US 2004/0106635 A1 · Spiroisoquinoline compound, a method for preparing the same and an intermediate thereof

A spiroisoquinoline derivative of the formula [I]:

1482
wherein ring A is an optionally substituted benzene ring,
R10 is a hydrogen atom or a group of the formula:
—Z—R1,
wherein R1 is a hydrogen atom, an optionally substituted lower alkyl group, or an optionally substituted lower alkenyl group,
Z is a group of the formula:
—CH2— or —CO—,
R2 is a hydrogen atom or an optionally substituted heterocyclic group,
B is a group of the formula:
1483
R3 is an optionally substituted amino group or an optionally substituted nitrogen-containing aliphatic heterocyclic group, and
Y is a group of the formula:
—CH2— or —CO—,
or a pharmaceutically acceptable salt thereof.

11 more elements

A spiroisoquinoline comnpound of the formula [I-h]:

1496
wherein R81, R82 and R83 are the same or different groups selected from the group of a hydrogen atom, a lower alkoxy group, an optionally protected hydroxyl group and a halogen atom,
R10 is a hydrogen atom or a group of the formula:
—Z—R1,
wherein Z is a group of the formula:
—CH2— or —CO—, and
R1 is
(1) a hydrogen atom,
(2) a lower alkyl group which may be substituted by a group(s) selected from the group consisting of:
(i) a halogen atom,
(ii) an optionally protected hydroxyl group,
(iii) an amino group which may be substituted by a group(s) selected from a lower alkyl group;
a lower cycloalkyl group;
an aryl-lower alkyl group;
a lower group;
1-(mono- or di-)lower alkyl amino-2-nitrovinyl group;
1-amino-2,2-dicyanovinyl group;
1-(mono- or di-)lower alkylamino-2,2-dicyanovinyl group;
3-aminocyclobut-3-en-1,2-dion-4-yl group;
3-(mono- or di-)lower alkylaminocyclobut-3-en-1,2-dion-4-yl group;
and a group which can be removed by enzymatic or chemical metabolic process in vivo,
(iv) a guanidino group which may be substituted by a group(s) selected from a lower alkyl group, a lower cycloalkyl group and a cyano group,
(v) an ureido group which may be substituted by a group(s) selected from a lower alkyl group and a lower cycloalkyl group, and
(vi) a thioureido group which may be substituted by a group(s) selected from a lower alkyl group and a lower cycloalkyl group, or
(3) a lower alkenyl group,
R30 is a nitrogen-containing heterocyclic group or its onium salt on nitrogen atom which may be substituted by a group(s) selected from an oxo group, an oxide group, a lower alkyl group, a cyano lower alkyl group, a lower cycloalkyl-lower alkyl group (a carbon atom(s) on said lower cycloalkyl group being optionally substituted by a sulfur atom(s)), a pyrrolidinylcarbonyl-lower alkyl group, a halogeno-lower alkyl group, a lower alkylthio-lower alkyl group, an aryl-lower alkyl group (the aryl moiety of said aryl-lower alkyl group being optionally substituted by a group(s) selected from a lower alkyl group, a lower alkoxy group, a halogen atom, a tri-halogenomethyl group, a tri-halogenomethoxy group, a nitro group, and a cyano group), a thienyl-lower alkyl group (the thienyl moiety of said thienyl-lower alkyl group being optionally substituted by a group(s) selected from a halogen atom), a furyl-lower alkyl group, an imidazolyllower alkyl group, a thiazolyl-lower alkyl group (the thiazolyl moiety of said thiazolyl-lower alkyl group being optionally substituted by a group(s) selected from a lower alkyl group), a pyrazolyl-lower alkyl group, a pyrimidinyl-lower alkyl group, a pyridazinyl-lower alkyl group, a pyridyl-lower alkyl group (the pyridyl moiety of said pyridyl-lower alkyl group being optionally substituted by a lower alkyl group or an oxide group), a carboxyl group, a lower alkoxycarbonyl group, a halogen atom, a hydroxy-lower alkyl group, a carboxyl-lower alkyl group, a lower alkoxycarbonyl-lower alkyl group, an aryl-lower alkoxy-lower alkyl group (the aryl moiety of said aryl-lower alkoxy-lower alkyl group being optionally substituted by a halogen atom(s)), an amino-protecting group, an amino group (said amino group being optionally substituted by a lower alkyl group(s)), a lower cycloalkyl group, an N-pyridyl-N-lower alkylcarbamoyl group, a lower alkenyl group, a halogeno-lower alkenyl group, and an aryl group (said aryl group being optionally substituted by a group(s) selected from a trifluoromethyl group, a lower alkoxy group, and a nitro group, or a pharmaceutically acceptable salt thereof.

