Takeda Chemical Industries, Inc.

Osamu Miyashita

Hiroshi Akimoto

Koichi Matsumura

Yoshiyasu Furukawa

Naoto Hashimoto

Hiroshi Shimadzu

New derivatives of the formula: ##STR1## (wherein X is O or NH; R.sub.1 is --OH which may optionally be etherified or esterified, etherified mercapto or --NH.sub.2 which may optionally be substituted; R.sub.2 and R.sub.3, respectively, mean H, lower alkyl or ##STR2## and Y is an esterified or amidated carboxyl group, or CN). These derivatives are produced, by fluorination of corresponding 1,2,3,4-tetrahydro-2,4-dioxopyrimidine compounds and can be converted into 5-fluorouracil derivatives under hydrolytic conditions. The new derivatives are able to prolong the lives of animals having carcinomas or have antiviral activity.

Uracil derivatives and production thereof

Novel maytansinoids of the formula: ##STR1## wherein Y is H or Cl, and R is C.sub.2-15 alkyl, phenyl-C.sub.1-4 alkyl, pyridyl-C.sub.1-4 alkyl, imidazolyl-C.sub.1-4 alkyl, indolyl-C.sub.1-4 alkyl, furyl-C.sub.1-4 alkyl or thienyl-C.sub.1-4 alkyl, said R group being substituted by hydroxyl, halogen or C.sub.1-5 alkanoyloxy at its .alpha.- and/or .beta.-position, have antimitotic, antitumor and antimicrobial activities.

Maytansinoids, their use and pharmaceutical compositions thereof

Novel maytansinoids of the formula: ##STR1## wherein X is hydrogen or chlorine,

Maytansinoids

Novel maytansinoids of the formula: ##STR1## wherein X is H or Cl, and Y is Cl, OH, SH, CN, NO.sub.2, --OR or --S(O).sub.n R wherein R is slkyl, aryl, aralkyl or azaheterocyclic group which may be substituted, and n is 0, 1 or 2, have antimitotic, antitumor and antimicrobial activities.

Maytansinoids, pharmaceutical compositions thereof and method of use

Novel maytansinoids of the formula: ##STR1## wherein X is H or Cl, and R is a hydrocarbon residue or an azaheterocyclic group, said R group having at least one of water-solubilizing substituents, have antimitotic, antitumor and antimicrobial activities.

Novel maytansinoid compounds of the formula: ##STR1## wherein X is H or Cl, R.sup.1 is an alkyl group of 2 to 4 carbon atoms and R.sup.2 is a lower alkyl group or an unsubstituted or substituted phenyl or aralkyl group, have antimitotic, antitumor and antimicrobial activities.

Novel maytansinoids of the formula: ##STR1## wherein X is H or Cl, and R is ##STR2## wherein R.sup.1 and R.sup.2 may be the same or different, and each is H or a substituted or unsubstituted hydrocarbon residue or heterocyclic group, or R.sup.1 and R.sup.2 may, taken together with the adjacent N atom, form a heterocyclic group, and R.sup.3 is a substituted or unsubstituted hydrocarbon residue, have antimitotic, antitumor and antimicrobial activities.

Novel maytansinoids of the formula: ##STR1## wherein R.sup.1 is hydrogen atom, an alkyl group which may optionally be substituted or a group of the formula: --A.sup.1 --Y.sup.1 wherein A.sup.1 is an alkylene group or a bond, and Y.sup.1 is a cycloalkyl, phenyl, indolyl or imidazolyl group which may optionally be substituted,

Maytansinoids, pharmaceutical compositions thereof and methods of use

Novel dechloromaytansinoids of the formula: ##STR1## wherein R is H or acyl having 1 to 20 carbon atoms, have antimitotic, antitumor and antimicrobial activities.

Dechloromaytansinoids, their pharmaceutical compositions and method of

Novel maytansinoids of the formula: ##STR1## wherein R is an alicyclic hydrocarbon group of 3 to 10 carbon atoms, phenyl or heterocyclic group, which may optionally be substituted, and

Maytansinoids and use

New compounds of the formula ##STR1## (wherein R.sub.1 represents a lower alkyl group: and ##STR2## represents an alkylidene radical in which at least one of R.sub.2 and R.sub.3 is a lower alkyl which may optionally be substituted by phenyl, phenyl or a 5- or 6-membered aromatic ring including S, N or O, and the remainder, if any, is hydrogen; or a cycloalkylidene radical of up to six carbon atoms, to which a benzene ring may optionally be fused). These compounds are produced by reacting the corresponding 6-acyloxy compounds with a compound of the formula ##STR3## The new compounds have antiviral activity and are useful to prolong the life spans of tumor-bearing animals.

Novel 3-(disubstituted)aminoisothiazolo[3,4-d]pyrimidines of the formula ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are respectively alkyl, alkenyl, aryl, aralkyl or aralkenyl, each of which may be substituted, or R.sup.1 and R.sup.2 form together with the adjacent nitrogen a heterocyclic ring which may be substituted, R.sup.4 is hydrogen or alkyl and X is oxygen or imino with a proviso that when X is imino R.sup.4 is hydrogen, show an eminent adenosine-3',5'-cyclic phosphate phosphodiesterase-inhibitory activity, and exhibit excellent pharmacological actions such as anti-inflammatory and sedative activities.

3-(Disubstituted)aminoisothiazolo[3,4-d]pyrimidines

Novel 3-(disubstituted)aminoisothiazolo[3,4-d]-pyrimidines of the formula ##SPC1## Wherein R.sup.1, R.sup.2 and R.sup.3 are respectively alkyl, alkenyl, aryl, aralkyl or aralkenyl, each of which may be substituted, or R.sup.1 and R.sup.2 form together with the adjacent nitrogen a heterocyclic ring which may be substituted, R.sup.4 is hydrogen or alkyl and X is oxygen or imino with a proviso that when X is imino R.sup.4 is hydrogen, show an eminent adenosine-3',5'-cyclic phosphate phosphodiesterase-inhibitory activity, and exhibit excellent pharmacological actions such as antiinflammatory and sedative activities.

Growing community of inventors

Osaka, Japan

Osamu Miyashita