ES2861180T3 - Derivados de 2-hidroxi-1-{4-[(4-fenil)fenil]carbonil}piperazin-1-il}etan-1-ona y compuestos relacionados como inhibidores de sintasa de ácido graso (FASN) para el tratamiento del cáncer - Google Patents
Derivados de 2-hidroxi-1-{4-[(4-fenil)fenil]carbonil}piperazin-1-il}etan-1-ona y compuestos relacionados como inhibidores de sintasa de ácido graso (FASN) para el tratamiento del cáncer Download PDFInfo
- Publication number
- ES2861180T3 ES2861180T3 ES19188403T ES19188403T ES2861180T3 ES 2861180 T3 ES2861180 T3 ES 2861180T3 ES 19188403 T ES19188403 T ES 19188403T ES 19188403 T ES19188403 T ES 19188403T ES 2861180 T3 ES2861180 T3 ES 2861180T3
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- Prior art keywords
- carbonyl
- cyclopropan
- phenyl
- piperazine
- piperazin
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- BRJSBJJUKKYZOK-UHFFFAOYSA-N [3-fluoro-4-(1-methylindazol-6-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound FC=1C=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=CC=1C1=CC=C2C=NN(C2=C1)C BRJSBJJUKKYZOK-UHFFFAOYSA-N 0.000 claims 1
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- BWFJFOHHHDJZHC-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-(4-pyrazolo[1,5-a]pyridin-2-ylphenyl)methanone Chemical compound N1=C(C=C2N1C=CC=C2)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O BWFJFOHHHDJZHC-UHFFFAOYSA-N 0.000 claims 1
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- CDQBKOSGLWCUTG-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-(5-quinolin-6-ylpyrazin-2-yl)methanone Chemical compound C1CN(C(=O)C=2N=CC(=NC=2)C=2C=C3C=CC=NC3=CC=2)CCN1C(=O)C1(O)CC1 CDQBKOSGLWCUTG-UHFFFAOYSA-N 0.000 claims 1
- RBOVKKKDUVEHRW-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-(5-quinolin-6-ylpyrimidin-2-yl)methanone Chemical compound C1CN(C(=O)C=2N=CC(=CN=2)C=2C=C3C=CC=NC3=CC=2)CCN1C(=O)C1(O)CC1 RBOVKKKDUVEHRW-UHFFFAOYSA-N 0.000 claims 1
- BHZMXZVSACEATR-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-(6-quinolin-6-ylpyridin-3-yl)methanone Chemical compound N1=CC=CC2=CC(=CC=C12)C1=CC=C(C=N1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O BHZMXZVSACEATR-UHFFFAOYSA-N 0.000 claims 1
- GDVPTCYEVUXYFJ-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)phenyl]methanone Chemical compound C1CN(CCC2=C1C=CC=C2)C2=CC=C(C(=O)N1CCN(CC1)C(=O)C1(CC1)O)C=C2 GDVPTCYEVUXYFJ-UHFFFAOYSA-N 0.000 claims 1
- TUXMMTCJSIBNDD-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1,3,4,5-tetrahydro-2-benzazepin-2-yl)phenyl]methanone Chemical compound C1N(CCCC2=C1C=CC=C2)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 TUXMMTCJSIBNDD-UHFFFAOYSA-N 0.000 claims 1
- QBKPAOAPYRGAGK-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)phenyl]methanone Chemical compound C1N(CCC=2NC=3C=CC=CC=3C=21)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 QBKPAOAPYRGAGK-UHFFFAOYSA-N 0.000 claims 1
- KYOLPUCFLAKSRF-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl)phenyl]methanone Chemical compound C1N(CCC2=C1NC1=CC=CC=C21)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 KYOLPUCFLAKSRF-UHFFFAOYSA-N 0.000 claims 1
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- XTLCWVVWJLKZKT-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1-methylbenzimidazol-2-yl)phenyl]methanone Chemical compound CN1C(=NC2=C1C=CC=C2)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O XTLCWVVWJLKZKT-UHFFFAOYSA-N 0.000 claims 1
- QWQJWXZTASLMET-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1-methylbenzimidazol-5-yl)phenyl]methanone Chemical compound CN1C=NC2=C1C=CC(=C2)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O QWQJWXZTASLMET-UHFFFAOYSA-N 0.000 claims 1
- VWHDQEYYAHUYTR-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1-methylindazol-5-yl)phenyl]methanone Chemical compound CN1N=CC2=CC(=CC=C12)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O VWHDQEYYAHUYTR-UHFFFAOYSA-N 0.000 claims 1
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- GRRIKAANZUFJSO-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1-methylindol-5-yl)phenyl]methanone Chemical compound C=1C=C2N(C)C=CC2=CC=1C(C=C1)=CC=C1C(=O)N(CC1)CCN1C(=O)C1(O)CC1 GRRIKAANZUFJSO-UHFFFAOYSA-N 0.000 claims 1
- RJZGLTCJKYEMSZ-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1-methylsulfonylindol-6-yl)phenyl]methanone Chemical compound CS(=O)(=O)N1C=CC2=CC=C(C=C12)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 RJZGLTCJKYEMSZ-UHFFFAOYSA-N 0.000 claims 1
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- GGTDEWHZSXBRIU-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1H-indol-2-yl)phenyl]methanone Chemical compound N1C(=CC2=CC=CC=C12)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O GGTDEWHZSXBRIU-UHFFFAOYSA-N 0.000 claims 1
- MDCZCLVNBDMNKU-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1H-indol-5-yl)phenyl]methanone Chemical compound N1C=CC2=CC(=CC=C12)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O MDCZCLVNBDMNKU-UHFFFAOYSA-N 0.000 claims 1
- MZSJGVIQXAUVRV-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(2-methyl-1H-indol-3-yl)phenyl]methanone Chemical compound CC=1NC2=CC=CC=C2C=1C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 MZSJGVIQXAUVRV-UHFFFAOYSA-N 0.000 claims 1
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- SMUWRJPHIUYDAM-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(2-methyl-3H-benzimidazol-5-yl)phenyl]methanone Chemical compound CC1=NC2=C(N1)C=CC(=C2)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 SMUWRJPHIUYDAM-UHFFFAOYSA-N 0.000 claims 1
- MZUOQWQHLFJFCU-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(2-methylbenzotriazol-5-yl)phenyl]methanone Chemical compound Cn1nc2ccc(cc2n1)-c1ccc(cc1)C(=O)N1CCN(CC1)C(=O)C1(O)CC1 MZUOQWQHLFJFCU-UHFFFAOYSA-N 0.000 claims 1
- RJEWTTBWQLZUQV-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(2-methylindazol-6-yl)phenyl]methanone Chemical compound C=1C2=NN(C)C=C2C=CC=1C(C=C1)=CC=C1C(=O)N(CC1)CCN1C(=O)C1(O)CC1 RJEWTTBWQLZUQV-UHFFFAOYSA-N 0.000 claims 1
- ZPEUFAAHWMLQRU-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(2-methylindol-1-yl)phenyl]methanone Chemical compound Cc1cc2ccccc2n1-c1ccc(cc1)C(=O)N1CCN(CC1)C(=O)C1(O)CC1 ZPEUFAAHWMLQRU-UHFFFAOYSA-N 0.000 claims 1
- CQHSTNLUXYFKHE-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(3-methoxypyridin-4-yl)phenyl]methanone Chemical compound COC1=CN=CC=C1C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(O)CC2)C=C1 CQHSTNLUXYFKHE-UHFFFAOYSA-N 0.000 claims 1
- UZOFLNVYDVKVGD-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(3-methyl-1,2-benzoxazol-6-yl)phenyl]methanone Chemical compound CC1=NOC2=C1C=CC(=C2)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O UZOFLNVYDVKVGD-UHFFFAOYSA-N 0.000 claims 1
- DVMTZWMGGLPOAT-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(3-methyl-2H-indazol-7-yl)phenyl]methanone Chemical compound CC1=NNC2=C(C=CC=C12)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 DVMTZWMGGLPOAT-UHFFFAOYSA-N 0.000 claims 1
- WITKBABFIFYZSJ-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(3-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)phenyl]methanone Chemical compound CC1=NNC2=NC=C(C=C21)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 WITKBABFIFYZSJ-UHFFFAOYSA-N 0.000 claims 1
- NCMOHOFVTIQLJS-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(3-methyl-3,4-dihydro-1H-isoquinolin-2-yl)phenyl]methanone Chemical compound CC1N(CC2=CC=CC=C2C1)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 NCMOHOFVTIQLJS-UHFFFAOYSA-N 0.000 claims 1
- RASRRBQBCBLRMT-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(3-methylindazol-2-yl)phenyl]methanone Chemical compound CC=1N(N=C2C=CC=CC=12)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 RASRRBQBCBLRMT-UHFFFAOYSA-N 0.000 claims 1
- SOGNGTAJVJOAOA-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(6-methoxy-1H-benzimidazol-2-yl)phenyl]methanone Chemical compound COC1=CC2=C(NC(=N2)C2=CC=C(C=C2)C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 SOGNGTAJVJOAOA-UHFFFAOYSA-N 0.000 claims 1
