Kyowa Hakko Kogyo Co., Ltd.

Kyowa Hakko Kogyo Kabushiki Kaisha

Kyowa Hakko Kogyo Kabushiki

Motomichi Kono

Masaji Kasai

Tadashi Ashizawa

Makoto Morimoto

Kunikatsu Shirahata

Yutaka Saito

Yutaka Kanda

Katsushige Gomi

Hitoshi Arai

Hiroshi Sano

Shinzo Ishii

Akira Sato

Shigeo Katsumata

Yuko Arai

Novel mitomycin derivatives represented by the formula (I) are obtained by introducing a substituent at the 6-position. The mitomycin derivatives of the present invention have an antitumor activity.

6-ethyl mitomycin derivatives

Mitomycin derivatives

Disclosed in a mitomycin derivative represented by the formula (I): ##STR1## wherein W is a heterocyclic group.

Mitomycin derivatives having potent anti-tumor activity having the formula: ##STR1## wherein one of R.sub.1 and R.sub.2 represents carbamoyloxymethyl and the other represents hydrogen or R.sub.1 and R.sub.2 are bonded together to form methylene;

7-N,8-N-Ethylenemitomycin 8-imines represented by the formula ##STR1## wherein one of the R.sub.1 and R.sub.2 represents carbamoyloxymethyl and another represents hydrogen or both are combined together to form methylene; R.sub.3, R.sub.4, R.sub.5 and R.sub.6 each independently represent hydrogen or C.sub.1-4 alkyl, or R.sub.3 and R.sub.4 may be combined together to represent --(CH.sub.2).sub.n --, wherein n is 3 or 4; and Y and Z represent hydrogen or methyl, provided that when R.sub.1 represents carbamoyloxymethyl and Y represents methyl, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6 and Z are not hydrogen simultaneously, has an excellent antitumor activity.

7-N,8-N-Ethylenemitomycin 8-imines

Mitomycin compound having potent antitumour activity having the formula: ##STR1## wherein ##STR2## (wherein Ra, Rb and Rc each independently represent lower alkyl, cycloalkyl having 3-7 carbon atoms or phenyl; or Ra and Rb are bonded together to form a poly-methylene group having 2-5 carbon atoms);

Mitomaycin compounds

Mitomycin derivatives of the formula: ##STR1## wherein X is ##STR2## [wherein R.sub.3 is alkyl, cycloalkyl or optionally substituted phenyl; and R.sub.4 is alkyl or cycloalkyl]; n is an integer of 2 to 8; one of R.sub.1 and R.sub.2 is a hydrogen atom and the other is a carbamoyloxymethyl group, or alternatively R.sub.1 and R.sub.2 may be combined together to form a methylene group (.dbd.CH.sub.2); and Y and Z independently represent hydrogen or methyl; exhibit anti-bacterial and anti-tumor activities.

Mitomycin derivatives having anti-tumor and antibacterial utility

Mitomycin derivatives represented by the formula (I): ##STR1## wherein R.sub.1 and R.sub.2 may be the same or different, and represent a hydrogen atom or a lower alkyl group; R.sub.3 and R.sub.4 mean that when R.sub.3 is a hydrogen atom, R.sub.4 represents --CH.sub.2 OCONH.sub.2 or ##STR2## (wherein R.sub.1 and R.sub.2 have the same significances as defined above), or R.sub.3 and R.sub.4 are combined to form .dbd.CH.sub.2 ; Y and Z may be the same or different, and represent a hydrogen atom or a methyl group;   represents .alpha.- or .beta.-bond, provided that Y represents a hydrogen atom when R.sub.4 takes .beta.-configuration, have an excellent anti-tumor activity.

7-n-aminomethylenemitomycin derivative

The present invention provides new mitomycin derivatives of general formula (I) ##STR1## [wherein Y and Z, which may be the same or different, each represents a hydrogen atom or a methyl group;

New mitomycin derivatives, preparation thereof and pharmaceutical

A substance designated by us as AX-2 and represented by the formula: ##STR1## This substance is produced by culturing a microorganism of the genus Streptomyces and capable of producing AX-2 in a medium to accumulate AX-2 in the cultured broth and isolating AX-2 therefrom. An anti-tumor composition comprising an effective amount of AX-2 in association with a physiologically acceptable carrier or excipient, which is active against Sarcoma 180.

Substance AX-2, a process for producing the same and an antitumor

Mitomycin compounds of the general formula (I): ##STR1## wherein X is selected from an alkoxy group having 1 to 4 carbon atoms and amino group; and Z is selected from --OH, --OCONH.sub.2 and --OCO.sub.2 C.sub.6 H.sub.5 groups. The compounds of this formula may be used as starting materials for the preparation of various mitomycin compounds. When X is as hereinbefore defined and Z is --OCONH.sub.2, the compounds exhibit antibacterial activity and are of potential interest as medicaments. Preferred examples of the compounds are 9-Epi-mitomycin B and 9-epi-mitomycin D. The compounds of the formula (I) may be obtained from known mitomycin B or mitomycin D.

9-Epi-mitomycin B and D compounds

New mitomycins are produced by synthetic processes. The compounds exhibit broad spectrum antibacterial activity and are useful as antibacterial agents.

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Machida, Japan

Motomichi Kono