APOPTOSIS INDUCING AGENTS FOR TREATING CANCER, IMMUNE AND AUTOIMMUNE DISEASES Russian patent published in 2015 - IPC C07D295/195 C07D211/56 C07C311/51 A61K31/451 A61K31/495 A61K31/18 A61P35/00 

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds specified in a group shown below. The compounds contain at least 5 rings including a fragment with a bridge structure with a carbon side of the central group C(O)-NH-SO₂, piperidinyl, or piperazinyl, or phenyl; phenyl attached to each carbon and sulphur atom of the group C(O)-NH-SO₂, wherein phenyl from the sulphur atom side is substituted by a nitro group and NH-CH₂(tetrahydro-2H-pyran-4-yl or cyclohexyl) group. The compounds possess the properties of Bcl-2 antiapoptotic protein activity inhibitor and can be used in treating the diseases expressing Bcl-2 protein. These diseases are malignant diseases specified in bladder cancer, cerebral cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukaemia etc. The compounds of the present invention are specified in a group consisting of 4-(4-{acetyl[(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]amino}piperidin-1-yl)-N-({4-[(cyclohexylmethyl)amino]-3-nitrophenyl}sulphonyl)benzamide; 4-(4-{benzoyl[(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]amino}piperidin-1-yl)-N-({4-[(cyclohexylmethyl)amino]-3-nitrophenyl}sulphonyl)benzamide; N-({4-[(cyclohexylmethyl)amino]-3-nitrophenyl}sulphonyl)-3′-{[(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]amino}biphenyl-4-carboxamide; N-({4-[(cyclohexylmethyl)amino]-3-nitrophenyl}sulphonyl)-4-(4-{(phenylacetyl)[(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]amino}piperidin-1-yl)benzamide; N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulphonyl)-4-(4-{2-[(1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl]benzylidene}piperidin-1-yl)benzamide; 4-[4-(2-{5-[8-azabicyclo[3.2.1]oct-8-ylmethyl]-2-thienyl}benzyl)piperazin-1-yl]-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulphonyl)benzamide; N-({4-[(cyclohexylmethyl)amino]-3-nitrophenyl}sulphonyl)-4-(4-{(3-phenylpropanoyl)[(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]amino}piperidin-1-yl)benzamide; 4-{4-[adamantan-1-ylmethyl]piperazin-1-yl}-N-({4-[(cyclohexylmethyl)amino]-3-nitrophenyl}sulphonyl)benzamide; 4-(4-{2-[adamantan-1-yl]-2-oxoethyl}piperazin-1-yl)-N-({4-[(cyclohexylmethyl)amino]-3-nitrophenyl}sulphonyl)benzamide; N-({4-[(cyclohexylmethyl)amino]-3-nitrophenyl}sulphonyl)-4-{4-[(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]piperazin-1-yl}benzamide and other compounds or their therapeutically acceptable salts listed in the patent claim.

EFFECT: compounds possess the properties of Bcl-2 antiapoptotic protein activity inhibitor and can be used in treating the diseases expressing Bcl-2 protein.

6 cl, 1 tbl, 85 ex