- CCAYMQSFOVUUJD-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(6-methoxyimidazo[1,2-a]pyridin-2-yl)phenyl]methanone Chemical compound COC=1C=CC=2N(C=1)C=C(N=2)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O CCAYMQSFOVUUJD-UHFFFAOYSA-N 0.000 claims 1
- BIZLFYRIBNWELZ-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(6-methoxynaphthalen-2-yl)phenyl]methanone Chemical compound COC=1C=C2C=CC(=CC2=CC=1)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O BIZLFYRIBNWELZ-UHFFFAOYSA-N 0.000 claims 1
- HYXKQGLCIRANSD-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(7-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)phenyl]methanone Chemical compound COC1=CC=C2CCN(CC2=C1)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 HYXKQGLCIRANSD-UHFFFAOYSA-N 0.000 claims 1
- OHFBTJBYDRYSPL-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-([1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl]methanone Chemical compound N=1N=CN2N=C(C=CC2=1)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O OHFBTJBYDRYSPL-UHFFFAOYSA-N 0.000 claims 1
- XJGSRVMXYLPVLR-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-[1-(2-hydroxyethyl)benzimidazol-5-yl]phenyl]methanone Chemical compound OCCn1cnc2cc(ccc12)-c1ccc(cc1)C(=O)N1CCN(CC1)C(=O)C1(O)CC1 XJGSRVMXYLPVLR-UHFFFAOYSA-N 0.000 claims 1
- VGGKDKMJOYAMTA-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-[2-(hydroxymethyl)-3H-benzimidazol-5-yl]phenyl]methanone Chemical compound OCC1=NC2=C(N1)C=CC(=C2)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 VGGKDKMJOYAMTA-UHFFFAOYSA-N 0.000 claims 1
- FKXMYOASAXZAHV-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl]phenyl]methanone Chemical compound FC(C=1N=C2N(C=C(C=C2)C2=CC=C(C=C2)C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=1)(F)F FKXMYOASAXZAHV-UHFFFAOYSA-N 0.000 claims 1
- KVETUDISFGPWCP-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-[3-(2-hydroxyethyl)benzimidazol-5-yl]phenyl]methanone Chemical compound OCCN1C=NC2=C1C=C(C=C2)C2=CC=C(C(=O)N1CCN(CC1)C(=O)C1(CC1)O)C=C2 KVETUDISFGPWCP-UHFFFAOYSA-N 0.000 claims 1
- IIRJIICPENMNKS-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-[3-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methanone Chemical compound Cc1nc(no1)-c1cccc(c1)-c1ccc(cc1)C(=O)N1CCN(CC1)C(=O)C1(O)CC1 IIRJIICPENMNKS-UHFFFAOYSA-N 0.000 claims 1
- JHPANAXJQWIGJW-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-[3-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]phenyl]methanone Chemical compound Cc1nnc(s1)-c1cccc(c1)-c1ccc(cc1)C(=O)N1CCN(CC1)C(=O)C1(O)CC1 JHPANAXJQWIGJW-UHFFFAOYSA-N 0.000 claims 1
- RJPFZFQKUDWKTH-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-[6-(trifluoromethyl)pyridin-3-yl]phenyl]methanone Chemical compound C1CN(C(=O)C=2C=CC(=CC=2)C=2C=NC(=CC=2)C(F)(F)F)CCN1C(=O)C1(O)CC1 RJPFZFQKUDWKTH-UHFFFAOYSA-N 0.000 claims 1
- OSTYMFGPUCHGGX-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-[7-(trifluoromethyl)quinolin-4-yl]phenyl]methanone Chemical compound FC(C1=CC=C2C(=CC=NC2=C1)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O)(F)F OSTYMFGPUCHGGX-UHFFFAOYSA-N 0.000 claims 1
- ZSJDKLCQAMBWPB-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-methyl-2-(1-methylindol-5-yl)-1,3-thiazol-5-yl]methanone Chemical compound CC=1N=C(SC=1C(=O)N1CCN(CC1)C(=O)C1(CC1)O)C=1C=C2C=CN(C2=CC=1)C ZSJDKLCQAMBWPB-UHFFFAOYSA-N 0.000 claims 1
- RGDJAAACWUNECJ-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-quinolin-6-yl-2-(trifluoromethyl)phenyl]methanone Chemical compound C1CN(C(=O)C=2C(=CC(=CC=2)C=2C=C3C=CC=NC3=CC=2)C(F)(F)F)CCN1C(=O)C1(O)CC1 RGDJAAACWUNECJ-UHFFFAOYSA-N 0.000 claims 1
- ALVHEQWNJNGKNM-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[5-(1-methylindol-5-yl)pyrazin-2-yl]methanone Chemical compound CN1C=CC2=CC(=CC=C12)C=1N=CC(=NC=1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O ALVHEQWNJNGKNM-UHFFFAOYSA-N 0.000 claims 1
- RGZCDUCRBQKLDS-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[5-(1-methylindol-5-yl)pyridin-2-yl]methanone Chemical compound CN1C=CC2=CC(=CC=C12)C=1C=CC(=NC=1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O RGZCDUCRBQKLDS-UHFFFAOYSA-N 0.000 claims 1
- OFAZGOCXIHZVBI-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[5-(2-methoxyquinolin-6-yl)pyridin-2-yl]methanone Chemical compound COC1=NC2=CC=C(C=C2C=C1)C=1C=CC(=NC=1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O OFAZGOCXIHZVBI-UHFFFAOYSA-N 0.000 claims 1
- YGASXHCEEIXIIZ-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[6-(1-methylindol-5-yl)pyridin-3-yl]methanone Chemical compound CN1C=CC2=CC(=CC=C12)C1=CC=C(C=N1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O YGASXHCEEIXIIZ-UHFFFAOYSA-N 0.000 claims 1
- PLYBTICDHNGJDH-UHFFFAOYSA-N [4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[6-(2-methoxyquinolin-6-yl)pyridin-3-yl]methanone Chemical compound COC1=NC2=CC=C(C=C2C=C1)C1=CC=C(C=N1)C(=O)N1CCN(CC1)C(=O)C1(O)CC1 PLYBTICDHNGJDH-UHFFFAOYSA-N 0.000 claims 1
- FAUKRSGLQDRCBB-UHFFFAOYSA-N [4-(1H-benzimidazol-4-yl)-2-chlorophenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound N1C=NC2=C1C=CC=C2C2=CC(=C(C(=O)N1CCN(CC1)C(=O)C1(CC1)O)C=C2)Cl FAUKRSGLQDRCBB-UHFFFAOYSA-N 0.000 claims 1
- ZWAJVFUZIBDYKG-UHFFFAOYSA-N [4-(2,1,3-benzothiadiazol-4-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound N=1SN=C2C=1C=CC=C2C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O ZWAJVFUZIBDYKG-UHFFFAOYSA-N 0.000 claims 1
- WZNWDDQJDLDGMB-UHFFFAOYSA-N [4-(2,3-dichlorophenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound C1CN(C(=O)C=2C=CC(=CC=2)C=2C(=C(Cl)C=CC=2)Cl)CCN1C(=O)C1(O)CC1 WZNWDDQJDLDGMB-UHFFFAOYSA-N 0.000 claims 1
- ACVTXNMRGBYAAJ-UHFFFAOYSA-N [4-(2,3-difluorophenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound C1CN(C(=O)C=2C=CC(=CC=2)C=2C(=C(F)C=CC=2)F)CCN1C(=O)C1(O)CC1 ACVTXNMRGBYAAJ-UHFFFAOYSA-N 0.000 claims 1
- WCZKKBQNZDWHJU-UHFFFAOYSA-N [4-(2,3-dihydroindol-1-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound OC1(CC1)C(=O)N1CCN(CC1)C(=O)C1=CC=C(C=C1)N1CCC2=CC=CC=C12 WCZKKBQNZDWHJU-UHFFFAOYSA-N 0.000 claims 1
- FXFYQYZXGOKRFA-UHFFFAOYSA-N [4-(2,4-dichloro-3-methoxyphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound COC1=C(Cl)C=CC(C=2C=CC(=CC=2)C(=O)N2CCN(CC2)C(=O)C2(O)CC2)=C1Cl FXFYQYZXGOKRFA-UHFFFAOYSA-N 0.000 claims 1
- KDVXLIKKHPTEHT-UHFFFAOYSA-N [4-(2,5-dichlorophenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC1=C(C=C(C=C1)Cl)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O KDVXLIKKHPTEHT-UHFFFAOYSA-N 0.000 claims 1
- MZRZCEBISQZPBQ-UHFFFAOYSA-N [4-(2,6-dimethoxypyridin-3-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound COC1=NC(OC)=CC=C1C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(O)CC2)C=C1 MZRZCEBISQZPBQ-UHFFFAOYSA-N 0.000 claims 1
- KPYMGJDBFZANBT-UHFFFAOYSA-N [4-(2-chloro-4-fluorophenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC1=C(C=CC(=C1)F)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O KPYMGJDBFZANBT-UHFFFAOYSA-N 0.000 claims 1
- BDRSMBBEDKDLAN-UHFFFAOYSA-N [4-(2-chloro-4-methoxyphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC1=CC(OC)=CC=C1C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(O)CC2)C=C1 BDRSMBBEDKDLAN-UHFFFAOYSA-N 0.000 claims 1
- PDAHKHBGLKMZAR-UHFFFAOYSA-N [4-(2-chloro-5-fluorophenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound C1CN(C(=O)C=2C=CC(=CC=2)C=2C(=CC=C(F)C=2)Cl)CCN1C(=O)C1(O)CC1 PDAHKHBGLKMZAR-UHFFFAOYSA-N 0.000 claims 1
- PDRCGCOHHSPREC-UHFFFAOYSA-N [4-(2-cyclopropylindazol-5-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound C1(CC1)N1N=C2C=CC(=CC2=C1)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O PDRCGCOHHSPREC-UHFFFAOYSA-N 0.000 claims 1
- FHAFBTPZCBMTJC-UHFFFAOYSA-N [4-(2-fluoro-3-methoxyphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound COC1=CC=CC(C=2C=CC(=CC=2)C(=O)N2CCN(CC2)C(=O)C2(O)CC2)=C1F FHAFBTPZCBMTJC-UHFFFAOYSA-N 0.000 claims 1
- DZOPJCJZNBBLKI-UHFFFAOYSA-N [4-(2-fluoro-3-methylphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound CC1=CC=CC(C=2C=CC(=CC=2)C(=O)N2CCN(CC2)C(=O)C2(O)CC2)=C1F DZOPJCJZNBBLKI-UHFFFAOYSA-N 0.000 claims 1
