公开(公告)号：US06713615B2

公开(公告)日：2004-03-30

申请号：US10344529

申请日：2003-02-12

申请人： Masato Kashimura ,  Hiroaki Kamiyama ,  Takeshi Kuwada ,  Nobuyuki Suzuki ,  Takashi Adachi

发明人： Masato Kashimura ,  Hiroaki Kamiyama ,  Takeshi Kuwada ,  Nobuyuki Suzuki ,  Takashi Adachi

IPC分类号： C07H100

CPC分类号： C07H17/08

摘要： There is provided a preparation process useful for an efficient synthesis of 6-O-substituted ketolide derivatives by combining a characterized step of introduction of a substituent at the 6-position by selective cleavage of a C—O bond of the cyclic acetal at the 9-position side via 6,9-cyclic acetal 5-O-desosaminyl erythronolide derivative, a step of conversion into carbonyl groups at the 9- and 3-positions, and a step of 11,12-cyclic carbamation to lead to 6-O-substituted ketolide derivatives.

摘要翻译： 提供了一种用于有效合成6-O-取代的酮内酯衍生物的制备方法，其通过组合在6位上引入取代基的特征性步骤，通过选择性裂解环状缩醛在9位上的CO键 通过6,9-环状缩醛5-O-去氨基酰基红新环素衍生物，在9位和3位转化为羰基的步骤和11,12-环状氨基甲酰化作用以产生6-O-取代的步骤 酮内酯衍生物。

公开(公告)号：US20080318923A1

公开(公告)日：2008-12-25

申请号：US11883236

申请日：2006-01-30

申请人： Yoshinori Sekiguchi ,  Takeshi Kuwada ,  Masato Hayashi ,  Dai Nozawa ,  Yuri Amada ,  Tsuyoshi Shibata ,  Shuji Yamamoto ,  Hiroshi Ohta ,  Taketoshi Okubo ,  Takeshi Koami

发明人： Yoshinori Sekiguchi ,  Takeshi Kuwada ,  Masato Hayashi ,  Dai Nozawa ,  Yuri Amada ,  Tsuyoshi Shibata ,  Shuji Yamamoto ,  Hiroshi Ohta ,  Taketoshi Okubo ,  Takeshi Koami

IPC分类号： A61K31/397 ,  C07D209/04 ,  C07D401/02 ,  C07D213/02 ,  C07D217/00 ,  C07D413/02 ,  C07D403/14 ,  C07D241/02 ,  C07D471/02 ,  A61P25/00 ,  C07C317/14 ,  A61K31/437 ,  A61K31/501 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/4725 ,  A61K31/4545 ,  A61K31/454 ,  A61K31/404

CPC分类号： C07D401/12 ,  C07C309/87 ,  C07D209/38 ,  C07D209/40 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D413/04 ,  C07D417/12

摘要： It is intended to provide a drug which is efficacious against pathological conditions relating to arginine-vasopressin V1b receptor. More particularly speaking, it is intended to provide a drug which has a therapeutic or preventive effect on depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, hypertension, digestive diseases, drug addiction, epilepsy, brain infarction, brain ischemia, brain edema, head injury, inflammation, immune diseases, alopecia and so on. As the results of intensive studies, a novel 1,3-dihydro-2H-indol-2-one compound and a pyrrolidin-2-one compound fused with a heteroaromatic ring, which are highly selective antagonists of arginine-vasopressin V1b receptor, have high metabolic stabilities and show favorable brain penetration and high plasma concentrations, are found, thereby achieving the above objective.

摘要翻译： 旨在提供对精氨酸 - 加压素V1b受体有关的病理状况有效的药物。 更具体地说，它旨在提供一种对抑郁，焦虑，阿尔茨海默病，帕金森病，亨廷顿氏舞蹈病，进食障碍，高血压，消化系统疾病，药物成瘾，癫痫，脑梗死，脑缺血具有治疗或预防作用的药物 ，脑水肿，头部损伤，炎症，免疫疾病，脱发等。 作为深入研究的结果，作为精氨酸 - 加压素V1b受体的高度选择性拮抗剂的与杂芳环稠合的新的1,3-二氢-2H-吲哚-2-酮化合物和吡咯烷-2-酮化合物具有 发现高代谢稳定性并显示有利的脑渗透和高血浆浓度，从而达到上述目的。

公开(公告)号：US20130197217A1

公开(公告)日：2013-08-01

申请号：US13824174

申请日：2011-09-30

申请人： Takeshi Kuwada ,  Mitsukane Yoshinaga ,  Tomoko Ishizaka ,  Daisuke Wakasugi ,  Shin-ichi Shirokawa ,  Nobutaka Hattori ,  Youichi Shimazaki ,  Naoki Miyakoshi

