RU2009149216A - Бициклические амиды как ингибиторы киназы - Google Patents
Бициклические амиды как ингибиторы киназы Download PDFInfo
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- RU2009149216A RU2009149216A RU2009149216/04A RU2009149216A RU2009149216A RU 2009149216 A RU2009149216 A RU 2009149216A RU 2009149216/04 A RU2009149216/04 A RU 2009149216/04A RU 2009149216 A RU2009149216 A RU 2009149216A RU 2009149216 A RU2009149216 A RU 2009149216A
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- Prior art keywords
- amide
- carboxylic acid
- yloxy
- aminopyrimidin
- trifluoromethylphenyl
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- 150000001408 amides Chemical class 0.000 title 1
- 229940043355 kinase inhibitor Drugs 0.000 title 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
- -1 6-aminopyrimidin-4-yl Chemical group 0.000 claims abstract 27
- 150000001875 compounds Chemical class 0.000 claims abstract 9
- VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 claims abstract 2
- FKXZPDZOOSTXJE-UHFFFAOYSA-N tert-butyl n-[4-[5-[[3-(trifluoromethyl)phenyl]carbamoyl]naphthalen-2-yl]sulfanylpyrimidin-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=NC=CC(SC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 FKXZPDZOOSTXJE-UHFFFAOYSA-N 0.000 claims abstract 2
- 229920002554 vinyl polymer Polymers 0.000 claims abstract 2
- 102000001253 Protein Kinase Human genes 0.000 claims 7
- 201000010099 disease Diseases 0.000 claims 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 7
- 108060006633 protein kinase Proteins 0.000 claims 7
- 230000001419 dependent effect Effects 0.000 claims 5
- 150000003839 salts Chemical class 0.000 claims 5
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 claims 2
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 claims 2
- 102100031983 Ephrin type-B receptor 4 Human genes 0.000 claims 2
- 108091008606 PDGF receptors Proteins 0.000 claims 2
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 claims 2
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000002062 proliferating effect Effects 0.000 claims 2
- QNFUUJBUCPJLBB-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxy-n-[4-(4-morpholin-4-ylcyclohexyl)phenyl]naphthalene-1-carboxamide Chemical compound NC1=NC=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=CC(=CC=2)C2CCC(CC2)N2CCOCC2)=N1 QNFUUJBUCPJLBB-UHFFFAOYSA-N 0.000 claims 1
- MCWVWPCAEFGXFI-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxy-n-[4-fluoro-3-(trifluoromethyl)phenyl]isoquinoline-1-carboxamide Chemical compound NC1=NC=CC(OC=2C=C3C=CN=C(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C(F)(F)F)=N1 MCWVWPCAEFGXFI-UHFFFAOYSA-N 0.000 claims 1
- NUFZRMLGTAIXCC-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-n-(2,6-dichloro-3,5-dimethoxyphenyl)naphthalene-1-carboxamide Chemical compound COC1=CC(OC)=C(Cl)C(NC(=O)C=2C3=CC=C(OC=4N=CN=C(N)C=4)C=C3C=CC=2)=C1Cl NUFZRMLGTAIXCC-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- TZHCMJVJHKKVDG-UHFFFAOYSA-N methyl n-[6-[1-[[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]carbamoyl]isoquinolin-6-yl]oxypyrimidin-4-yl]carbamate Chemical compound C1=NC(NC(=O)OC)=CC(OC=2C=C3C=CN=C(C3=CC=2)C(=O)NC=2C=C(C(CN3CCN(C)CC3)=CC=2)C(F)(F)F)=N1 TZHCMJVJHKKVDG-UHFFFAOYSA-N 0.000 claims 1