23 more elements

A compound selected from

(1α,4β)-2′-methyl-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-(3-methyl-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-diethoxy-4-[4-(1-(3-ethoxyphenylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-2′-methyl-3′,4′-dihydro-6′,7′-diethoxy-4-[4-(1-(6-methylpyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-2′-dimethylaminoacetyl-3′,4′-dihydro-6′-methoxy-4-[4-(1-(6-methylpyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-(1-(6-ethylpyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-diethoxy-4-(4-(1-(6-ethylpyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-ishyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)- isoquinoline], pyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline], ′(2′H)-isoquinoline], yridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cycolhexane-1,1′(2′H)-isoquinoline],
(1α,4β)-2′-ethyl-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-(1-(6-ethylpyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-2′-dimethylaminoacetyl-3′,4′-dihydro-6′,7′-diethoxy-4-[4-(1-(6-ethylpyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-(1-(2-ethylthiazol-4-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-2′-dimethylaminoacetyl-3′,4′-dihydro-6′-ethoxy-4-[4-(1-(6-methylpyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-2′-dimethylaminoacetyl-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-(1-(2-methylthiazol-4-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(N,N-dimethylamino)propionyl]-4-[4-(1-(3-methylbenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(N,N-dimethylamino)propionyl]-4-[4-(1-(3-methoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro [cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[2-(N,N-dimethylamino)ethyl]-4-[4-(1-(6-methylpyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-diethoxy-4-[4-(1-(6-methylpyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-diethoxy-2′-[2-(N,N-dimethylamino)acetyl]-4-[4-(1-(3-methylbenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-(1-(3-ethoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,40β)-3′,4′-dihydro-6′-methoxy-4-[4-(1-(3-ethoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-2′-[2-(N-methylamino)acetyl]-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-(1-(3-ethoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-2′-[2-(N-methylamino)acetyl]-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-(1-(3-trifluoromethoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-2′-[2-(N-methylamino)acetyl]-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-(1-(6-ethylpyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-(1-(6-n-propylpyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-2′-[2-(N,N-dimethylamino)acetyl]-3′,4′-dihydro-6′-ethoxy-4-[4-(1-(6-ethoxypyridin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(1-methyl-amino-2-nitrovinylamino)propyl]-4-[4-[1-(2-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(1-amino-2-nitrovinylamino)propyl]-4-[4-[1-(2-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(N-(n-butyl)ureido)propyl]-4-[4-[1-(2-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(N-ethylureido)propyl]-4-[4-[1-(2-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(3-dimethylamino-3-cyclobuten-1,2-dion-4-yl)aminopropyl]-4-[4-[1-(2-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(3-methylamino-3-cyclobuten-1,2-dion-4-yl)aminopropy]4-[4-[1-(2-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(3-amino-3-cyclobuten-1,2-dion-4-yl)aminopropyl]-4-[4-[1-(2-nitro-benzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(1-amino-2,2-dicyanovinylamino)propyl]-4-[4-[1-(2-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(1,3-dimethyl-2-cyanoguanidino)propyl]-4-[4-[1-(2-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(N-isopropylamino)propyl]-4-[4-[1-(2-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-(N,N-dimethylaminoacetyl)-4-[4-(1-(2-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro-[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-ethyl-4-[4-[1-(3-methylbenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-piperadin-1-yl)carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-methyl-4-[4-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-piperadin-1-yl]carbonyl-spiro[cyciohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(N-ethoxy-carbonylamino)propyl]-4-[4-[1-(2-bromobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(N-ethoxy-carbonylamino)propyl]-4-[4-[1-(2-chlorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-2′-[3-(N-ethoxy-carbonylamino)propyl]-4-[4-[1-(2-cyanobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperadin-1-yl]carbonyl-4-[4-[1-(2-cyanobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-
(1α,4β)-3′,4′-dihydro-6′,7′-diethoxy-2′-methyl-4-[4-[1-(3-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline], and
(1α,4β)-3′,4′-dihydro-6′,7′-diethoxy-2′-methyl-4-[4-(1-(3-chlorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperadin-1-yl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
or a pharmaceutically acceptable salt thereof.

