ES2569528T3 - 4-pirazolil-N-arilpirimidin-2-aminas y 4-pirazolil-N-heteroarilpirimidin-2-aminas como inhibidores de quinasas Janus - Google Patents
4-pirazolil-N-arilpirimidin-2-aminas y 4-pirazolil-N-heteroarilpirimidin-2-aminas como inhibidores de quinasas Janus Download PDFInfo
- Publication number
- ES2569528T3 ES2569528T3 ES08848610.5T ES08848610T ES2569528T3 ES 2569528 T3 ES2569528 T3 ES 2569528T3 ES 08848610 T ES08848610 T ES 08848610T ES 2569528 T3 ES2569528 T3 ES 2569528T3
- Authority
- ES
- Spain
- Prior art keywords
- pyrazol
- pyrimidin
- phenylamino
- carbonyl
- ylamino
- Prior art date
- 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.)
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- 229940122245 Janus kinase inhibitor Drugs 0.000 title 1
- -1 haloC1-6alkyl Chemical group 0.000 claims abstract 47
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 24
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 6
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims 6
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 5
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 5
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- JCWBDPZBFFJJLV-NVHKAFQKSA-N (3r)-1-[4-[[4-[1-(2-cyano-1-cyclopropylethyl)pyrazol-4-yl]pyrimidin-2-yl]amino]benzoyl]pyrrolidine-3-carbonitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C(CC#N)C2CC2)C=CC=1C(=O)N1CC[C@@H](C#N)C1 JCWBDPZBFFJJLV-NVHKAFQKSA-N 0.000 claims 1
- LJEBDNPJFQCMMC-OEPVSBQMSA-N (3s)-1-[4-[[4-[1-(2-cyano-1-cyclopentylethyl)pyrazol-4-yl]pyrimidin-2-yl]amino]benzoyl]pyrrolidine-3-carbonitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C(CC#N)C2CCCC2)C=CC=1C(=O)N1CC[C@H](C#N)C1 LJEBDNPJFQCMMC-OEPVSBQMSA-N 0.000 claims 1
- CWCFUURQCJAWTH-UHFFFAOYSA-N 1-[4-[[4-[1-[3-cyano-1-(cyanomethyl)cyclobutyl]pyrazol-4-yl]pyrimidin-2-yl]amino]benzoyl]pyrrolidine-3-carbonitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C2(CC#N)CC(C2)C#N)C=CC=1C(=O)N1CCC(C#N)C1 CWCFUURQCJAWTH-UHFFFAOYSA-N 0.000 claims 1
- DAKLTKIALMRNMH-UHFFFAOYSA-N 2-(azetidin-3-yl)acetonitrile Chemical compound N#CCC1CNC1 DAKLTKIALMRNMH-UHFFFAOYSA-N 0.000 claims 1
- JWTGMDPCSARKPF-UHFFFAOYSA-N 2-[1-ethylsulfonyl-3-[4-[2-[4-(3-methoxypyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]azetidin-3-yl]acetonitrile Chemical compound C1N(S(=O)(=O)CC)CC1(CC#N)N1N=CC(C=2N=C(NC=3C=CC(=CC=3)C(=O)N3CC(CC3)OC)N=CC=2)=C1 JWTGMDPCSARKPF-UHFFFAOYSA-N 0.000 claims 1
- QZTTVFJXTAGTRG-UHFFFAOYSA-N 2-[1-ethylsulfonyl-3-[4-[2-[4-(morpholine-4-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]azetidin-3-yl]acetonitrile Chemical compound C1N(S(=O)(=O)CC)CC1(CC#N)N1N=CC(C=2N=C(NC=3C=CC(=CC=3)C(=O)N3CCOCC3)N=CC=2)=C1 QZTTVFJXTAGTRG-UHFFFAOYSA-N 0.000 claims 1
- NBPQKEMQAHIRBO-UHFFFAOYSA-N 2-[3-[4-[2-[4-(azetidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]-1-ethylsulfonylazetidin-3-yl]acetonitrile Chemical compound C1N(S(=O)(=O)CC)CC1(CC#N)N1N=CC(C=2N=C(NC=3C=CC(=CC=3)C(=O)N3CCC3)N=CC=2)=C1 NBPQKEMQAHIRBO-UHFFFAOYSA-N 0.000 claims 1
- KQHKNYWIKYAGIT-UHFFFAOYSA-N 2-[3-[4-[2-[4-[3-(dimethylamino)pyrrolidine-1-carbonyl]anilino]pyrimidin-4-yl]pyrazol-1-yl]-1-ethylsulfonylazetidin-3-yl]acetonitrile Chemical compound C1N(S(=O)(=O)CC)CC1(CC#N)N1N=CC(C=2N=C(NC=3C=CC(=CC=3)C(=O)N3CC(CC3)N(C)C)N=CC=2)=C1 KQHKNYWIKYAGIT-UHFFFAOYSA-N 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- WTFUAZUTVJVMBL-UHFFFAOYSA-N 3-(cyanomethyl)-3-[4-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]pyrazol-1-yl]cyclobutane-1-carbonitrile Chemical compound C1=C(C=2N=C(NC=3C=CC(=CC=3)N3CCOCC3)N=CC=2)C=NN1C1(CC#N)CC(C#N)C1 WTFUAZUTVJVMBL-UHFFFAOYSA-N 0.000 claims 1
