US 2009/0264404 A1 · Derivatives of 4-piperazin-1-yl-4-benzo[b]thiophene suitable for the treatment of cns disorders

Abstract

A heterocyclic compound or a salt thereof represented by the formula (1): where R2 represents a hydrogen atom or a lower alkyl group; A represents a lower alkylene group or lower alkenylene group; and R1 represents an aromatic group or a heterocyclic group. The compound of the present invention has a wide treatment spectrum for mental disorders including central nervous system disorders, no side effects and high safety.

A heterocyclic compound or a salt thereof represented by the formula (1):

where R2 represents a hydrogen atom or a lower alkyl group;
A represents a lower alkylene group or a lower alkenylene group;
and
R1 represents a cyclo C3-C8 alkyl group, an aromatic group or a heterocyclic group selected from the group consisting of (I) to (IV) below:
(I) a cyclo C3-C8 alkyl group;
(II) an aromatic group selected from a phenyl group, a naphthyl group, a dihydroindenyl group and a tetrahydronaphthyl group;
(III) a saturated or unsaturated heteromonocyclic group having 1 to 4 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom;
and
(IV) a benzene fused heterocyclic group that has 1 to 4 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom and that is selected from the group consisting of (1) a tetrahydroquinoxalinyl group, (2) a tetrahydroquinazolinyl group, (3) a dihydroquinazolinyl group, (4) an indolinyl group, (5) an indolyl group, (6) an isoindolinyl group, (7) a benzimidazolyl group, (8) a dihydrobenzimidazolyl group, (9) a tetrahydrobenzazepinyl group, (10) a tetrahydrobenzodiazepinyl group, (11) a hexahydrobenzazocinyl group, (12) a dihydrobenzoxazinyl group, (13) a dihydrobenzoxazolyl group, (14) a benzisoxazolyl group, (15) a benzoxadiazolyl group, (16) a tetrahydrobenzoxazepinyl group, (17) a dihydrobenzothiazinyl group, (18) a benzothiazolyl group, (19) a benzoxathiolyl group, (20) a chromenyl group, (21) a dihydrobenzofuryl group, (22) a carbazolyl group, (23) a dibenzofuryl group and (24) a quinoxalinyl group
wherein at least one group selected from the group consisting of the groups (1) to (66) below may be present as a substituent on the cyclo C3-C8 alkyl group, the aromatic group and the heterocyclic group represented by R1:
(1) a lower alkyl group,
(2) a lower alkenyl group,
(3) a halogen substituted lower alkyl group,
(4) a lower alkoxy group,
(5) an aryloxy group,
(6) a lower alkylthio group,
(7) a halogen substituted lower alkoxy group,
(8) a hydroxy group,
(9) a protected hydroxy group,
(10) a hydroxy lower alkyl group,
(11) a protected hydroxy lower alkyl group,
(12) a halogen atom,
(13) a cyano group,
(14) an aryl group,
(15) a nitro group,
(16) an amino group,
(17) an amino group having a group(s) selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group, a carbamoyl group, a lower alkyl carbamoyl group, an amino lower alkanoyl group, a lower alkanoylamino lower alkanoyl group and a lower alkoxy carbonylamino lower alkanoyl group as a substituent,
(18) a lower alkanoyl group,
(19) an arylsulfonyl group that may have a lower alkyl group(s) on the aryl group,
(20) a carboxy group,
(21) a lower alkoxycarbonyl group,
(22) a carboxy lower alkyl group,
(23) a lower alkoxycarbonyl lower alkyl group,
(24) a lower alkanoylamino lower alkanoyl group,
(25) a carboxy lower alkenyl group,
(26) a lower alkoxycarbonyl lower alkenyl group,
(27) a carbamoyl lower alkenyl group that may have a group(s) selected from the group consisting of a lower alkyl group and a halogen substituted lower alkyl group as a substituent,
(28) a carbamoyl group that may have a group(s) selected from the group consisting of the groups (i) to (lxxviii) below as a substituent:
(i) a lower alkyl group,
(ii) a lower alkoxy group,
(iii) a hydroxy lower alkyl group,
(iv) a lower alkoxy lower alkyl group,
(v) an aryloxy lower alkyl group,