39 more elements

A compound selected from

2′-[3-(methylamino)propionyl]-3′,4′-dihydro-6′,7′-dimethoxy-2-(2-ethyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)-4-[4-[1-(4-pyridylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinylmethyl]carbonyl-spiro[cyclohexane-1,1′(2-′H)-isoquinoline],
2′-[3-(methylamino)propionyl]-3′,4′-dihydro-6′,7′-dimethoxy-2-(2-ethyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)-4-[4-[1-(2-pyridylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-[3-(methylamino)propionyl]-3′,4′-dihydro-6′,7′-dimethoxy-2-(2-ethyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)-4-[4-[1-(3-pyridylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline), pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline], -tetrahydro-6,7-dimethoxy-1-isoquinolyl)-4-[4-(4-n-butyl-4H-imidazo[4,5-b]pyridin-7-yl)-1-piperazinyljcarbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline), -yl)-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline], -tetrahydro-6,7-dimethoxy-1-isoquinolyl)-4-[4-(3-methyl-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-yl)-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-[3-(methylamino)propionyl]-3′,4′-dihydro-6′,7′-dimethoxy-2-(2-ethyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)-4-[4-(1-n-propyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-[3-(methylamino)propionyl]-3′,4′-dihydro-6′,7′-dimethoxy-2-(2-ethyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)-4-[4-[1-(2-chrolophenylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-[3-(methylamino)propionyl]-3′,4′-dihydro-6′,7′-dimethoxy-2-(2-ethyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)-4-[4-[1-(3-methylphenylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-(3-aminopropyl)-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-[1-(2-pyridylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-(3-aminopropyl)-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-[1-(2-nitrophenylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-[3-(2-cyano-3,3-dimethylguanidino)propyl]-3′,4′-dihydro-6′,7′-dimethoxy-4-4-[1-(2-nitrophenylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl4-[4-[1-(2-nitrophenylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline], 4-[4-[1-(2-chlorophenylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-(3-aminopropyl)-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-[1-(2-bromophenylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-[3-[N-(propionyloxymethyloxycarbonyl)-N-methylamino]-propionyl]-3′,4′-dihydro-6′,7′-dimethoxy-2-(2-ethyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)-4-[4-[1-(4-pyridylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-[3-[N-(pivaloyloxymethyloxycarbonyl)-N-methylamino]-propionyl]-3′,4′-dihydro-6′,7′
2′-[3-[N-(pivaloyloxymethyloxycarbonyl)-N-methylamino-propionyl]-3′,4′-dihydro-6′,7′4-pyridylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-[3-[N-(pivaloyloxymethyloxycarbonyl)-N-methyl-amino]propionyl]-3′,4′-dihydro-6′,7′-dimethoxy-2-(2-ethyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)-4-[4-(3-methyl-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-yl)-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-[3-[N-(cyclopropylcarbonyloxymethyloxycarbonyl)-N-methylamino]propionyl]-3′,41′-dihydro-6′,7′-dimethoxy-2-(2-ethyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)-4-[4-[1-(4-pyridylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
2′-[3-(pivaloyloxymethyloxycarbonylamino)propyl]-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-[1-(2-nitrophenylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-[1-(3-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[syclohexane-1,1′(2′H)-isoquinoline],
(1α,4β)-2′-dimethylaminoacetyl-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-[1-(3-methylbenzyl)-1H-pyrazolo(3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane--(3-methylbenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-
(1α,4β)-2′-methyl-3′,4′-dihydro-6′,7′-dimethoxy-4-[4-(3-methyl-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-yl)-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline], and
(1α,4β)-2′-ethyl-3′,4′-dihydro-6′,7′-diethoxy-4-[4-[1-(2-pyridylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-1-piperazinyl]carbonyl-spiro[cyclohexane-1,1′(2′H)-isoquinoline],
or a pharmaceutically acceptable salt thereof.

