公开(公告)号：US5424434A

公开(公告)日：1995-06-13

申请号：US260835

申请日：1994-06-16

申请人： Kazunori Ohno ,  Osamu Odai ,  Yukio Tominaga ,  Kiyoshi Furukawa ,  Makoto Oka

发明人： Kazunori Ohno ,  Osamu Odai ,  Yukio Tominaga ,  Kiyoshi Furukawa ,  Makoto Oka

IPC分类号： A61K31/4245 ,  A61K31/435 ,  A61K31/4375 ,  C07D271/02 ,  C07D271/06 ,  C07D271/10 ,  C07D471/04

CPC分类号： C07D471/04

摘要： 3-Oxadiazolyl-5,6,7,8-tetrahydro-1,6-naphthyridine derivative of the formula (I): ##STR1## wherein Het is an oxadiazole ring, R.sub.1 is hydrogen atom, an acyl group, a lower alkyl group or a group of the formula: --CH.sub.2 R.sub.1 ' (in which R.sub.1 ' is a cyclo-lower alkyl group, a lower alkenyl group, a lower alkynyl group, benzyl group, aryl group or a heteroaromatic group), R.sub.2 is a lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkynyl group, aryl group, a heteroaromatic group, a halogeno-lower alkyl group, a lower alkoxy-lower alkyl group, a lower alkoxy group, a lower alkenyloxy group, a phenoxy group or a lower alkylthio group, or a pharmaceutically acceptable acid addition salt thereof, which are useful as benzodiazepine receptor agonist.

摘要翻译： 式（I）的3-恶二唑基-5,6,7,8-四氢-1,6-萘啶衍生物：其中Het是恶二唑环，R 1是氢原子，酰基， 低级烷基或式-CH 2 R 1'（其中R 1'为环低级烷基，低级烯基，低级炔基，苄基，芳基或杂芳族基团）的基团，R 2为 低级烷基，低级烷基，低级烯基，低级炔基，芳基，杂芳基，卤代低级烷基，低级烷氧基 - 低级烷基，低级烷氧基，低级烷基 烯氧基，苯氧基或低级烷硫基，或其药学上可接受的酸加成盐，可用作苯并二氮杂受体激动剂。

公开(公告)号：US5367078A

公开(公告)日：1994-11-22

申请号：US112660

申请日：1993-08-27

申请人： Kazunori Ohno ,  Osamu Odai ,  Yukio Tominaga ,  Kiyoshi Furukawa ,  Makoto Oka

发明人： Kazunori Ohno ,  Osamu Odai ,  Yukio Tominaga ,  Kiyoshi Furukawa ,  Makoto Oka

IPC分类号： A61K31/4245 ,  A61K31/435 ,  A61K31/4375 ,  C07D271/02 ,  C07D271/06 ,  C07D271/10 ,  C07D471/04

CPC分类号： C07D471/04

摘要： 3-Oxadiazolyl-5,6,7,8-tetrahydro-1,6-naphthyridine derivative of the formula (I): ##STR1## wherein Het is an oxadiazole ring, R.sub.1 is hydrogen atom, an acyl group, a lower alkyl group or a group of the formula: --CH.sub.2 R.sub.1 ' (in which R.sub.1 ' is a cyclo-lower alkyl group, a lower alkenyl group, a lower alkynyl group, benzyl group, aryl group or a heteroaromatic groups), R.sub.2 is a lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkynyl group, aryl group, a heteroaromatic group, a halogeno-lower alkyl group, a lower alkoxy-lower alkyl group, a lower alkoxy group, a lower alkenyloxy group, a phenoxy group, or a lower alkylthio group, or a pharmaceutically acceptable acid addition salt thereof, which are useful as benzodiazedine receptor agonist.

