公开(公告)号：US5843954A

公开(公告)日：1998-12-01

申请号：US976398

申请日：1997-11-21

申请人： Takashi Yaegashi ,  Seigo Sawada ,  Tomio Furuta ,  Teruo Yokokura

发明人： Takashi Yaegashi ,  Seigo Sawada ,  Tomio Furuta ,  Teruo Yokokura

IPC分类号： A61K31/47 ,  A61K31/4745 ,  A61P35/00 ,  C07D209/00 ,  C07D221/00 ,  C07D471/14 ,  C07D487/02

CPC分类号： C07D471/14

摘要： New camptothecin derivatives of the general formula (1): ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group, R.sup.2 represents a hydrogen or a C.sub.1 -C.sub.6 alkoxy group, R.sup.3 represents a hydrogen or halogen atom or a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, C.sub.2 -C.sub.6 acyloxy or methoxyethoxymethoxy group, R.sup.4 represents a hydrogen or halogen atom, and R.sup.5 represents a C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 unsaturated alkyl, alkylthioalkyl, alkoxyalkyl, pyridyl or substituted phenyl group, with the proviso that all of the R.sup.2, R.sup.3 and R.sup.4 substituents should not be a hydrogen atom, and a process for preparing the new camptothecin derivatives by subjecting the camptothecin derivatives of the general formula (2): ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the same meanings as given above, to the reaction with N,N-dimethylethylenediamine without solvent to open the E-lactone ring followed by acylation of 17-hydroxyl group with corresponding acylating agents and an antitumor agent containing the same as an active ingredient.

摘要翻译： （1）的新喜树碱衍生物：其中R1表示氢原子或C1-C6烷基，R2表示氢或C1-C6烷氧基，R3表示氢或卤素原子 或C 1 -C 6烷基，C 1 -C 6烷氧基，羟基，C 2 -C 6酰氧基或甲氧基乙氧基甲氧基，R 4表示氢或卤素原子，R 5表示C 1 -C 6烷基，C 3 -C 6不饱和烷基，烷硫基烷基，烷氧基烷基，吡啶基 或取代的苯基，条件是所有的R 2，R 3和R 4取代基不应该是氢原子，以及通过使通式（2）的喜树碱衍生物进行制备来制备新的喜树碱衍生物的方法： （2）其中R 1，R 2，R 3和R 4具有与上述相同的含义，与没有溶剂的N，N-二甲基乙二胺反应以打开E-内酯环，随后用相应的酰化剂酰化17-羟基， 含有与活性物质相同的抗肿瘤剂 e成分。

公开(公告)号：US5061800A

公开(公告)日：1991-10-29

申请号：US298976

申请日：1989-01-19

申请人： Takashi Yaegashi ,  Satoru Okajima ,  Seigo Sawada ,  Kenichiro Nokata ,  Kenichi Tezuka ,  Hiroshi Nagata ,  Teruo Yokokura ,  Tadashi Miyasaka ,  Tadashi Miyasaka

发明人： Takashi Yaegashi ,  Satoru Okajima ,  Seigo Sawada ,  Kenichiro Nokata ,  Kenichi Tezuka ,  Hiroshi Nagata ,  Teruo Yokokura ,  Tadashi Miyasaka ,  Tadashi Miyasaka

IPC分类号： C07D491/147 ,  A61K31/47 ,  A61K31/475 ,  A61P35/00 ,  C07D491/22

CPC分类号： C07D491/22

摘要： New campotothecin derivatives and a process for preparing same are disclosed, which are represented by the general formula: ##STR1## wherein R.sup.1 represents a lower alkyl group, R.sup.2 represents a hydrogen atom or an amino, hydroxyl, lower acylamino or lower alkoxy group, R.sup.3 represents a hydrogen or halogen atom or a lower alkyl, hydroxyl, lower alkoxy, nitro, amino, cyano or di(lower alkyl)amino group, R.sup.4 represents a hydrogen or halogen atom or a lower alkyl, hydroxyl, lower alkoxy, lower alkylthio, amino, cyano or di(lower alkyl)amino group, and R.sup.5 represents a hydrogen or halogen atom or a hydroxyl or lower alkoxy group, with the proviso that all of the R.sup.2, R.sup.3, R.sup.4 and R.sup.5 substituents should not be a hydrogen atom and also that if any one of the R.sup.2, R.sup.3, R.sup.4 and R.sup.5 is a hydroxyl or lower alkoxy group, all of the other three substituents should not be a hydrogen atom.