18 more elements

A process for preparing a compound of the formula[III]:

1524
wherein D1 and D2 are the same or different and each a group of the formula:
—N═ or —CH═,
one of E1 and E2 is a group of the formula:
—N═, and the other is a group of the formula:
—N═ or —CH═, other is a group of the formula:
—N═ or —CH═, hydrogen atom, an oxo group, an oxide group, a lower alkyl group, a cyano lower alkyl group, a lower cycloalkyl-lower alkyl group (a carbon atom(s) on said lower cycloalkyl group being optionally substituted by a sulfur atom(s)), a pyrrolidonocarbonyl-lower alkyl group, a halogeno-lower alkyl group, a lower alkylthio-lower alkyl group, an aryl-lower alkyl group (the aryl moiety of said aryl-lower alkyl group being optionally substituted by a groupfs) selected from a lower alkyl group, a lower alkoxy group, a halogen atom, a tri-halogenomethyl group, a tri-halogenomethoxy group, a nitro group, and a cyano group), a thienyl-lower alkyl group (the thienyl moiety of said thienyl-lower alkyl group being optionally substituted by a group(s) selected from a halogen atom), a furyl-lower alkyl group, an imidazolyl-lower alkyl group, athiazolyl-lower alkyl group (the thiazolyl moiety of said thiazolyl-lower alkyl group being optionally substituted by a group(s) selected from a lower alkyl group), a pyrazolyl-lower alkyl group, a pyrimidinyl-lower alkyl group, a pyridazinyl-lower alkyl group, a pyridyl-lower alkyl group (the pyridyl moiety of said pyridyl-lower alkyl group being optionally substituted by a lower alkyl group or an oxide group), a carboxyl group, a lower alkoxycarbonyl group, a halogen atom, a hydroxy-lower alkyl group, a carboxyl-lower alkyl group, a lower alkoxycarbonyl-lower alkyl group, an aryl-lower alkoxy-lower alkyl group (the aryl moiety of said aryl-lower alkoxy-lower alkyl group being optionally substituted by a halogen atom(s)), an amino-protecting group, an amino group (said amino group being optionally substituted by a lower alkyl group(s)), a lower cycloalkyl group, an N-pyridyl-N-lower alkylcarbamoyl group, a lower alkenyl group, a halogeno-lower alkenyl group, and an aryl group (said aryl group being optionally substituted by a group(s) selected from a trifluoromethyl group, a lower alkoxy group, and a nitro group, and G is an amino protecting group, or a salt thereof,
which comprises reacting a compound of the formula [28]:
1525
wherein the symbols are the same as defined above, or a salt thereof,
with a compound of the formula[29]:
1526
wherein G is the same as defined above, or a salt thereof, and if necessary, followed by converting the product into a salt thereof.

10 more elements

Spiroisoquinoline compound, a method for preparing the same and an intermediate thereof

Life of this patent

Abstract

Claims45

Spiroisoquinoline compound, a method for preparing the same and an intermediate thereof

Life of this patent

Abstract

Claims45