JP2014530238A5 - - Google Patents

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Publication number: JP2014530238A5
Authority: JP; Japan
Prior art keywords: methyl; dec; ylcarbamoyl; benzothiazol; carboxylic acid
Prior art date: 2012-10-11
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Granted

Application number

JP2014535869A

Other languages

English (en)

Japanese (ja)

Other versions

JP2014530238A (ja

JP6155270B2 (ja

Filing date

2012-10-11

Publication date

2015-12-03

2012-10-11 Application filed filed Critical

2012-10-11 Priority claimed from PCT/US2012/059720 external-priority patent/WO2013055897A1/en

2014-11-17 Publication of JP2014530238A publication Critical patent/JP2014530238A/ja

2015-12-03 Publication of JP2014530238A5 publication Critical patent/JP2014530238A5/ja

2017-06-28 Application granted granted Critical

2017-06-28 Publication of JP6155270B2 publication Critical patent/JP6155270B2/ja

Status Active legal-status Critical Current

2032-10-11 Anticipated expiration legal-status Critical

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-1 heterocyclic alkane Chemical class 0.000 claims description 122
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 54
229910052799 carbon Inorganic materials 0.000 claims description 45
229910052739 hydrogen Inorganic materials 0.000 claims description 38
229910004013 NO 2 Inorganic materials 0.000 claims description 36
101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims description 30
229910052794 bromium Inorganic materials 0.000 claims description 30
229910052740 iodine Inorganic materials 0.000 claims description 30
229910052801 chlorine Inorganic materials 0.000 claims description 29
229910052731 fluorine Inorganic materials 0.000 claims description 27
125000000753 cycloalkyl group Chemical group 0.000 claims description 24
125000001424 substituent group Chemical group 0.000 claims description 24
125000000217 alkyl group Chemical group 0.000 claims description 21
125000000392 cycloalkenyl group Chemical group 0.000 claims description 20
150000001924 cycloalkanes Chemical class 0.000 claims description 18
150000001925 cycloalkenes Chemical class 0.000 claims description 18
125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 18
125000001072 heteroaryl group Chemical group 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
125000005549 heteroarylene group Chemical group 0.000 claims description 9
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 8
SIOXPEMLGUPBBT-UHFFFAOYSA-N Picolinic acid Natural products OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims 40
150000001875 compounds Chemical class 0.000 claims 22
150000003839 salts Chemical class 0.000 claims 17
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 12
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 11
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 11
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 11
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 10
239000001257 hydrogen Substances 0.000 claims 10
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 9
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 6
208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 6
208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 6
206010035226 Plasma cell myeloma Diseases 0.000 claims 6
125000003342 alkenyl group Chemical group 0.000 claims 6
125000000304 alkynyl group Chemical group 0.000 claims 6
208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 6