(vi) a halogen substituted lower alkyl group,
(vii) an amino lower alkyl group that may have a group(s) selected from the group consisting of a lower alkyl group, a lower alkanoyl group, an aroyl group and a carbamoyl group,
(viii) a cyclo C3-C8 alkyl group that may have a group(s) selected from the group consisting of a lower alkyl group, a hydroxy group, a lower alkoxycarbonyl group and a phenyl lower alkoxy group as a substituent,
(ix) a cyclo C3-C8 alkyl substituted lower alkyl group,
(x) a lower alkenyl group,
(xi) a carbamoyl lower alkyl group that may have a group(s) selected from the group consisting of a lower alkyl group, phenyl group that may have a lower alkyl group(s) and a phenyl group(s) that may have a lower alkoxy group(s) as a substituent,
(xii) a lower alkoxycarbonyl lower alkyl group,
(xiii) a furyl lower alkyl group (that may have a lower alkyl group(s) as a substituent) on the furyl group,
(xiv) a tetrahydrofuryl lower alkyl group,
(xv) a 1,3-dioxolanyl lower alkyl group,
(xvi) a tetrahydropyranyl lower alkyl group,
(xvii) a pyrrolyl lower alkyl group (that may have a lower alkyl group(s) as a substituent on the pyrrolyl group),
(xviii) a lower alkyl group substituted with a dihydropyrazolyl group that may have an oxo group(s),
(xix) a pyrazolyl lower alkyl group (that may have a lower alkyl group(s) as a substituent on the pyrazolyl group),
(xx) an imidazolyl lower alkyl group,
(xxi) a pyridyl lower alkyl group,
(xxii) a pyrazinyl lower alkyl group (that may have a lower alkyl group(s) as a substituent on the pyrazinyl group),
(xxiii) a pyrrolidinyl lower alkyl group (that may have a group(s) selected from the group consisting of an oxo group(s) and a lower alkyl group as a substituent on the pyrrolidinyl group),
(xxiv) a piperidyl lower alkyl group (that may have a group(s) selected from the group consisting of a benzoyl group and a lower alkanoyl group as a substituent on the piperidyl group),
(xxv) a piperazinyl lower alkyl group (that may have a lower alkyl group(s) as a substituent on the piperazinyl group),
(xxvi) a morpholinyl lower alkyl group,
(xxvii) a thienyl lower alkyl group (that may have a lower alkyl group(s) as a substituent on the thienyl group),
(xxviii) a thiazolyl lower alkyl group,
(xxix) a dihydrobenzofuryl lower alkyl group,
(xxx) a benzopyranyl lower alkyl group (that may have an oxo group(s) as a substituent on the benzopyranyl group),
(xxxi) a benzimidazolyl lower alkyl group,
(xxxii) an indolyl lower alkyl group that may have a lower alkoxycarbonyl group(s) on the lower alkyl group),
(xxxiii) an imidazolyl lower alkyl group that has a substituent(s) selected from the group consisting of a carbamoyl group and a lower alkoxycarbonyl group on the lower alkyl group,
(xxxiv) a pyridyl group that may have a group(s) selected from the group consisting of a lower alkyl group, a lower alkoxy group and a lower alkylthio lower alkyl group as a substituent,
(xxxv) a pyrrolidinyl group that may have a group(s) selected from the group consisting of a lower alkyl group, a lower alkoxycarbonyl group, a lower alkanoyl group and an aroyl group as a substituent,
(xxxvi) a piperidyl group that may have a group(s) selected from the group consisting of a lower alkyl group, a lower alkoxycarbonyl group, a lower alkanoyl group and an aroyl group that may have a group(s) selected from the group consisting of a lower alkyl group and a halogen atom as a substituent,
(xxxvii) a tetrahydrofuryl group that may have an oxo group(s),
(xxxviii) a hexahydroazepinyl group that may have an oxo group(s),
(xxxix) a pyrazolyl group that may have a group(s) selected from the group consisting of a lower alkyl group, an aryl group and a furyl group as a substituent,
(xl) a thiazolyl group,
(xli) a thiadiazolyl group that may have a lower alkyl group(s),
(xlii) an isoxazolyl group that may have a lower alkyl group(s),
(xliii) an indazolyl group,
(xliv) an indolyl group,
