Thiazolopyrimidine compounds, its production and use
AssigneeTakeda Chemical Industries, Ltd.
InventorsShigenori Ohkawa, Naoyuki Kanzaki, Seiji Miwatashi
Life of this patent
Estimating the term…
Abstract
Compounds represented by general formula (I): and salts thereof, exhibiting excellent adenosine A3 receptor antagonism: wherein A is an optionally substituted benzene ring; B may be further substituted; and R1 is an optionally substituted cyclic group.
Claims23
A compound represented by the formula:
- wherein:
- ring A is a benzene ring which may have 1 to 5 substituents selected from the group consisting of (i) halogen atom, (ii) C1-3 alkylenedioxy, (iii) nitro, (iv) cyano, (v) optionally halogenated C1-6 alkyl, (vi) optionally halogenated C2-6 alkenyl, (vii) carboxy C1-6 alkyl, (viii) carboxy C2-6 alkenyl, (ix) optionally halogenated C2-6 alkynyl, (x) optionally halogenated C3-6 cycloalkyl, (xi) C6-14 aryl, (xii) optionally halogenated C1-6 alkoxy, (xiii) C1-6 alkoxy-carbonyl-C1-6 alkoxy, (xiv) hydroxy, (xv) C6-14 aryloxy, (xvi) C7-16 aralkyloxy, (xvii) mercapto, (xviii) optionally halogenated C1-6 alkylthio, (xix) C6-14 arylthio, (xx) C7-16 aralkylthio, (xxi) amino, (xxii) mono-C1-6 alkylamino, (xxiii) mono-C6-14 arylamino, (xxiv) mono-C7-16 aralkylamino, (xxv) di-C7-16 aralkylamino, (xxvi) di-C1-6 alkylamino, (xxvii) di-C6-14 arylamino, (xxviii) formyl, (xxix) carboxy, (xxx) C1-6 alkyl-carbonyl, (xxxi) C3-6 cycloalkyl-carbonyl, (xxxii) C1-6 alkoxy-carbonyl, (xxxiii) C6-14 aryl-carbonyl, (xxxiv) C7-16 aralkyl-carbonyl, (xxxv) C6-14 aryloxy-carbonyl, (xxxvi) C7-16 aralkyloxy-carbonyl, (xxxvii) 5- or 6-membered heterocyclic-carbonyl selected from the group consisting of nicotinoyl, isonicotinoyl, thienoyl, furoyl, morpholinocarbonyl, thiomorpholinocarbonyl, piperazin-1-ylcarbonyl and pyrrolidin-1-ylcarbonyl, (xxxviii) carbamoyl, (xxxix) thiocarbamoyl, (xxxx) mono-C1-6 alkyl-carbamoyl, (xxxxi) di-C1-6 alkyl-carbamoyl, (xxxxii) C6-14 aryl-carbamoyl, (xxxxiii) 5- or 6-membered heterocylic carbamoyl selected from the group consisting of 2-pyridylcarbamoyl, 3-pyridylcarbamoyl, 4-pyridylcarbamoyl, 2-thienylcarbamoyl and 3-thienylcarbamoyl, (xxxxiv) C1-6 alkylsulfonyl, (xxxxv) C6-14 arylsulfonyl, (xxxxvi) formylamino, (xxxxvii) C1-6 alkyl-carbonylamino, (xxxxviii) C6-14 aryl-carbonylamino, (xxxxix) C1-6 alkoxy-carbonylamino, (xxxxx) C1-6 alkylsulfonylamino, (xxxxxi) C6-14 arylsulfonylamino, (xxxxxii) C1-6 alkyl-carbonyloxy, (xxxxxiii) C6-14 aryl-carbonyloxy, (xxxxxiv) C1-6 alkoxy-carbonyloxy, (xxxxxv) mono-C1-6 alkyl-carbamoyloxy, (xxxxxvi) di-C1-6 alkyl-carbamoyloxy, (xxxxxvii) C6-14 aryl-carbamoyloxy, (xxxxxviii) nicotinoyloxy, (xxxxxix) 5- to 7-membered saturated cyclic amino which may be substituted by a substituent selected from the group consisting of C1-6 alkyl, C6-14 aryl, C1-6 alkyl-carbonyl, oxo, and 5- to 10-membered aromatic heterocylic group selected from 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 8-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 1-indolyl, 2-indolyl, 3-indolyl, 2-benzothiazolyl, 2-benzo[b]thienyl, 3-benzo[b]thienyl, 2-benzo[b]furanyl, or 3-benzo[b]furanyl, (xxxxxx) 5- to 10-membered aromatic heterocylic group selected from 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 8-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 1-indolyl, 2-indolyl, 3-indolyl, 2-benzothiazolyl, 2-benzo[b]thienyl, 3-benzo[b]thienyl, 2-benzo[b]furanyl, or 3-benzo[b]furanyl, and (xxxxxxi) sulfo;
- ring B may have 1 or 2 substituents selected from the same substituents as defined for ring A;
- and
- R1 is C3-6 cycloalkyl group, C6-14 aryl group or a monovalent group formed by removing any one hydrogen atom from a 5- to 14-membered heterocyclic ring selected from the group consisting of (i) 5- to 14-membered aromatic heterocyclic ring selected from the group consisting of thiophene, benzo[b]thiophene, benzo[b]furan, benzimidazole, benzoxazole, benzothiazole, benzisothiazole, naphtho[2,3-b]thiophene, furan, pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, indole, isoindole, 1H-indazole, purine, 4H-quinolizine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, carbazole, β-carboline, phenanthridine, acridine, phenazine, thiazole, isothiazole, phenothiazine, isoxazole, furazan and phenoxazine, and a ring formed by fusion of the 5- to 14-membered aromatic heterocyclic ring with one or two benzene rings, (ii) 5- to 10-membered aliphatic heterocyclic ring selected from the group consisting of pyrrolidine, imidazoline, pyrazolidine, pyrazoline, piperidine, piperazine, morpholine, thiomorpholine, dioxazole, oxadiazoline, thiadiazoline, triazoline, thiadiazole and dithiazole, and (iii) 7- to 10-membered bridged heterocyclic ring selected from the group consisting of quinuclidine and 7-azabicyclo[2.2.1]heptane;
- each of which may have 1 to 5-substitutents selected from the same substituents as defined for ring A;
- or a salt thereof.
(1) 5-amino-3-(4-methoxyphenyl)-2-(4-pyridyl)-7H-thiazolo[3,2-a]pyrimidin-7-one or its salt, (2) 5-amino-3-[4-(1,1-dimethylethyl)phenyl]-2-(4-pyridyl)-7H-thiazolo[3,2-a]pyrimidin-7-one or its salt, or (3) 5-amino-3-(3,5-dimethylphenyl)-2-(4-pyridyl)-7H-thiazolo(3,2-a]pyrimidin-7-one or its salt.
Dependencies are inferred from the claim text.