公开(公告)号：US06310210B1

公开(公告)日：2001-10-30

申请号：US09530828

申请日：2000-05-03

申请人： Takanori Ogawa ,  Takashi Yaegashi ,  Seigo Sawada ,  Tomio Furuta

发明人： Takanori Ogawa ,  Takashi Yaegashi ,  Seigo Sawada ,  Tomio Furuta

IPC分类号： C07D47104

CPC分类号： C07D471/14

摘要： The present invention relates to new camptothecin derivatives shown by the below formula, which are water-soluble and excellent in an anti-tumor activity, and to salts thereof. In the formula, R1 represents a hydrogen atom or an alkyl group with 1-6 carbon atoms, R2 represents identically or differently 0-4 alkyl groups with 1-6 carbon atoms, a halogen atom, an alkoxyl or hydroxyl group, R3 represents a lower alkylamino, di-lower alkylamino, arylamino, cyclicamino or lower alkoxyl group, and salts thereof.

摘要翻译： 本发明涉及由下式表示的新的喜树碱衍生物，它是水溶性的，抗肿瘤活性优异的盐及其盐。式中R1表示氢原子或1-6位烷基 碳原子，R2表示相同或不同的具有1-6个碳原子的0-4个烷基，卤素原子，烷氧基或羟基，R3表示低级烷基氨基，二低级烷基氨基，芳基氨基，环氨基或低级烷氧基， 的盐。

公开(公告)号：US06743918B2

公开(公告)日：2004-06-01

申请号：US10239113

申请日：2002-11-25

申请人： Takashi Yaegashi ,  Takanori Ogawa ,  Seigo Sawada

发明人： Takashi Yaegashi ,  Takanori Ogawa ,  Seigo Sawada

IPC分类号： C07D49112

CPC分类号： C07D491/22 ,  A61K31/475

摘要： Problem: A large scale production of camptothecin, which is a starting compound of irinotecan hydrochloride and various camptothecin derivatives, at a low cost and with ease. Solution: A process for preparing camptothecin, characterized in that it comprises the following steps (a) and (b); (a) the step to hydrolyze 9-methoxycamptothecin or a natural material containing 9-methoxycamptothecin; (b) the step to convert 9-hydroxycamptothecin obtained in the step (a) into camptothecin by 9-O—perfluoro-lower-alkylsulfonylation or 9-O—phenyltetrazolylation, followed by hydrogenolysis.

摘要翻译： 问题：大量生产喜树碱，它是伊立替康盐酸盐和各种喜树碱衍生物的起始化合物，成本低，易于使用。溶液：一种制备喜树碱的方法，其特征在于它包括以下步骤（a）和 （b）;（a）水解9-甲氧基喜树碱或含有9-甲氧基喜树碱的天然物质的步骤;（b）将步骤（a）中得到的9-羟基喜树碱通过9-O-全氟低级 - 烷基磺酰化或9-O-苯基四唑化，然后氢解。

公开(公告)号：US09174979B2

公开(公告)日：2015-11-03

申请号：US13125698

申请日：2009-10-23

申请人： Takashi Ikeda ,  Seigo Sawada ,  Takashi Yaegashi ,  Takeshi Matsuzaki ,  Shusuke Hashimoto ,  Ryuta Yamazaki

发明人： Takashi Ikeda ,  Seigo Sawada ,  Takashi Yaegashi ,  Takeshi Matsuzaki ,  Shusuke Hashimoto ,  Ryuta Yamazaki

IPC分类号： C07D471/04 ,  A61K31/437 ,  A61P29/00 ,  A61P35/00 ,  C07D491/147

CPC分类号： C07D471/04 ,  C07D491/147

摘要： A novel compound having an excellent NFκB inhibitory effect is provided and specifically disclosed is a compound represented by the following formula (1) or a salt thereof:wherein, R1 represents a hydrogen atom, a lower alkyl group, a lower alkyloxy group, or a halogen atom;R2 represents a hydroxyl group, or a lower alkyloxy group;R3 represents a hydrogen atom, a lower alkyl group, or a halogen atom;R4 represents a hydrogen atom or a lower alkyloxy group;R5 represents a hydrogen atom, a lower alkyloxy group, a halogen atom, a hydroxyl group, or a methylenedioxy group formed together with R6 or an isopropylidenedioxy group formed together with R6;R6 represents a hydrogen atom, a lower alkyloxy group, or a methylenedioxy group formed together with R5 or an isopropylidenedioxy group formed together with R5;R7 represents a hydrogen atom or a lower alkyl group; andR8 represents a hydrogen atom, a hydroxyl group, an amino group, or a lower alkylcarbonyloxy group (excluding the case where R1, R3, R4 and R7 are hydrogen atoms, R2 and R8 are hydroxyl groups, and R5 and R6 are methoxy groups).