(xlv) a tetrahydrobenzothiazolyl group,
(xlvi) a tetrahydroquinolyl group that may have a group(s) selected from the group consisting of a lower alkyl group, a lower alkoxy group, a halogen atom and an oxo group as a substituent,
(xlvii) a quinolyl group that may have a lower alkyl group(s),
(xlviii) a benzodioxolyl lower alkyl group,
(xlix) an aryl group that may have a group(s) as a substituent, selected from the group consisting of
a halogen atom;
a lower alkyl group;
a lower alkoxy group;
a halogen substituted lower alkyl group;
a halogen substituted lower alkoxy group;
a lower alkenyl group;
an amino group that may have a group selected from the group consisting of a lower alkanoyl group, a lower alkyl sulfonyl group, a lower alkyl group and an aryl group;
a sulfamoyl group;
a lower alkylthio group;
a lower alkanoyl group;
a lower alkoxycarbonyl group;
a pyrrolyl group;
a lower alkynyl group;
a cyano group;
a nitro group;
an aryloxy group;
an aryl lower alkoxy group;
a hydroxy group;
a hydroxy lower alkyl group;
a carbamoyl group that may have a group(s) selected from the group consisting of a lower alkyl group and an aryl group;
a pyrazolyl group;
a pyrrolidinyl group that may have an oxo group(s);
an oxazolyl group;
an imidazolyl group that may have a lower alkyl group(s);
a dihydrofuryl group that may have an oxo group(s);
a thiazolidinyl lower alkyl group that may have an oxo group(s);
an imidazolyl lower alkanoyl group and a piperidinylcarbonyl group,
(l) a cyano lower alkyl group,
(li) a dihydroquinolyl group that may have a group(s) selected from the group consisting of a lower alkyl group and an oxo group,
(lii) a halogen substituted lower alkylamino group,
(liii) a lower alkylthio lower alkyl group,
(liv) an amidino group that may have a lower alkyl group(s),
(lv) an amidino lower alkyl group,
(lvi) a lower alkenyloxy lower alkyl group,
(lvii) an arylamino group that may have a substituent(s) selected from the group consisting of a lower alkyl group, a lower alkoxy group, a halogen substituted lower alkyl group and a halogen substituted lower alkoxy group, on the aryl group,
(lviii) an aryl lower alkenyl group,
(lix) a pyridylamino group that may have a lower alkyl group(s),
(lx) an aryl lower alkyl group (that may have on the aryl group and/or the lower alkyl group a group(s) selected from the group consisting of a halogen atom, a lower alkyl group, a halogen substituted lower alkyl group, a halogen substituted lower alkoxy group, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group as a substituent),
(lxi) a lower alkynyl group,
(lxii) an aryloxy lower alkyl group (that may have as a substituent on the aryl group a group(s) selected from the group consisting of a lower alkoxy group;
a carbamoyl group that may have a group(s) selected from the group consisting of a lower alkoxy group and a lower alkyl group;
and a pyrrolidinyl group that may have an oxo group(s)),
(lxiii) an isoxazolidinyl group that may have an oxo group(s),
(lxiv) a dihydroindenyl group,
(lxv) an aryl lower alkoxy lower alkyl group,
(lxvi) a tetrahydropyranyl group,
(lxvii) an azetidinyl group that may have a group(s) selected from the group consisting of a lower alkanoyl group and an aroyl group,
(lxviii) an azetidinyl lower alkyl group that may have a group(s) selected from the group consisting of a lower alkanoyl group and aroyl group,
(lxix) a tetrazolyl group,
(lxx) an indolinyl group that may have an oxo group(s),
(lxxi) a triazolyl group that may have a group(s) selected from the group consisting of a lower alkyl group and a lower alkylthio group,
(lxxii) an imidazolyl group that may have a carbamoyl group(s),
(lxxiii) an oxazolyl group that may have a lower alkyl group(s),
(lxxiv) an isothiazolyl group that may have a lower alkyl group(s),
(lxxv) a benzimidazolyl group,
(lxxvi) a dihydrobenzothiazolyl group that may have an oxo group(s),
(lxxvii) a thienyl group that may have a lower alkoxycarbonyl group(s), and
