RU2012156844A - Апоптоз-индуцирующие средства для лечения рака и иммунных и аутоиммунных заболеваний - Google Patents
Апоптоз-индуцирующие средства для лечения рака и иммунных и аутоиммунных заболеваний Download PDFInfo
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Abstract
1. Соединение или его фармацевтически приемлемая соль, где соединение выбрано из группы, включающей:метил транс-4-{[(4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}-2-нитрофенил)амино]метил}циклогексанкарбоксилат;транс-4-{[(4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}-2-нитрофенил)амино]метил}циклогексанкарбоновую кислоту;N-(4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}-2-нитрофенил)-4-цианопиперидин-1-карбоксамид;4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[4-({[цис-4-(метоксиметил)циклогексил]метил}амино)-3-нитрофенил]сульфонил}-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[4-({[транс-4-(метоксиметил)циклогексил]метил}амино)-3-нитрофенил]сульфонил}-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)-N-{[1-(тетрагидро-2H-пиран-4-илметил)-1H-бензотриазол-5-ил]сульфонил}бензамид;N-({5-хлор-6-[(2-оксо-1-окса-3-азаспиро[4.5]дец-8-ил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;N-(4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}-2-нитрофенил)-4-метоксипиперидин-1-карбоксамид;N-({5-хлор-6-[(2-метил-4,5,6,7-тетрагидро-1,3-бензотиазол-5-ил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]
Claims (5)
1. Соединение или его фармацевтически приемлемая соль, где соединение выбрано из группы, включающей:
метил транс-4-{[(4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}-2-нитрофенил)амино]метил}циклогексанкарбоксилат;
транс-4-{[(4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}-2-нитрофенил)амино]метил}циклогексанкарбоновую кислоту;
N-(4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}-2-нитрофенил)-4-цианопиперидин-1-карбоксамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[4-({[цис-4-(метоксиметил)циклогексил]метил}амино)-3-нитрофенил]сульфонил}-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[4-({[транс-4-(метоксиметил)циклогексил]метил}амино)-3-нитрофенил]сульфонил}-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)-N-{[1-(тетрагидро-2H-пиран-4-илметил)-1H-бензотриазол-5-ил]сульфонил}бензамид;
N-({5-хлор-6-[(2-оксо-1-окса-3-азаспиро[4.5]дец-8-ил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
N-(4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}-2-нитрофенил)-4-метоксипиперидин-1-карбоксамид;
N-({5-хлор-6-[(2-метил-4,5,6,7-тетрагидро-1,3-бензотиазол-5-ил)метокси]пиридин-3-ил}сульфонил)-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)-N-{[1-(тетрагидро-2H-пиран-4-илметил)-1H-пирроло[2,3-b]пиридин-5-ил]сульфонил}бензамид;
4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-{[3-хлор-1-(тетрагидро-2H-пиран-4-илметил)-1H-пирроло[2,3-b]пиридин-5-ил]сульфонил}-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)-4-(метоксиметил)-4-метилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-({3-нитро-4-[(тетрагидро-2H-пиран-4-илметил)амино]фенил}сульфонил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
N-[(4-{[4,4-бис(гидроксиметил)циклогексил]метокси}-3-нитрофенил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
N-(2-хлор-4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}фенил)-4-метоксипиперидин-1-карбоксамид;
N-(2-хлор-4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}фенил)-4-цианопиперидин-1-карбоксамид;
N-(2-хлор-4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}фенил)-4-гидрокси-4-метилпиперидин-1-карбоксамид;
N-(2-хлор-4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}фенил)-4-(метоксиметил)пиперидин-1-карбоксамид;
N-[(5-хлор-6-{[(5r,8r)-2-оксо-1-окса-3-азаспиро[4.5]дец-8-ил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
N-[(5-хлор-6-{[(5s,8s)-2-оксо-1-окса-3-азаспиро[4.5]дец-8-ил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
N-(2-хлор-4-{[4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензоил]сульфамоил}фенил)-4-(морфолин-4-ил)пиперидин-1-карбоксамид;
N-[(5-хлор-6-{[транс-4-гидрокси-4-(метоксиметил)циклогексил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
N-[(5-хлор-6-{[цис-4-гидрокси-4-(гидроксиметил)циклогексил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
N-[(5-хлор-6-{[транс-4-гидрокси-4-(гидроксиметил)циклогексил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-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-метокси-5-метилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
4-(4-{[2-(4-хлорфенил)циклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-N-({3-нитро-4-[(тетрагидро-2H-пиран-4-илметил)амино]фенил}сульфонил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид;
4-(4-хлорфенил)-1-метил-3-[(4-{4-[({3-нитро-4-[(тетрагидро-2H-пиран-4-илметил)амино]фенил}сульфонил)карбамоил]-3-(1H-пирроло[2,3-b]пиридин-5-илокси)фенил}пиперазин-1-ил)метил]циклогекс-3-ен-1-карбоновую кислоту;
N-[(5-хлор-6-{[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-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид.
2. N-[(5-хлор-6-{[транс-4-гидрокси-4-(метоксиметил)циклогексил]метокси}пиридин-3-ил)сульфонил]-4-(4-{[2-(4-хлорфенил)-4,4-диметилциклогекс-1-ен-1-ил]метил}пиперазин-1-ил)-2-(1H-пирроло[2,3-b]пиридин-5-илокси)бензамид или его фармацевтически приемлемая соль.
3. Композиция для лечения рака мочевого пузыря, рака головного мозга, рака молочной железы, рака костного мозга, цервикального рака, хронического лимфоцитарного лейкоза, колоректального рака, рака пищевода, гепатоцеллюлярного рака, лимфобластного лейкоза, фолликулярной лимфомы, лимфоидных злокачественных заболеваний T-клеточного или B-клеточного происхождения, меланомы, миелогенного лейкоза, миеломы, рака ротовой полости, рака яичника, немелкоклеточного рака легкого, рака предстательной железы, мелкоклеточного рака легкого или рака селезенки, при этом указанная композиция включает эксципиент и терапевтически эффективное количество соединения по п.1 или 2.
4. Способ лечения рака мочевого пузыря, рака головного мозга, рака молочной железы, рака костного мозга, цервикального рака, хронического лимфоцитарного лейкоза, колоректального рака, рака пищевода, гепатоцеллюлярного рака, лимфобластного лейкоза, фолликулярной лимфомы, лимфоидных злокачественных заболеваний T-клеточного или B-клеточного происхождения, меланомы, миелогенного лейкоза, миеломы, рака ротовой полости, рака яичника, немелкоклеточного рака легкого, рака предстательной железы, мелкоклеточного рака легкого или рака селезенки у пациента, при этом указанный способ включает введение пациенту терапевтически эффективного количества соединения по п.1 или 2.
5. Способ лечения рака мочевого пузыря, рака головного мозга, рака молочной железы, рака костного мозга, цервикального рака, хронического лимфоцитарного лейкоза, колоректального рака, рака пищевода, гепатоцеллюлярного рака, лимфобластного лейкоза, фолликулярной лимфомы, лимфоидных злокачественных заболеваний T-клеточного или B-клеточного происхождения, меланомы, миелогенного лейкоза, миеломы, рака ротовой полости, рака яичника, немелкоклеточного рака легкого, рака предстательной железы, мелкоклеточного рака легкого или рака селезенки у пациента, при этом указанный способ включает введение пациенту терапевтически эффективного количества соединения по п.1 или 2 и терапевтически эффективного количества одного дополнительного терапевтического средства или нескольких дополнительных терапевтических средств.
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