摘要翻译： 提供了具有优异的NF＆Kgr B抑制效果的新化合物，具体公开了下式（1）表示的化合物或其盐：其中，R1表示氢原子，低级烷基，低级烷氧基， 或卤素原子; R2表示羟基或低级烷氧基; R3表示氢原子，低级烷基或卤素原子; R4表示氢原子或低级烷氧基; R5表示与R6一起形成的与R6或异丙烯二氧基一起形成的氢原子，低级烷氧基，卤素原子，羟基或亚甲二氧基; R6表示与R5一起形成的氢原子，低级烷氧基或亚甲二氧基，或与R5形成的异丙烯二氧基; R7表示氢原子或低级烷基; 并且R 8表示氢原子，羟基，氨基或低级烷基羰基氧基（R 1，R 3，R 4和R 7为氢原子的情况除外，R 2和R 8为羟基，R 5和R 6为甲氧基 ）。

公开(公告)号：US6025385A

公开(公告)日：2000-02-15

申请号：US147521

申请日：1999-01-14

申请人： Hideaki Shimizu ,  Atsuhiro Abe ,  Takashi Yaegashi ,  Seigo Sawada ,  Hiroshi Nagata

发明人： Hideaki Shimizu ,  Atsuhiro Abe ,  Takashi Yaegashi ,  Seigo Sawada ,  Hiroshi Nagata

IPC分类号： C07D305/14 ,  C07D405/12 ,  C07D413/12 ,  C07D413/14 ,  A61K31/335

CPC分类号： C07D405/12 ,  C07D305/14 ,  C07D413/12 ,  C07D413/14

摘要： This invention relates to a taxane derivative represented by the following formula (1): wherein at least one of X and Y represents a group --CO--A--B in which A represents a single bond, an alkylenecarbonyl group or the like and B represents a substituted or unsubstituted piperidino group or the like, the other represents a tert-butoxycarbonyl group or the like, and Z represents a hydrogen atom or a triethylenesilyl group, and also to a drug containing the same.This compound has high solubility in water and also has excellent antitumor activities.

摘要翻译： PCT No.PCT / JP97 / 02431 Sec。 371日期1999年1月14日第 102（e）1999年1月14日PCT PCT 1997年7月14日PCT公布。 出版物WO98 / 02426 日本特开2003-12-04本发明涉及下述式（1）表示的紫杉烷衍生物：其中X和Y中的至少一个表示A表示单键的-CO-AB基团，亚烷基羰基等 B表示取代或未取代的哌啶子基等，另一方表示叔丁氧基羰基等，Z表示氢原子或三亚甲基甲硅烷基，也可以是含有该取代基的药物。 该化合物在水中的溶解度高，抗肿瘤活性也优异。

公开(公告)号：US08476438B2

公开(公告)日：2013-07-02

申请号：US12226506

申请日：2007-04-27

申请人： Seigo Sawada ,  Takashi Yaegashi

发明人： Seigo Sawada ,  Takashi Yaegashi

IPC分类号： C07D471/00

CPC分类号： C07B53/00 ,  C07D491/22

摘要： Disclosed is a process for production of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin from a camptothecin composition containing 18,19-dehydrocamptothecin without producing any vinyl form of the compound. The process is characterized by catalytically reducing at least one compound selected from a compound (1) and others in the process of producing a compound (5) from a composition containing the compound (1).

摘要翻译： 公开了一种从不含任何乙烯基形式的化合物生产含有18,19-脱氢喜树碱的喜树碱组合物的7-乙基-10- [4-（1-哌啶子基）-1-哌啶子基]羰氧基喜树碱的方法。 该方法的特征在于在含有化合物（1）的组合物的制备方法中催化还原至少一种选自化合物（1）和其它化合物的化合物。

公开(公告)号：US4914205A

公开(公告)日：1990-04-03

申请号：US210918

申请日：1988-06-24

申请人： Seigo Sawada ,  Kenichiro Nokata ,  Satoru Okajima ,  Hisako Nagai ,  Takashi Yaegashi ,  Kenichi Tezuka ,  Tadashi Miyasaka

发明人： Seigo Sawada ,  Kenichiro Nokata ,  Satoru Okajima ,  Hisako Nagai ,  Takashi Yaegashi ,  Kenichi Tezuka ,  Tadashi Miyasaka

