属蛋白酶抑制剂。

公开(公告)号：EP0830338B1

公开(公告)日：2001-12-12

申请号：EP96914618.2

申请日：1996-05-13

申请人： WARNER-LAMBERT COMPANY

发明人： GROTE, Todd, Michel ,  HUCKABEE, Brian, Keith ,  MULHERN, Thomas ,  SOBIERAY, Denis, Martin ,  TITUS, Robert, Daniel

IPC分类号： C07C229/08 ,  C07C255/19 ,  C07C255/22 ,  C07C227/04

CPC分类号： C07C227/34 ,  C07C227/10 ,  C07C229/08 ,  C07C255/19 ,  C07C255/22

摘要： A method of making (±)-3-(aminomethyl)-5-methylhexanoic acid that comprises condensing isovaleraldehyde with (II) to form primarily (III); reacting the (III) with a cyanide source to form (IV); decarboxylating the (IV) to form (V); hydrolyzing the (V) with an alkali or alkaline earth metal hydroxide to form an alkali or alkaline earth metal carboxylate salt; and hydrogenating the alkali or alkaline earth metal carboxylate salt to form (±)-3-(aminomethyl)-5-methylhexanoic acid, wherein R1 and R2 are the same or different and are hydrogen, C1-C6 alkyl, aryl, benzyl, or C3-C6 cycloalkyl. The present invention also provides a method of making (±)-3-(aminomethyl)-5-methylhexanoic acid that comprises condensing isovaleraldehyde with (II) to form primarily (III); reacting the (III) with a cyanide source to form (IV); decarboxylating the (IV) to form an alkali or alkaline earth metal carboxylate salt; and hydrogenating the alkali or alkaline earth metal carboxylate salt to form (±)-3-(aminomethyl)-5-methylhexanoic acid.

公开(公告)号：EP0806410A2

公开(公告)日：1997-11-12

申请号：EP97303043.0

申请日：1997-05-02

申请人： ELI LILLY AND COMPANY

发明人： Hornback, William Joseph ,  Mauldin, Scott Carl ,  Munroe, John Edwin

IPC分类号： C07C69/757 ,  C07C69/753 ,  C07C251/44 ,  C07C61/39 ,  C07C229/08 ,  C07C271/22 ,  C07C237/36

CPC分类号： C07C69/00 ,  C07C61/39 ,  C07C229/08 ,  C07C237/12 ,  C07C251/44 ,  C07C271/22 ,  C07C2603/00 ,  C07C2603/26

摘要： The present invention provides compounds which inhibit an envelope virus by inhibiting the fusion of the virus with the host cell. The virus may be inhibited in an infected cell, a cell susceptible of infection or a mammal in need thereof.

公开(公告)号：EP0748791A2

公开(公告)日：1996-12-18

申请号：EP96304313.8

申请日：1996-06-07

申请人： Ajinomoto Co., Inc.

发明人： Hasegawa, Kazuhiro, Ajinomoto Co., Inc. ,  Kaneko, Tetsuya, Ajinomoto Co., Inc. ,  Takahashi, Noriko, Ajinomoto Co., Inc. ,  Sano, Chiaki, Ajinomoto Co., Inc.

IPC分类号： C07C227/40 ,  C07C227/42 ,  C07C229/08

CPC分类号： C07C229/08 ,  C07C227/40

摘要： The present invention addresses the need to provide a process for purifying valine having a high purity in high yield by a simple method and using an inexpensive precipitant.
A valine-containing aqueous solution is reacted with p-isopropylbenzenesulfonic acid or its water-soluble salt to form a valine p-isopropylbenzenesulfonate crystal. Valine p-isopropylbenzenesulfonate is separated and then dissociated to purify and obtain valine. The p-Isopropylbenzenesulfonic acid used may be in the form of a free acid, or a salt eg an alkali metal salt or an ammonium salt.
The procedure of forming an adduct comprising 1 mol of valine and 1 mol of p-isopropylbenzenesulfonic acid and purifying valine has the effects that since the solubility of valine p-isopropylbenzenesulfonate is low, valine may be obtained at high efficiency, and that valine may be separated at a high rate from leucine and isoleucine, which are in general hard to separate from valine, because of the specificity of the adduct. p-Isopropylbenzenesulfonic acid can be easily produced by sulfonating inexpensive isopropylbenzene.

公开(公告)号：EP0410005B1

公开(公告)日：1995-12-27

申请号：EP90902838.3

申请日：1990-02-09

申请人： AJINOMOTO CO., INC.

发明人： SHIROSHITA, Yoshinari, c/o Kyusyu Plant ,  TOYOMASU, Ryuta, c/o Kyusyu Plant ,  SAEKI, Masaru, c/o Kyusyu Plant

IPC分类号： C07C229/00 ,  B01D9/02 ,  C07C227/42 ,  C07C229/08 ,  C07C229/36 ,  C07D209/20

CPC分类号： C07C227/42 ,  C07D209/20

摘要： This invention relates to a method for crystallizing an amino acid characterized by adding a surfactant and/or an alcohol to an amino acid solution.

公开(公告)号：EP0456838B1

公开(公告)日：1995-11-02

申请号：EP91900338.4

申请日：1990-12-05

申请人： MITSUI TOATSU CHEMICALS, Inc.

发明人： FUJIWARA, Kenji ,  UEDA, Nobutaka ,  MATSUU, Yuuji ,  KATO, Hiroshi ,  HIAI, Atsuhiko

IPC分类号： C07C229/08 ,  C07C227/12

CPC分类号： C07C227/26 ,  C07C227/12

摘要： A process for producing glycine by the reaction of glycolonitrile with carbon dioxide and ammonia in the presence of water, which comprises the steps of conducting a preliminary reaction of glycolonitrile, with carbon dioxide, ammonia and water at 80 to 120 °C for 0.5 to 1 hr, conducting a main reaction at 150 to 200 °C, separating glycine thus formed from the reaction mixture, and recycling the remaining mother liquor to the reaction system comprising glycolonitrile, carbon dioxide, ammonia and water to conduct the preliminary and/or main reaction.