125000000623 heterocyclic group Chemical group 0.000 claims 6
201000000050 myeloid neoplasm Diseases 0.000 claims 6
125000003118 aryl group Chemical group 0.000 claims 5
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 5
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims 4
150000002431 hydrogen Chemical class 0.000 claims 4
206010005003 Bladder cancer Diseases 0.000 claims 3
208000003174 Brain Neoplasms Diseases 0.000 claims 3
206010006187 Breast cancer Diseases 0.000 claims 3
208000026310 Breast neoplasm Diseases 0.000 claims 3
101100240521 Caenorhabditis elegans nhr-16 gene Proteins 0.000 claims 3
206010008342 Cervix carcinoma Diseases 0.000 claims 3
208000000461 Esophageal Neoplasms Diseases 0.000 claims 3
208000003445 Mouth Neoplasms Diseases 0.000 claims 3
206010030155 Oesophageal carcinoma Diseases 0.000 claims 3
206010033128 Ovarian cancer Diseases 0.000 claims 3
206010061535 Ovarian neoplasm Diseases 0.000 claims 3
208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 3
206010060862 Prostate cancer Diseases 0.000 claims 3
208000000236 Prostatic Neoplasms Diseases 0.000 claims 3
206010041067 Small cell lung cancer Diseases 0.000 claims 3
208000000277 Splenic Neoplasms Diseases 0.000 claims 3
210000001744 T-lymphocyte Anatomy 0.000 claims 3
208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 3
208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 3
210000003719 b-lymphocyte Anatomy 0.000 claims 3
125000005873 benzo[d]thiazolyl group Chemical group 0.000 claims 3
201000006491 bone marrow cancer Diseases 0.000 claims 3
201000010881 cervical cancer Diseases 0.000 claims 3
239000003814 drug Substances 0.000 claims 3
201000004101 esophageal cancer Diseases 0.000 claims 3
201000003444 follicular lymphoma Diseases 0.000 claims 3
125000005843 halogen group Chemical group 0.000 claims 3
206010073071 hepatocellular carcinoma Diseases 0.000 claims 3
208000012987 lip and oral cavity carcinoma Diseases 0.000 claims 3
208000003747 lymphoid leukemia Diseases 0.000 claims 3
201000001441 melanoma Diseases 0.000 claims 3
208000025113 myeloid leukemia Diseases 0.000 claims 3
208000000587 small cell lung carcinoma Diseases 0.000 claims 3
201000002471 spleen cancer Diseases 0.000 claims 3
201000005112 urinary bladder cancer Diseases 0.000 claims 3
206010009944 Colon cancer Diseases 0.000 claims 2
208000001333 Colorectal Neoplasms Diseases 0.000 claims 2
125000004429 atom Chemical group 0.000 claims 2
125000004432 carbon atom Chemical group C* 0.000 claims 2
201000010099 disease Diseases 0.000 claims 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
231100000844 hepatocellular carcinoma Toxicity 0.000 claims 2
230000003211 malignant effect Effects 0.000 claims 2
208000002154 non-small cell lung carcinoma Diseases 0.000 claims 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
229940124597 therapeutic agent Drugs 0.000 claims 2
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
WMXKKYYYZPZSJA-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-3,5-dimethylpyrazol-4-yl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(C)N(CC45CC6CC(CC(C6)C4)C5)N=C3C)=NC2=C1 WMXKKYYYZPZSJA-UHFFFAOYSA-N 0.000 claims 1
DPXXHOZGVBDFCX-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-5-cyano-2-methylpyrrol-3-yl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(C(C#N)=C3)CC34CC5CC(CC(C5)C3)C4)C)=NC2=C1 DPXXHOZGVBDFCX-UHFFFAOYSA-N 0.000 claims 1