IPC分类号： C07D471/14

CPC分类号： C07D471/14

摘要： New camptothecin derivatives, useful as antitumor agents or intermediates therefor, of the general formula (I) ##STR1## wherein X is a lower alkyl group, and R is a hydrogen atom or the grouping -COY where Y is a linear or branched unsubstituted C.sub.1 -C.sub.18 alkyl group; a lower alkyl group substituted by a halogen atom or a lower alkylthio, amino, acylamino, hydroxyl, lower alkoxy, aryloxy or lower alkoxycarbonyl group; a C.sub.3 -C.sub.19 alkenyl, C.sub.3 -C.sub.19 alkynyl or C.sub.3 -C.sub.8 cycloalkyl group; a C.sub.3 -C.sub.8 cycloalkyl group substituted by an acylamino-lower alkyl group; an N-acylpyrrolidyl group; a phenyl group; a phenyl group substituted by a halogen atom or a trifluoromethyl, nitro, amino, lower alkoxycarbonyl, lower alkyl, phenyl or lower alkoxy; a cinnamyl group; a benzyl group; a naphthyl group; a pyridyl group; a furyl group; or a thienyl group, as well as acid addition salts and quaternary ammonium salts thereof,and a process for preparing the new camptothecin derivatives by subjecting 7-ethylcamptothecin to the treatment with an N-di-X-ethylenediamine followed by acylation.

公开(公告)号：US08569327B2

公开(公告)日：2013-10-29

申请号：US13124554

申请日：2009-10-23

申请人： Takashi Ikeda ,  Seigo Sawada ,  Takashi Yaegashi ,  Takeshi Matsuzaki ,  Shusuke Hashimoto ,  Ryuta Yamazaki

发明人： Takashi Ikeda ,  Seigo Sawada ,  Takashi Yaegashi ,  Takeshi Matsuzaki ,  Shusuke Hashimoto ,  Ryuta Yamazaki

IPC分类号： A61K31/403 ,  C07D221/18

CPC分类号： C07D471/04

摘要： A novel compound having an excellent NFκB inhibitory effect is provided. Specifically disclosed is a compound represented by the following formula (1) or a salt thereof: wherein, R1 represents a hydrogen atom, a lower alkyl group, or the like; R2 represents a hydrogen atom, a lower alkyl group, a halogen atom, or the like; R3 represents a hydrogen atom, a lower alkyl group, a hydroxyl group, or a halogen atom; R4 represents a hydrogen atom or a lower alkyloxy group; R5 represents a hydrogen atom, a lower alkyloxy group, a halogen atom, a hydroxyl group, or a methylenedioxy group formed together with R6 or an isopropylidenedioxy group formed together with R6; R6 represents a hydrogen atom, a lower alkyloxy group, or a methylenedioxy group formed together with R5 or an isopropylidenedioxy group formed together with R5; R7 represents a hydrogen atom or a lower alkyl group; and R8 represents a hydrogen atom, a hydroxyl group, an amino group, a lower alkylcarbonyloxy group, or a halogen atom.

摘要翻译： 提供了具有优异NFκB抑制作用的新型化合物。 具体公开的是由下式（1）表示的化合物或其盐：其中，R1表示氢原子，低级烷基等; R2表示氢原子，低级烷基，卤素原子等; R3表示氢原子，低级烷基，羟基或卤素原子; R4表示氢原子或低级烷氧基; R5表示与R6一起形成的与R6或异丙烯二氧基一起形成的氢原子，低级烷氧基，卤素原子，羟基或亚甲二氧基; R6表示与R5一起形成的氢原子，低级烷氧基或亚甲二氧基，或与R5形成的异丙烯二氧基; R7表示氢原子或低级烷基; R8表示氢原子，羟基，氨基，低级烷基羰基氧基或卤素原子。

公开(公告)号：US07488825B2

公开(公告)日：2009-02-10

申请号：US10546687

申请日：2004-02-24

申请人： Hideaki Shimizu ,  Atsuhiro Abe ,  Takashi Yaegashi ,  Seigo Sawada

发明人： Hideaki Shimizu ,  Atsuhiro Abe ,  Takashi Yaegashi ,  Seigo Sawada

IPC分类号： C07D491/22

CPC分类号： C07D491/22

摘要： A method for preparing a novel crystalline polymorphic irinotecan hydrochloride which is excellent in the solubility in water and reduced in the content of impurities is provided. A method for preparing c-type crystals of irinotecan hydrochloride having diffraction peaks (2θ) at 9.15°, 10.00°, 11.80°, 12.20°, 13.00° and 13.40° in the powder X-ray diffractometry characterized by mixing irinotecan with one or more solvents selected from the group consisting of acetone, acetonitrile and tetrahydrofuran, adding hydrochloric acid, and collecting the formed crystals.

摘要翻译： 提供了一种制备在水中的溶解性优异且杂质含量降低的新型结晶多晶异氟酸盐酸伊立替康的方法。 在粉末X射线衍射法中，制备在9.15°，10.00°，11.80°，12.20°，13.00°和13.40°具有衍射峰（2θ）的伊立替康盐酸盐的c型晶体的方法，其特征在于将伊立替康与一种或多种 选自丙酮，乙腈和四氢呋喃的溶剂，加入盐酸，收集形成的晶体。