- CPSVQQLTLPGEEC-UHFFFAOYSA-N 3-(cyanomethyl)-3-[4-[2-[4-(3-fluoropyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]cyclobutane-1-carbonitrile Chemical compound C1C(F)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C2(CC#N)CC(C2)C#N)=N1 CPSVQQLTLPGEEC-UHFFFAOYSA-N 0.000 claims 1
- UZOICBWRKGPGGI-UHFFFAOYSA-N 3-(cyanomethyl)-3-[4-[2-[4-(3-hydroxypyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]cyclobutane-1-carbonitrile Chemical compound C1C(O)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C2(CC#N)CC(C2)C#N)=N1 UZOICBWRKGPGGI-UHFFFAOYSA-N 0.000 claims 1
- RDEMHYQMQSBPEG-UHFFFAOYSA-N 3-(cyanomethyl)-3-[4-[2-[4-(3-methoxypyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]cyclobutane-1-carbonitrile Chemical compound C1C(OC)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C2(CC#N)CC(C2)C#N)=N1 RDEMHYQMQSBPEG-UHFFFAOYSA-N 0.000 claims 1
- LHWNPIDCQHJDKN-UHFFFAOYSA-N 3-(cyanomethyl)-3-[4-[2-[4-(4-methoxypiperidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]cyclobutane-1-carbonitrile Chemical compound C1CC(OC)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C2(CC#N)CC(C2)C#N)=N1 LHWNPIDCQHJDKN-UHFFFAOYSA-N 0.000 claims 1
- ACWRXNXRRLEPAE-UHFFFAOYSA-N 3-(cyanomethyl)-3-[4-[2-[4-(4-methylpiperazine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]cyclobutane-1-carbonitrile Chemical compound C1CN(C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C2(CC#N)CC(C2)C#N)=N1 ACWRXNXRRLEPAE-UHFFFAOYSA-N 0.000 claims 1
- NFNUNUMBHNANCV-UHFFFAOYSA-N 3-(cyanomethyl)-3-[4-[2-[4-(morpholine-4-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]cyclobutane-1-carbonitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C2(CC#N)CC(C2)C#N)C=CC=1C(=O)N1CCOCC1 NFNUNUMBHNANCV-UHFFFAOYSA-N 0.000 claims 1
- ANXNYBPJAXAZPZ-UHFFFAOYSA-N 3-(cyanomethyl)-3-[4-[2-[4-(pyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]cyclobutane-1-carbonitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C2(CC#N)CC(C2)C#N)C=CC=1C(=O)N1CCCC1 ANXNYBPJAXAZPZ-UHFFFAOYSA-N 0.000 claims 1
- LXDOJUVLROBRRO-UHFFFAOYSA-N 3-[4-[2-[4-(4-acetylpiperazine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]-3-(cyanomethyl)cyclobutane-1-carbonitrile Chemical compound C1CN(C(=O)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C2(CC#N)CC(C2)C#N)=N1 LXDOJUVLROBRRO-UHFFFAOYSA-N 0.000 claims 1
- JJXMYGFSVKQKED-UHFFFAOYSA-N 3-[4-[2-[4-(4-acetylpiperazine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]-3-cyclopentylpropanenitrile Chemical compound C1CN(C(=O)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CCCC2)=N1 JJXMYGFSVKQKED-UHFFFAOYSA-N 0.000 claims 1
- NIYQOFMBILWWRH-UHFFFAOYSA-N 3-[4-[2-[4-(4-acetylpiperazine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]-3-cyclopropylpropanenitrile Chemical compound C1CN(C(=O)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CC2)=N1 NIYQOFMBILWWRH-UHFFFAOYSA-N 0.000 claims 1
- OFNKJXLBSOWCQO-UHFFFAOYSA-N 3-[4-[2-[4-(azetidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]-3-(cyanomethyl)cyclobutane-1-carbonitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C2(CC#N)CC(C2)C#N)C=CC=1C(=O)N1CCC1 OFNKJXLBSOWCQO-UHFFFAOYSA-N 0.000 claims 1
- VUPTUFXNTWGUGM-UHFFFAOYSA-N 3-[4-[2-[4-(azetidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]-3-cyclopropylpropanenitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C(CC#N)C2CC2)C=CC=1C(=O)N1CCC1 VUPTUFXNTWGUGM-UHFFFAOYSA-N 0.000 claims 1
- OOFCWWDIXDSJNO-UHFFFAOYSA-N 3-cyclopentyl-3-[4-[2-[4-(3-fluoropyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C1C(F)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CCCC2)=N1 OOFCWWDIXDSJNO-UHFFFAOYSA-N 0.000 claims 1
- NUHNUVYBUGKNNH-UHFFFAOYSA-N 3-cyclopentyl-3-[4-[2-[4-(3-methoxypyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C1C(OC)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CCCC2)=N1 NUHNUVYBUGKNNH-UHFFFAOYSA-N 0.000 claims 1