- MEHDNJCJPHYECG-UHFFFAOYSA-N [4-(2-fluoro-3-propan-2-yloxyphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound CC(C)OC1=CC=CC(C=2C=CC(=CC=2)C(=O)N2CCN(CC2)C(=O)C2(O)CC2)=C1F MEHDNJCJPHYECG-UHFFFAOYSA-N 0.000 claims 1
- DSVULCMBCUFQAD-UHFFFAOYSA-N [4-(2-fluoro-4-methoxyphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound FC1=CC(OC)=CC=C1C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(O)CC2)C=C1 DSVULCMBCUFQAD-UHFFFAOYSA-N 0.000 claims 1
- KAKJDTHQYHWXCM-UHFFFAOYSA-N [4-(2-fluoro-4-methylphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound FC1=CC(C)=CC=C1C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(O)CC2)C=C1 KAKJDTHQYHWXCM-UHFFFAOYSA-N 0.000 claims 1
- DORFXLCJWPCVNU-UHFFFAOYSA-N [4-(2-fluoro-5-methoxyphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound COC1=CC=C(F)C(C=2C=CC(=CC=2)C(=O)N2CCN(CC2)C(=O)C2(O)CC2)=C1 DORFXLCJWPCVNU-UHFFFAOYSA-N 0.000 claims 1
- OTIDFBGXVVSAMZ-UHFFFAOYSA-N [4-(2-fluoro-5-methylphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound CC1=CC=C(F)C(C=2C=CC(=CC=2)C(=O)N2CCN(CC2)C(=O)C2(O)CC2)=C1 OTIDFBGXVVSAMZ-UHFFFAOYSA-N 0.000 claims 1
- HPUMOKUACKSFKC-UHFFFAOYSA-N [4-(3,4-dichlorophenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC=1C=C(C=CC=1Cl)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O HPUMOKUACKSFKC-UHFFFAOYSA-N 0.000 claims 1
- WFIHQFFKKNIAAQ-UHFFFAOYSA-N [4-(3,4-dihydro-1H-isoquinolin-2-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound C1N(CCC2=CC=CC=C12)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 WFIHQFFKKNIAAQ-UHFFFAOYSA-N 0.000 claims 1
- IECDNNCRJOGNKW-UHFFFAOYSA-N [4-(3,4-dihydro-2H-quinolin-1-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound N1(CCCC2=CC=CC=C12)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 IECDNNCRJOGNKW-UHFFFAOYSA-N 0.000 claims 1
- GNLVARBIFOTWLF-UHFFFAOYSA-N [4-(3-amino-1,2-benzoxazol-5-yl)phenyl]-[4-(1-aminocyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound NC1(CC1)C(=O)N1CCN(CC1)C(=O)C1=CC=C(C=C1)C=1C=CC2=C(C(=NO2)N)C=1 GNLVARBIFOTWLF-UHFFFAOYSA-N 0.000 claims 1
- AXTWTAGICVTTCT-UHFFFAOYSA-N [4-(3-chloro-4-fluorophenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound C1CN(C(=O)C=2C=CC(=CC=2)C=2C=C(Cl)C(F)=CC=2)CCN1C(=O)C1(O)CC1 AXTWTAGICVTTCT-UHFFFAOYSA-N 0.000 claims 1
- AAQQHOAFDSMEMW-UHFFFAOYSA-N [4-(3-chloroimidazo[1,2-a]pyridin-2-yl)-2-fluorophenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC1=C(N=C2N1C=CC=C2)C1=CC(=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1)F AAQQHOAFDSMEMW-UHFFFAOYSA-N 0.000 claims 1
- CYMFEKLTVQPPSO-UHFFFAOYSA-N [4-(3-chloroimidazo[1,2-a]pyridin-2-yl)-3-fluorophenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC1=C(N=C2N1C=CC=C2)C1=C(C=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1)F CYMFEKLTVQPPSO-UHFFFAOYSA-N 0.000 claims 1
- OWLYCFXJPBRKCL-UHFFFAOYSA-N [4-(3-chloroimidazo[1,2-a]pyridin-2-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC1=C(N=C2N1C=CC=C2)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O OWLYCFXJPBRKCL-UHFFFAOYSA-N 0.000 claims 1
- BWXJBQGGUZAZDK-UHFFFAOYSA-N [4-(3-chlorophenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC=1C=C(C=CC=1)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O BWXJBQGGUZAZDK-UHFFFAOYSA-N 0.000 claims 1
- LVQIZECMOHFIMN-UHFFFAOYSA-N [4-(3-cyclopropyl-2H-indazol-6-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound C1(CC1)C1=NNC2=CC(=CC=C12)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 LVQIZECMOHFIMN-UHFFFAOYSA-N 0.000 claims 1
- HUGOSTQGCIFMQY-UHFFFAOYSA-N [4-(3-cyclopropyloxyphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound C1(CC1)OC=1C=C(C=CC=1)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O HUGOSTQGCIFMQY-UHFFFAOYSA-N 0.000 claims 1
- KRNRHTBMKPSUNQ-KRWDZBQOSA-N [4-(3-cyclopropylsulfonylphenyl)phenyl]-[(3S)-4-(1-hydroxycyclopropanecarbonyl)-3-methylpiperazin-1-yl]methanone Chemical compound C1(CC1)S(=O)(=O)C=1C=C(C=CC=1)C1=CC=C(C(=O)N2C[C@@H](N(CC2)C(=O)C2(CC2)O)C)C=C1 KRNRHTBMKPSUNQ-KRWDZBQOSA-N 0.000 claims 1
- XPWJLCOHULZLDD-UHFFFAOYSA-N [4-(3-fluoro-2-methoxyphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound FC=1C(=C(C=CC=1)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O)OC XPWJLCOHULZLDD-UHFFFAOYSA-N 0.000 claims 1
- DHYVGNIAAFYIOV-UHFFFAOYSA-N [4-(4,5-difluoro-2-methoxyphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound COC1=CC(F)=C(F)C=C1C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(O)CC2)C=C1 DHYVGNIAAFYIOV-UHFFFAOYSA-N 0.000 claims 1
- ZDXXGYJANACGKG-UHFFFAOYSA-N [4-(4-chloro-1H-benzimidazol-2-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC1=CC=CC=2NC(=NC=21)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O ZDXXGYJANACGKG-UHFFFAOYSA-N 0.000 claims 1
- GTMKLXVQCOOUPF-UHFFFAOYSA-N [4-(4-chloro-2-fluorophenyl)-2-fluorophenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound OC1(CC1)C(=O)N1CCN(CC1)C(=O)c1ccc(cc1F)-c1ccc(Cl)cc1F GTMKLXVQCOOUPF-UHFFFAOYSA-N 0.000 claims 1
- GMUAYYIBCAQIKV-CQSZACIVSA-N [4-(4-chloro-2-fluorophenyl)phenyl]-[(2R)-4-(1-hydroxycyclopropanecarbonyl)-2-methylpiperazin-1-yl]methanone Chemical compound ClC1=CC(=C(C=C1)C1=CC=C(C(=O)N2[C@@H](CN(CC2)C(=O)C2(CC2)O)C)C=C1)F GMUAYYIBCAQIKV-CQSZACIVSA-N 0.000 claims 1
- GMUAYYIBCAQIKV-AWEZNQCLSA-N [4-(4-chloro-2-fluorophenyl)phenyl]-[(2S)-4-(1-hydroxycyclopropanecarbonyl)-2-methylpiperazin-1-yl]methanone Chemical compound ClC1=CC(=C(C=C1)C1=CC=C(C(=O)N2[C@H](CN(CC2)C(=O)C2(CC2)O)C)C=C1)F GMUAYYIBCAQIKV-AWEZNQCLSA-N 0.000 claims 1
- PYTRHWUISUVNLV-CQSZACIVSA-N [4-(4-chloro-2-fluorophenyl)phenyl]-[(3R)-4-(1-hydroxycyclopropanecarbonyl)-3-methylpiperazin-1-yl]methanone Chemical compound ClC1=CC(=C(C=C1)C1=CC=C(C(=O)N2C[C@H](N(CC2)C(=O)C2(CC2)O)C)C=C1)F PYTRHWUISUVNLV-CQSZACIVSA-N 0.000 claims 1
- AKMJLOIJLUMKGY-GASCZTMLSA-N [4-(4-chloro-2-fluorophenyl)phenyl]-[(3R,5S)-4-(1-hydroxycyclopropanecarbonyl)-3,5-dimethylpiperazin-1-yl]methanone Chemical compound ClC1=CC(=C(C=C1)C1=CC=C(C(=O)N2C[C@@H](N([C@@H](C2)C)C(=O)C2(CC2)O)C)C=C1)F AKMJLOIJLUMKGY-GASCZTMLSA-N 0.000 claims 1
- FZPSKSCJJYPAIW-KRWDZBQOSA-N [4-(4-chloro-2-fluorophenyl)phenyl]-[(3S)-4-(1-hydroxycyclopropanecarbonyl)-3-(hydroxymethyl)piperazin-1-yl]methanone Chemical compound ClC1=CC(=C(C=C1)C1=CC=C(C=C1)C(=O)N1C[C@H](N(CC1)C(=O)C1(CC1)O)CO)F FZPSKSCJJYPAIW-KRWDZBQOSA-N 0.000 claims 1
- PYTRHWUISUVNLV-AWEZNQCLSA-N [4-(4-chloro-2-fluorophenyl)phenyl]-[(3S)-4-(1-hydroxycyclopropanecarbonyl)-3-methylpiperazin-1-yl]methanone Chemical compound ClC1=CC(=C(C=C1)C1=CC=C(C(=O)N2C[C@@H](N(CC2)C(=O)C2(CC2)O)C)C=C1)F PYTRHWUISUVNLV-AWEZNQCLSA-N 0.000 claims 1
- WYXZDVGBLSBNFV-UHFFFAOYSA-N [4-(4-chloro-2-fluorophenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)-2,2-dimethylpiperazin-1-yl]methanone Chemical compound ClC1=CC(=C(C=C1)C1=CC=C(C(=O)N2C(CN(CC2)C(=O)C2(CC2)O)(C)C)C=C1)F WYXZDVGBLSBNFV-UHFFFAOYSA-N 0.000 claims 1
- ORKQZIKMFJZORB-UHFFFAOYSA-N [4-(4-chloro-2-fluorophenyl)phenyl]-[7-(1-hydroxycyclopropanecarbonyl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound ClC1=CC(=C(C=C1)C1=CC=C(C(=O)N2C3(CC3)CN(CC2)C(=O)C2(CC2)O)C=C1)F ORKQZIKMFJZORB-UHFFFAOYSA-N 0.000 claims 1
- BGYRGTLMNWOGSX-UHFFFAOYSA-N [4-(4-chloro-2-methoxyphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound COC1=CC(Cl)=CC=C1C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(O)CC2)C=C1 BGYRGTLMNWOGSX-UHFFFAOYSA-N 0.000 claims 1
- YKTCJYYSQVIWRY-UHFFFAOYSA-N [4-(4-chloro-3-fluorophenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound C1CN(C(=O)C=2C=CC(=CC=2)C=2C=C(F)C(Cl)=CC=2)CCN1C(=O)C1(O)CC1 YKTCJYYSQVIWRY-UHFFFAOYSA-N 0.000 claims 1
- GWOKRESKQHTSEB-UHFFFAOYSA-N [4-(4-chlorophenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC1=CC=C(C=C1)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O GWOKRESKQHTSEB-UHFFFAOYSA-N 0.000 claims 1
- LLBZPTSMCQCYFF-UHFFFAOYSA-N [4-(4-fluoro-1,3-dihydroisoindol-2-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound FC1=C2CN(CC2=CC=C1)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 LLBZPTSMCQCYFF-UHFFFAOYSA-N 0.000 claims 1