(lxxviii) an oxazolyl lower alkyl group that may have a lower alkyl group(s)
(29) an amino lower alkyl group that may have a group(s) selected from the group consisting of a lower alkyl group, a halogen substituted lower alkyl group, a lower alkoxycarbonyl group, a lower alkanoyl group, an aryl group, an aryl lower alkyl group, an aroyl group and an amino substituted alkyl group (that may have a lower alkyl group(s) as a substituent on the amino group) on the amino group,
(30) a lower alkyl group substituted with a carbamoyl group that may have a group(s) selected from the group consisting of a lower alkyl group and a halogen substituted lower alkyl group,
(31) a thiocarbamoyl group that may have a lower alkyl group(s),
(32) a sulfamoyl group,
(33) an oxazolidinyl group that may have an oxo group(s),
(34) an imidazolidinyl group that may have a substituent(s) selected from the group consisting of an oxo group and a lower alkyl group,
(35) a pyrrolidinyl group that may have an oxo group(s),
(36) an imidazolyl group,
(37) a triazolyl group,
(38) an isoxazolyl group,
(39) a piperidyl group that may have a substituent(s) selected from the group consisting of a lower alkyl group, a lower alkanoyl group, an arylsulfonyl group, an oxo group, a hydroxy group, and an amino group that may have a group(s) selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a lower alkoxycarbonyl group and lower alkanoylamino lower alkanoyl group,
(40) a piperidylcarbonyl group that may have a substituent(s) selected from the group consisting of a lower alkyl group, a hydroxy group, a hydroxy lower alkyl group, a lower alkanoyl group, a carboxy lower alkyl group, a lower alkyl carbamoyl lower alkyl group, a carbamoyl group, a lower alkoxy group, a carboxy group, a lower alkoxycarbonyl group, an amino group (on which 1 to 2 groups selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a lower alkoxycarbonyl group and an aroyl group may be present), a piperidyl group (on which a group(s) selected from the group consisting of a lower alkanoyl group, a lower alkoxycarbonyl group and an aroyl group may be present), piperazinyl group (on which a lower alkyl group(s) may be present as a substituent), a 1,4-dioxa-8-azaspiro[4.5]decyl group, a morpholinyl group, a hexahydro-1,4-diazepinyl group (on which a lower alkyl group(s) may be present as a substituent), a pyridyl group, a pyridyloxy group, a pyridyl lower alkoxy group, a tetrahydroquinolyl group (on which an oxo group(s) may be present), a benzodioxolyl group, an aryl lower alkoxy group (that may have a group(s) selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkoxy group and a halogen substituted lower alkoxy group on the aryl group), an aryl group (on which a group(s) selected from the group consisting of a halogen atom, a lower alkoxy group, hydroxy group may be present), an aryloxy group (that may have on the aryl group a group(s) selected from the group consisting of a cyano group, a halogen atom, lower alkyl group, a lower alkoxy group and a halogen substituted lower alkyl group), an aryl lower alkyl group (that may have on the aryl group a group(s) selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkoxy group and a halogen substituted lower alkyl group), and an aroyl group (that may have on the aryl group a group(s) selected from the group consisting of a halogen atom and a lower alkoxy group),
(41) a pyrrolidinylcarbonyl group that may have a group as a substituent, selected from the group consisting of a hydroxy lower alkyl group, a carbamoyl group, a hydroxy group, an amino group (that may have on the amino group a group(s) selected from the group consisting of a lower alkyl group, a lower alkanoyl group and an aroyl group), a morpholinyl lower alkyl group, a pyrrolidinyl lower alkyl group, a piperidyl lower alkyl group, a piperazinyl lower alkyl group (that may have a lower alkyl group(s) as a substituent on the piperazinyl group), an amino lower alkyl group (that may have a lower alkyl group(s) as a substituent on the amino group), an aryloxy group (that may have a halogen substituted lower alkoxy group(s) on the aryl group), an aryloxy lower alkyl group (that may have a halogen substituted lower alkoxy group(s) on the aryl group) and a tetrahydroquinolyl group (on which an oxo group(s) may be present),