- IGWZMCHGTKIDCH-UHFFFAOYSA-N methyl n-[6-[1-[[4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]carbamoyl]isoquinolin-6-yl]oxypyrimidin-4-yl]carbamate Chemical compound C1=NC(NC(=O)OC)=CC(OC=2C=C3C=CN=C(C3=CC=2)C(=O)NC=2C=C(C(CN3CCN(CC3)C(C)C)=CC=2)C(F)(F)F)=N1 IGWZMCHGTKIDCH-UHFFFAOYSA-N 0.000 claims 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- 0 *C(*)(*)c1cc(NC(c2c(ccc(Oc3nc(N)ncc3)c3)c3ccn2)=O)ccc1 Chemical compound *C(*)(*)c1cc(NC(c2c(ccc(Oc3nc(N)ncc3)c3)c3ccn2)=O)ccc1 0.000 description 1
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Abstract
1. Соединение формулы ! ! где ! ! выбран из ! , , или , ! соединение формулы ! ! где ! ! выбран из ! , , или , ! (3-Трифторметилфенил)-амид 6-[(2)-2-(6-аминопиримидин-4-ил)-винил]-нафталин-1-карбоновой кислоты, ! (3-Трифторметилфенил)-амид 6-[(E)-2-(6-аминопиримидин-4-ил)-винил]-нафталин-1-карбоновой кислоты, ! (3-Трифторметилфенил)-амид 6-(2-хлорпиримидин-4-илсульфанил)-нафталин-1-карбоновой кислоты, ! трет-бутиловый эфир{4-[5-(3-трифторметилфенилкарбамоил)-нафталин-2-илсульфанил]-пиримидин-2-ил}-карбаминовой кислоты, ! (3-Трифторметилфенил)-амид 6-(2-аминопиримидин-4-илсульфанил)-нафталин-1-карбоновой кислоты, ! (2,4-дихлор-3,5-диметоксифенил)-амид 6-(6-аминопиримидин-4-илокси)-нафталин-1-карбоновой кислоты, ! (2,6-дихлор-3,5-диметоксифенил)-амид 6-(6-аминопиримидин-4-илокси)-нафталин-1-карбоновой кислоты, ! (2,4-Дихлор-3,5-диметоксифенил)-амид 6-(2-аминопиримидин-4-илокси)-нафталин-1-карбоновой кислоты, ! (2,6-дихлор-3,5-диметоксифенил)-амид 6-(2-аминопиримидин-4-илокси)-нафталин-1-карбоновой кислоты, ! (4-Фтор-3-трифторметилфенил)-амид 6-(6-ацетиламинопиримидин-4-илокси)-изохинолин-1-карбоновой кислоты, ! (4-Фтор-3-трифторметилфенил)-амид 6-(6-аминопиримидин-4-илокси)-изохинолин-1-карбоновой кислоты, ! (3-Трифторметилфенил)-амид 6-(6-аминопиримидин-4-илокси)-изохинолин-1-карбоновой кислоты, ! [4-(4-метилпиперазин-1-илметил)-3-трифторметилфенил]-амид 6-(6-ацетиламинопиримидин-4-илокси)-изохинолин-1-карбоновой кислоты, ! метиловый эфир(6-{1-[4-(4-метилпиперазин-1-илметил)-3-трифторметилфенилкарбамоил]изохинолин-6-илокси}-пиримидин-4-ил)-карбаминовой кислоты, ! [4-(4-изопропилпиперазин-1-илметил)-3-трифторметилфенил]-амид 6-(6-ацетиламинопиримидин-4-илокси)-изохинолин-1-карбоновой кислоты, ! метил�
Claims (7)
1. Соединение формулы
где
выбран из
соединение формулы
где
выбран из
(3-Трифторметилфенил)-амид 6-[(2)-2-(6-аминопиримидин-4-ил)-винил]-нафталин-1-карбоновой кислоты,
(3-Трифторметилфенил)-амид 6-[(E)-2-(6-аминопиримидин-4-ил)-винил]-нафталин-1-карбоновой кислоты,
(3-Трифторметилфенил)-амид 6-(2-хлорпиримидин-4-илсульфанил)-нафталин-1-карбоновой кислоты,
трет-бутиловый эфир{4-[5-(3-трифторметилфенилкарбамоил)-нафталин-2-илсульфанил]-пиримидин-2-ил}-карбаминовой кислоты,
(3-Трифторметилфенил)-амид 6-(2-аминопиримидин-4-илсульфанил)-нафталин-1-карбоновой кислоты,
(2,4-дихлор-3,5-диметоксифенил)-амид 6-(6-аминопиримидин-4-илокси)-нафталин-1-карбоновой кислоты,
(2,6-дихлор-3,5-диметоксифенил)-амид 6-(6-аминопиримидин-4-илокси)-нафталин-1-карбоновой кислоты,
(2,4-Дихлор-3,5-диметоксифенил)-амид 6-(2-аминопиримидин-4-илокси)-нафталин-1-карбоновой кислоты,
(2,6-дихлор-3,5-диметоксифенил)-амид 6-(2-аминопиримидин-4-илокси)-нафталин-1-карбоновой кислоты,
(4-Фтор-3-трифторметилфенил)-амид 6-(6-ацетиламинопиримидин-4-илокси)-изохинолин-1-карбоновой кислоты,