- LGJDOGQQWAZVLU-UHFFFAOYSA-N [4-(5,6-difluoro-1H-benzimidazol-2-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound FC1=CC2=C(NC(=N2)C2=CC=C(C=C2)C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1F LGJDOGQQWAZVLU-UHFFFAOYSA-N 0.000 claims 1
- YXMAQWMYTNFEDD-UHFFFAOYSA-N [4-(5-chloro-2-propan-2-yloxyphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound CC(C)OC1=CC=C(Cl)C=C1C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(O)CC2)C=C1 YXMAQWMYTNFEDD-UHFFFAOYSA-N 0.000 claims 1
- WHEHVOIBRBLUPG-UHFFFAOYSA-N [4-(5-fluoro-1,3-dihydroisoindol-2-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound FC=1C=C2CN(CC2=CC=1)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 WHEHVOIBRBLUPG-UHFFFAOYSA-N 0.000 claims 1
- SWIWCNPVVAULDH-UHFFFAOYSA-N [4-(5-fluoro-2,3-dihydroindol-1-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound FC=1C=C2CCN(C2=CC1)C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 SWIWCNPVVAULDH-UHFFFAOYSA-N 0.000 claims 1
- LWDYGGVZKQQKCC-UHFFFAOYSA-N [4-(5-fluoro-2-methylphenyl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound CC1=CC=C(F)C=C1C1=CC=C(C(=O)N2CCN(CC2)C(=O)C2(O)CC2)C=C1 LWDYGGVZKQQKCC-UHFFFAOYSA-N 0.000 claims 1
- ATXRMAXEGGLRHJ-UHFFFAOYSA-N [4-(5-fluoropyridin-3-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound C1CN(C(=O)C=2C=CC(=CC=2)C=2C=C(F)C=NC=2)CCN1C(=O)C1(O)CC1 ATXRMAXEGGLRHJ-UHFFFAOYSA-N 0.000 claims 1
- LISAVSBEFPGTRG-UHFFFAOYSA-N [4-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound S1C=CC=2CN(CCC21)C2=CC=C(C(=O)N1CCN(CC1)C(=O)C1(CC1)O)C=C2 LISAVSBEFPGTRG-UHFFFAOYSA-N 0.000 claims 1
- JEAQIOQWWGBKPR-UHFFFAOYSA-N [4-(6,8-dihydro-5H-1,7-naphthyridin-7-yl)-2-fluorophenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound FC1=C(C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=CC(=C1)N1CCC=2C=CC=NC=2C1 JEAQIOQWWGBKPR-UHFFFAOYSA-N 0.000 claims 1
- RVZNVYTUBDZVNT-KRWDZBQOSA-N [4-(6,8-dihydro-5H-1,7-naphthyridin-7-yl)phenyl]-[(3S)-4-(1-hydroxycyclopropanecarbonyl)-3-methylpiperazin-1-yl]methanone Chemical compound C[C@@H]1N(CCN(C1)C(C1=CC=C(C=C1)N1CCC=2C=CC=NC=2C1)=O)C(=O)C1(CC1)O RVZNVYTUBDZVNT-KRWDZBQOSA-N 0.000 claims 1
- COVVWFGSPIAAOP-UHFFFAOYSA-N [4-(6-chloro-1,3-benzoxazol-2-yl)-3-fluorophenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC1=CC2=C(N=C(O2)C2=C(C=C(C(=O)N3CCN(CC3)C(=O)C3(CC3)O)C=C2)F)C=C1 COVVWFGSPIAAOP-UHFFFAOYSA-N 0.000 claims 1
- XGXXMXMQLAEZMH-UHFFFAOYSA-N [4-(6-chloro-1H-benzimidazol-2-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC1=CC2=C(NC(=N2)C2=CC=C(C=C2)C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 XGXXMXMQLAEZMH-UHFFFAOYSA-N 0.000 claims 1
- XKXKDSJBUDOIMG-UHFFFAOYSA-N [4-(6-chloroimidazo[1,2-a]pyridin-3-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound ClC=1C=CC=2N(C=1)C(=CN=2)C1=CC=C(C=C1)C(=O)N1CCN(CC1)C(=O)C1(CC1)O XKXKDSJBUDOIMG-UHFFFAOYSA-N 0.000 claims 1
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- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
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- 229940080237 sodium caseinate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
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- ODFAPIRLUPAQCQ-UHFFFAOYSA-M sodium stearoyl lactylate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC(C)C(=O)OC(C)C([O-])=O ODFAPIRLUPAQCQ-UHFFFAOYSA-M 0.000 description 1
- 229940080352 sodium stearoyl lactylate Drugs 0.000 description 1
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- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000003734 thymidylate synthase inhibitor Substances 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
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- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61P35/00—Antineoplastic agents
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
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- C—CHEMISTRY; METALLURGY
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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- C07D213/62—Oxygen or sulfur atoms
- C07D213/69—Two or more oxygen atoms
-
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
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- C07D235/08—Radicals containing only hydrogen and carbon atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
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- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
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Abstract
Un acoplamiento (34) que une unos elementos de tubo (56, 58) en una relación de extremo con extremo, comprendiendo dicho acoplamiento (34) dichos elementos de tubo (56, 58); una pluralidad de segmentos (42, 44) fijados entre sí extremo con extremo y que rodean un espacio central (46), presentando cada uno de dichos segmentos (42, 44) un canal (48) que se extiende circunferencialmente alrededor de y encarado hacia dicho espacio central (46); unos miembros de conexión (50) que están situados en los extremos opuestos de cada uno de dichos segmentos (42, 44), pudiendo dichos miembros de conexión (50) ser apretados de manera ajustable acercando dichos 10 segmentos (42, 44) uno en dirección al otro; una junta (10) situada entre dichos segmentos (42, 44), comprendiendo dicha junta (10): un anillo (12) que presenta una pared periférica (14) que se extiende circunferencialmente alrededor de aquél, siendo dicho anillo (12) recibido dentro de dichos canales (48); un primer lóbulo (16) fijado a dicha pared periférica (14), extendiéndose dicho primer lóbulo (16) 15 circunferencialmente alrededor de dicho anillo (12); una primera superficie de sellado (18) situada sobre dicho primer lóbulo (16), extendiéndose dicha primera superficie de sellado (18) circunferencialmente alrededor de dicho anillo (12); al menos una primera proyección (20) que se extiende desde dicha primera superficie de sellado (18); un segundo lóbulo (36) fijado a dicha pared periférica (14) opuesta a dicho primer lóbulo (16), extendiéndose dicho segundo lóbulo (36) circunferencialmente alrededor de dicho anillo (12); una segunda superficie de sellado (38) situada sobre dicho segundo lóbulo (36), extendiéndose dicha segunda superficie de sellado (38) circunferencialmente alrededor de dicho anillo (12); siendo dichos segmentos (42, 44) soportados en un estado pre-ensamblado en relación espaciada suficiente para permitir que dichos elementos de tubo (56, 58) sean insertados en dicho espacio central (46) mientras dichos segmentos (42, 44) son fijados entre sí, situándose en contacto dichas primera y segunda superficies de sellado (38), respectivamente, con dichos elementos de tubo (56, 58), encajando dicha primera proyección (20) con uno de dichos elementos de tubo (56, 58) y manteniendo una porción de dicha primera superficie de sellado (18) en relación espaciada a distancia de aquélla; en el que el apriete de dichos miembros de conexión (50) acerca dichos segmentos (42, 44) uno en dirección al otro comprimiendo de esta manera dicha porción de dicha primera superficie de sellado (18) para un encaje de estanqueidad con dicho un elemento de tubo (56, 58) cerrando de esta manera dicho trayecto de fuga (22), en el que el acoplamiento (34) presenta una de las siguientes características: - dicho primer lóbulo (16) comprende un borde libre (40), estando dicha primera proyección (20) situada próxima a dicho borde libre (40); - dicho primer lóbulo comprende un borde libre, estando dicha primera proyección situada en posición distal respecto a dicho borde libre. o una sal farmacéuticamente aceptable de los mismos.
Description
DESCRIPCIÓN
Derivados de 2-hidroxi-1-{4-[(4-fenil)fenil]carbonil}piperazin-1-il}etan-1-ona y compuestos relacionados como inhibidores de sintasa de ácido graso (FASN) para el tratamiento del cáncer
Campo de la invención
La presente invención se refiere a compuestos y composición para la inhibición de la sintasa de ácido graso ("FASN"), su síntesis, aplicaciones y antídoto. Esta aplicación no reclama la prioridad de cualquier otra aplicación.