摘要翻译： 式（I）的3-恶二唑基-5,6,7,8-四氢-1,6-萘啶衍生物：其中Het是恶二唑环，R 1是氢原子，酰基， 低级烷基或式-CH 2 R 1'（其中R 1'为环低级烷基，低级烯基，低级炔基，苄基，芳基或杂芳族基团）的基团，R 2为 低级烷基，低级烷基，低级烯基，低级炔基，芳基，杂芳基，卤代低级烷基，低级烷氧基 - 低级烷基，低级烷氧基，低级烷基 烯氧基，苯氧基或低级烷硫基，或其药学上可接受的酸加成盐，其可用作苯并二嗪二受体激动剂。

公开(公告)号：US06458824B1

公开(公告)日：2002-10-01

申请号：US09661577

申请日：2000-09-14

申请人： Motokazu Iwata ,  Teruaki Kuriyama ,  Megumi Fujita ,  Keiichi Fujiwara ,  Shiro Kato ,  Hiroshi Harada ,  Akihito Fujii ,  Osamu Odai ,  Hitoshi Kawashima

发明人： Motokazu Iwata ,  Teruaki Kuriyama ,  Megumi Fujita ,  Keiichi Fujiwara ,  Shiro Kato ,  Hiroshi Harada ,  Akihito Fujii ,  Osamu Odai ,  Hitoshi Kawashima

IPC分类号： A61K3140

CPC分类号： C07D209/16

摘要： The present invention provides a solid preparation comprising a crystal of [3-[(2R)-[[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yloxy]acetic acid (Compound A), especially a crystal of Compound A having a particle size of not larger than 100 &mgr;m at the cumulative weight distribution value of 50%, and not larger than 200 &mgr;m at the cumulative weight distribution value of 95%, preferably a solid preparation having the excellent stability and the content uniformity of Compound A, which is prepared by preparing granules of the crystal of Compound A with fillers, disintegrants and binders, and then followed by mixing said granules with external excipients.

摘要翻译： 本发明提供包含[3 - [（2R） - [[（2R） - （3-氯苯基）-2-羟乙基]氨基]丙基] -1H-吲哚-7-基氧基]乙酸的晶体的固体制剂 （化合物A），特别是在累积重量分布值为50％，粒径不大于100μm的化合物A的晶体，累积重量分布值为95％以下为200μm以下，优选为固体 通过用填料，崩解剂和粘合剂制备化合物A的晶体颗粒，然后将所述颗粒与外部赋形剂混合制备的具有优异的化合物A的稳定性和含量均匀性的制剂。

公开(公告)号：US06277993B1

公开(公告)日：2001-08-21

申请号：US09654782

申请日：2000-09-01

申请人： Kazunori Ohno ,  Osamu Odai ,  Kaoru Masumoto ,  Kiyoshi Furukawa ,  Makoto Oka

发明人： Kazunori Ohno ,  Osamu Odai ,  Kaoru Masumoto ,  Kiyoshi Furukawa ,  Makoto Oka

IPC分类号： C07D47104

CPC分类号： C07D471/04

摘要： A 5-substituted-3-oxadiazolyl-1,6-naphthyridin-2(1H)-one derivative of the formula (I): wherein Het is oxadiazolyl, R1 is H, lower alkyl, cyclo-lower alkyl, trifluoromethyl, lower alkenyl, lower alkynyl, lower alkoxy, lower alkoxy-lower alkyl, hydroxy-lower alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group, and R2 is H, lower alkyl, cyclo-lower alkyl, cyclo-lower alkylmethyl, lower alkenyl, cyclo-lower alkenyl, lower alkynyl, substituted or unsubstituted aryl, or substituted or unsubstituted hetero-aromatic group, or a pharmaceutically acceptable acid addition salt thereof, which has high selective affinity to benzodiazepine receptor and is useful particularly as a benzodiazepine inverse agonist, for example, as psychoanaleptic drug or a drug for the treatment of dysmnesia in senile dementia or Alzheimer's disease.

摘要翻译： 式（I）的5-取代-3-恶二唑基-1,6-二氮杂萘-2（1H） - 酮衍生物：其中Het是恶二唑基，R 1是H，低级烷基，环低级烷基，三氟甲基，低级烯基 低级炔基，低级烷氧基，低级烷氧基 - 低级烷基，羟基 - 低级烷基，取代或未取代的芳基，或取代或未取代的杂芳基，R2是H，低级烷基，环低级烷基，环低级烷基甲基， ，环低级烯基，低级炔基，取代或未取代的芳基，或取代或未取代的杂芳族基团或其药学上可接受的酸加成盐，其对苯并二氮杂受体具有高选择性亲和力，并且特别用作苯二氮卓反相激动剂， 例如，作为精神无菌药物或用于治疗老年痴呆或阿尔茨海默病的失聪症的药物。

