Kabushiki Kaisha Yakult Honsha

Terumo Kabushiki Kaisha

Daiichi Pharmaceutical Co., Ltd.

Seigo Sawada

Takashi Yaegashi

Tadashi Miyasaka

Kenichiro Nokata

Hideaki Shimizu

Masahiko Mutai

Takanori Ogawa

Atsuhiro Abe

Hiroyuki Nishiyama

Hiroshi Nagata

Takeshi Matsuzaki

Miyuki Uchida

Takashi Ikeda

Shusuke Hashimoto

Teruo Yokokura

Ryuta Yamazaki

Kenichi Tezuka

Tomio Furuta

Satoru Okajima

Yasuo Kurosaki

Shigenori Nozawa

Masashi Isozaki

Keisuke Yoshino

Ikuo Kato

Hisao Hagiwara

Tsuneo Matsumoto

Eiichi Sugino

Norimasa Kaneda

Hisako Nagai

Hiroshi Kodaira

Yoshitaka Ogata

A novel compound having an excellent NF&#x3ba;B inhibitory effect is provided and specifically disclosed is a compound represented by the following formula (1) or a salt thereof: wherein, Rrepresents a hydrogen atom, a lower alkyl group, a lower alkyloxy group, or a halogen atom; Rrepresents a hydroxyl group, or a lower alkyloxy group; Rrepresents a hydrogen atom, a lower alkyl group, or a halogen atom; Rrepresents a hydrogen atom or a lower alkyloxy group; Rrepresents a hydrogen atom, a lower alkyloxy group, a halogen atom, a hydroxyl group, or a methylenedioxy group formed together with Ror an isopropylidenedioxy group formed together with R; Rrepresents a hydrogen atom, a lower alkyloxy group, or a methylenedioxy group formed together with Ror an isopropylidenedioxy group formed together with R; Rrepresents a hydrogen atom or a lower alkyl group; and Rrepresents a hydrogen atom, a hydroxyl group, an amino group, or a lower alkylcarbonyloxy group (excluding the case where R, R, Rand Rare hydrogen atoms, Rand Rare hydroxyl groups, and Rand Rare methoxy groups). 

Phenanthroindolizidine compound and NF&#x3ba;B inhibitor containing same as active ingredient

A novel compound having an excellent NF&#x3ba;B inhibitory effect is provided. Specifically disclosed is a compound represented by the following formula (1) or a salt thereof: 

Phenanthroindolizidine derivative and NF&#x3ba;B inhibitor containing same as active ingredient

It is intended to provide a novel compound that has an excellent &#x3b3;-secretase inhibitory effect and specifically inhibits A&#x3b2; production. The present invention provides a compound of the following formula (1) or a pharmaceutically acceptable salt thereof: wherein Rrepresents a linear or branched alkyl group having 1 to 4 carbon atoms or a phenyl group; Rrepresents a linear or branched alkyl group having 1 to 4 carbon atoms which may be substituted by one or more phenyl or halogenophenyl groups; Rrepresents a linear or branched alkyl group having 1 to 4 carbon atoms which may be substituted by one or more hydroxyl groups; Rrepresents a linear or branched alkyl group having 1 to 4 carbon atoms; and the symbol '*' represents a chiral center. 

&#x3b3;-secretase inhibitor

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).

Process for production of camptothecin derivative

In order to efficiently supply CPT, which is a starting compound of irinotecan hydrochloride and a variety of camptothecin derivatives, by a practical total synthesis, the invention provides a means of efficiently preparing a tricyclic ketone that corresponds to a CDE ring moiety of a camptothecin (CPT) skeleton.

Process for producing tricyclic ketone

The present invention is directed to an irinotecan acid addition salt which is formed through addition of an acid selected from the group consisting of sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, citric acid, maleic acid, and succinic acid to irinotecan, to a method for producing the salt, and to a pharmaceutical composition containing the salt. The addition salt requires no heating process during drug preparation and provides an aqueous drug product in which the salt is stably dissolved.

Acid addition salt of irinotecan

Provided is an irinotecan formulation capable of supporting irinotecan and/or a salt thereof in a closed vesicle carrier at a high concentration and existing in blood for a long period of time by dramatically improved retentivity in blood compared to a conventionally known irinotecan liposome formulation. That is, an irinotecan formulation including a closed vesicle formed by a lipid membrane, in which irinotecan and/or a salt thereof is encapsulated at a concentration of at least 0.07 mol/mol (drug mol/membrane total lipid mol). There is an ion gradient between an inner aqueous phase and an outer aqueous phase in the irinotecan formulation. The closed vesicle is preferably liposome, in which only the outer surface of the liposome is preferably modified with a surface-modifying agent containing a hydrophilic polymer.

Irinotecan preparation

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 (2&#x3b8;) at 9.15&#xb0;, 10.00&#xb0;, 11.80&#xb0;, 12.20&#xb0;, 13.00&#xb0; and 13.40&#xb0; 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.

Method for preparing polymorphism of irinotecan hydrochloride

The present invention is to prepare efficiently 2'-amino-5&#x2032;-hydroxypropiophenone corresponding to the AB-ring part of camptothecin (CPT) skeleton and a tricyclic ketone corresponding to the CDE-ring part in order to provide efficiently CPT by the total synthesis, which is a starting material for irinotecan hydrochloride and various kinds of camptothecin derivatives, and to provide stably CPT and its derivatives.

Method of synthesizing camptothecin-relating compounds

Process for producing camptothecin

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.

Camptothecin derivatives

The present invention relates to taxane derivatives each represented by the following formula (1):

Taxane derivatives

Growing community of inventors

Tokyo, Japan

Seigo Sawada