Antecedentes de la invención
La sintasa de ácido graso (en adelante "FASN;" también conocido como "FAS") desempeña papeles fundamentales tanto en el metabolismo celular como en la señalización celular. FASN cataliza la formación de ácidos grasos de cadena larga a partir de acetil-CoA, malonil-CoA y nicotinamida adenina dinucleótido fosfato (NADPH), por lo tanto participar en la producción de energía y el almacenamiento, estructura celular y formación de intermediarios en la biosíntesis de las hormonas y otras moléculas biológicamente importantes.
Una amplia investigación se ha llevado a cabo para estudiar la expresión, función y regulación de ambos genes de codificación de FASN y las diversas formas de proteínas Fasn. Varios estudios indican que FASN está implicado en la oncogénesis andtumor progresión de varios tipos de cáncer. Por ejemplo, FASN amplificación de genes y la sobreexpresión de proteínas se líneas celulares de cáncer de mama humano observedin. (Hunt DA, el carril HM, Zygmont ME, Dervan PA, Hennigar RA (2007), la estabilidad y la sobreexpresión de ARNm de la sintasa de ácido graso en líneas celulares de cáncer de mama humano Anticancer Res 27 (1A): 27-34; Kuhaja FP, (2006) sintasa de ácido graso y el cáncer: Nueva aplicación de una vía antigua Cancer Research, 66 (12) 5977-5980; Menéndez JA, Lupu Rsintasa (2007) Ácidos grasos y el fenotipo lipogénico en la patogénesis del cáncer. Nature Review Cancer, 7, 763-777.) Además, un estudio centrado en los tumores de ovario reveló que los niveles elevados de FASN sirven un indicador de menor supervivencia del sujeto. (Gansler TS, Hardman W, Hunt DA, Schaffel S, Hennigar RA (junio de 1997) El aumento de expresión de la sintasa de ácido graso (OA-519) en tumores de ovario predice una supervivencia más corta Hum Pathol, 28 (6): 686-92). En resumen, la correlación de la expresión de FASN o actividad elevada con alto grado tumoral y etapa avanzada en mama primario, próstata, y cánceres colorrectales ha llamado la atención a la enzima como un posible marcador diana y fármaco de mal pronóstico. 28 (6): 686-92). En resumen, la correlación de la expresión de FASN o actividad elevada con alto grado tumoral y etapa avanzada en mama primario, próstata, y cánceres colorrectales ha llamado la atención a la enzima como un posible marcador diana y fármaco de mal pronóstico. 28 (6): 686-92). En resumen, la correlación de la expresión de FASN o actividad elevada con alto grado tumoral y etapa avanzada en mama primario, próstata, y cánceres colorrectales ha llamado la atención a la enzima como un posible marcador diana y fármaco de mal pronóstico.
Además de la participación en la oncogénesis, FASN también se ha identificado como un factor que puede influenciar la progresión de enfermedades como la diabetes y los leiomiomas uterinos. En particular, un estudio encontró que un inhibidor de FASN, platensimicina, la reducción de los niveles de glucosa ambientales en modelos de ratón de diabetes. Además, inhibidores de FASN han demostrado ser potencialmente eficaces en la inducción de la pérdida de peso (por ejemplo, EP0869784-A). Del mismo modo, un estudio de todo el genoma sugiere que FASN puede contribuir a la predisposición a leiomiomas uterinos.
Además, FASN ha sido identificado como una diana para el tratamiento de infecciones microbianas. En particular, síntesis de ácido graso o el nivel de ácido graso se ha reportado ser crítico en la patogénesis viral. Además, FASN ha sido implicado en pathogeneiss de virus humano citomegalovirus (HCMV), los virus de la gripe A y la hepatitis C (Véase, por ejemplo, Mungeret al, Nature Biotechnology, 26: 1179-1186 (2008)). También se ha informado de que la expresión de FASN ha aumentado las células infectadas por virus coxsackie B3 (CVB3), un picornavirus, y la replicación del CVB3 está bloqueada por inhibidores FASN. (Ver Rassmann y otros, Antiviral Research, 76: 150-158 (2007)). Además, FASN se ha informado a ser importante en la replicación viral lítica del virus de Epstein-Barr (EBV). (Li et al, Journal of Virology, 78 (8): 4197 a 4,206 (2004)). FASN también se ha implicado a tener un papel en la replicación del virus del dengue (véase, por ejemplo, Heaton et al, Proc Natl.Acad Sci, 107 (40): 17345-17350 (2010); y Samsa et al., PLoS Pathegens, 5 (10): e1000632 (2009)). Por otra parte, FASN juega un papel importante en la infección por VHC mediante el control de la entrada y la producción viral (Yang W, Capucha BL, Chadwick SL, Watkins, Luo G, Conrads TP, Wang T (2008), sintasa de ácido graso se regula al alza durante la infección de virus de hepatitis C y regula la entrada del virus de la hepatitis C y la producción. Hepatology, 48, 13,967 a 1403)
Importantes esfuerzos se han centrado en la generación de inhibidores de FASN que pueden ayudar a proporcionar un tratamiento de cáncer y otras enfermedades relacionadas. Un número de inhibidor de familias se han identificado y publicado, como la serie de azabencimidazoles (WO 2011/066211 y las publicaciones relacionadas) y la serie de derivados de sulfonamida (WO2008/075070 y las publicaciones relacionadas) de AstraZeneca Uk Ltd. Sin embargo, debido a la importancia de FASN y las deficiencias en los compuestos
publicados, todavía hay una necesidad insatisfecha de inhibidores de FASN potentes y altamente específicos.
La presente invención introduce un nuevo conjunto de compuestos que inhibe selectivamente actividades FASN y modula el crecimiento y la proliferación de líneas celulares de cáncer. También se incluyen los procesos de síntesis de los nuevos compuestos. Estos compuestos pueden tener implicaciones significativas farmacéuticas en el tratamiento del cáncer, así como otras enfermedades como infecciones virales, obesidad y diabetes.
Las carboxamidas y las caboxamidas inversas y el uso de las carboxamidas y las caboxamidas inversas en el tratamiento del cáncer se describen en la WO 2013/028445 A1.
Sumario de la invención
La invención se define en las reivindicaciones adjuntas. Un aspecto de esta divulgación es la provisión de compuestos, composiciones, y kits para inhibición de FASN que comprende un compuesto de fórmula I:
en donde
R1 es hidroxil-alquilo C1-C3 no sustituido o sustituido con -CH3 o -CHzF3-z, cicloalquilo de 5 miembros no sustituido o sustituido con sustituyentes seleccionados del grupo que consiste de deuterio, -Rp, -ORp, -NHRp, y -NRpRp1,
o cicloalquilo o heterocicloalquilo de 3 o 4 miembros en donde (i) el miembro del anillo heteroátomo del heterocicloalquilo de 3 o 4 miembros se selecciona independientemente entre O, S o N, y (ii) cada uno de dichos cicloalquilo o heterocicloalquilo de 3 o 4 miembros no está sustituido o está opcionalmente sustituido con sustituyentes seleccionados del grupo que consiste de deuterio, -Ra, -ORa, -NHRa y -NRaRa1;
L es un anillo monocíclico de 5-10 miembros o alquilo bicíclico o heteroalquilo en donde (i) los miembros del anillo heteroátomo del heteroalquilo monocíclico o bicíclico de 5-10 miembros se seleccionan independientemente de O, S, o N, y (ii) cada uno de los 5-10 miembros monocíclico o bicíclico alquilo o heteroalquilo está o bien sustituido u opcionalmente sustituido con sustituyentes seleccionados del grupo que consiste de deuterio y -Rb;
A y B son independientemente O o S;
Ar1 es
un anillo monocíclico de 4-10 miembros o arilo bicíclico, heteroarilo o heterocicloalquilo, en donde (i) dichos 4-10 miembros monocíclicos o heteroarilo bicíclico o heterocicloalquilo tienen 1, 2, 3 ó 4 heteroátomos que son independientemente seleccionados de N, S u O, y (ii) cada uno de dichos arilo , heteroarilo, o heterocicloalquilo monocíclico o bicíclico de 4-10 miembros es o bien sin sustituir u opcionalmente sustituido independientemente con 1 o más sustituyentes que pueden ser el mismo o diferente y se seleccionan independientemente del grupo que consiste de deuterio, halo, alquilo, - CHzF3-z, ciano, hidroxilo, hidroxialquilo, amino, aminoalquilo, (amino)alcoxi, - CONH2 , -C(O)NH(alquilo), -C(O)N(alquilo)2 , -C(O)NH(arilo), -C(O)N(arilo)2, - OCHzF3-z, -alquilo, -alquenilo, alquinilo, alcoxi o (alcoxialquilo)amino-, -N(Rc)-(O)alquilo, -N(Rc)-C(O)arilo, cicloalquilo, heterocicloalquilo, arilo, y - heteroarilo, con la condición de que no hay dos heteroátomos de anillo adyacentes son ambos S o ambos O;
R2 es H o un arilo, heteroarilo, cicloalquilo, o heterocicloalquilo monocíclico, bicíclico, o tricíclico de 4-15 miembros, (i) heteroarilo o heterocicloalquilo monocíclico, bicíclico o tricíclico de 4-15 miembros tiene 1, 2, 3, 4, 5, 6, 7, u 8 heteroátomos que se seleccionan independientemente de N, S u O, y (ii) en donde cada uno de dicho arilo, heteroarilo, cicloalquilo, y heterocicloalquilo o bien no sustituido o sustituido opcionalmente con 1 o más sustituyentes que pueden ser el mismo o diferente y se seleccionan independientemente del grupo que consiste de deuterio, halo, ciano, hidroxilo, hidroxilalquil, hidroxilcicloalquilo-, hidroxilo-heterocicloalquilo, hidroxilo-aril-, hidroxilo-heteroaril, amino, aminoalquilo, (amino)alcoxi, - CONH2, -C(O)NH(alquilo), -C(O)N(alquilo)2 , -C(O)NH(arilo), -C(O)N(arilo)2, - CHzF3-z, -OCHzF3-z, -alquilo, alcoxi, alquenilo, alquinilo, ariloxi, (alcoxialquilo)amino-, cicloalquilo, heterocicloalquilo, (heterocicloalquil)alquilo, - arilo, heteroarilo, -O(alquilo), -O(cicloalquilo), -O(heterocicloalquilo), -O(arilo), -O(heteroarilo), ONH2, -C(O)NH(alquilo), -C(O)N(arilo)2 , -C(O)NH(cicloalquilo), -NH(CO)cicloalquilo, -NH(SO2), -NH(SO2)alquilo, -NH(SO2)arilo, -NH(SO2)heteroarilo, -N(SO2)cicloalquilo, -C(O)N(alquilo)2 , (Aril)alquilo, heteroarilo, (heteroaril)alquilo, -S(O)2alquilo, -S(O)2-arilo, -S(O)2cicloalquilo, -C(O)N(alquilo)2 , -C(O)alquilo, -NH-(O)alquilo, -NH-C(O)-cicloalquilo, NH-C(O)heterocicloalquilo, NH-C(O)heterocicloalquilo-Rd, -NH-C(O)-Rd-(O)alquilo, -NH-C(O)-arilo, -NH-C(O)-NH-alquilo, NH-C(O)-NH-cicloalquilo, NH2(CO)-alquilo, NH-C(O)-NH-arilo, -NH-C(O)-O-alquilo, NH-C(O)-NH-cicloalquilo, -NH-C(O)-O-cicloalquilo, -NH(Rd)(O)-alquilo, -NH(Rd)-(O)-arilo, -NH(Rd)-SO2)cicloalquilo, -S(O2)NH2 , - SO2) NH(alquilo), -S(O2)N(Rd)cicloalquilo, -S(O2)N(alquilo)2 , -C(O)N(H)(alquilo), -C(O)N(Rd)(cicloalquilo), metilendioxi, -CHzF3-z, -OCHzF3-z, y alcoxi;
Rp y Rp1 son independientemente H, halo, alquilo C1-C4 , o cicloalquilo C3-C4 ;
Ra y Ra1 son independientemente H, halo, alquilo C1-C4 , o cicloalquilo C3-C4 ;
Rb es H, halo, C1-C4 alquilo, C1-C3 hidroxilo-alquilo, o C3-C4 cicloalquilo;
Rc es H, halo, C1-C4 alquilo, o C3-C4 cicloalquilo;
Rd es H, halo, C1-C4 alquilo, o C3-C4 cicloalquilo;
y z es 0 , 1 ó 2 ;
y sales farmacéuticamente aceptables, solvatos, ésteres, profármacos e isómeros de los mismos.