- MXXPKDDYDFGPPV-UHFFFAOYSA-N 3-cyclopentyl-3-[4-[2-[4-(3-oxo-2,8-diazaspiro[4.5]decane-8-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C(CC#N)C2CCCC2)C=CC=1C(=O)N(CC1)CCC21CNC(=O)C2 MXXPKDDYDFGPPV-UHFFFAOYSA-N 0.000 claims 1
- LPVPQBQOFRHSNG-UHFFFAOYSA-N 3-cyclopentyl-3-[4-[2-[4-(3-pyridin-2-yloxypyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C(CC#N)C2CCCC2)C=CC=1C(=O)N(C1)CCC1OC1=CC=CC=N1 LPVPQBQOFRHSNG-UHFFFAOYSA-N 0.000 claims 1
- UQAAVQMLMPWQQK-UHFFFAOYSA-N 3-cyclopentyl-3-[4-[2-[4-(4-methoxypiperidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C1CC(OC)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CCCC2)=N1 UQAAVQMLMPWQQK-UHFFFAOYSA-N 0.000 claims 1
- HBTHWGNTZZEKTD-UHFFFAOYSA-N 3-cyclopentyl-3-[4-[2-[4-(morpholine-4-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C(CC#N)C2CCCC2)C=CC=1C(=O)N1CCOCC1 HBTHWGNTZZEKTD-UHFFFAOYSA-N 0.000 claims 1
- ILQCGNDTPJZGFE-UHFFFAOYSA-N 3-cyclopentyl-3-[4-[2-[4-[3-(dimethylamino)pyrrolidine-1-carbonyl]anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CCCC2)=N1 ILQCGNDTPJZGFE-UHFFFAOYSA-N 0.000 claims 1
- VLAMQWPDPICALA-UHFFFAOYSA-N 3-cyclopropyl-3-[4-[2-[4-(3-fluoropyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C1C(F)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CC2)=N1 VLAMQWPDPICALA-UHFFFAOYSA-N 0.000 claims 1
- WZUWCGJTZXLPKD-UHFFFAOYSA-N 3-cyclopropyl-3-[4-[2-[4-(3-methoxypyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C1C(OC)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CC2)=N1 WZUWCGJTZXLPKD-UHFFFAOYSA-N 0.000 claims 1
- OYSPEILBMGTDEP-UHFFFAOYSA-N 3-cyclopropyl-3-[4-[2-[4-(4-hydroxypiperidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C1CC(O)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CC2)=N1 OYSPEILBMGTDEP-UHFFFAOYSA-N 0.000 claims 1
- BVIFQNOFYQWFJS-UHFFFAOYSA-N 3-cyclopropyl-3-[4-[2-[4-(4-methoxypiperidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C1CC(OC)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CC2)=N1 BVIFQNOFYQWFJS-UHFFFAOYSA-N 0.000 claims 1
- WSXAZBCOKNZEQJ-UHFFFAOYSA-N 3-cyclopropyl-3-[4-[2-[4-(4-methylpiperazine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C1CN(C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CC2)=N1 WSXAZBCOKNZEQJ-UHFFFAOYSA-N 0.000 claims 1
- SMQORXYBUBYFBG-UHFFFAOYSA-N 3-cyclopropyl-3-[4-[2-[4-(morpholine-4-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C(CC#N)C2CC2)C=CC=1C(=O)N1CCOCC1 SMQORXYBUBYFBG-UHFFFAOYSA-N 0.000 claims 1
- DBTOQSSCDXHDJV-UHFFFAOYSA-N 3-cyclopropyl-3-[4-[2-[4-(pyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C(CC#N)C2CC2)C=CC=1C(=O)N1CCCC1 DBTOQSSCDXHDJV-UHFFFAOYSA-N 0.000 claims 1
- IMZDJMNJEZSMNB-UHFFFAOYSA-N 3-cyclopropyl-3-[4-[2-[4-[3-(dimethylamino)pyrrolidine-1-carbonyl]anilino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CC2)=N1 IMZDJMNJEZSMNB-UHFFFAOYSA-N 0.000 claims 1
- DXGSKKPAAZHYQN-UHFFFAOYSA-N 4-[[4-[1-(2-cyano-1-cyclopentylethyl)pyrazol-4-yl]-5-methoxypyrimidin-2-yl]amino]benzoic acid Chemical compound N1=C(C2=CN(N=C2)C(CC#N)C2CCCC2)C(OC)=CN=C1NC1=CC=C(C(O)=O)C=C1 DXGSKKPAAZHYQN-UHFFFAOYSA-N 0.000 claims 1
- VFBRLYVOCBPPCB-UHFFFAOYSA-N 4-[[4-[1-(2-cyano-1-cyclopentylethyl)pyrazol-4-yl]pyrimidin-2-yl]amino]-n-(1-pyridin-2-ylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(NC=2N=C(C=CN=2)C2=CN(N=C2)C(CC#N)C2CCCC2)C=CC=1C(=O)NC(C1)CCN1C1=CC=CC=N1 VFBRLYVOCBPPCB-UHFFFAOYSA-N 0.000 claims 1
- BJQCBZDEGUCZOI-UHFFFAOYSA-N 4-[[4-[1-(2-cyano-1-cyclopropylethyl)pyrazol-4-yl]pyrimidin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CC2)=N1 BJQCBZDEGUCZOI-UHFFFAOYSA-N 0.000 claims 1
