Sankyo Company, Limited

Director-general of the Agency of Industrial Science and Technology

Tomowo Kobayashi

Yukio Sugimura

Tomoyuki Shibata

Kimio Iino

Masakatsu Kaneko

Kazuhiko Sasagawa

Koichi Kojima

Yoshio Tsujita

Shigeki Muramatsu

Toshihiko Hashimoto

Takeshi Kagasaki

Kazuhiko Tamaki

Makoto Kamokari

Yukiko Kameyama

Yoko Shimada

Akira Matsuda

Takuma Sasaki

Takafumi Kohama

Masami Arai

Tetsuo Hiraoka

Hitoshi Hotoda

Yoshihiro Mitsuhashi

Kazuhiko Tanzawa

Shigeru Tsukagoshi

Akio Shiraishi

Masao Shiozaki

Noboru Ishida

Masaru Shiraki

Takashi Hirano

Satoshi Morimoto

Keishiro Tsuda

Shinichi Ohashi

Shinwa Kurihara

Naomi Shimazaki

Yuzuru Akamatsu

Masahiro Nishijima

A method for treatment or prevention of prostate cancer by administering an effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt or ester thereof. In formula (I) (which follows) , each of R,and R,is a hydrogen atom, a hydroxyl group, a protected hydroxyl group or a lower alkoxy group.

Method for prevention of prostate cancer

A method for treatment or prevention of prostate cancer by administering an effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt or ester thereof. In formula (I) (which follows), each of R.sup.1 and R.sup.2 is a hydrogen atom, a hydroxyl group, a protected hydroxyl group or a lower alkoxy group. ##STR1##

Method for treating prostate cancer

Compounds of formula (I): ##STR1## in which: R.sup.1 is hydroxy, protected hydroxy, fluorine, or --OP(O)(OH).sub.2 ; R.sup.2 and R.sup.3 are independently optionally substituted C.sub.6 -C.sub.20 aliphatic acyl; R.sup.4 is hydroxy, protected hydroxy, or --OP(O)(OH).sub.2, where at least one of R.sup.1 and R.sup.4 is --OP(O)(OH).sub.2 ; and R.sup.5 is hydroxy, protected hydroxy, or fluorine; provided that, except where at least one of R.sup.1 and R.sup.5 is fluorine, then at least one of R.sup.2 and R.sup.3 is a substituted C.sub.6 -C.sub.20 aliphatic acyl having (i) at least one halogen substituent and (ii) at least one substituent selected from the group consisting of halogen, hydroxy and C.sub.6 -C.sub.20 aliphatic acyloxy or at least one of R.sup.2 and R.sup.3 is a substituted C.sub.6 -C.sub.20 aliphatic acyl which is substituted by at least one halogen-substituted C.sub.6 -C.sub.20 aliphatic carboxylic acyloxy; have Lipid A-like activity and may be used for the treatment, prophylaxis, diagnosis and support of an animal suffering a disease or disorder arising from a deficiency in the immune system or from a tumor. They may be prepared by phosphorylation of corresponding compounds lacking a phosphoryl group.

Lipid A analogs having immunoactivating and anti-tumor activity

Compounds of formula (I): ##STR1## wherein: R.sup.1, R.sup.2 and R.sup.3 are independently selected from the group consisting of hydrogen atoms, optionally substituted alkanoyl groups and alkenylcarbonyl groups, PROVIDED THAT at least one of R.sup.1, R.sup.2 and R.sup.3 represents an unsubstituted alkanoyl group having from 5 to 24 carbon atoms, said substituted alkanoyl group or said alkenylcarbonyl group; and one of R.sup.4 and R.sup.5 represents a hydrogen atom and the other represents a cyano group; have valuable anti-tumor activity.

Pyrimidine nucleoside derivatives having anti-tumor activity, their

Radicicol derivatives in which one or both hydroxy groups are acylated have valuable anti-tumor activity or may be used as chemical intermediates.

Radicicol derivatives, their preparation and their anti-tumor activity

Collagenase inhibitor

Compounds of formula (I): ##STR1## in which: A and B are separately monoamines or together diamines; and Z is a group of formula (II) or (III): ##STR2## (in which R.sup.1, R.sup.2 and R.sup.7 are various organic groups, n is 0, 1 or 2 and X is a direct carbon-carbon bond or lower alkylene) show valuable anti-tumor activity and may be prepared by reacting an amine-platinum complex with a compound providing the group represented by Z.