Otro aspecto de esta divulgación es la provisión de compuestos, composiciones, y kits para la inhibición de FASN que comprende un compuesto de fórmula I-A:
en donde:
R1 es hidroxil-alquilo C1-C3 no sustituido o sustituido con -CH3 o -CHzF3-z, cicloalquilo de 5 miembros no sustituido o sustituido con sustituyentes seleccionados del grupo que consiste de deuterio, -Rp, -ORp, -NHRp, y -NRpRp1,
o cicloalquilo o heterocicloalquilo de 3 o 4 miembros en donde (i) el miembro del anillo heteroátomo del heterocicloalquilo de 3 o 4 miembros se selecciona independientemente de O, S o N, y (ii) cada uno de dichos cicloalquilo o heterocicloalquilo de 3 o 4 miembros no está sustituido o está opcionalmente sustituido con sustituyentes seleccionados del grupo que consiste de deuterio, -Ra, -ORa, -NHRa y -NRaRa1;
Ar1 es un anillo monocíclico de 4-10 miembros o arilo bicíclico, heteroarilo o heterocicloalquilo, en donde (i) dicho heteroarilo o heterocicloalquilo monocíclico o bicíclico de 4-10 miembros tienen 1, 2, 3 ó 4 heteroátomos que son independientemente seleccionados de N, S u O, y (ii) cada uno de dicho arilo , heteroarilo, o heterocicloalquilo monocíclico o bicíclico de 4-10 miembros es o bien sin sustituir u opcionalmente sustituido independientemente con 1 o más sustituyentes que pueden ser el mismo o diferente y se seleccionan independientemente del grupo que consiste de deuterio, halo, alquilo, - CHzF3-z, ciano, hidroxilo, hidroxialquilo, amino, aminoalquilo, (amino)alcoxi, - CONH2 , -C(O)NH(alquilo), -C(O)N(alquilo)2 , -C(O)NH(arilo), -C(O)N(arilo)2 , - OCHzF3-z, -alquilo, -alquenilo, alquinilo, alcoxi o (alcoxialquilo)amino-, -N(Rc)-(O)alquilo, -N(Rc)-C(O)arilo, cicloalquilo, heterocicloalquilo, arilo, y - heteroarilo, con la condición de que no hay dos heteroátomos de anillo adyacente adyacentes son ambos S o ambos O; R2 es H o un arilo, heteroarilo, cicloalquilo, o heterocicloalquilo monocíclico, bicíclico, o tricíclico de 4-15 miembros, (i) heterocicloalquilo o heteroarilo monocíclico, bicíclico o tricíclico de 4-15 miembros tiene 1, 2, 3, 4, 5, 6 , 7, o 8 heteroátomos que se seleccionan independientemente de N, S u O, y (ii) en donde cada uno de dichos arilo, heteroarilo, cicloalquilo, y heterocicloalquilo es no sustituido o sustituido opcionalmente con 1 o más sustituyentes que pueden ser los mismos o diferentes y se seleccionan independientemente del grupo que consiste de deuterio, halo, ciano, hidroxilo, hidroxilalquil, hidroxilcicloalquilo-, hidroxiloheterocicloalquilo, hidroxilo-aril-, hidroxilo-heteroaril, amino, aminoalquilo, (amino)alcoxi, - CONH2 , -C(O)NH(alquilo), -C(O)N(alquilo)2 , -C(O)NH(arilo), -C(O)N(arilo)2 , - CHzFa-z, -OCHzFa-z, -alquilo, alcoxi, alquenilo, alquinilo, ariloxi, (alcoxialquilo)amino-, cicloalquilo, heterocicloalquilo, (heterocicloalquil)alquilo, -arilo, heteroarilo, -O(alquilo), -O(cicloalquilo), -O(heterocicloalquilo), -O(arilo), -O(heteroarilo), ONH2 , -C(O)NH(alquilo), -C(O)N(arilo)2 , -C(O)NH(cicloalquilo), -NH(CO)cicloalquilo, -NH(SO2), -NH(SO2)alquilo, -NH(SO2)arilo, -NH(SO2)heteroarilo, -N(SO2)cicloalquilo, -C(O)N(alquilo)2 , (Aril)alquilo, heteroarilo, (heteroaril)alquilo, -S(O)2alquilo, -S(O)2arilo, -S(O)2cicloalquilo, -C(O)N(alquilo)2 , -C(O)alquilo, -NH-(O)alquilo, -NH-C(O)-cicloalquilo, NH-C(O)heterocicloalquilo, NH-C(O)heterocicloalquilo-Rd, -NH-C(O)-Rd-(O)alquilo, -NH-C(O)-arilo, -NH-C(O)-NH-alquilo, NH-C(O)-NH-cicloalquilo, NH2 (CO)-alquilo, NH-C(O)-NH-arilo, -NH-C(O)-O-alquilo, NH-C(O)-NH-cicloalquilo, -NH-C(O)-O cicloalquilo, -NH(Rd)-(O)-alquilo, -NH(Rd)-(O)-arilo, -NH(Rd)-SO2)cicloalquilo, -S(O2)NH2 , - SO2)NH(alquilo), -S(O2)N(Rd)cicloalquilo, -S(O2)N(alquilo)2 , -C(O)N(H)(alquilo), -C(O)N(Rd)(cicloalquilo), metilendioxi, -CHzF3-z, -Oc HzF3-z, y alcoxi;
Rp y Rp1 son independientemente H, halo, alquilo C1-C4 , o cicloalquilo C3-C4 ;
Ra y Ra1 son independientemente H, halo, alquilo C1-C4 , o cicloalquilo C3-C4 ;
Rc es H, halo, C1-C4 alquilo, o C3-C4 cicloalquilo;
Rd es H, halo, C1-C4 alquilo, o C3-C4 cicloalquilo;
y z es 0 , 1 ó 2 ;
y las sales farmacéuticamente aceptables, solvatos, ásteres, profármacos e isómeros de los mismos.
