RU2012127760A - Bcl-2-селективные апоптоз-индуцирующие средства для лечения рака и иммунных заболеваний - Google Patents
Bcl-2-селективные апоптоз-индуцирующие средства для лечения рака и иммунных заболеваний Download PDFInfo
- Publication number
- RU2012127760A RU2012127760A RU2012127760/04A RU2012127760A RU2012127760A RU 2012127760 A RU2012127760 A RU 2012127760A RU 2012127760/04 A RU2012127760/04 A RU 2012127760/04A RU 2012127760 A RU2012127760 A RU 2012127760A RU 2012127760 A RU2012127760 A RU 2012127760A
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- RU
- Russia
- Prior art keywords
- methyl
- chlorophenyl
- yloxy
- piperazin
- benzamide
- Prior art date
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- 239000003814 drug Substances 0.000 title claims 7
- 206010028980 Neoplasm Diseases 0.000 title 1
- 201000011510 cancer Diseases 0.000 title 1
- 208000026278 immune system disease Diseases 0.000 title 1
- -1 {5-chloro-6 - [(4,4-difluorocyclohexyl) methoxy] pyridin-3-yl} sulfonyl Chemical group 0.000 claims abstract 136
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract 25
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims abstract 21
- 150000001875 compounds Chemical class 0.000 claims abstract 9
- 150000003839 salts Chemical class 0.000 claims abstract 6
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims abstract 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 7
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 6
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 5
- 206010005003 Bladder cancer Diseases 0.000 claims 5
- 208000003174 Brain Neoplasms Diseases 0.000 claims 5
- 206010006187 Breast cancer Diseases 0.000 claims 5
- 208000026310 Breast neoplasm Diseases 0.000 claims 5
- 206010008342 Cervix carcinoma Diseases 0.000 claims 5
- 206010009944 Colon cancer Diseases 0.000 claims 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 5
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 5
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 5
- 208000003445 Mouth Neoplasms Diseases 0.000 claims 5
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 5
- 206010033128 Ovarian cancer Diseases 0.000 claims 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 5
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 5
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 5
- 206010060862 Prostate cancer Diseases 0.000 claims 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 5
- 208000000277 Splenic Neoplasms Diseases 0.000 claims 5
- 210000001744 T-lymphocyte Anatomy 0.000 claims 5
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 5
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 5
- 201000006491 bone marrow cancer Diseases 0.000 claims 5
- 201000010881 cervical cancer Diseases 0.000 claims 5
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 5
- 201000004101 esophageal cancer Diseases 0.000 claims 5
- 201000003444 follicular lymphoma Diseases 0.000 claims 5
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 5
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 claims 5
- 208000014018 liver neoplasm Diseases 0.000 claims 5
- 208000003747 lymphoid leukemia Diseases 0.000 claims 5
- 208000019420 lymphoid neoplasm Diseases 0.000 claims 5
- 201000001441 melanoma Diseases 0.000 claims 5
- 208000025113 myeloid leukemia Diseases 0.000 claims 5
- 201000000050 myeloid neoplasm Diseases 0.000 claims 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 5
- 201000002471 spleen cancer Diseases 0.000 claims 5
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 5
- 201000005112 urinary bladder cancer Diseases 0.000 claims 5
- 206010041067 Small cell lung cancer Diseases 0.000 claims 4
- 210000003719 b-lymphocyte Anatomy 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 4
- 229940124597 therapeutic agent Drugs 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 2
- IFOAYUDCZBURRF-UHFFFAOYSA-N C(C1=CC=CC=C1)(=O)NOC1=C2C=NNC2=CC=C1 Chemical compound C(C1=CC=CC=C1)(=O)NOC1=C2C=NNC2=CC=C1 IFOAYUDCZBURRF-UHFFFAOYSA-N 0.000 claims 1
- 206010010071 Coma Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- CTJNLQGMBWGPQO-UHFFFAOYSA-N n-[4-[[4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-indazol-4-yloxy)benzoyl]sulfamoyl]-2-nitrophenyl]-4-cyanopiperidine-1-carboxamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=3C=NNC=3C=CC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC(=O)N1CCC(C#N)CC1 CTJNLQGMBWGPQO-UHFFFAOYSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
Classifications
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
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- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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Abstract
