1,2-ethanediol derivative and salt thereof process for producing the same, and cerebral function-improving agent comprising the same

A cerebral function-improving agent comprising a 1,2-ethanediol dervivative represented by the following formula or a salt thereof:

• ##STR549## wherein R.sup.1 represents a substituted or unsubstituted phenyl group;
• R.sup.2 represents a hydrogen atom, a lower alkyl group or a hydroxyl-protecting group;
• R.sup.3 represents a hydrogen atom or a lower alkyl group;
• nR.sup.4 's and nR.sup.5 's are the same as or different from one another and represent hydrogen atoms or lower alkyl groups;
• R.sup.6 represents a substituted or unsubstituted amino group;
• and n represents an integer of 1 to 6, wherein the substituent or R.sup.1 is selected from the group consisting of halogen atoms, substituted or unsubstituted amino, lower alkyl, aryl, ar-lower alkyl, lower alkoxy, ar-lower alkoxy, aryloxy, carbamoyloxy, lower alkylthio, lower alkenyl, lower alkanyloxy, ar-lower alkylthio, ar-lower alkylsolfonyl, arylsulfonyl, lower alkylsulfonylamino, arylsulfonylamino and heterocyclic groups, protected amino groups, protected or unprotected hydroxyl groups, nitro group, and lower alkylenedioxy groups;
• the substituted lower alkyl, aryl, ar-lower alkyl, lower alkoxy, ar-lower alkoxy, aryloxy, carbamoyloxy, lower alklthio, lower alkenyl, lower alkenyloxy, ar-lower alkylthio, ar-lower alkylsulfonyl, arylsulfonyl, lower alkylsulfonylamino, arylsulfonylamino or heterocyclic group as the substituent of R.sup.1 and the substituted amino group as the substituent of R.sup.1 and the substituted amino group as R.sup.6 have at least one substituent selected from the group consisting of protected or unprotected hydroxyl groups, unsubstituted lower alkyl groups, lower alkyl groups substituted by a protected or unprotected carboxyl or hydroxyl groups, cycloalkyl groups, aryl groups, lower acyl groups, ar-lower alkyl groups, heterocyclic groups, unsubstituted or oxo-substituted heterocyclic-CO-- groups, adamantyl group, lower alkylsulfonyl groups and arylsulfonyl groups, provided that there are excluded the compounds in which R.sup.1 is a phenyl group which may optionally be substituted by the halogen atom or the lower alkyl, lower alkylenedioxy, lower alkoxy or protected or unprotected hydroxyl group and R.sup.6 is --NR.sup.7 R.sup.8 in which R.sup.7 represents an ar-lower alkyl or heterocyclic group and R.sup.8 represents a hydrogen atom or a lower alkyl group;
• all the above heterocyclic groups being selected from the group consisting of furyl, thienyl, benzothienyl, pyranyl, isobenzofuranyl, oxazolyl, benzofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, quinoxalyl, dihydroquinoxalyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzopyrrolyl, 2,3-dihydro-4H-1-thianaphthyl, 2,3-dihydrobenzofuranyl, benzo[b]dioxanyl, imidazo[2,3-a]pyridyl, benzo[b]piperazinyl, chromenyl, isothiazolyl, isoxazolyl, oxadiazolyl, pyridazinyl, isoindolyl and isoquinolyl groups in combination with a pharmaceutically acceptable inert axcipient, diluent or carrier.

A method of treating cerebrovascular dementia, senile dementia, alzheimer's dementia, sequelae of ischemic encephalopathyl or cerebral apoplexy in a patient comprising:

• a 1,2-ethanediol derivative representee by the following formula or a salt thereof:
• ##STR550## wherein R.sup.1 represents a substituted or unsubstituted phenyl group;
• R.sup.2 represents a hydrogen atom, a lower alkyl group or a hydroxyl-protecting group;
• R.sup.3 represents a hydrogen atom or a lower alkyl group;
• nR.sup.4 's and nR.sup.5 's are the same as or different from one another and represent hydrogen atoms or lower alkyl groups;
• R.sup.6 represents an ammonio group or a substituted or unsubstituted amino group;
• and n represents an 0 or an integer of 1 to 6, wherein the substituent or R.sup.1 is selected from the group consisting of halogen atoms, substituted or unsubstituted amino, lower alkyl, aryl, ar-lower alkyl, lower alkoxy, ar-lower alkoxy, aryloxy, carbamoyloxy, lower alkylthio, lower alkenyl, lower alkanyloxy, ar-lower alkylthio, ar-lower alkylsolfonyl, arylsulfonyl, lower alkylsulfonylamino, arylsulfonylamino and heterocyclic groups, protected amino groups, protected or unprotected hydroxyl groups, nitro group, and lower alkylenedioxy groups;
• the substituted lower alkyl, aryl, ar-lower alkyl, lower alkoxy, ar-lower alkoxy, aryloxy, carbamoyloxy, lower alklthio, lower alkenyl, lower alkenyloxy, ar-lower alkylthio, ar-lower alkylsulfonyl, arylsulfonyl, lower alkylsulfonylamino, arylsulfonylamino or heterocyclic group as the substituent of R.sup.1 and the substituted amino group as the substituent of R.sup.1 and the substituted amino group as R.sup.6 have at least one substituent selected from the group consisting of protected or unprotected hydroxyl groups, unsubstituted lower alkyl groups, lower alkyl groups substituted by a protected or unprotected carboxyl or hydroxyl groups, cycloalkyl groups, aryl groups, lower acyl groups, ar-lower alkyl groups, heterocyclic groups, unsubstituted or oxo-substituted heterocyclic-CO-- groups, adamantyl group, lower alkylsulfonyl groups and arylsulfonyl groups, provided that there are excluded the compounds in which R.sup.1 is a phenyl group which may optionally be substituted by the halogen atom or the lower alkyl, lower alkylenedioxy, lower alkoxy or protected or unprotected hydroxyl group and R.sup.6 is --NR.sup.7 R.sup.8 in which R.sup.7 represents an ar-lower alkyl or heterocyclic group and R.sup.8 represents a hydrogen atom or a lower alkyl group;
• all the above heterocyclic groups being selected from the group consisting of furyl, thienyl, benzothienyl, pyranyl, isobenzofuranyl, oxazolyl, benzofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, quinoxalyl, dihydroquinoxalyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzopyrrolyl, 2,3-dihydro-4H-1-thianaphthyl, 2,3-DIHYDROBENZOFURANYL, benzo[b]dioxanyl, imidazo[2,3-a]pyridyl, benzo[b]piperazinyl, chromenyl, iso-thiazolyl, isoxazolyl, oxadiazolyl, pyridazinyl, isoindolyl and isoquinolyl groups.

A method of treating cerebrovascular dementia, senile dementia, Alzheimer's dementia, sequelae of ischemic encephalopathy of cerebral apoplexy in a patient comprising administering to a patient in need a therapeutically effective amount of a 1,2-ethanediol derivative represented by the following formula or a salt thereof:

• ##STR551## wherein R.sup.1 represents a substituted or unsubstituted phenyl group;
• R.sup.2 represents a hydrogen atom, a lower alkyl group or a hydroxyl-protecting group;
• R.sup.3 represents a hydrogen atom or a lower alkyl group;
• nR.sup.4 's and nR.sup.5 's are the same as or different from one another and represent hydrogen atoms or lower alkyl groups;
• R.sup.6 represents an ammonio group or a substituted or unsubstituted amino group;
• and n represents an 0 or an integer of 1 to 6, wherein the substituent or R.sup.1 is selected from the group consisting of halogen atoms, substituted or unsubstituted amino, lower alkyl, aryl, ar-lower alkyl, lower alkoxy, ar-lower alkoxy, aryloxy, carbamoyloxy, lower alkylthio, lower alkenyl, lower alkanyloxy, ar-lower alkylthio, ar-lower alkylsolfonyl, arylsulfonyl, lower alkylsulfonylamino, arylsulfonylamino and heterocyclic groups, protected amino groups, protected or unprotected hydroxyl groups, nitro group, and lower alkylenedioxy groups;
• the substituted lower alkyl, aryl, ar-lower alkyl, lower alkoxy, ar-lower alkoxy, aryloxy, carbamoyloxy, lower alklthio, lower alkenyl, lower alkenyloxy, ar-lower alkylthio, ar-lower alkylsulfonyl, arylsulfonyl, lower alkylsulfonylamino, arylsulfonylamino or heterocyclic group as the substituent of R.sup.1 and the substituted amino group as the substituent of R.sup.1 and the substituted amino group as R.sup.6 have at least one substituent selected from the group consisting of protected or unprotected hydroxyl groups, unsubstituted lower alkyl groups, lower alkyl groups substituted by a protected or unprotected carboxyl or hydroxyl groups, cycloalkyl groups, aryl groups, lower acyl groups, ar-lower alkyl groups, heterocyclic groups, unsubstituted or oxo-substituted heterocyclic-CO-- groups, adamantyl group, lower alkylsulfonyl groups and arylsulfonyl groups, provided that there are excluded the compounds in which R.sup.1 is a phenyl group which may optionally be substituted by the halogen atom or the lower alkyl, lower alkylenedioxy, lower alkoxy or protected or unprotected hydroxyl group and R.sup.6 is --NR.sup.7 R.sup.8 in which R.sup.7 represents an ar-lower alkyl or heterocyclic group and R.sup.8 represents a hydrogen atom or a lower alkyl group;
• all the above heterocyclic groups being selected from the group consisting of furyl, thienyl, benzothienyl, pyranyl, isobenzofuranyl, oxazolyl, benzofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, quinoxalyl, dihydroquinoxalyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzopyrrolyl, 2,3-dihydro-4H-1-thianaphthyl, 2,3-DIHYDROBENZOFURANYL, benzo[b]dioxanyl, imidazo[2,3-a]pyridyl, benzo[b]piperazinyl, chromenyl, iso-thiazolyl, isoxazolyl, oxadiazolyl, pyridazinyl, isoindolyl and isoquinolyl groups.