NKMWBPIMEXAUCU-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-5-methylpyrazol-4-yl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-1-methyl-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1C(C2)CC(C3)CC2CC13CN1N=CC(C2=CC=C(N=C2C(O)=O)N2C(C3=C(C(=O)NC=4SC5=CC=CC=C5N=4)C=CC=C3CC2)C)=C1C NKMWBPIMEXAUCU-UHFFFAOYSA-N 0.000 claims 1
QCQQONWEDCOTBV-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-5-methylpyrazol-4-yl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34CC5CC(CC(C5)C3)C4)C)=NC2=C1 QCQQONWEDCOTBV-UHFFFAOYSA-N 0.000 claims 1
XQWAUHSNIXVETH-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-5-methylpyrazol-4-yl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-4,4-dimethyl-1,3-dihydroisoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C3=C4CN(CC(C)(C)C4=CC=C3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34CC5CC(CC(C5)C3)C4)C)=NC2=C1 XQWAUHSNIXVETH-UHFFFAOYSA-N 0.000 claims 1
SRYPCRRVZAWVJL-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-5-methylpyrazol-4-yl]-6-[8-([1,3]thiazolo[4,5-b]pyridin-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34CC5CC(CC(C5)C3)C4)C)=NC2=N1 SRYPCRRVZAWVJL-UHFFFAOYSA-N 0.000 claims 1
SYLKGSBVKMSQMT-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-5-methylpyrazol-4-yl]-6-[8-([1,3]thiazolo[4,5-c]pyridin-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound N1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34CC5CC(CC(C5)C3)C4)C)=NC2=C1 SYLKGSBVKMSQMT-UHFFFAOYSA-N 0.000 claims 1
BXSCGJPJCIGHLT-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-5-methylpyrazol-4-yl]-6-[8-([1,3]thiazolo[5,4-b]pyridin-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CN=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34CC5CC(CC(C5)C3)C4)C)=NC2=C1 BXSCGJPJCIGHLT-UHFFFAOYSA-N 0.000 claims 1
AGLXJYUZHSHVGW-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-5-methylpyrazol-4-yl]-6-[8-([1,3]thiazolo[5,4-c]pyridin-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=NC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34CC5CC(CC(C5)C3)C4)C)=NC2=C1 AGLXJYUZHSHVGW-UHFFFAOYSA-N 0.000 claims 1
IJARDSRRNICYGG-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-5-methylpyrazol-4-yl]-6-[8-(imidazo[1,2-a]pyridin-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=CC2=NC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34CC5CC(CC(C5)C3)C4)C)=CN21 IJARDSRRNICYGG-UHFFFAOYSA-N 0.000 claims 1
HIDAZKFPIYYHBS-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-5-methylpyrazol-4-yl]-6-[8-(imidazo[1,2-b]pyridazin-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound N1=CC=CC2=NC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34CC5CC(CC(C5)C3)C4)C)=CN21 HIDAZKFPIYYHBS-UHFFFAOYSA-N 0.000 claims 1
WQOZTYXEAIOXHM-UHFFFAOYSA-N 3-[1-(1-adamantylmethyl)-5-methyltriazol-4-yl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=N3)CC34CC5CC(CC(C5)C3)C4)C)=NC2=C1 WQOZTYXEAIOXHM-UHFFFAOYSA-N 0.000 claims 1
LEDCZSOKLOQIDL-UHFFFAOYSA-N 3-[1-[2-(1-adamantyl)ethyl]-5-cyano-2-methylpyrrol-3-yl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(C(C#N)=C3)CCC34CC5CC(CC(C5)C3)C4)C)=NC2=C1 LEDCZSOKLOQIDL-UHFFFAOYSA-N 0.000 claims 1
IWMMMZGYHDPBMY-UHFFFAOYSA-N 3-[2-(1-adamantylamino)-3-methylpyridin-4-yl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=CC=NC(NC45CC6CC(CC(C6)C4)C5)=C3C)=NC2=C1 IWMMMZGYHDPBMY-UHFFFAOYSA-N 0.000 claims 1
CSLZXOVQZOFAEC-UHFFFAOYSA-N 3-[3-(1-adamantylsulfonyl)-2-cyanophenyl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C=3N=C(C(=CC=3)C=3C(=C(C=CC=3)S(=O)(=O)C34CC5CC(CC(C5)C3)C4)C#N)C(=O)O)=NC2=C1 CSLZXOVQZOFAEC-UHFFFAOYSA-N 0.000 claims 1