1. Соединение или его терапевтически приемлемая соль, где соединение выбрано из следующих:N-({5-хлор-6-[(4,4-дифторциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;N-({6-[(транс-4-карбамоилциклогексил)метокси]-5-хлорпиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(4-{[(транс-4-цианоциклогексил)метил]амино}-3-нитрофенил)сульфонил]-2-(1Н-индазол-4-илокси)бензамид;N-({5-хлор-6-[2-(1Н-имидазол-1-ил)этокси]пиридин-3ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;N-({5-хлор-6-[(1-метил-1Н-имидазол-5-ил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[5-фтор-6-(тетрагидро-2Н-пиран-4-илметокси)пиридин-3-ил]сульфонил}-2-(1Н-индазол-4-илокси)бензамид;N-{[5-хлор-6-(1,4-диоксан-2-илметокси)пиридин-3ил]сульфонил}-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;N-({5-хлор-6-[(4,4-дифтор-1-гидроксициклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;N-({5-хлор-6-[(2,2-дифторциклопропил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;N-({5-хлор-6-[(транс-4-цианоциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]ме
Claims (6)
1. Соединение или его терапевтически приемлемая соль, где соединение выбрано из следующих:
N-({5-хлор-6-[(4,4-дифторциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({6-[(транс-4-карбамоилциклогексил)метокси]-5-хлорпиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(4-{[(транс-4-цианоциклогексил)метил]амино}-3-нитрофенил)сульфонил]-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[2-(1Н-имидазол-1-ил)этокси]пиридин-3ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(1-метил-1Н-имидазол-5-ил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[5-фтор-6-(тетрагидро-2Н-пиран-4-илметокси)пиридин-3-ил]сульфонил}-2-(1Н-индазол-4-илокси)бензамид;
N-{[5-хлор-6-(1,4-диоксан-2-илметокси)пиридин-3ил]сульфонил}-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(4,4-дифтор-1-гидроксициклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(2,2-дифторциклопропил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(транс-4-цианоциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(цис-4-гидрокси-4-метилциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(транс-4-гидрокси-4-метилциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({3-хлор-4-[(4-фтортетрагидро-2Н-пиран-4-ил)метокси]фенил}сульфонил)-4-(4-{[4-(4-хлорфенил)-6,6-диметил-5,6-дигидро-2Н-пиран-3-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-({4-[(4-фтортетрагидро-2Н-пиран-4-ил)метокси]-3-(трифторметил)фенил}сульфонил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[3-хлор-4-(тетрагидро-2Н-пиран-4-илметокспи)фенил]сульфонил}-2-(1Н-индазол-4-илокси)бензамид;
2-(1Н-бензимидазол-4-илокси)-N-({3-хлор-4-[(4-фтортетрагидро-2Н-пиран-4-ил)метокси]фенил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)бензамид;
2-(1Н-бензимидазол-4-илокси)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[5-хлор-6-(тетрагидро-2Н-пиран-4-илметокси)пиридин-3-ил]сульфонил}бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-({3-циано-4-[(4-фтортетрагидро-2Н-пиран-4-ил)метокси]фенил}сульфонил)-2-(1Н-индазол-4-илокси)бензамид;
N-{[3-хлор-4-(1,4-диоксан-2-илметокси)фенил]сульфонил}-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
2-(1Н-бензимидазол-4-илокси)-N-[(5-хлор-6-{[(2S)-4-циклопропилморфолин-2-ил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)бензамид;
N-[(5-хлор-6-{[(2S)-4-циклопропилморфолин-2-ил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
метил 2-{[(4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензоил]сульфамоил}-2-нитрофенил)амино]метил}морфолин-4-карбоксилат;
2-{[(4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензоил]сульфамоил}-2-нитрофенил)амино]метил}-N-этил-N-метилморфолин-4-карбоксамид;
2-{[(4-{[2-(1Н-бензимидазол-4-илокси)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)бензоил]сульфамоил}-2-нитрофенил)амино]метил}-N-этил-N-метилморфолин-4-карбоксамид;
N-({5-хлор-6-[(транс-4-этил-4-гидроксициклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(цис-4-этил-4-гидроксициклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
5-хлор-N-({5-хлор-6-[(4-фтортетрагидро-2Н-пиран-4-ил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
5-хлор-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(4-{[(4-фтортетрагидро-2Н-пиран-4-ил)метил]амино}-3-нитрофенил)сульфонил]-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(цис-1-фтор-4-гидрокси-4-метилциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илоксил) бензамид;
N-({5-хлор-6-[(транс-1-фтор-4-гидрокси-4-метилциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси) бензамид;
2-(1Н-бензотриазол-4-илокси)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(4-{[(4-фтортетрагидро-2Н-пиран-4-ил)метил]амино}-3-нитрофенил)сульфонил]бензамид;
2-(1Н-бензотриазол-4-илокси)-N-({5-хлор-6-[(4-фтортетрагидро-2Н-пиран-4-ил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)бензамид;
2-(1Н-бензимидазол-4-илокси)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[3-хлор-4-(тетрагидро-2Н-пиран-4-илметокси)фенил]сульфонил}бензамид;
N-[(3-хлор-4-{[4-фтор-1-(оксетан-3-ил)пиперидин-4-ил]метокси}фенил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(цис-1-фтор-4-гидроксициклогекси)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
2-(1Н-бензотриазол-4-илокси)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-({4-[(4-фтортетрагидро-2Н-пиран-4-ил)метокси]-3-нитрофенил}сульфонил)бензамид;
