公开(公告)号：US5072007A

公开(公告)日：1991-12-10

申请号：US547132

申请日：1990-07-03

申请人： Daisuke Fukuoka ,  Takeshi Ishitoku ,  Katsuya Takahashi ,  Takashi Tashiro ,  Junichi Imuta ,  Hiroaki Tan ,  Masaharu Ishiguro ,  Noriaki Kihara ,  Teruaki Mukaiyama

发明人： Daisuke Fukuoka ,  Takeshi Ishitoku ,  Katsuya Takahashi ,  Takashi Tashiro ,  Junichi Imuta ,  Hiroaki Tan ,  Masaharu Ishiguro ,  Noriaki Kihara ,  Teruaki Mukaiyama

IPC分类号： C07D311/20

CPC分类号： C07D311/20

摘要： Process for preparing polyalkyl-2-alkoxy-7-hydroxychroman derivative of the general formula (V): ##STR1## wherein R.sup.1 denotes lower primary alkyl, R.sup.2 denotes hydrogen or lower primary alkyl and R.sup.3 denotes loweralkyl, by reacting resorcin with either an aliphatic ketone of the general formula (I): ##STR2## wherein R.sup.1 and R.sup.2 are as defined above, and an alcohol of the formula (II):R.sup.3 OH (II)wherein R.sup.3 is as defined above, in the presence of an acid catalyst, or an aliphatic ketone acetal of the general formula (III): ##STR3## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above, in the presence of an acid catalyst.

公开(公告)号：US4814500A

公开(公告)日：1989-03-21

申请号：US91850

申请日：1987-09-01

申请人： Noriaki Kihara ,  Teruaki Mukaiyama ,  Takeshi Ishitoku ,  Katsuya Takahashi

发明人： Noriaki Kihara ,  Teruaki Mukaiyama ,  Takeshi Ishitoku ,  Katsuya Takahashi

IPC分类号： C07C319/18 ,  C07C319/20 ,  C07C323/44 ,  C07C129/08

CPC分类号： C07C323/44

摘要： A novel cyanoguanidine derivative represented by the following general formula (I): ##STR1## wherein X stands for a hydrogen atom, a chlorine atom or a bromine atom, and R stands for a lower alkyl group, is an effective precursor for the synthesis of N-cyano-N'-methyl-N"-(2-(5-methyl-4-imidazolylmethylthio(ethyl)-guanidine (Cimetidine) which has an action of controlling secretion of gastric acid and is valuable as an agent for the remedy of a gastric ulcer.This cyanoguanidine derivative is prepared by reacting a methylvinylketone derivative with a mercaptoguanidine derivative or by reacting an amidinoketone derivative with a halogenating agent.

公开(公告)号：US4973703A

公开(公告)日：1990-11-27

申请号：US267379

申请日：1988-11-04

申请人： Junichi Imuta ,  Noriaki Kihara ,  Takeshi Ishitoku

发明人： Junichi Imuta ,  Noriaki Kihara ,  Takeshi Ishitoku

IPC分类号： C07D233/54 ,  C07D233/64

CPC分类号： C07D233/64

摘要： A process for the purification of N-cyano-N'-methyl-N"-[2-{(5-methyl-1H-imidazol-4-yl)methylthio}-ethyl]guanidine, which comprises bringing a crude product of N-cyano-N'-methyl-N"-[2-{(5-methyl-1H-imidazol-4-yl)-methylthio}ethyl]guanidine into contact with activated carbon in water in the presence of an organic acid.

公开(公告)号：US5037977A

公开(公告)日：1991-08-06

申请号：US390903

申请日：1989-08-08

申请人： Hiroaki Tan ,  Naoya Sakamoto ,  Eiichiro Hata ,  Takeshi Ishitoku ,  Noriaki Kihara

发明人： Hiroaki Tan ,  Naoya Sakamoto ,  Eiichiro Hata ,  Takeshi Ishitoku ,  Noriaki Kihara

IPC分类号： C07D519/04

CPC分类号： C07D519/04

摘要： This invention concerns a method for the production of dimeric alkaloids, characterized by reacting of catharanthine with vindoline in the presence of Fe.sup.3+ and (1) removing or inactivating the Fe.sup.3+ and allowing the reaction product to react with a reducing agent or (2) allowing presence of oxygen and a dicarboxylic acid or a derivative thereof in the reaction system and allowing the reaction product to react with a hydride source.In accordance with this invention, such dimeric alkaloid as vinblastine, leurosidin, and 3',4'-anhydrovinblastine which are useful as antineoplastic drugs can be produced in high yields.

