Kabushiki Kaisha Yakult Honsha

Daiichi Pharmaceutical Co., Ltd.

Tomio Furuta

Seigo Sawada

Hiroshi Hatano

Shusuke Hashimoto

Ryuta Yamazaki

Takashi Yaegashi

Takeshi Matsuzaki

Masato Nagaoka

Ritsuo Aiyama

Yukiko Nishiyama

Oh Yoshida

Yoshikazu Sugimoto

Teruo Yokokura

Takanori Ogawa

A breast cancer resistance protein (BCRP/ABCG2) inhibitor. The BCRP inhibitor contains, as an active ingredient, an acrylonitrile derivative or a salt thereof.

BCRP/ABCG2 inhibitor

The invention provides a drug which inhibits BCRP. A breast cancer resistance protein inhibitor containing, as an active ingredient, a diphenylacrylonitrile derivative represented by the following formula (1): [wherein, each of 8 R's, which are the same or different from one another, represents a hydrogen atom, a hydroxyl group, a nitro group, an amino group, an acetylamino group (&#x2014;NHCOCHgroup); a cyano group (&#x2014;CN group); a formyl group (&#x2014;CHO group), &#x2014;COOR(Ris hydrogen or C1-C4 alkyl), &#x2014;O(CH)COOR(n=1&#x2212;7: Ris hydrogen or C1-C4 alkyl), &#x2014;OOCCHCHCOOR(Ris hydrogen, C1-C4 alkyl, (Z)-2-(3,4-dimethoxy-phenyl)-3-(4-hydroxy-phenyl)-acrylonitrile, or glycopyranosyl), a C1-C8 alkoxy group, a C1-C4 alkyl group, a halogen atom, a C1-C4 alkoxy C1-C4 alkoxy C1-C4 alkoxy group, a C2-C8 acyloxy group, a C2-C8 halogenoacyloxy group, a methylenedioxy group, a trifluoromethyl group, a phosphate group (i.e., &#x2014;OP(O) (OH)) or a salt thereof, a sulfate group (i.e., &#x2014;OSOH) or a salt thereof, a glycopyranosyl group or a salt thereof, a phosphate ester of a glycopyranosyl group or a salt of the ester, a sulfate ester of a glycopyranosyl group or a salt of the ester, or a piperidinopiperidinocarbonyloxy group], an ester thereof, or a salt thereof.

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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

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.

Camptothecin derivatives, preparations thereof and antitumor agents

Growing community of inventors

Minato-ku, Japan

Tomio Furuta