Otro aspecto de esta divulgación es la provisión de compuestos, composiciones, y kits para inhibición de FASN que comprende un compuesto de fórmula I-B:
en donde:
Ari es un anillo monocíclico de 4-10 miembros o arilo bicíclico, heteroarilo o heterocicloalquilo, en donde (i) dicho heteroarilo o heterocicloalquilo monocíclico o bicíclico de 4-10 miembros tiene 1, 2, 3, o 4 heteroátomos que se seleccionan independientemente a partir de N, S u O, y (ii) cada uno de dichos arilo, heteroarilo, o heterocicloalquilo monocíclico o bicíclico de 4-10 miembros es o bien no sustituido u opcionalmente sustituido independientemente con 1 o más sustituyentes que pueden ser el mismo o diferente y se seleccionan independientemente del grupo que consiste de deuterio, halo, alquilo, - CHzF3-z, ciano, hidroxilo, hidroxialquilo, amino, aminoalquilo, (amino)alcoxi, - CONH2 , -C(O)NH(alquilo), -C(O)N(alquilo)2 , -C(O)NH(arilo), -C(O)N(arilo)2 , - oCHzF3-z, -alquilo, -alquenilo, alquinilo, alcoxi o (alcoxialquilo)amino-, -N(Rc)-(O)alquilo, -N(Rc)-C(O)arilo, cicloalquilo, heterocicloalquilo, arilo, y - heteroarilo, con la condición de que no hay dos heteroátomos de anillo adyacente adyacentes son ambos S o ambos O; R2 es H o un arilo, heteroarilo, cicloalquilo, o heterocicloalquilo monocíclico, bicíclico, o tricíclico de 4-15 miembros, (i) heterocicloalquilo o heteroarilo monocíclico, bicíclico o tricíclico de 4-15 miembros tiene 1, 2, 3, 4, 5, 6 , 7, o 8 heteroátomos que se selecciona independientemente de N, S u O, y (ii) en donde cada uno de dichos arilo, heteroarilo, cicloalquilo, y heterocicloalquilo es no sustituido o sustituido opcionalmente con 1 o más sustituyentes que pueden ser los mismos o diferentes y se seleccionan independientemente del grupo que consiste de deuterio, halo, ciano, hidroxilo, hidroxilalquil, hidroxilcicloalquilo-, hidroxiloheterocicloalquilo, hidroxilo-aril-, hidroxilo-heteroaril, amino, aminoalquilo, (amino)alcoxi, - CONH2 , -C(O)NH(alquilo), -C(O)N(alquilo)2 , -C(O)NH(arilo), -C(O)N(arilo)2 , - CHzF3-z, -OCHzF3-z, -alquilo, alcoxi, alquenilo, alquinilo, ariloxi, (alcoxialquilo)amino-, cicloalquilo, heterocicloalquilo, (heterocicloalquil)alquilo, -arilo, heteroarilo, -O(alquilo), -O(cicloalquilo), -O(heterocicloalquilo), -O(arilo), -O(heteroarilo), ONH2 , -C(O)NH(alquilo), -C(O)N(arilo)2 , -C(O)NH(cicloalquilo), -NH(CO)cicloalquilo, -NH(SO2 ), -NH(SO2 )alquilo, -NH(SO2)arilo, -NH(SO2)heteroarilo, -N(SO2)cicloalquilo, -C(O)N(alquilo)2 , (Aril)alquilo, heteroarilo, (heteroaril)alquilo, -S(O)2alquilo, -S(O)2-arilo, -S(O)2cicloalquilo, -C(O)N(alquilo)2 , -C(O)alquilo, -NH-(O)alquilo, -NH-C(O)-cicloalquilo, NH-C(O)heterocicloalquilo, NH-C(O)heterocicloalquilo-Rd, -NH-C(O)-Rd-(O)alquilo, -NH-C(O)-arilo, -NH-C(O)-NH-alquilo, NH-C(O)-NH-cicloalquilo, NH2 (CO)-alquilo, NH-C(O)-NH-arilo, -NH-C(O)-O-alquilo, NH-C(O)-NH-cicloalquilo, -NH-C(O)-O cicloalquilo, -NH(Rd)-(O)-alquilo, -NH(Rd)-(O)-arilo, -NH(Rd)-SO2 )cicloalquilo, -S(O2 )NH2 , - SO2 )NH(alquilo), -S(O2 )N(Rd)cicloalquilo, -S(O2 )N(alquilo)2 , -C(O)N(H)(alquilo), -C(O)N(Rd)(cicloalquilo), metilendioxi, -CHzF3-z, -OCzF3-z, y alcoxi;
Rc es H, halo, C1-C4 alquilo, o C3-C4 cicloalquilo;
Rd es H, halo, C1-C4 alquilo, o C3-C4 cicloalquilo;
y z es 0 , 1 ó 2 ;
y sales farmacéuticamente aceptables, solvatos, ásteres, profármacos e isómeros de los mismos.
Otro aspecto de esta divulgación es la provisión de compuestos, composiciones, y kits para inhibición de FASN que comprende un compuesto de fórmula I-C:
en donde:
R1 es hidroxil-alquilo C1-C3 no sustituido o sustituido con -CH3 o -CHzF3-z, cicloalquilo de 5 miembros no sustituido o sustituido con sustituyentes seleccionados del grupo que consiste de deuterio, -Rp, -ORp, -NHRp, y -NRpRp1,
o cicloalquilo o heterocicloalquilo de 3 o 4 miembros en donde (i) el miembro del anillo heteroátomo del heterocicloalquilo de 3 o 4 miembros se selecciona independientemente de O, S o N, y (ii) cada uno de dichos cicloalquilo o heterocicloalquilo de 3 o 4 miembros no está sustituido o está opcionalmente sustituido con sustituyentes seleccionados del grupo que consiste de deuterio, -Ra, -ORa, -NHRa y -NRaRa1;
R2 es H o un anillo monocíclico, bicíclico o tricíclico arilo, heteroarilo, cicloalquilo, o heterocicloalquilo de 4 15 miembros, (i) heteroarilo o heterocicloalquilo monocíclico, bicíclico o tricíclico de 4-15 miembros o tiene 1, 2, 3, 4, 5, 6 , 7, o 8 heteroátomos que se seleccionan independientemente de N, S u O, y (ii) en donde cada uno de dichos arilo, heteroarilo, cicloalquilo, y heterocicloalquilo o bien no sustituido o sustituido opcionalmente con 1 o más sustituyentes que pueden ser los mismos o diferentes y se seleccionan independientemente del grupo que consiste en deuterio, halo, ciano, hidroxilo, hidroxilalquil, hidroxilcicloalquilo-, hidroxilo-heterocicloalquil, hidroxilo-aril-, hidroxilo-heteroaril, amino, aminoalquilo, (amino)alcoxi, - CONH2 , -C(O)NH(alquilo), -C(O)N(alquilo)2 , -C(O)NH(arilo), -C(O)N(arilo)2 , - CHzF3-z, -OCHzF3-z, -alquilo, alcoxi, alquenilo, alquinilo, ariloxi, (alcoxialquilo)amino-, cicloalquilo, heterocicloalquilo, (heterocicloalquil)alquilo, - arilo, heteroarilo, -O(alquilo), -O(cicloalquilo), -O(heterocicloalquilo), -O(arilo), -O(heteroarilo), ONH2, -C(O)NH(alquilo), -C(O)N(arilo)2 , -C(O)NH(cicloalquilo), -NH(CO)cicloalquilo, -NH(SO2), -NH(SO2)alquilo, -NH(SO2)arilo, -NH(SO2)heteroarilo, -N(SO2)cicloalquilo, -C(O)N(alquilo)2 , (aril)alquilo, heteroarilo, (heteroaril)alquilo, -S(O)2alquilo, -S(O)2-arilo, -S(O)2cicloalquilo, -C(O)N(alquilo)2 , -C(O)alquilo, -NH-(O)alquilo, -NH-C(O)-cicloalquilo, NH-C(O)heterocicloalquilo, NH-C(O)heterocicloalquilo-Rd, -NH-C(O)-Rd-(O)alquilo, -NH-C(O)-arilo, -NH-C(O)-NH-alquilo, NH-C(O)-NH-cicloalquilo, NH2(CO)-alquilo, NH-C(O)-NH-arilo, -NH-C(O)-O-alquilo, NH-C(O)-NH-cicloalquilo, -NH-C(O)-O-cicloalquilo, -NH(Rd)-(O)-alquilo, -NH(Rd)-(O)-arilo, -NH(Rd)-SO2)cicloalquilo, -S(O2)NH2 , - SO2)NH(alquilo), -S(O2)N(Rd)cicloalquilo, -S(O2)N(alquilo)2 , -C(O)N(H)(alquilo), -C(O)N(Rd)(cicloalquilo), metilendioxi, -CHzF3-z, -OCHzF3-z, y alcoxi;
Rp y Rp1 son independientemente H, halo, alquilo C1-C4 , o cicloalquilo C3-C4 ;
Ra y Ra1 son independientemente H, halo, alquilo C1-C4 , o cicloalquilo C3-C4 ;
Rd es H, halo, C1-C4 alquilo, o C3-C4 cicloalquilo;
Rq es H, halo, C1-C4 alquilo, o C3-C4 cicloalquilo;
y z es 0 , 1 ó 2 ;
y sales farmacéuticamente aceptables, solvatos, ésteres, profármacos e isómeros de los mismos.
Otro aspecto de esta divulgación es la provisión de compuestos, composiciones y kits para la inhibición FASN que comprende un compuesto de fórmula I-D:
en donde:
(I-D)
en donde:
R1' es OH o NH2 ;
R2 es H o un arilo, heteroarilo, cicloalquilo, o heterocicloalquilo monocíclico, bicíclico, o tricíclico de 4-15 miembros, (i) heterocicloalquilo o heteroarilo monocíclico, bicíclico o tricíclico de 4-15 miembros tiene 1, 2, 3, 4, 5, 6 , 7, o 8 heteroátomos que se seleccionan independientemente de N, S u O, y (ii) en donde cada uno de dichos arilo, heteroarilo, cicloalquilo, y heterocicloalquilo es no sustituido o sustituido opcionalmente con 1 o más sustituyentes que pueden ser los mismos o diferentes y se seleccionan independientemente del grupo que consiste de deuterio, halo, ciano, hidroxilo, hidroxilalquil, hidroxilcicloalquilo-, hidroxiloheterocicloalquilo, hidroxilo-aril-, hidroxilo-heteroaril, amino, aminoalquilo, (amino)alcoxi, - CONH2 , -C(O)NH(alquilo), -C(O)N(alquilo)2 , -C(O)NH(arilo), -C(O)N(arilo)2 , - CHzF3-z, -OCHzF3-z, -alquilo, alcoxi, alquenilo, alquinilo, ariloxi, (alcoxialquilo)amino-, cicloalquilo, heterocicloalquilo, (heterocicloalquil)alquilo, -arilo, heteroarilo, -O(alquilo), -O(cicloalquilo), -O(heterocicloalquilo), -O(arilo), -O(heteroarilo), ONH2 ,
C(O)NH(alquilo), -C(O)N(arilo)2 , -C(O)NH(cicloalquilo), -NH(CO)cicloalquilo, -NH(SÜ2), -NH(SO2)alquilo, -NH(SO2)arilo, -NH(SO2)heteroarilo, -N(SO2)cicloalquilo, -C(O)N(alquilo)2 , (aril)alquilo, heteroarilo, (heteroaril)alquilo, -S(O)2alquilo, -S(O)2-arilo, -S(O)2cicloalquilo, -C(O)N(alquilo)2 , -C(O)alquilo, -NH-(O)alquilo, -NH-C(O)-cicloalquilo, NH-C(O)heterocicloalquilo, NH-C(O)heterocicloalquilo-Rd, -NH-C(O)-Rd-(O)alquilo, -NH-C(O)-arilo, -NH-C(O)-NH-alquilo, NH-C(O)-NH-cicloalquilo, NH2 (CO)-alquilo, NH-C(O)-NH-arilo, -NH-C(O)-O-alquilo, NH-C(O)-NH-cicloalquilo, -NH-C(O)-O cicloalquilo, -NH(Rd)-(O)-alquilo, -NH(Rd)-(O)-arilo, -NH(Rd)-SO2)cicloalquilo, -S(O2)NH2, - SO2)NH(alquilo), -S(O2)N(Rd)cicloalquilo, -S(O2)N(alquilo)2 , -C(O)N(H)(alquilo), -C(O)N(Rd)(cicloalquilo), metilendioxi, -CHzF3-z, -OcHzFa-z, y alcoxi;
Rd es H, halo, C1-C4 alquilo, o C3-C4 cicloalquilo;
y z es 0 , 1 o 2 ;
y sales farmacéuticamente aceptables, solvatos, ásteres, profármacos e isómeros de los mismos.