公开(公告)号：US4886910A

公开(公告)日：1989-12-12

申请号：US156658

申请日：1988-02-17

申请人： Hiroaki Tan ,  Koji Kato ,  Junichi Imuta ,  Noriaki Kihara

发明人： Hiroaki Tan ,  Koji Kato ,  Junichi Imuta ,  Noriaki Kihara

IPC分类号： C07C319/20 ,  C07C67/00 ,  C07C313/00 ,  C07C323/44 ,  C07D233/54 ,  C07D233/64

CPC分类号： C07D233/64 ,  C07C323/44

摘要： The present invention provides a cyanoguanidine derivtive which is a precursor for the synthesis of N-cyano-N'-methyl-N"-[2-{(5-methyl-1H-imidazol-4-yl)methylothio}ethyl]-guanidine (Cimetidine) or its relted compound, which has an action of controlling secretion of acid in the stomach based on the histamine H.sub.2 receptor antagonism and is valuable as a drug for treating gastric ulcer. This cyanoguanidine derivative is prepared by reacting a haloketone derivative with an ammonium salt and a lower fatty acid salt or by reacting other cyanoguanidine derivative with an ammonium salt.

公开(公告)号：US4894475A

公开(公告)日：1990-01-16

申请号：US138076

申请日：1987-12-28

申请人： Hiroaki Tan ,  Koji Kato ,  Junichi Imuta ,  Noriaki Kihara

发明人： Hiroaki Tan ,  Koji Kato ,  Junichi Imuta ,  Noriaki Kihara

IPC分类号： C07D233/64 ,  C07C67/00 ,  C07C313/00 ,  C07C323/44 ,  C07D233/54

CPC分类号： C07D233/64 ,  C07C323/44

摘要： Disclosed are alpha-acyloxyketone derivatives which are useful as intermediates for production of N-cyano-N'-methyl-N"-[2-{(5-methyl-1H-imidazol-4-yl)methylthio}ethyl]guanidine (common name: Cimetidine; Cimetidine applies hereinafter) and Cimetidine-related compounds which have an action of controlling secretion of gastric acid and are useful as a drug for treating gastric ulcer.

公开(公告)号：US4808726A

公开(公告)日：1989-02-28

申请号：US91849

申请日：1987-09-01

申请人： Isao Hashimoto ,  Ikuo Tomino ,  Houji Kato ,  Noriaki Kihara ,  Teruaki Mukaiyama

发明人： Isao Hashimoto ,  Ikuo Tomino ,  Houji Kato ,  Noriaki Kihara ,  Teruaki Mukaiyama

IPC分类号： C07D233/54 ,  C07D233/64

CPC分类号： C07D233/64

摘要： N-cyano-N'-methyl-N"-(2-(5-methyl-4-imidazolylmethylthio)ethyl)guanidine (Cimetidine), which is valuable as an agent for controlling secretion of gastric acid, is prepared in a high yield by reacting N-cyano-N'-methyl-N"-(2-(butane-2,3-dionyl)thioethyl)-guanidine as the starting compound with an ammonium salt of a carboxylic acid and formaldehyde.