Anti-tumor platinum complexes, their preparation and their therapeutic

A compound of the formula ##STR1## in which: R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen atoms and groups of formula R.sup.3 --CO--, wherein R.sup.3 represents a group selected from the group consisting of unsubstituted alkyl groups having from 9 to 20 carbon atoms; substituted alkyl groups having from 10 to 20 carbon atoms; unsubstituted alkenyl groups having from 9 to 20 carbon atoms; substituted alkenyl group having from 10 to 20 carbon atoms; unsubstituted alkynyl groups having from 8 to 10 carbon atoms; and substituted alkynyl groups having from 8 to 10 carbon atoms wherein R.sup.1 and R.sup.2 are not both hydrogen atoms or acetyl groups. The compounds have antitumor activity.

A new compound, which we have named Leustroducsin H, has formula (I): ##STR1## and pharmaceutically acceptable salts thereof. This compound may be prepared by hydrolysis of naturally occurring Leustroducsins and the compound may be used for the treatment or prophylaxis of thrombocytopenia.

Leustroducsin H, its preparation and its therapeutic use

Rhizoxin and rhizoxin-2-ene derivatives of formula (I): ##STR1## in which: n is 1 to 25: A is an extra bond or oxygen, X is oxygen, sulfur, nitrogen or carbonyl; and R is hydrogen, carboxylic acyl having from 1 to 25 carbon atoms, alkoxycarbonyl group having from 2 to 26 carbon atoms, phosphono, alkylphosphono group in which the alkyl part has from 1 to 25 carbon atoms, dialkylphosphono group in which each alkyl part has from 1 to 25 carbon atoms, alkyl group having from 1 to 25 carbon atoms, aralkyl, cycloalkyl, heterocyclic, alkylthio group in which the alkyl part has from 1 to 25 carbon atoms, aralkylthio, or heterocyclylthio, or when X represents a nitrogen atom, R is R.sup.1 and R.sup.2, where R.sup.1 and R.sup.2 are hydrogen, alkyl, acyl, alkoxycarbonyl, phosphono, alkylphosphono or dialkylphosphono have valuable anti-tumor activity. They may be prepared by acylation of rhizoxin or rhizoxin-2-ene.

Rhizoxin derivatives and their use as anti-tumor agents

Rhizoxin and rhizoxin-2-ene derivatives of formula ##STR1## in which: n is 1 to 25; A is an extra bond or oxygen, X is oxygen, sulfur, nitrogen or carbonyl; and R is hydrogen, carboxylic acyl having from 1 to 25 carbon atoms, alkoxycarbonyl group having from 2 to 26 carbon atoms, phosphono, alkylphosphono group in which the alkyl part has from 1 to 25 carbon atoms, dialkylphosphono group in which each alkyl part has from 1 to 25 carbon atoms, alkyl group having from 1 to 25 carbon atoms, aralkyl, cycloalkyl, heterocyclic, alkylthio group in which the alkyl part has from 1 to 25 carbon atoms, aralkylthio, or heterocyclylthio, or when X represents a nitrogen atom, R is R.sup.1 and R.sup.2, where R.sup.1 and R.sup.2 are hydrogen, alkyl, acyl, alkoxycarbonyl, phosphono, alkylphosphono or dialkylphosphono, have valuable anti-tumor activity. They may be prepared by acylation of rhizoxin or rhizoxin-2-ene.

The novel polymeric compound proposed in the invention has a backbone structure formed of a copolymeric moiety of maleic anhydride and divinyl ether and pendant groups thereon derived from an anthracycline-type anti-tumor agent, e.g. adriamycin and daunomycin, or 1-.beta.-D-arabinofuranosylcytosine bonded to the maleic anhydride units in the backbone structure by forming amide linkages, the remaining anhydride units in the backbone structure being hydrolyzed into free acid form or a salt thereof. Both in vitro and in vivo tests indicate that the anti-tumor active pendant groups in the polymeric compound can be released sustainedly to exhibit the anti-tumor activity with greatly decreased side effects unavoidable when the above mentioned anti-tumor agents as such are administrated to a patient in a relatively large dose.

Polymeric compounds with sustained anti-tumor activity and a method for

Growing community of inventors

Tokyo, Japan

Tomowo Kobayashi