- NSDQJFQLPRUICH-UHFFFAOYSA-N 4-[[4-[1-[3-(cyanomethyl)-1-ethylsulfonylazetidin-3-yl]pyrazol-4-yl]pyrimidin-2-yl]amino]benzoic acid Chemical compound C1N(S(=O)(=O)CC)CC1(CC#N)N1N=CC(C=2N=C(NC=3C=CC(=CC=3)C(O)=O)N=CC=2)=C1 NSDQJFQLPRUICH-UHFFFAOYSA-N 0.000 claims 1
- QZOSARGQGHPUQQ-UHFFFAOYSA-N 4-[[4-[1-[3-cyano-1-(cyanomethyl)cyclobutyl]pyrazol-4-yl]pyrimidin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=CC(C2=CN(N=C2)C2(CC#N)CC(C2)C#N)=N1 QZOSARGQGHPUQQ-UHFFFAOYSA-N 0.000 claims 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 1
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- YKOUDTFFCQQDLK-UHFFFAOYSA-N n'-(cyclopropylmethyl)acetohydrazide Chemical compound CC(=O)NNCC1CC1 YKOUDTFFCQQDLK-UHFFFAOYSA-N 0.000 claims 1
- HOKJHFHSIPMSIR-LETIRJCYSA-N n-[(3r)-1-[4-[[4-[1-(2-cyano-1-cyclopropylethyl)pyrazol-4-yl]pyrimidin-2-yl]amino]benzoyl]pyrrolidin-3-yl]acetamide Chemical compound C1[C@H](NC(=O)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CC2)=N1 HOKJHFHSIPMSIR-LETIRJCYSA-N 0.000 claims 1
- IEHFEXNNXJHASJ-QSAPEBAKSA-N n-[(3s)-1-[4-[[4-[1-(2-cyano-1-cyclopentylethyl)pyrazol-4-yl]pyrimidin-2-yl]amino]benzoyl]pyrrolidin-3-yl]acetamide Chemical compound C1[C@@H](NC(=O)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC(C2=CN(N=C2)C(CC#N)C2CCCC2)=N1 IEHFEXNNXJHASJ-QSAPEBAKSA-N 0.000 claims 1
- QMRZMCCTPQZZSR-UHFFFAOYSA-N n-[3-[[4-[1-(2-cyano-1-cyclopentylethyl)pyrazol-4-yl]pyrimidin-2-yl]amino]phenyl]-2-morpholin-4-ylacetamide Chemical compound C=1C=CC(NC=2N=C(C=CN=2)C2=CN(N=C2)C(CC#N)C2CCCC2)=CC=1NC(=O)CN1CCOCC1 QMRZMCCTPQZZSR-UHFFFAOYSA-N 0.000 claims 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 17
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 16
- 125000005843 halogen group Chemical group 0.000 abstract 15
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 14
- 125000001072 heteroaryl group Chemical group 0.000 abstract 13
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 12
- 125000003118 aryl group Chemical group 0.000 abstract 10
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 9
- 125000001424 substituent group Chemical group 0.000 abstract 9
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 abstract 6
- 102100038417 Cytoplasmic FMR1-interacting protein 1 Human genes 0.000 abstract 6
- 101710181791 Cytoplasmic FMR1-interacting protein 1 Proteins 0.000 abstract 6
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 abstract 6
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 abstract 6
- 125000000217 alkyl group Chemical group 0.000 abstract 4
- 125000005311 halosulfanyl group Chemical group 0.000 abstract 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 4
- 125000003545 alkoxy group Chemical group 0.000 abstract 3
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 2
- 101100310920 Caenorhabditis elegans sra-2 gene Proteins 0.000 abstract 2
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
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- Tropical Medicine & Parasitology (AREA)
Abstract
Un compuesto de Fórmula IIa, IIb, IIc, IId, IIe, IIf o IIg:**Fórmula** o sal farmacéuticamente aceptable del mismo, en el que: El anillo A es arilo o heteroarilo; Q es H, Cy1, halo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)NRc1Rd1, NRc1C(O)ORa1, C(>=NRg)NRc1Rd1, NRc1C(>=NRg)NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1, o S(O)2NRc1Rd1, en donde dichos alquilo C1-6, alquenilo C2-6 o alquinilo C2-6, están opcionalmente sustituidos con 1, 2, 3, 4 ó 5 sustituyentes seleccionados independientemente de halo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, halosulfanilo, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)NRc1Rd1, NRc1C(O)ORa1, C(>=NRg)NRc1Ra1, NRc1C(>=NRg)NRc1Ra1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1 y S(O)2NRc1Rd1; X es