(42) a piperazinylcarbonyl group that may have a group(s) as a substituent, selected from the group consisting of a lower alkyl group, a cyclo C3-C8 alkyl group, a lower alkanoyl group, a hydroxy lower alkyl group, a lower alkoxy lower alkyl group, a lower alkoxycarbonyl group, an amino lower alkyl group (that may have a lower alkyl group(s) as a substituent on the amino group), a piperidyl lower alkyl group (that may have a lower alkyl group(s) as a substituent on the piperidyl group), a morpholinyl lower alkyl group, a pyrrolidinyl lower alkyl group, a 1,3-dioxolanyl lower alkyl group, a tetrahydrofuryl lower alkyl group, a pyridyl lower alkyl group (that may have a phenyl group(s) as a substituent on the lower alkyl group), a imidazolyl lower alkyl group, a furyl lower alkyl group, a pyrrolidinylcarbonyl lower alkyl group, a piperidyl group that may have a lower alkyl group(s) as a substituent, pyridyl group (that may have on the pyridyl group a group(s) selected from the group consisting of a lower alkyl group, a cyano group and a halogen substituted lower alkyl group as a substituent), a thieno[2,3-b]pyridyl group, an aryl group (on which a group(s) selected from the group consisting of a halogen atom and a lower alkyl group may be present), an aroyl group, a furyl carbonyl group, an aryl lower alkoxycarbonyl group and an oxo group,
(43) a hexahydroazepinylcarbonyl group,
(44) a hexahydro-1,4-diazepinylcarbonyl group that may have a substituent(s) selected from the group consisting of a lower alkyl group and a pyridyl group,
(45) a dihydropyrrolylcarbonyl group that may have a lower alkyl group(s),
(46) a thiomorpholinylcarbonyl group,
(47) a morpholinylcarbonyl group that may have a group(s) selected from the group consisting of a lower alkyl group, a piperidyl lower alkyl group and an aryl group,
(48) a thiazolidinyl carbonyl group that may have an aryl group(s) that may have a group(s) selected from the group consisting of a lower alkoxy group and a cyano group,
(49) an azabicyclo[3.2.2]nonylcarbonyl group,
(50) an 8-azabicyclo[3.2.1]octylcarbonyl group that may have a halogen substituted or unsubstituted aryloxy group(s),
(51) an indolinylcarbonyl group,
(52) a tetrahydroquinolylcarbonyl group,
(53) a tetrahydropyrido[3.4-b]indolylcarbonyl group,
(54) a morpholinyl lower alkyl group,
(55) a piperazinyl lower alkyl group that may have a lower alkyl group(s) on the piperazinyl group,
(56) a morpholinylcarbonyl lower alkyl group,
(57) a piperazinylcarbonyl lower alkyl group that may have a lower alkyl group(s) on the piperazinyl group,
(58) an oxo group,
(59) an amino lower alkoxy group (that may have a lower alkyl group(s) on the amino group),
(60) a lower alkoxy lower alkoxy group,
(61) a piperazinyl group that may have a group(s) selected from the group consisting of an oxo group, a lower alkyl group, a lower alkanoyl group and a lower alkoxycarbonyl group,
(62) a morpholinyl group,
(63) a 1,3,8-triazaspiro[4.5]decanylcarbonyl group that may have a group(s) selected from the group consisting of an oxo group and an aryl group,
(64) a tetrahydropyridylcarbonyl group that may have a pyridyl group(s),
(65) an imidazolidinylcarbonyl group that may have a thioxo group(s), and
(66) a 1,4-dioxa-8-azaspiro[4.5]decanyl group.

180 more elements

Derivatives of 4-piperazin-1-yl-4-benzo[b]thiophene suitable for the treatment of cns disorders

Life of this patent

Derivatives of 4-piperazin-1-yl-4-benzo[b]thiophene suitable for the treatment of cns disorders

Life of this patent

Abstract

Claims24