公开(公告)号：US06172079B2

公开(公告)日：2001-01-09

申请号：US09462412

申请日：2000-01-10

申请人： Kazunori Ohno ,  Osamu Odai ,  Kaoru Masumoto ,  Kiyoshi Furukawa ,  Makoto Oka

发明人： Kazunori Ohno ,  Osamu Odai ,  Kaoru Masumoto ,  Kiyoshi Furukawa ,  Makoto Oka

IPC分类号： A61K31435

CPC分类号： C07D471/04

摘要： A 5-substituted-3-oxadiazolyl-1,6-naphthyridin-2(1H)-one derivative of the formula (I): wherein Het is oxadiazolyl, R1 is H, lower alkyl, cyclo-lower alkyl, trifluoromethyl, lower alkenyl, lower alkynyl, lower alkoxy, lower alkoxy-lower alkyl, hydroxy-lower alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group, and R2 is H, lower alkyl, cyclo-lower alkyl, cyclo-lower alkylmethyl, lower alkenyl, cyclo-lower alkenyl, lower alkynyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group, or a pharmaceutically acceptable acid addition salt thereof, which has high selective affinity to benzodiazepine receptor and is useful particularly as a benzodiazepine inverse agonist, for example, as psychoanaleptic drug or a drug for the treatment of dysmnesia in senile dementia or Alzheimer's disease.

摘要翻译： 式（I）的5-取代-3-恶二唑基-1,6-二氮杂萘-2（1H） - 酮衍生物：其中Het是恶二唑基，R 1是H，低级烷基，环低级烷基，三氟甲基，低级烯基 低级炔基，低级烷氧基，低级烷氧基 - 低级烷基，羟基 - 低级烷基，取代或未取代的芳基，或取代或未取代的杂芳基，R2是H，低级烷基，环低级烷基，环低级烷基甲基， ，环低级烯基，低级炔基，取代或未取代的芳基或取代或未取代的杂芳族基团或其药学上可接受的酸加成盐，其对苯并二氮杂受体具有高选择性亲和力，并且特别用作苯二氮卓反相激动剂，例如 作为精神无菌药物或用于治疗老年痴呆或阿尔茨海默氏症的失聪症的药物。

公开(公告)号：US5424433A

公开(公告)日：1995-06-13

申请号：US260800

申请日：1994-06-16

申请人： Kazunori Ohno ,  Osamu Odai ,  Yukio Tominaga ,  Kiyoshi Furukawa ,  Makoto Oka

发明人： Kazunori Ohno ,  Osamu Odai ,  Yukio Tominaga ,  Kiyoshi Furukawa ,  Makoto Oka

IPC分类号： A61K31/4245 ,  A61K31/435 ,  A61K31/4375 ,  C07D271/02 ,  C07D271/06 ,  C07D271/10 ,  C07D471/04

CPC分类号： C07D471/04

摘要： 3-Oxadiazolyl-5,6,7,8-tetrahydro-1,6-naphthyridine derivative of the formula (I): ##STR1## wherein Het is an oxadiazole ring, R.sub.1 is hydrogen atom, an acyl group, a lower alkyl group or a group of the formula: --CH.sub.2 R.sub.1' (in which R.sub.1' is a cyclo-lower alkyl group, a lower alkenyl group, a lower alkynyl group, benzyl group, aryl group or a heteroaromatic group), R.sub.2 is a lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkynyl group, aryl group, a heteroaromatic group, a halogeno-lower alkyl group, a lower alkoxy-lower alkyl group, a lower alkoxy group, a lower alkenyloxy group, a phenoxy group or a lower alkylthio group, or a pharmaceutically acceptable acid addition salt thereof, which are useful as benzodiazepine receptor agonist.

摘要翻译： 式（I）的3-恶二唑基-5,6,7,8-四氢-1,6-萘啶衍生物：其中Het是恶二唑环，R 1是氢原子，酰基， 低级烷基或式-CH 2 R 1'（其中R 1'为环低级烷基，低级烯基，低级炔基，苄基，芳基或杂芳族基团）的基团，R 2为 低级烷基，低级烷基，低级烯基，低级炔基，芳基，杂芳基，卤代低级烷基，低级烷氧基 - 低级烷基，低级烷氧基，低级烷基 烯氧基，苯氧基或低级烷硫基，或其药学上可接受的酸加成盐，可用作苯并二氮杂受体激动剂。