MMXDTUDYYBOMAB-UHFFFAOYSA-N 3-[3-[1-adamantylmethyl(methyl)amino]-2-methylphenyl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C=3C=CC=C(C=3C)N(CC34CC5CC(CC(C5)C3)C4)C)=NC2=C1 MMXDTUDYYBOMAB-UHFFFAOYSA-N 0.000 claims 1
VDXYLGSKAFNVQM-UHFFFAOYSA-N 3-[3-[2-adamantyl(methyl)sulfamoyl]-2-methylphenyl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C=3C=CC=C(C=3C)S(=O)(=O)N(C3C4CC5CC(C4)CC3C5)C)=NC2=C1 VDXYLGSKAFNVQM-UHFFFAOYSA-N 0.000 claims 1
HJYSWLUWOJOXJI-UHFFFAOYSA-N 3-[3-[adamantane-1-carbonyl(methyl)amino]-2-methylphenyl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C=3C=CC=C(C=3C)N(C(=O)C34CC5CC(CC(C5)C3)C4)C)=NC2=C1 HJYSWLUWOJOXJI-UHFFFAOYSA-N 0.000 claims 1
CJJMAWPEZKYJAP-UHFFFAOYSA-N 3-hydroxyadamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2(O)CC1(C(=O)O)C3 CJJMAWPEZKYJAP-UHFFFAOYSA-N 0.000 claims 1
SIMWKAPKJBPDFW-UHFFFAOYSA-N 6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-3-[1-(2-oxatricyclo[3.3.1.13,7]decan-1-ylmethyl)pyrazol-4-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C=3N=C(C(=CC=3)C3=CN(CC45OC6CC(CC(C6)C4)C5)N=C3)C(=O)O)=NC2=C1 SIMWKAPKJBPDFW-UHFFFAOYSA-N 0.000 claims 1
RQLRRVMPMGMPFK-UHFFFAOYSA-N 6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-3-[5-cyano-2-methyl-1-[(3-methyl-2-oxatricyclo[3.3.1.13,7]decan-1-yl)methyl]pyrrol-3-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(C(C#N)=C3)CC34OC5(C)CC(CC(C5)C3)C4)C)=NC2=C1 RQLRRVMPMGMPFK-UHFFFAOYSA-N 0.000 claims 1
XGVPFJVDQQIOQE-UHFFFAOYSA-N 6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]-3-[1-(spiro[3.5]nonan-7-ylmethyl)pyrazol-4-yl]pyridine-2-carboxylic acid Chemical compound OC(=O)C1=NC(N2CC3=C(C(=O)NC=4SC5=CC=CC=C5N=4)C=CC=C3CC2)=CC=C1C(=C1)C=NN1CC(CC1)CCC21CCC2 XGVPFJVDQQIOQE-UHFFFAOYSA-N 0.000 claims 1
DIKNGMWFGWLQSZ-UHFFFAOYSA-N 6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]-3-[1-[(3,5,7-trimethyl-1-adamantyl)methyl]pyrazol-4-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=CN(N=C3)CC34CC5(C)CC(C3)(C)CC(C5)(C4)C)=NC2=C1 DIKNGMWFGWLQSZ-UHFFFAOYSA-N 0.000 claims 1
OADAEYHGDXGPOT-UHFFFAOYSA-N 6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]-3-[1-[(3,5-dimethyl-1-adamantyl)methyl]-5-methylpyrazol-4-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34CC5(C)CC(C)(CC(C5)C3)C4)C)=NC2=C1 OADAEYHGDXGPOT-UHFFFAOYSA-N 0.000 claims 1
QPGIGJKUNAAHCG-UHFFFAOYSA-N 6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]-3-[1-[(3,5-dimethyl-1-adamantyl)methyl]pyrazol-4-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=CN(N=C3)CC34CC5(C)CC(C4)CC(C5)(C3)C)=NC2=C1 QPGIGJKUNAAHCG-UHFFFAOYSA-N 0.000 claims 1
TTYCXRNLXMYOFM-UHFFFAOYSA-N 6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]-3-[1-[(3-methoxy-5,7-dimethyl-1-adamantyl)methyl]-5-methylpyrazol-4-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C=3C=NN(C=3C)CC34CC5(CC(C4)(C)CC(C3)(C5)OC)C)=NC2=C1 TTYCXRNLXMYOFM-UHFFFAOYSA-N 0.000 claims 1
YBQQRSGYPYSEJQ-UHFFFAOYSA-N 6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]-3-[1-[(3-morpholin-4-yl-1-adamantyl)methyl]pyrazol-4-yl]pyridine-2-carboxylic acid Chemical compound OC(=O)C1=NC(N2CC3=C(C(=O)NC=4SC5=CC=CC=C5N=4)C=CC=C3CC2)=CC=C1C(=C1)C=NN1CC(C1)(C2)CC(C3)CC1CC32N1CCOCC1 YBQQRSGYPYSEJQ-UHFFFAOYSA-N 0.000 claims 1
IFRNQHMRUMRVLH-UHFFFAOYSA-N 6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]-3-[1-[(3-propan-2-yloxy-1-adamantyl)methyl]pyrazol-4-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=CN(N=C3)CC34CC5CC(C4)CC(C3)(C5)OC(C)C)=NC2=C1 IFRNQHMRUMRVLH-UHFFFAOYSA-N 0.000 claims 1
