US 7,622,479 B2 · Bicyclic derivative, its production and use

Abstract

The present invention provides a heterocyclic compound having potent tyrosine kinase-inhibiting activity represented by formula: (wherein, R1b is a C6-10 aryl group which has substituent(s), and the like; Ta is a single bond, a C1-6 alkyl group, —CH2O—, and the like; X and Y are the same or different, and each is a nitrogen atom which may have substituent(s), and the like; the broken line is a single bond or a double bond; Za is a nitrogen atom or CH; W is a single bond, an oxygen atom, and the like; Q is a C6-10 aryl group which may have substituent(s) or an aromatic heterocyclic group which may have substituent(s)); or a salt thereof and a pharmaceutical composition comprising thereof.

A compound represented by the formula (VII′):

wherein,
R1d is
a C6-10 aryl group which may have 1-3 substituents selected from the substituent group B mentioned below,
a C3-8 cycloalkyl group which may have 1-3 substituents selected from the substituent group B mentioned below or
a heterocyclic group which may have 1-5 substituents selected from the substituent group A mentioned below;
Ta is a single bond, a C1-6 alkyl group, —CH2O—, —OCH2—, —CH2S—, —SCH2—, —CH2—CH2— or —CH═CH—;
R2 is a hydrogen atom, a C1-6 alkyl group which may have 1-3 substituents selected from the substituent group B mentioned below, a C6-10 aryl group which may have 1-3 substituents selected from the substituent group B mentioned below or a C3-8 cycloalkyl group which may have 1-3 substituents selected from the substituent group B mentioned below;
W is a single bond;
Q is a C6-10 aryl group which may have 1-3 substituents selected from the substituent group B mentioned below or an aromatic heterocyclic group which may have 1-5 substituents selected from the substituent group C mentioned below;
or a salt thereof,
wherein
substituent group A consists of:
(i) a C1-6 alkyl group which may have 1-3 substituents selected from the substituent group B mentioned below,
(ii) a C2-6 alkenyl group which may have 1-3 substituents selected from the substituent group B mentioned below,
(iii) a C2-6 alkynyl group which may have 1-3 substituents selected from the substituent group B mentioned below,
(iv) a C6-14 aryl group which may have 1-3 substituents selected from the substituent group B mentioned below,
(v) a C7-11 aralkyl group which may have 1-3 substituents selected from the substituent group B mentioned below,
(vi) a C3-7 cycloalkyl group which may have 1-3 substituents selected from the substituent group B mentioned below,
(vii) a C3-7 cycloalkenyl group which may have 1-3 substituents selected from the substituent group B mentioned below,
(viii) a heterocyclic group which may have 1-5 substituents selected from the substituent group C mentioned below,
(ix) an amino group which may have 1 or 2 substituents selected from the substituent group D mentioned below, a C1-6 alkylimidoyl, a C1-6 alkoxyimidoyl, a C1-6 alkylthioimidoyl and amidino, and 2 of the substituents may combine together with a nitrogen atom to form a cyclic amino group,
(x) an imidoyl group which may have 1 or 2 substituents selected from the substituent group D mentioned below,
(xi) an amidino group which may have 1-3 substituents selected from the substituent group D mentioned below,
(xii) a hydroxyl group which may have a substituent selected from the substituent group D mentioned below,
(xiii) a thiol group which may have a substituent selected from the substituent group D mentioned below,
(xiv) a C1-6 alkylsulfinyl group which may have 1-3 substituents selected from the substituent group B mentioned below,
(xv) a carboxyl group which may be esterified or amidated,
(xvi) a thiocarbamoyl group which may have 1 or 2 substituents selected from the substituent group E mentioned below,
(xvii) a sulfamoyl group which may have 1 or 2 substituents selected from the substituent group E mentioned below,
(xviii) a halogen atom,
(xix) a cyano group,
(xx) an isocyano group,
(xxi) a cyanate group,
(xxii) an isocyanate group,
(xxiii) a thiocyanate group,
(xxiv) an isothiocyanate group,
(xxv) a nitro group,
(xxvi) a nitroso group,
(xxvii) an acyl group derived from sulphonic acid,
(xxviii) an acyl group derived from a carboxylic acid, and
(xxix) an oxo group;
substituent group B consists of:
(i) a nitro group,
(ii) a carboxyl group,
(iii) a C1-6 alkoxy group,
(iv) a halogen atom,
(v) a C1-6 alkyl group,
(vi) a C2-6 alkenyl group,
(vii) a C2-6 alkynyl group,
(viii) an amino group which may have 1 or 2 substituents selected from the substituent group D mentioned below, a C1-6 alkylimidoyl, a C1-6 alkoxyimidoyl, a C1-6 alkylthioimidoyl and amidino, and 2 of the substituents may combine together with a nitrogen atom to form a cyclic amino group,
(ix) a hydroxyl group which may have a substituent selected from the substituent group D mentioned below,
(x) a cyano group,
(xi) an amidino group which may have 1-3 substituents selected from the substituent group D mentioned below,
(xii) a carboxy group,
(xiii) a C1-6 alkoxycarbonyl group,
(xiii) a carbamoyl group which may be substituted by a C1-6 alkyl group which may further be substituted by a 5- or 6-membered aromatic monocyclic heterocyclic group or an acyl group, and
(xiv) an alicyclic hydrocarbon group which may contain 1 or more hetero atoms as a ring-constituting atom;
substituent group C consists of:
(i) a C1-6 alkyl group,
(ii) a C2-6 alkenyl group,
(iii) a C2-6 alkynyl group,
(iv) an acyl group,
(v) an amino group which may have 1 or 2 substituents selected from the substituent group D mentioned below, a C1-6 alkylimidoyl, a C1-6 alkoxyimidoyl, a C1-6 alkylthioimidoyl and amidino, and 2 of the substituents may combine together with a nitrogen atom to form a cyclic amino group,
(vi) a hydroxyl group which may have a substituent selected from the substituent group D mentioned below,
(vii) a halogen atom,
(viii) an imidoyl group which may have 1 or 2 substituents selected from the substituent group D mentioned below, and
(ix) an amidino group which may have 1-3 substituents selected from the substituent group D mentioned below;
substituent group D consists of:
(i) a C1-6 alkyl group which may have substituents selected from the group consisting of a halogen atom, a C1-6 alkoxy group which may be halogenated and a C7-11 alkyl-aryl group,
(ii) an acyl group,
(iii) benzoyl,
(iv) a C1-6 alkylsulfonyl,
(v) benzensulfonyl,
(vi) a C1-6 alkoxycarbonyl group which may be halogenated,
(vii) a C1-6 alkoxycarbonyl group which may be substituted by phenyl,
(viii) a C6-10 aryl group,
(ix) a C7-10 aralkyl group,
(x) a C8-10 arylalkenyl, and
(xi) a heterocyclic group;
and
substituent group E consists of:
(i) a C1-6 alkyl,
(ii) a C2-6 alkenyl,
(iii) a C3-6 cycloalkyl,
(iv) a C6-10 aryl,
(v) a C7-10 aralkyl,
(vi) a C8-10 aryl alkenyl, and
(vii) a heterocyclic group.

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Bicyclic derivative, its production and use

Life of this patent

Bicyclic derivative, its production and use

Life of this patent

Abstract

Claims17