halo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)NRcRd, NRcC(O)ORa, C(>=NRg)NRcRd, NRcC(>=NRg)NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, NRcS(O)2Rb, o S(O)2NRcRd, Y es H, Cy2, halo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)NRc1Rd1, NRc1C(O)ORa1, C(>=NRg)NRc1Rd1, NRc1C(>=NRg)NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1, o S(O)2NRc1Rd1, en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6 o haloalquilo C1-6 están opcionalmente sustituidos con 1, 2, 3, 4 ó 5 sustituyentes seleccionados independientemente de halo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, halosulfanilo, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)NRc1Rd1, NRc1C(O)ORa1, C(>=NRg)NRc1Ra1, NRc1C(>=NRg)NRc1Ra1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1 y S(O)2NRc1Rd1; R1, R2, R3 y R4 se seleccionan independientemente de H, halo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, CN, (CH2)mCN, NO2, ORa, (CH2)mORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, NRcRd, (CH2)mNRcRd, NRcC(O)Rb, NRcS(O)2Rb, y S(O)2NRcRd; Cy1 y Cy2 son seleccionados independientemente de arilo, cicloalquilo, heteroarilo y heterocicloalquilo, cada uno opcionalmente sustituido por 1, 2, 3, 4 ó 5 sustituyentes seleccionados independientemente de halo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, haloalquilo C1-6, halosulfanilo, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)NRc1Rd1, NRc1C(O)ORa1, C(>=NRg)NRc1Rd1, NRc1C(>=NRg)NRc1Ra1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1 y S(O)2NRc1Rd1, en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo o heterocicloalquilo que está sustituido en Cy1 o Cy2 está además opcionalmente sustituido por 1, 2 ó 3 sustituyentes seleccionados independientemente de halo, haloalquilo C1-6, halosulfanilo, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)NRc1Rd1, NRc1C(O)ORa1, C(>=NRg)NRc1Rd1, NRc1C(>=NRg)NRc1Ra1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1 y S(O)2NRc1Rd1; Ra, Rb, Rc y Rd se seleccionan independientemente de H, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo y heterocicloalquilalquilo, en donde dicho alquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo o heterocicloalquilalquilo está opcionalmente sustituido con 1, 2, 3, 4 ó 5 sustituyentes seleccionados independientemente de OH, CN, amino, halo, alquilo C1-6, alcoxi C1-6, haloalquilo C1-6 y haloalcoxi C1-6. o Rc y Rd junto al átomo de N al que están unidos forman un grupo heterocicloalquilo o heteroarilo de 4-, 5-, 6- o 7- miembros, cada uno opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente de OH, CN, amino, halo, alquilo C1-6, alcoxi C1-6, haloalquilo C1-6 y haloalcoxi C1-6. Ra1, Rb1 Rc1 y Rd1 se seleccionan independientemente de H, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo y heterocicloalquilalquilo, en donde dicho alquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo o heterocicloalquilalquilo está opcionalmente sustituido con 1, 2, 3, 4 ó 5 sustituyentes seleccionados independientemente de alquilo C1-6, halo, CN, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, C(>=NRg)NRc2Rd2, NRc2C(>=NRg)NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, NRc2S(O)2Rb2 y S(O)2NRc2Rd2; o Rc1 y Rd1 junto al átomo de N al que están unidos forman un grupo heterocicloalquilo o heteroarilo de 4-, 5-, 6- o 7- miembros, cada uno opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente de alquilo C1-6, halo, CN, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, C(>=NRg)NRc2Rd2, NRc2C(>=NRg)NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, NRc2S(O)2Rb2 y S(O)2NRc2Rd2; Ra2, Rb2 Rc2 y Rd2 se seleccionan independientemente de H, alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo y heterocicloalquilalquilo, en donde dicho alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo o heterocicloalquilalquilo está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente de OH, CN, amino, halo, alquilo C1-6, alcoxi C1-6, haloalquilo C1-6 y haloalcoxi C1-6; o Rc2 y Rd2 junto al átomo de N al que están unidos forman un grupo heterocicloalquilo o heteroarilo de 4-, 5-, 6- o 7- miembros, cada uno opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente de OH, CN, amino, halo, alquilo C1-6, alcoxi C1-6, haloalquilo C1-6 y haloalcoxi C1-6; Rg es H, CN o NO2; y m es 0, 1, 2 ó 3.