N-[(5-хлор-6-{[(1R,2R,4R,5R)-5-гидрокси-5-метилбицикло[2,2,1]гепт-2-ил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(4-фтортетрагидро-2Н-пиран-4-ил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-5,5-дифторциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-[(5-хлор-6-{[4-фтор-1-(оксетан-3-ил)пиперидин-4-ил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-5,5-дифторциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
2-(1Н-бензотриазол-4-илокси)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-({3-нитро-4-[(тетрагидро-2Н-пиран-4-илметил)амино]фенил}сульфонил)бензамид;
4-(4-{[2-(4-хлорфенил)-5,5-дифторциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)-N-({3-нитро-4-[(тетрагидро-2Н-пиран-4-илметил)амино]фенил}сульфонил)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(4-{[(транс-4-гидрокси-4-метилциклогексил)метил]амино}-3-нитрофенил)сульфонил]-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(4-{[(цис-4-гидрокси-4-метилциклогексил)метил]амино}-3-нитрофенил)сульфонил]-2-(1Н-индазол-4-илокси)бензамид;
2-(1Н-бензотриазол-4-илокси)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[4-({[(2S)-4-циклопропилморфолин-2-ил]метил}амино)-3-нитрофенил]сульфонил}бензамид;
N-[(5-хлор-6-{[4-фтор-1-(оксетан-3-ил)пиперидин-4-ил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[4-({[(2S)-4-циклопропилморфолин-2-ил]метил}амино)-3-нитрофенил]сульфонил}-2-(1Н-индазол-4-илокси)бензамид;
2-(1Н-бензимидазол-4-илокси)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[4-({[(2S)-4-циклопропилморфолин-2-ил]метил}амино)-3-нитрофенил]сульфонил}бензамид;
N-({5-хлор-6-[(транс-4-гидрокси-4-метилциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-5,5-дифторциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-({4-[(цис-4-гидрокси-4-метилциклогексил)метокси]-3-нитрофенил}сульфонил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-({4-[(транс-4-гидрокси-4-метилциклогексил)метокси]-3-нитрофенил}сульфонил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(3-циано-4-{[4-фтор-1-(оксетан-3-ил)пиперидин-4-ил]метокси}фенил)сульфонил]-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)-N-{[3-нитро-4-(2-оксаспиро[3.5]нон-7-илметокси)фенил]сульфонил}бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[5-хлор-6-(5,6,7,8-тетрагидроимидазо[1,2-а]пиридин-6-илметокси)пиридин-3-ил]сульфонил}-2-(1Н-индазол-4-илокси)бензамид;
2-(1Н-бензимидазол-4-илокси)-N-({5-хлор-6-[(транс-4-гидрокси-4-метилциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(5-циано-6-{[4-фтор-1-(оксетан-3-ил)пиперидин-4-ил]метокси}пиридин-3-ил)сульфонил]-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(транс-4-гидрокси-4-метилциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-5-(метоксиметил)-5-метилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)-N-{[3-нитро-4-({[(2S)-4-(оксетан-3-ил)морфолин-2-ил]метил}амино)фенил]сульфонил}бензамид;
2-(1Н-бензимидазол-4-илокси)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[3-нитро-4-({[(2S)-4-(оксетан-3-ил)морфолин-2-ил]метил}амино)фенил]сульфонил}бензамид;
N-[(5-хлор-6-{[транс-4-(2-гидроксипропан-2-ил)циклогексил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-({3-циано-4-[(транс-4-гидрокси-4-метилциклогексил)метокси]фенил}сульфонил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-({5-циано-6-[(транс-4-гидрокси-4-метилциклогексил)метокси]пиридин-3-ил}сульфонил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)-N-({5-нитро-6-[(тетрагидро-2Н-пиран-4-илметил)амино]пиридин-3-ил-}сульфонил)бензамид;
2-(1Н-бензотриазол-4-илокси)-N-({5-хлор-6-[(транс-4-гидрокси-4-метилциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)бензамид;
N-({3-хлор-4-[(цис-4-циано-1-фторциклогексил)метокси]фенил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({3-хлор-4-[(транс-4-циано-1-фторциклогексил)метокси]фенил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(цис-4-циано-1-фторциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(транс-4-циано-1-фторциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
N-({5-хлор-6-[(транс-4-гидрокси-4-метилциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[4-(4-хлорфенил)-6,6-диметил-5,6-дигидро-2Н-пиран-3-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
2-(1Н-бензимидазол-4-илокси)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(4-{[(транс-4-гидрокси-4-метилциклогексил)метил]амино}-3-нитрофенил)сульфонил]бензамид;
N-({5-хлор-6-[(транс-4-гидрокси-4-метилциклогексил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-5-метокси-5-метилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(5-хлор-6-{[1-(1,3-тиазол-2-ил)пиперидин-4-ил]метокси}пиридин-3-ил)сульфонил]-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(6-{[(цис-4-гидрокси-4-метилциклогексил)метил]амино}-5-нитропиридин-3-ил)сульфонил]-2-(1Н-индазол-4-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-({6-[(транс-4-гидрокси-4-метилциклогексил)метокси]-5-(трифторметил)пиридин-3-ил-}сульфонил)-2-(1Н-индазол-4-илокси)бензамид;
2-(1Н-бензимидазол-4-илокси)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-[(4-{[(цис-4-гидрокси-4-метилциклогексил)метил]амино}-3-нитрофенил)сульфонил]бензамид;
N-(4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1Н-индазол-4-илокси)бензоил]сульфамоил}-2-нитрофенил)-4-цианопиперидин-1-карбоксамид.
