Yamasa Shoyu Kabushiki Kaisha

Yoshitomi Pharmaceutical Industries, Ltd.

Yamasa Shoyu Co., Ltd.

Toa Eiyo Ltd.

Sumitomo Pharmaceuticals Company Limited

Tohru Ueda

Akira Matsuda

Takuma Sasaki

Haruhiko Machida

Keiji Yamagami

Akihiro Fujii

Kenji Takenuki

Shinji Sakata

Kentaro Kogi

Toichi Abiru

Takanori Miyashita

Toyofumi Yamaguchi

Noriaki Minakawa

Yoshikazu Yanagi

2'-Methylidenepyrimidine nucleoside compounds of the general formula: ##STR1## wherein R.sup.1 stands for amino or hydroxy group; R.sup.2 stands for a halogen or a lower alkyl when R.sup.1 is amino or R.sup.2 stands for an alkyl having 2 to 4 carbon atoms, an alkynyl having 2 to 4 carbon atoms or a haloalkyl when R.sup.1 is hydroxy group; and R.sup.3 stands for hydrogen or a phosphoric acid residue, or salts thereof, anticancer compositions containing one or more of these compounds and methods for production of these compounds. Said compounds and salts thereof exhibit noticeable antitumor activities and are useful as anticancer agents.

2'-methylidenepyrimidine nucleoside compounds

The present invention relates to a novel compound represented by the following formula [I] which is useful as a synthetic intermediate of a 2-alkynyladenosine. The present invention also relates to a process for producing the compound and a process for producing a 2-alkynyladenosine [IV] by way of the compound. Further, the present invention relates to a 2-alkynyladenosine derivative represented by the following formula [V] having excellent storage stability and, to a method of storing the 2-alkynyladenosine in the form of that derivative. ##STR1## [I] A=a leaving group, [II] A=NH.sub.2, [V] A=NHR.sup.4, wherein R.sup.1 through R.sup.4 represent a hydrogen atom or a protective group, and n denotes an integer of 1 to 15, provided that R.sup.1 through R.sup.4 do not represent a hydrogen atom simultaneously.

Process for preparing synthetic intermediates of 2-alkynyladenosines and

Disclosed are novel 2'-alkylidenepyrimidine nucleoside derivatives represented by formula [I]: ##STR1## R.sup.1 is an amino group or a hydroxy group, R.sup.2 is a hydrogen atom, a halogen atom or a lower alkyl group, R.sup.3 is a hydrogen atom or a lower alkyl group, and R.sup.4 is a hydrogen atom or a phosphate residue, or salts thereof. These novel compounds can be produced from uridine or cytidine derivatives by alkylidenating the 2'-position in the sugar moiety thereof with Wittig's reagent. Furthermore, the compounds have remarkable antiviral activities and therefore can provide novel antiviral agents.

2'-alkylidenepyrimidine nucleoside derivatives, process for production

2'-Methylidenepyrimidine nucleoside compounds of the general formula: ##STR1## wherein R.sup.1 stands for amino or hydroxy group; R.sup.2 stands for a halogen or a lower alkyl when R.sup.1 is amino or R.sup.2 stands for an alkyl having 2 to 4 carbon atoms, an alkynyl having 2 to 4 carbon atoms or a haloalkyl when R.sup.1 is hydroxy group; and R.sup.3 stands for hydrogen or a phosphoric acid residue, or salts thereof, compositions containing one or more of these compounds and methods for production of these compounds are disclosed. Said compounds and salts thereof exhibit noticeable antitumor activities.

2'methylidenepyrimidine nucleoside compounds, their use and method for

Disclosed are novel 2'-alkylidenepyrimidine nucleoside derivatives represented by formula [I]: ##STR1## wherein R.sup.1 is an amino group or a hydroxy group, R.sup.2 is a hydrogen atom, a halogen atom or a lower alkyl group, R.sup.3 is a hydrogen atom or a lower alkyl group, and R.sup.4 is a hydrogen atom or a phosphate residue, or salts thereof. These novel compounds can be produced from uridine or cytidine derivatives by alkylidenating the 2'-position in the sugar moiety thereof with Wittig's reagent. Furthermore, the compounds have remarkable antiviral activities and therefore can provide novel antiviral agents.

2'-alkylidenepyrimidine nucleoside compounds and a process for

Tri-O-acetyl-2-alkynyladenosines

Disclosed are imidazole derivatives represented by formula [I]: ##STR1## wherein R is a hydrogen atom or ##STR2## wherein R.sup.2 is a hydrogen atom or a hydroxy protecting group, R.sup.2 protecting either a single hydroxy or two hydroxies together when R.sup.2 is a hydroxy protecting group, and R.sup.3 is a hydrogen atom or OR.sup.2 ; A is CONH.sub.2 or CN; and R.sup.1 is a hydrogen atom, lower alkyl, hydroxy lower alkyl, or phenyl. Also disclosed are six processes for producing these novel compounds among which a typical process comprises reacting a starting imidazole compound having a halogen at the 5-position thereof with an acetylene derivative to alkynylate the 5-position. Furthermore, the compounds have remarkable antitumor activities and therefore can provide novel antitumor agents.

Imidazole derivatives and use thereof

Disclosed are imidazole derivatives represented by formula [I]: ##STR1## wherein R is a hydrogen atom or ##STR2## wherein R.sup.2 is a hydrogen atom or a hydroxy protecting group, R.sup.2 protecting either a single hydroxy or two hydroxies together when R.sup.2 is a hydroxy protecting group, and R.sup.3 is a hydrogen atom or OR.sup.2 ; A is CONH.sub.2 or CN; and R.sup.1 is a hydrogen atom, lower alkyl, hydroxy lower alkyl, or phenyl. Also disclosed are six processes for producing these novel compounds among which a typical process comprises reacting a starting imidazole compound having a halogen at the 5-position thereof with an acetylene derivative to alkynylate the 5-position. Furthermore, the compounds having remarkable antitumor activities and therefore can provide novel antitumor agents.

Imidazole derivatives, process for production thereof, and use thereof

Pyrimidine 2'-deoxy-2'-methylidene nucleoside compounds: ##STR1## wherein R.sup.1 represents amino, hydroxy, silylamino, silyloxy, acylamino or acyloxy; R.sup.2 represents hydrogen, halogen, a lower alkyl, a lower alkenyl, a lower alkynyl or haloalkyl; R.sup.3 and R.sup.4 represent the same or different hydrogen, silyl, acyl or aminoacyl, or a pharmaceutically acceptable salt or hydrate thereof, except that R.sup.1 is amino or hydroxy, and both of R.sup.3 and R.sup.4 are hydrogen. Said compounds possess excellent antitumor and antiviral activities, thus providing novel anticancer and antiviral agent.

Growing community of inventors

Sapporo, Japan

Tohru Ueda