Description
Claims (1)
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imagen1 imagen2 imagen3 imagen4 imagen5 imagen6 imagen7 (ciclopropilmetilamino)acetamida; N-(4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)fenil)-2-(1-metoxipropan-2ilamino)acetamida; 3-ciclopentil-3-(4-(2-(4-(morfolin-4-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; 4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)-N-((tetrahidro-2H-piran-4il)metil)benzamida; 3-ciclopentil-3-(4-(2-(4-((3-endo)-3-hidroxi-8-azabiciclo[3.2.1]octano-8-carbonil)fenilamino)pirimidin-4-il)-1Hpirazol-1-il)propanonitrilo; 3-ciclopentil-3-(4-(2-(4-(2-oxa-6-azatriciclo[3.3.1.1 (3,7)]dec-6-ilcarbonil)fenil)aminopirimidin-4-il)-1Hpirazol-1il)propanonitrilo; 4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)-N-(cis-4-hidroxiciclohexil)-Nmetilbenzamida; 4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)-N-metil-N-(tetrahidro-2H-piran-4il)benzamida; 3-ciclopentil-3-(4-(2-(4-(S*)-(4,4-dimetil-2-oxo-1-oxa-3,7-diazaspiro[4.4]nonano-7-carbonil)fenilamino)pirimidin4-il)-1H-pirazol-1-il)propanonitrilo; 3-ciclopentil-3-(4-(2-(4-(4,4-dimetil-1-oxa-7-azaspiro[4.4]nonano-7-carbonil)fenilamino)pirimidin-4-il)-1Hpirazol-1-il)propanonitrilo; 3-ciclopentil-3-(4-(2-(4-(4-metoxipiperidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; N-((3S)-1-(4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)benzoil)pirrolidin-3-il)acetamida; 4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)-N-(cis-4-hidroxiciclohexil)benzamida; 3-(4-(2-(4-(4-acetilpiperazina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)-3-ciclopentilpropanonitrilo; (3S)-1-(4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)benzoil)pirrolidina-3-carbonitrilo; 3-ciclopentil-3-(4-(2-(4-(3-metoxipirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; 4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)-N-(1-metilpiperidin-4-il)benzamida; 3-ciclopentil-3-(4-(2-(4-(3-oxo-2,8-diazaspiro[4.5]decano-8-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1il)propanonitrilo; 3-ciclopentil-3-(4-(2-(4-(3-fluoropirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; 3-ciclopentil-3-(4-(2-(4-(3-(dimetilamino)pirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1 H-pirazol-1il)propanonitrilo; etil 4-(4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)benzamido)piperidina-1-carboxilato; 4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)-N-(1-(piridin-2-il)pirrolidin-3-il)benzamida; 3-ciclopentil-3-(4-(2-(4-(3-(piridin-2-iloxi)pirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1il)propanonitrilo; 1-(4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pinmidin-2-ilamino)benzoil)-N,N-dimetilpiperidina-4carboxamida; 4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)-N-(1-(dimetilamino)-1-oxobutan-2il)benzamida; N-(3-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)fenil)-2-(4-metilpiperazin-1-il)acetamida; N-(3-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)fenil)-2-(3-hidroxipirrolidin-1il)acetamida; N-(3-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)fenil)-2-(3-oxopiperazin-1-il)acetamida; N-(3-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)fenil)-2-(4-hidroxipiperidin-1il)acetamida; N-(3-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)fenil)-2-(4-(2-hidroxietil)piperazin-1il)acetamida; N-(3-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)fenil)-2(ciclopropilmetilamino)acetamida; N-(3-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)fenil)-2-morfolinoacetamida; N-(3-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)fenil)-2-(etilamino)acetamida; 