2. Композиция для лечения рака мочевого пузыря, рака головного мозга, рака молочной железы, рака костного мозга, цервикального рака, хронического лимфоцитарного лейкоза, колоректального рака, эзофагеального рака, гепатоцеллюлярного рака, лимфобластного лейкоза, фолликулярной лимфомы, лимфоидной опухоли Т-клеточного или В-клеточного происхождения, меланомы, миелогенного лейкоза, миеломы, орального рака, рака яичника, немелкоклеточного рака легкого, рака предстательной железы, мелкоклеточного рака легкого или рака селезенки, где указанная композиция включает эксципиент и терапевтически эффективное количество соединения по п.1.
3. Соединение по п.1 или его терапевтически приемлемая соль для применения в лечении рака мочевого пузыря, рака головного мозга, рака молочной железы, рака костного мозга, цервикального рака, хронического лимфоцитарного лейкоза, колоректального рака, эзофагеального рака, гепатоцеллюлярного рака, лимфобластного лейкоза, фолликулярной лимфомы, лимфоидной опухоли Т-клеточного или В-клеточного происхождения, меланомы, миелогенного лейкоза, миеломы, орального рака, рака яичника, немелкоклеточного рака легкого, рака предстательной железы, мелкоклеточного рака легкого или рака селезенки у пациента.
4. Соединение по п.1 или его терапевтически приемлемая соль и одно дополнительное терапевтическое средство или несколько дополнительных терапевтических средств для применения в лечении рака мочевого пузыря, рака головного мозга, рака молочной железы, рака костного мозга, цервикального рака, хронического лимфоцитарного лейкоза, колоректального рака, эзофагеального рака, гепатоцеллюлярного рака, лимфобластного лейкоза, фолликулярной лимфомы, лимфоидной опухоли Т-клеточного или В-клеточного происхождения, меланомы, миелогенного лейкоза, миеломы, орального рака, рака яичника, немелкоклеточного рака легкого, рака предстательной железы, мелкоклеточного рака легкого или рака селезенки у пациента.
5. Применение соединения по п.1 или его терапевтически приемлемой соли для получения лекарственного средства для лечения рака мочевого пузыря, рака головного мозга, рака молочной железы, рака костного мозга, цервикального рака, хронического лимфоцитарного лейкоза, колоректального рака, эзофагеального рака, гепатоцеллюлярного рака, лимфобластного лейкоза, фолликулярной лимфомы, лимфоидной опухоли Т-клеточного или В-клеточного происхождения, меланомы, миелогенного лейкоза, миеломы, орального рака, рака яичника, немелкоклеточного рака легкого, рака предстательной железы, мелкоклеточного рака легкого или рака селезенки у пациента.
6. Применение соединения по п.1 или его терапевтически приемлемой соли и одного дополнительного терапевтического средства или нескольких дополнительных терапевтических средств для получения лекарственного средства для лечения рака мочевого пузыря, рака головного мозга, рака молочной железы, рака костного мозга, цервикального рака, хронического лимфоцитарного лейкоза, колоректального рака, эзофагеального рака, гепатоцеллюлярного рака, лимфобластного лейкоза, фолликулярной лимфомы, лимфоидной опухоли Т-клеточного или В-клеточного происхождения, меланомы, миелогенного лейкоза, миеломы, орального рака, рака яичника, немелкоклеточного рака легкого, рака предстательной железы, мелкоклеточного рака легкого или рака селезенки у пациента.
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| US12/631,404 US8563735B2 (en) | 2008-12-05 | 2009-12-04 | Bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
| US12/631,404 | 2009-12-04 | ||
| PCT/US2010/036919 WO2011068561A1 (en) | 2009-12-04 | 2010-06-01 | Sulfonamide derivatives as bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
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