发明人： Takeshi Kuwada ,  Mitsukane Yoshinaga ,  Tomoko Ishizaka ,  Daisuke Wakasugi ,  Shin-ichi Shirokawa ,  Nobutaka Hattori ,  Youichi Shimazaki ,  Naoki Miyakoshi

IPC分类号： C07D249/12 ,  C07D403/10 ,  C07D401/10 ,  C07D401/04 ,  C07D451/06 ,  C07D413/10 ,  C07D491/107 ,  C07D498/08

CPC分类号： C07D249/12 ,  C07D401/04 ,  C07D401/10 ,  C07D403/10 ,  C07D405/10 ,  C07D405/12 ,  C07D413/10 ,  C07D413/14 ,  C07D451/06 ,  C07D491/08 ,  C07D491/107 ,  C07D498/08

摘要： The present invention provides a 1,2,4-triazolone derivative represented by Formula (1A) having an antagonistic activity on the arginine-vasopressin 1b receptor or a pharmaceutically acceptable salt thereof and provides a pharmaceutical composition comprising the compound or the salt as an active ingredient, in particular, a therapeutic or preventive agent exhibiting favorable pharmacokinetics in a disease such as mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastrointestinal disease, drug addiction, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, head injury, inflammation, immune-related disease, or alopecia.

摘要翻译： 本发明提供对精氨酸 - 加压素1b受体或其药学上可接受的盐具有拮抗作用的由式（1A）表示的1,2,4-三唑酮衍生物，并提供包含该化合物或其盐作为活性物质的药物组合物 成分，特别是在疾病如情绪障碍，焦虑障碍，精神分裂症，阿尔茨海默病，帕金森病，亨廷顿舞蹈病，进食障碍，高血压，胃肠道疾病，药物成瘾，癫痫，脑梗死等疾病中表现出有利的药代动力学的治疗或预防药物 ，脑缺血，脑水肿，头部损伤，炎症，免疫相关疾病或脱发。

公开(公告)号：US20050159371A1

公开(公告)日：2005-07-21

申请号：US10504088

申请日：2003-02-12

申请人： Masato Kashimura ,  Takeshi Kuwada

发明人： Masato Kashimura ,  Takeshi Kuwada

IPC分类号： A61K31/7056 ,  A61P31/04 ,  C07H17/08 ,  A61K31/7052

CPC分类号： C07H17/08 ,  A61K31/7056

摘要： An efficient process for producing an 11,12-cyclic carbamate 6-O-substituted ketolide derivatives having the natural stereochemistry at the 10-position.

摘要翻译： 制备在10位具有天然立体化学的11,12环氨基甲酸酯6-O-取代的酮内酯衍生物的有效方法。

公开(公告)号：US09193695B2

公开(公告)日：2015-11-24

申请号：US13824174

申请日：2011-09-30

申请人： Takeshi Kuwada ,  Mitsukane Yoshinaga ,  Tomoko Ishizaka ,  Daisuke Wakasugi ,  Shin-ichi Shirokawa ,  Nobutaka Hattori ,  Youichi Shimazaki ,  Naoki Miyakoshi

发明人： Takeshi Kuwada ,  Mitsukane Yoshinaga ,  Tomoko Ishizaka ,  Daisuke Wakasugi ,  Shin-ichi Shirokawa ,  Nobutaka Hattori ,  Youichi Shimazaki ,  Naoki Miyakoshi

IPC分类号： C07D265/30 ,  C07D249/12 ,  C07D401/04 ,  C07D401/10 ,  C07D403/10 ,  C07D405/10 ,  C07D405/12 ,  C07D413/10 ,  C07D413/14 ,  C07D451/06 ,  C07D491/08 ,  C07D491/107 ,  C07D498/08

CPC分类号： C07D249/12 ,  C07D401/04 ,  C07D401/10 ,  C07D403/10 ,  C07D405/10 ,  C07D405/12 ,  C07D413/10 ,  C07D413/14 ,  C07D451/06 ,  C07D491/08 ,  C07D491/107 ,  C07D498/08

摘要： The present invention provides a 1,2,4-triazolone derivative represented by Formula (1A) having an antagonistic activity on the arginine-vasopressin 1b receptor or a pharmaceutically acceptable salt thereof and provides a pharmaceutical composition comprising the compound or the salt as an active ingredient, in particular, a therapeutic or preventive agent exhibiting favorable pharmacokinetics in a disease such as mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastrointestinal disease, drug addiction, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, head injury, inflammation, immune-related disease, or alopecia.