3-(cianometil)-3-(4-(2-(4-morfolinofenilamino)pirimidin-4-il)-1H-pirazol-1-il)ciclobutanocarbonitrilo; ácido 4-(4-(1-(3-(cianometil)-1-(etilsulfonil)azetidin-3-il)-1H-pirazol-4-il)pirimidin-2-ilamino)benzoico; ácido 4-(4-(1-(2-ciano-1-ciclopropiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)benzoico; 3-ciclopropil-3-(4-(2-(4-(4-hidroxipiperidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; 3-ciclopropil-3-(4-(2-(4-((3-endo)-3-hidroxi-8-azabiciclo[3.2.1]octano-8-carbonil)fenilamino)pirimidin-4-il)-1Hpirazol-1-il)propanonitrilo; 3-ciclopropil-3-(4-(2-(4-(pirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; 4-(4-(1-(2-ciano-1-ciclopropiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)-N-(tetrahidro-2H-piran-4-il)benzamida; 2-(1-(etilsulfonil)-3-(4-(2-(4-(morfolin-4-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)azetidin-3il)acetonitrilo; 2-(1-(etilsulfonil)-3-(4-(2-(4-(4-hidroxipiperidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)azetidin-3il)acetonitrilo; 2-(1-(etilsulfonil)-3-(4-(2-(4-((3-endo)-3-hidroxi-8-azabiciclo[3.2.1]octano-8-carbonil)fenilamino)pirimidin-4-il)1H-pirazol-1-il)azetidin-3-il)acetonitrilo; 2-(1-(etilsulfonil)-3-(4-(2-(4-(pirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)azetidin-3152il)acetonitrilo; 4-(4-(1-(3-(cianometil)-1-(etilsulfonil)azetidin-3-il)-1H-pirazol-4-il)pirimidin-2-ilamino)-N-(tetrahidro-2H-piran-4il)benzamida; 3-ciclopropil-3-(4-(2-(4-(morfolin-4-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; 3-(4-(2-(4-(azetidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)-3-ciclopropilpropanonitrilo; 3-ciclopropil-3-(4-(2-(4-(2-oxa-6-azatriciclo[3.3.1.1(3,7)]dec-6-ilcarbonil)fenil)aminopirimidin-4-il)-1H-pirazol-1il)propanonitrilo; 3-ciclopropil-3-(4-(2-(4-(4-metoxipiperidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; (3R)-1-(4-(4-(1-(2-ciano-1-ciclopropiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)benzoil)pirrolidina-3-carbonitrilo; 3-ciclopropil-3-(4-(2-(4-(3-metoxipirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; 3-ciclopropil-3-(4-(2-(4-(3-hidroxipirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; 3-ciclopropil-3-(4-(2-(4-(4-metilpiperazina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; N-((3R)-1-(4-(4-(1-(2-ciano-1-ciclopropiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)benzoil)pirrolidin-3-il)acetamida; 3-(4-(2-(4-(4-acetilpiperazina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)-3-ciclopropilpropanonitrilo; 3-ciclopropil-3-(4-(2-(4-(3-(dimetilamino)pirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1il)propanonitrilo; 3-ciclopropil-3-(4-(2-(4-(3-fluoropirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)propanonitrilo; etil 4-(4-(4-(1-(2-ciano-1-ciclopropiletil)-1H-pirazol-4-il)pirimidin-2-ilamino)benzoil)aminopiperidina-1carboxilato; 2-(3-(4-(2-(4-(azetidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)-1-(etilsulfonil)azetidin-3il)acetonitrilo; 1-(etilsulfonil)-3-(4-(2-(4-(2-oxa-6-azatriciclo[3.3.1.1(3,7)]dec-6-ilcarbonil)fenil)aminopirimidin-4-il)-1H-pirazol1-il)azetidin-3-ilacetonitrilo; (1-(etilsulfonil)-3-4-(2-(4-((4-metoxipiperidin-1-il)carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-ilazetidin-3il)acetonitrilo; 