(4-Фтор-3-трифторметилфенил)-амид 6-(6-аминопиримидин-4-илокси)-изохинолин-1-карбоновой кислоты,
(3-Трифторметилфенил)-амид 6-(6-аминопиримидин-4-илокси)-изохинолин-1-карбоновой кислоты,
[4-(4-метилпиперазин-1-илметил)-3-трифторметилфенил]-амид 6-(6-ацетиламинопиримидин-4-илокси)-изохинолин-1-карбоновой кислоты,
метиловый эфир(6-{1-[4-(4-метилпиперазин-1-илметил)-3-трифторметилфенилкарбамоил]изохинолин-6-илокси}-пиримидин-4-ил)-карбаминовой кислоты,
[4-(4-изопропилпиперазин-1-илметил)-3-трифторметилфенил]-амид 6-(6-ацетиламинопиримидин-4-илокси)-изохинолин-1-карбоновой кислоты,
метиловый эфир(6-{1-[4-(4-изопропилпиперазин-1-илметил)-3-трифторметилфенилкарбамоил]изохинолин-6-илокси}-пиримидин-4-ил)-карбаминовой кислоты,
(4-фтор-3-трифторметилфенил)-амид 6-(2-аминопиримидин-4-илокси)-изохинолин-1-карбоновой кислоты,
6-[(6-Аминопиримидин-4-ил)окси]-Н-[4-(4-морфолин-4-илциклогексил)фенил]-1-нафтамид, или
6-[(2-Аминопиримидин-4-ил)окси]-N-[4-(4-морфолин-4-илциклогексил)фенил]-1-нафтамид,
или его таутомер, или его соль.
2. Фармацевтическая композиция, включающая соединение формулы I по п.1, или его таутомер, или его фармацевтически приемлемую соль и фармацевтически приемлемый носитель.
3. Соединение формулы I по п.1, или его таутомер, или его фармацевтически приемлемая соль, предназначенное для применения для лечения организма животного или человека, предпочтительно для лечения зависимого от протеинкиназы заболевания.
4. Соединение по п.3, где подвергающееся лечению зависимое от протеинкиназы заболевание, предпочтительно пролиферативное заболевание, зависит от одной или более следующих протеинкиназ: EphB4, c-Abl, Bcr-Abl, c-Kit, Raf, RET, PDGF-R и/или VEGF-R, предпочтительно VEGF-R.
5. Применение соединения формулы I по п.1, или его таутомера, или его фармацевтически приемлемой соли для лечения зависимого от протеинкиназы заболевания.
6. Применение соединения формулы I по п.1, или его таутомера, или его фармацевтически приемлемой соли для приготовления фармацевтической композиции, предназначенной для применения для лечения зависимого от протеинкиназы заболевания.
7. Применение по п.5 или 6, где зависимое от протеинкиназы заболевание, предпочтительно пролиферативное заболевание, зависит от одной или более следующих протеинкиназ: EphB4, c-Abl, Bcr-Abl, c-Kit, Raf, RET, PDGF-R и/или VEGF-R, предпочтительно VEGF-R.
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| RU2010138639/04A RU2448103C2 (ru) | 2004-09-15 | 2005-09-14 | Бициклические амиды как ингибиторы киназы |
| RU2009149216/04A RU2009149216A (ru) | 2004-09-15 | 2009-12-30 | Бициклические амиды как ингибиторы киназы |
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| RU2010138639/04A RU2448103C2 (ru) | 2004-09-15 | 2005-09-14 | Бициклические амиды как ингибиторы киназы |
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| JP (2) | JP4950889B2 (ru) |
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| GB0604937D0 (en) * | 2006-03-10 | 2006-04-19 | Novartis Ag | Organic compounds |
| GB0605120D0 (en) | 2006-03-14 | 2006-04-26 | Novartis Ag | Organic Compounds |
| EP2574340A3 (en) | 2006-04-07 | 2013-04-17 | Novartis AG | Combination comprising a pyrimidylaminobenzamide compound and a THR315LLEe kinase inhibitor |
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