公开(公告)号：US5932759A

公开(公告)日：1999-08-03

申请号：US800149

申请日：1997-02-13

申请人： Yoshio Motoyama ,  Naoshi Nagai ,  Takeshi Ishitoku ,  Noriaki Kihara

发明人： Yoshio Motoyama ,  Naoshi Nagai ,  Takeshi Ishitoku ,  Noriaki Kihara

IPC分类号： C07C239/20 ,  C07C261/00

CPC分类号： C07C239/20

摘要： The present invention relates to a process for producing a substituted amine represented by the general formula (IV):R.sup.2 NHOR.sup.3 (IV)(wherein R.sup.2 represents a hydrogen atom, a hydrocarbon group or a heteroatom-containing hydrocarbon group, and R.sup.3 represents a hydrocarbon group or a heteroatom-containing hydrocarbon group), which comprises the steps of:(b) reacting a hydroxamic acid represented by the general formula (II):R.sup.1 CONHOH (II)(wherein R.sup.1 represents a hydrogen atom or a hydrocarbon group) in the presence of a base with a reaction reagent capable of introducing a hydrocarbon or a heteroatom-containing hydrocarbon group to an oxygen atom and/or a nitrogen atom to form a substituted hydroxamic acid represented by the general formula (III): ##STR1## (wherein R.sup.1, R.sup.2 and R.sup.3 possess the same meanings as defined above),(c) hydrolyzing said substituted hydroxamic acid (III) in the presence of a base or an acid to produce a substituted amine represented by the general formula (IV):R.sup.2 NHOR.sup.3 (IV)(wherein R.sup.2 and R.sup.3 possess the same meanings as defined above). The present further relates to a method for purifying a synthetic intermediate for said substituted amine.

摘要翻译： 本发明涉及由通式（IV）表示的取代胺的制备方法：R2NHOR3（IV）（其中R2表示氢原子，烃基或含杂原子的烃基，R3表示烃基 或含杂原子的烃基），其包括以下步骤：（b）使通式（II）表示的异羟肟酸：R 1 CONHOH（II）（其中R 1表示氢原子或烃基） 的具有能够将烃或含杂原子的烃基引入氧原子和/或氮原子的反应试剂形成由通式（III）表示的取代的异羟肟酸的反应试剂：其中R1，R2和 R3具有与上述相同的含义），（c）在碱或酸的存在下水解所述取代的异羟肟酸（III）以产生由通式（IV）表示的取代胺：R2NHOR3（IV）（其中 R 2和R3具有与上述相同的含义）。 本发明还涉及纯化所述取代胺的合成中间体的方法。

公开(公告)号：US5175313A

公开(公告)日：1992-12-29

申请号：US695323

申请日：1991-05-03

申请人： Junichi Imuta ,  Aiichiro Ori ,  Noriaki Kihara

发明人： Junichi Imuta ,  Aiichiro Ori ,  Noriaki Kihara

IPC分类号： C07D307/33

CPC分类号： C07D307/33

摘要： The present invention provides a process for preparing dihydrofuranone derivative of the formula (I): ##STR1## wherein R.sup.1 and R.sup.3 are individually lower alkyl, and R.sup.2 is hydrogen or lower alkyl, by reacting a dihydrofuranone derivative of the formula(I): ##STR2## wherein R.sup.1 is as defined above, with a malonic acid derivative of the formula (II): ##STR3## wherein R.sup.2 and R.sup.3 are as defined above, in the presence of an alkalimetal alkoxide and/or an alkalimetal hydroxide.

公开(公告)号：US5358945A

公开(公告)日：1994-10-25

申请号：US836283

申请日：1992-03-30

申请人： Akira Mizuchi ,  Ken Ikeda ,  Yuichiro Kokubun ,  Kazutoshi Horikomi ,  Tadayuki Sasaki ,  Akira Awaya ,  Ikuo Tomino ,  Masaharu Ishiguro ,  Takumi Kitahara ,  Noriaki Kihara

发明人： Akira Mizuchi ,  Ken Ikeda ,  Yuichiro Kokubun ,  Kazutoshi Horikomi ,  Tadayuki Sasaki ,  Akira Awaya ,  Ikuo Tomino ,  Masaharu Ishiguro ,  Takumi Kitahara ,  Noriaki Kihara

IPC分类号： C07D239/48 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  A61K31/505 ,  C07D401/02

CPC分类号： C07D239/48 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04

摘要： The present invention relates to pyrimidine compounds represented by the formula ##STR1## (wherein X is a substituted or a cyclic amino group and Y is a substituted amino group or a substituted carbonyl group) or their pharmaceutically acceptable salts, and a therapeutic agent for neurological diseases comprising the compounds.These compounds are useful for treatment of various disorders in nervous systems since they are effective on growth of neurons and promotion of the formation and elongation of neutrites.

摘要翻译： PCT No.PCT / JP91 / 00898 371日期：1992年3月30日 102（e）1992年3月30日PCT PCT 1991年7月3日PCT公布。 出版物WO92 / 00970 本发明涉及由式（IMAGE）表示的嘧啶化合物（其中X为取代或环状氨基，Y为取代氨基或取代羰基）或其药学上可接受的盐 ，以及包含该化合物的神经疾病治疗剂。 这些化合物可用于治疗神经系统中的各种疾病，因为它们对神经元的生长有效并促进中性粒细胞的形成和延长。