1-(4-(4-(1-(3-(cianometil)-1-(etilsulfonil)azetidin-3-il)-1H-pirazol-4-il)pirimidin-2-ilamino)benzoil)pirrolidina-3carbonitrilo; 2-(1-(etilsulfonil)-3-(4-(2-(4-(3-metoxipirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)azetidin-3il)acetonitrilo; 2-(1-(etilsulfonil)-3-(4-(2-(4-(3-hidroxipirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)azetidin-3 il)acetonitrilo; 2-(1-(etilsulfonil)-3-(4-(2-(4-(4-metilpiperazina-l-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)azetidin-3 il)acetonitrilo; N-(1-(4-(4-(1-(3-(cianometil)-1-(etilsulfonil)azetidin-3-il)-1H-pirazol-4-il)pirimidin-2-ilamino)benzoil)pirrolidin-3il)acetamida; 2-(3-(4-(2-(4-(4-acetilpiperazina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)-1-(etilsulfonil)azetidin-3il)acetonitrilo; 2-(3-(4-(2-(4-(3-(dimetilamino)pirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)-1(etilsulfonil)azetidin-3-il)acetonitrilo; 2-(1-(etilsulfonil)-3-(4-(2-(4-(3-fluoropirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)azetidin-3il)acetonitrilo; etil 4-(4-(4-(1-(3-(cianometil)-1-(etilsulfonil)azetidin-3-il)-1H-pirazol-4-il)pirimidin-2ilamino)benzamido)piperidina-1-carboxilato; ácido 4-(4-(1-(3-ciano-1-(cianometil)ciclobutil)-1H-pirazol-4-il)pirimidin-2-ilamino)benzoico; ácido 4-(4-(1-(2-ciano-1-ciclopentiletil)-1H-pirazol-4-il)-5-metoxipirimidin-2-ilamino)benzoico; 3-(cianometil)-3-(4-(2-(4-(morfolin-4-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)ciclobutanocarbonitrilo; 3-(cianometil)-3-(4-(2-(4-(pirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)ciclobutanocarbonitrilo; 4-(4-(1-(3-ciano-1-(cianometil)ciclobutil)-1H-pirazol-4-il)pirimidin-2-ilamino)-N-(tetrahidro-2H-piran-4il)benzamida; 3-(cianometil)-3-(4-(2-(4-(3-hidroxipirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1 H-pirazol-1il)ciclobutanocarbonitrilo; 4-(4-(1-(3-ciano-1-(cianometil)ciclobutil)-1H-pirazol-4-il)pirimidin-2-ilamino)-N-((5-metilisoxazol-3il)metil)benzamida; 3-(4-(2-(4-(azetidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)-3-(cianometil)ciclobutanocarbonitrilo; 3-(cianometil)-3-(4-(2-(4-(4-metilpiperazina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1il)ciclobutanocarbonitrilo; 3-(cianometil)-3-(4-(2-(4-(3-fluoropirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1il)ciclobutanocarbonitrilo; 3-(cianometil)-3-(4-(2-(4-(4-metoxipiperidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1il)ciclobutanocarbonitrilo; 3-(cianometil)-3-(4-(2-(4-(3-metoxipirrolidina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1il)ciclobutanocarbonitrilo; 1-(4-(4-(1-(3-ciano-1-(cianometil)ciclobutil)-1H-pirazol-4-il)pirimidin-2-ilamino)benzoil)pirrolidina-3-carbonitrilo; 3-(4-(2-(4-(4-acetilpiperazina-1-carbonil)fenilamino)pirimidin-4-il)-1H-pirazol-1-il)-3(cianometil)ciclobutanocarbonitrilo;153imagen8 imagen9 imagen10 imagen11
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| PCT/US2008/083319 WO2009064835A1 (en) | 2007-11-16 | 2008-11-13 | 4-pyrazolyl-n-arylpyrimidin-2-amines and 4-pyrazolyl-n-heteroarylpyrimidin-2-amines as janus kinase inhibitors |
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| ECSP10010263A (es) | 2010-07-30 |
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| AU2008321046B2 (en) | 2013-10-24 |
| JP2011503194A (ja) | 2011-01-27 |
| KR101580482B1 (ko) | 2015-12-28 |
| JP5480813B2 (ja) | 2014-04-23 |
| WO2009064835A1 (en) | 2009-05-22 |
| EA020777B1 (ru) | 2015-01-30 |
| CO6280420A2 (es) | 2011-05-20 |
| BRPI0820544A2 (pt) | 2015-06-16 |
| AU2008321046A1 (en) | 2009-05-22 |
| NZ585139A (en) | 2012-05-25 |
| CR11430A (es) | 2010-07-01 |
| US20090318405A1 (en) | 2009-12-24 |
| ZA201004055B (en) | 2012-09-26 |
| UA104849C2 (uk) | 2014-03-25 |
| EA201070618A1 (ru) | 2010-12-30 |
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