摘要翻译： 本发明提供对精氨酸 - 加压素1b受体或其药学上可接受的盐具有拮抗作用的由式（1A）表示的1,2,4-三唑酮衍生物，并提供包含该化合物或其盐作为活性物质的药物组合物 成分，特别是在疾病如情绪障碍，焦虑障碍，精神分裂症，阿尔茨海默病，帕金森病，亨廷顿舞蹈病，进食障碍，高血压，胃肠道疾病，药物成瘾，癫痫，脑梗死等疾病中表现出有利的药代动力学的治疗或预防药物 ，脑缺血，脑水肿，头部损伤，炎症，免疫相关疾病或脱发。

公开(公告)号：US08030499B2

公开(公告)日：2011-10-04

申请号：US11883236

申请日：2006-01-30

申请人： Yoshinori Sekiguchi ,  Takeshi Kuwada ,  Masato Hayashi ,  Dai Nozawa ,  Yuri Amada ,  Tsuyoshi Shibata ,  Shuji Yamamoto ,  Hiroshi Ohta ,  Taketoshi Okubo ,  Takeshi Koami

发明人： Yoshinori Sekiguchi ,  Takeshi Kuwada ,  Masato Hayashi ,  Dai Nozawa ,  Yuri Amada ,  Tsuyoshi Shibata ,  Shuji Yamamoto ,  Hiroshi Ohta ,  Taketoshi Okubo ,  Takeshi Koami

IPC分类号： C07D209/04 ,  A61K31/404

CPC分类号： C07D401/12 ,  C07C309/87 ,  C07D209/38 ,  C07D209/40 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D413/04 ,  C07D417/12

摘要： It is intended to provide a drug which is efficacious against pathological conditions relating to arginine-vasopressin V1b receptor. More particularly speaking, it is intended to provide a drug which has a therapeutic or preventive effect on depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, hypertension, digestive diseases, drug addiction, epilepsy, brain infarction, brain ischemia, brain edema, head injury, inflammation, immune diseases, alopecia and so on. As the results of intensive studies, a novel 1,3-dihydro-2H-indol-2-one compound and a pyrrolidin-2-one compound fused with a heteroaromatic ring, which are highly selective antagonists of arginine-vasopressin V1b receptor, have high metabolic stabilities and show favorable brain penetration and high plasma concentrations, are found, thereby achieving the above objective.

摘要翻译： 旨在提供对精氨酸 - 加压素V1b受体有关的病理状况有效的药物。 更具体地说，它旨在提供一种对抑郁，焦虑，阿尔茨海默病，帕金森病，亨廷顿氏舞蹈病，进食障碍，高血压，消化系统疾病，药物成瘾，癫痫，脑梗死，脑缺血具有治疗或预防作用的药物 ，脑水肿，头部损伤，炎症，免疫疾病，脱发等。 作为深入研究的结果，作为精氨酸 - 加压素V1b受体的高度选择性拮抗剂的与杂芳环稠合的新的1,3-二氢-2H-吲哚-2-酮化合物和吡咯烷-2-酮化合物具有 发现高代谢稳定性并显示有利的脑渗透和高血浆浓度，从而实现上述目的。

公开(公告)号：US20060276449A1

公开(公告)日：2006-12-07

申请号：US10569833

申请日：2004-08-27

申请人： Toshihito Kumagai ,  Takeshi Kuwada ,  Tsuyoshi Shibata ,  Masato Hayashi ,  Yuri Fujisawa ,  Yoshinori Sekiguchi

发明人： Toshihito Kumagai ,  Takeshi Kuwada ,  Tsuyoshi Shibata ,  Masato Hayashi ,  Yuri Fujisawa ,  Yoshinori Sekiguchi

IPC分类号： A61K31/404 ,  C07D403/14 ,  C07D403/04

CPC分类号： C07D403/04

摘要： A 1,3-dihydro-2H-indol-2-one derivative expressed by Formula 1 (wherein R1 is a halogen atom, a C1 to C4 alkyl group, etc., and R2 is a hydrogen atom, a halogen atom, etc., or R2 is in the 6-position of the indol-2-one and R1 and R2 join together to form a C3 to C6 alkylene group, R3 is a halogen atom, a hydroxyl group, etc., and R4 is a hydrogen atom, a halogen atom, a C1 to C4 alkyl group, etc., or R4 is in the 3-position of the phenyl and R3 and R4 join together to form a methylenedioxy group, R5 is a hydrogen atom or a fluorine atom, R6 is an ethylamino group, a dimethylamino group, etc., R7 is a C1 to C4 alkoxy group, and R8 is a C1 to C4 alkoxy group), or a pharmaceutically acceptable salt of this derivative. This is a novel compound that has antagonistic activity against an aruginine-vasopressin V1b receptor.

