Tanabe Seiyaku Company, Limited

Kousuke Yasuda

Masakatsu Ozeki

Yukitsuka Kudo

Shin-ichi Kodato

Kayoko Maeda

Thiazine derivatives of the formula [I]: ##STR1## wherein R.sup.1, R.sup.2, R.sup.4 and R.sup.5 are each hydrogen atom; R.sup.3 is hydrogen atom or a halogen atom; X is sulfur atom; R.sup.6 is naphthyl, a sulfur-containing monoheterocyclic group or a substituted phenyl; Z.sup.1 is two hydrogen atoms; Z.sup.2 is oxygen atom; A is a lower alkylene; R.sup.7 and R.sup.8 are the same or different and are each i) hydrogen atom, ii) a lower alkyl, iii) a lower alkenyl, iv) a lower alkynyl, or v) a lower alkyl which is substituted by a substituted phenyl, or both form together with the adjacent nitrogen atom a nitrogen-containing monoheterocyclic group; except for the compound [I] wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each hydrogen atom, X is sulfur atom, R.sup.6 is a halogenophenyl, Z.sup.1 is two hydrogen atoms, Z.sup.2 is oxygen atom, A is a lower alkylene, R.sup.7 and R.sup.8 are the same or different and each a lower alkyl; or a pharmaceutically acceptable salt thereof, which have calcium antagonistic activity within the cerebral tissues and are useful for prophylaxis and treatment of ischemic encephalopathia.

Thiazine (or oxazine) derivatives and preparation thereof

Thiazine derivatives of the formula [I]: ##STR1## wherein R.sup.1 and R.sup.2 are both H or form a naphthalene ring together with the benzene ring; R.sup.3 and R.sup.4 are both H, or one of them is halogen and another is H; X is S or O; R.sup.5 and R.sup.6 are each i) H, ii) lower alkyl, iii) cycloalkyl, iv) substituted phenyl, v) naphthyl, vi) lower alkyl which is substituted by substituted or unsubstituted phenyl, or vii) S-containing heterocyclic group; one of Z.sup.1 and Z.sup.2 is O and another is H.sub.2 ; A is lower alkylene; R.sup.7 and R.sup.8 are each i) H, ii) lower alkyl, iii) lower alkenyl, iv) lower alkynyl, or v) lower alkyl which is substituted by substituted or unsubstituted phenyl, or both form together N-containing heterocyclic group; provided that when both of R.sup.1 and R.sup.2 are H, Z.sup.2 is O and either one of R.sup.5 and R.sup.6 is substituted phenyl, naphthyl or S-containing heterocyclic group, or their salts, which have calcium antagonistic activity within the cerebral tissues and are useful for prophylaxis and treatment of ischemic encephalopathia and/or cerebral neurocyte dyscrasia, and process for preparing said compounds.

Thiazine derivatives and preparation thereof

Thiazine (or oxazine) derivatives of the formula [I]: ##STR1## wherein R.sup.1 and R.sup.2 are both H or form a naphthalene ring together with the benzene ring; R.sup.3 and R.sup.4 are both H, or one of them is halogen and another is H; X is S or O; R.sup.5 and R.sup.6 are each i) H, ii) lower alkyl, iii) cycloalkyl, iv) substituted phenyl, v) naphthyl, vi) lower alkyl which is substituted by substituted or unsubstituted phenyl, or vii) S-containing heterocyclic group; one of Z.sup.1 and Z.sup.2 is O and another is H.sub.2 ; A is lower alkylene; R.sup.7 and R.sup.8 are each i) H, ii) lower alkyl, iii) lower alkenyl, iv) lower alkynyl, or v) lower alkyl which is substituted by substituted or unsubstituted phenyl, or both form together N-containing heterocyclic group; provided that when both of R.sup.1 and R.sup.2 are H, Z.sup.2 is O and either one of R.sup.5 and R.sup.6 is substituted phenyl, naphthyl or S-containing heterocyclic group, or their salts, which have calcium antagonistic activity within the cerebral tissues and are useful for prophylaxis and treatment of ischemic encephalopathia and/or cerebral neurocyte dyscrasia, and process for preparing said compounds.

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Kounosu, Japan

Kousuke Yasuda