DYFNZDQOCYJSDS-UHFFFAOYSA-N 6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]-3-[1-[(7-methoxyspiro[2.5]octan-7-yl)methyl]-5-methylpyrazol-4-yl]pyridine-2-carboxylic acid Chemical compound C1C(OC)(CN2C(=C(C=N2)C=2C(=NC(=CC=2)N2CC3=C(C(=O)NC=4SC5=CC=CC=C5N=4)C=CC=C3CC2)C(O)=O)C)CCCC21CC2 DYFNZDQOCYJSDS-UHFFFAOYSA-N 0.000 claims 1
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JESAQMQUUABFQK-UHFFFAOYSA-N 6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1h-isoquinolin-2-yl]-3-[1-[[3-(2-methoxyethoxy)-1-adamantyl]methyl]-5-methylpyrazol-4-yl]pyridine-2-carboxylic acid Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C=3C=NN(C=3C)CC34CC5CC(C4)CC(C3)(C5)OCCOC)=NC2=C1 JESAQMQUUABFQK-UHFFFAOYSA-N 0.000 claims 1
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XPCVRYRUUUMVTI-UHFFFAOYSA-N C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(C(C#N)=C3)CC34OC5CC(CC(C5)C3)C4)C)=NC2=C1 Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(C(C#N)=C3)CC34OC5CC(CC(C5)C3)C4)C)=NC2=C1 XPCVRYRUUUMVTI-UHFFFAOYSA-N 0.000 claims 1
JTDXSZVTTZNZLD-UHFFFAOYSA-N C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34OC5CC(CC(C5)C3)C4)C)=NC2=C1 Chemical compound C1=CC=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34OC5CC(CC(C5)C3)C4)C)=NC2=C1 JTDXSZVTTZNZLD-UHFFFAOYSA-N 0.000 claims 1
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HYAXKVJHFGIGOL-UHFFFAOYSA-N C1=CN=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34OC5CC(CC(C5)C3)C4)C)=NC2=C1 Chemical compound C1=CN=C2SC(NC(=O)C=3C=CC=C4CCN(CC4=3)C3=CC=C(C(=N3)C(O)=O)C3=C(N(N=C3)CC34OC5CC(CC(C5)C3)C4)C)=NC2=C1 HYAXKVJHFGIGOL-UHFFFAOYSA-N 0.000 claims 1
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 1
206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
206010028980 Neoplasm Diseases 0.000 claims 1
208000015634 Rectal Neoplasms Diseases 0.000 claims 1
201000011510 cancer Diseases 0.000 claims 1
210000004027 cell Anatomy 0.000 claims 1
210000001072 colon Anatomy 0.000 claims 1
229910052805 deuterium Inorganic materials 0.000 claims 1
201000005202 lung cancer Diseases 0.000 claims 1
208000020816 lung neoplasm Diseases 0.000 claims 1
230000036210 malignancy Effects 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
125000002912 morpholin-4-ylsulfonyl group Chemical group O1C([H])([H])C([H])([H])N(S(=O)(=O)[*])C([H])([H])C1([H])[H] 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
125000003226 pyrazolyl group Chemical group 0.000 claims 1
125000004076 pyridyl group Chemical group 0.000 claims 1
125000000168 pyrrolyl group Chemical group 0.000 claims 1
206010038038 rectal cancer Diseases 0.000 claims 1
201000001275 rectum cancer Diseases 0.000 claims 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims 1
125000001425 triazolyl group Chemical group 0.000 claims 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 description 7
125000004366 heterocycloalkenyl group Chemical group 0.000 description 6
125000000732 arylene group Chemical group 0.000 description 1
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1

JP2014535869A 2011-10-14 2012-10-11 癌ならびに免疫疾患および自己免疫疾患の治療のためのアポトーシス誘発剤としての８−カルバモイル−２−（２，３−ジ置換ピリド−６−イル）−１，２，３，４−テトラヒドロイソキノリン誘導体 Active JP6155270B2 (ja)

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PCT/US2012/059720 WO2013055897A1 (en)	2011-10-14	2012-10-11	8 - carbamoyl - 2 - (2,3- di substituted pyrid - 6 - yl) -1,2,3,4 -tetrahydroisoquinoline derivatives as apoptosis - inducing agents for the treatment of cancer and immune and autoimmune diseases

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