摘要翻译： 由式1表示的1,3-二氢-2H-吲哚-2-酮衍生物（其中R 1是卤素原子，C 1至C 1烷基， 4个烷基等，R 2是氢原子，卤原子等，或R 2 2位在6位的 吲哚-2-酮和R 1和R 2连接在一起以形成C 6 -C 6亚烷基， 亚烷基，R 3是卤素原子，羟基等，R 4是氢原子，卤原子，C 1， / SUB→C 4烷基等，或R 4在苯基的3位和R 3和R 3 连接在一起形成亚甲二氧基，R 5是氢原子或氟原子，R 6是乙氨基，二甲基氨基 基团等，R 7是C 1-4烷氧基的C 1至C 8，并且R 8是 C 1至C 4烷氧基），或该衍生物的药学上可接受的盐。 这是一种新的化合物，具有对抗葡萄糖酸加压素V1b受体的拮抗作用。

公开(公告)号：US20100113776A1

公开(公告)日：2010-05-06

申请号：US12519083

申请日：2007-12-14

申请人： Toshio Nakamura ,  Dai Nozawa ,  Makoto Tatsuzuki ,  Hiroahi Ohta ,  Takeshi Kuwada ,  Tomoko Ishizaka ,  Tomoko Tamita ,  Seiji Masuda

发明人： Toshio Nakamura ,  Dai Nozawa ,  Makoto Tatsuzuki ,  Hiroahi Ohta ,  Takeshi Kuwada ,  Tomoko Ishizaka ,  Tomoko Tamita ,  Seiji Masuda

IPC分类号： C07D401/14 ,  C07D401/12 ,  C07D413/14 ,  C07D403/14

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D413/14

摘要： A novel pyrazole derivative of the following formula having a histamine H3 receptor antagonistic effect: or a pharmaceutically acceptable salt thereof or a pharmaceutical preparation comprising the same as an active ingredient is effective for prevention or treatment of dementia, Alzheimer's disease, attention-deficit hyperactivity disorder, schizophrenia, eating disorders, obesity, diabetes, hyperlipidemia, sleep disorders, narcolepsy, sleep apnea syndrome, circadian rhythm disorder, depression, allergic rhinitis or other diseases.

摘要翻译： 具有组胺H3受体拮抗作用的下式的新型吡唑衍生物或其药学上可接受的盐或包含其作为活性成分的药物制剂可有效预防或治疗痴呆，阿尔茨海默病，注意力缺陷多动障碍 精神分裂症，进食障碍，肥胖症，糖尿病，高脂血症，睡眠障碍，发作性睡眠障碍，睡眠呼吸暂停综合征，昼夜节律紊乱，抑郁症，过敏性鼻炎或其他疾病。

公开(公告)号：US07528124B2

公开(公告)日：2009-05-05

申请号：US10569833

申请日：2004-08-27

申请人： Toshihito Kumagai ,  Takeshi Kuwada ,  Tsuyoshi Shibata ,  Masato Hayashi ,  Yuri Fujisawa ,  Yoshinori Sekiguchi

发明人： Toshihito Kumagai ,  Takeshi Kuwada ,  Tsuyoshi Shibata ,  Masato Hayashi ,  Yuri Fujisawa ,  Yoshinori Sekiguchi

IPC分类号： A61K31/404 ,  C07D209/04 ,  C07D403/04

CPC分类号： C07D403/04

摘要： A 1,3-dihydro-2H-indol-2-one derivative expressed by Formula 1 (wherein R1 is a halogen atom, a C1 to C4 alkyl group, etc., and R2 is a hydrogen atom, a halogen atom, etc., or R2 is in the 6-position of the indol-2-one and R1 and R2 join together to form a C3 to C6 alkylene group, R3 is a halogen atom, a hydroxyl group, etc., and R4 is a hydrogen atom, a halogen atom, a C1 to C4 alkyl group, etc., or R4 is in the 3-position of the phenyl and R3 and R4 join together to form a methylenedioxy group, R5 is a hydrogen atom or a fluorine atom, R6 is an ethylamino group, a dimethylamino group, etc., R7 is a C1 to C4 alkoxy group, and R8 is a C1 to C4 alkoxy group), or a pharmaceutically acceptable salt of this derivative. This is a novel compound that has antagonistic activity against an aruginine-vasopressin V1b receptor.

摘要翻译： 由式1表示的1,3-二氢-2H-吲哚-2-酮衍生物（其中，R 1为卤素原子，C 1〜C 4烷基等，R 2为氢原子，卤素原子等） ，或R2为吲哚-2-酮的6-位，R 1和R 2连接在一起形成C 3〜C 6亚烷基，R 3为卤素原子，羟基等，R 4为氢原子 卤素原子，C 1〜C 4烷基等，或者R 4在苯基的3-位，R3和R4连接在一起形成亚甲二氧基，R5是氢原子或氟原子，R6是 乙基氨基，二甲基氨基等，R7为C1〜C4烷氧基，R8为C1〜C4烷氧基）或该衍生物的药学上可接受的盐。 这是一种新的化合物，具有对抗葡萄糖酸加压素V1b受体的拮抗作用。