Otro aspecto de esta invención es la provisión de compuestos o formulaciones farmacéuticas de la presente invención para uso en métodos de tratamiento de una enfermedad a través de la inhibición de FASN en un sujeto (por ejemplo, un humano) en necesidad del mismo administrando al sujeto una cantidad eficaz del compuesto o de la formulación farmacéutica de la presente invención.
Otra realización preferida es una formulación farmacéutica que comprende un compuesto farmacéuticamente aceptable de la presente invención, que proporciona, tras la administración a un ser humano, una disminución de la carga tumoral y/o metástasis. La formulación farmacéutica se puede administrar por vía oral u otros medios adecuados, por ejemplo, por vía intravenosa o por inyección.
Otra realización más de la descripción es un método de tratamiento de cáncer de ovario en un sujeto (por ejemplo, un humano) en necesidad del mismo mediante la administración al sujeto de una cantidad terapéuticamente eficaz del compuesto o la formulación farmacéutica de la presente invención.
Otra realización más de la descripción es un método de tratamiento de cáncer de colon en un sujeto (por ejemplo, un humano) en necesidad del mismo mediante la administración al sujeto de una cantidad eficaz del compuesto o la formulación farmacéutica de la presente invención.
Otra realización más de la descripción es un método de tratamiento de cáncer de mama en un sujeto (por ejemplo, un humano) en necesidad del mismo mediante la administración al sujeto de una cantidad eficaz de la formulación farmacéutica de la presente invención.
Otra realización más de la descripción es un método de tratamiento de la leucemia en un sujeto (por ejemplo, un humano) en en necesidad del mismo mediante la administración al sujeto de una cantidad eficaz del compuesto o la formulación farmacéutica de la presente invención.
Otra realización más de la descripción es un método de tratamiento de cáncer de colon, antes o después de la resección quirúrgica y/o terapia de radiación, en un sujeto (por ejemplo, un ser humano) en necesidad del mismo mediante la administración al sujeto de una cantidad eficaz del compuesto o la formulación farmacéutica de la presente invención.
Otra realización más de la descripción es un método de tratamiento del cáncer, antes o después de la resección quirúrgica y/o terapia de radiación, en un sujeto (por ejemplo, un ser humano) en necesidad del mismo mediante la administración al sujeto de una cantidad eficaz del compuesto o la formulación farmacéutica de la presente invención, incluyendo terapia coadyuvante para tratar las náuseas, con o sin dexametasona.
Otra realización más de la descripción es un método de tratamiento del cáncer, antes o después de la resección quirúrgica y/o radioterapia, en un sujeto (por ejemplo, un ser humano) en necesidad del mismo mediante la administración al sujeto de una cantidad eficaz del compuesto o la formulación farmacéutica de la presente invención, incluyendo la terapia adyuvante con uno o más agentes terapéuticos adicionales, o sus sales farmacéuticamente aceptables de los mismos. Los ejemplos no limitantes de tales agentes terapéuticos adicionales incluyen agentes citotóxicos (tales como por ejemplo, pero no limitados a, agentes interactivos de ADN (tales como cisplatin o doxorrubicina)); taxanos (por ejemplo, taxotere, taxol); inhibidores de la topoisomerasa II (tales como etopósido); inhibidores topoisomerasel (tales como irinotecan (o CPT-11), camptostar, o topotecan); agentes de interacción de tubulina (tales como paclitaxel, docetaxel o las epotilonas); agentes hormonales (tales como tamoxifeno); inhibidores de sintasa de timidilato (tales como 5-fluorouracil o 5-FU); antimetabolitos (tales como metotrexato); agentes alquilantes (tales como temozolomida, ciclofosfamida); inhibidores de transferasa de proteína de farnesil (tales como, SARASAR™ (4-[2-[4-[(11R)-3,10-dibromo-8-cloro-6,11-dihidro-5H-benzo[5,-6]ciclohepta[1,2-b]piridin-11 -il-]-1 -piperidinil]-2-oxoetil]-1 -piperidina-carboxamida, o SCH 66336), tipifarnib (Zarnestra® o R115777 de Janssen Pharmaceuticals), L778, 123 (un inhibidor de la transferasa de proteína de farnesil de Merck & Company, Whitehouse Station, NJ), BMS 214662 (a la transferasa de proteína de farnesil de Bristol-Myers Squibb Pharmaceuticals, Princeton, NJ); inhibidores de transducción de señal (tales como, Iressa® (desde productos
farmacéuticos Astra Zeneca, Inglaterra), Tarceva® (inhibidores de cinasa de EGFR), anticuerpos contra EGFR (por ejemplo, C225), GLEEVEC® (inhibidor de quinasa C-abl de Novartis Pharmaceuticals, East Hanover, NJ); interferones tales como, por ejemplo, INTRON® (de Merck & Company), Peg-Intron® (de Merck & Company); combinaciones de terapia hormonal; combinaciones de aromatasa; ara-C, adriamicina, citoxano, y gemcitabina.
Otros agentes anti-cáncer (también conocido como anti-neoplásicos) incluyen, pero no se limitan a mostaza de uracilo, clormetina, ifosfamida, melfalán, clorambucilo, pipobromán, trietilenmelamina, trietilentiofosforamina, busulfán, carmustina, lomustina, estreptozocina, dacarbazina, floxuridina, citarabina, 6 -mercaptopurina, 6 -tioguanina, fosfato de fludarabina, oxaliplatino, leucovirina, oxaliplatino (ELOXATIN®. de Sanofi-Synthelabo Pharmaceuticals, Francia), pentostatina, vinblastina, vincristina, vindesina, bleomicina, dactinomicina, daunorubicina, doxorubicina, epirubicina, idarubicina, mitramicina, desoxicoformicina, mitomicina-C, L-asparaginasa, tenipósido 17a-Etinilestradiol, dietilestilbestrol, testosterona, prednisona, fluoximesterona, propionato de dromostanolona, testolactona, acetato de megestrol, metilprednisolona, metiltestosterona, prednisolona, triamcinolona, clorotrianiseno, hidroxiprogesterona, aminoglutetimida, estramustina, acetato de medroxiprogesterona, leuprolida, flutamida, toremifeno, goserelina, cisplatino, carboplatino, hidroxiurea, amsacrina, procarbazina, mitotano, mitoxantrona, levamisol, Navelbeno, anastrazol, Letrazol, capecitabina, Reloxafina, Droloxafina, Hexametilmelamina, Avastin, Herceptin, Bexxar, Velcade, Zevalin, Trisenox, Xeloda, vinorelbina, Porfimer, Erbitux, liposomal, tiotepa, altretamina, melfalán, Trastuzumab, Lerozole, fulvestrant, exemestano, ifosfamida, Rituximab, C225 y Campath, 5-fluorouracilo y leucovorina, con o sin un inhibidor del receptor 5 -HT3 (por ejemplo, dolansetron, granisetrón, ondansetrón) con o sin dexametasona.
Otra realización más de la descripción es un método de tratamiento de la diabetes en un sujeto (por ejemplo, un humano) en necesidad del mismo mediante la administración al sujeto de una cantidad eficaz del compuesto o la formulación farmacéutica de la presente invención.
Otra realización más de la descripción es un método de tratamiento de la obesidad o sobrepeso en un sujeto (por ejemplo, un humano) en necesidad del mismo mediante la administración al sujeto de una cantidad eficaz del compuesto o la formulación farmacéutica de la presente invención.
Otra realización más de la descripción es un método de tratamiento de leiomiomas uterinos en un sujeto (por ejemplo, un humano) en necesidad del mismo mediante la administración al sujeto de una cantidad eficaz del compuesto o la formulación farmacéutica de la presente invención.
Otra realización más de la descripción es un método de tratamiento de infecciones microbianas en un sujeto (por ejemplo, un humano) en necesidad del mismo mediante la administración al sujeto de una cantidad eficaz del compuesto o la formulación farmacéutica de la presente invención.
Otra realización más de la descripción es un método de tratamiento de infecciones virales, incluyendo pero no limitado a infecciones causadas por HCMV, virus de influenza A, Hepatis de virus C, CVB3, virus de picorna, EBC y el virus dengue en un sujeto (por ejemplo, un ser humano) en necesidad del mismo mediante la administración al sujeto de una cantidad eficaz del compuesto o la formulación farmacéutica de la presente invención.
Si se formula como una dosis fija, tales productos de combinación emplean los compuestos de esta invención dentro del intervalo de dosis descrito en el presente documento (o como es conocido por los expertos en la técnica) y el otro agente farmacéuticamente activo o tratamiento dentro de su intervalo de dosificación. Por ejemplo, se ha encontrado el inhibidor de olomucina de CDC2 actúa sinérgicamente con agentes citotóxicos conocidos en la inducción de apoptosis (J. Cell Sci., (1995) 108, 2897). Los compuestos de la invención también pueden ser administrados secuencialmente con agentes anticáncer conocidos o citotóxicos cuando una formulación de combinación es inapropiada. En cualquier tratamiento de combinación, la invención no está limitada en la secuencia de administración; compuestos de las Fórmulas pueden administrarse ya sea antes o después de la administración del agente anticanceroso o citotóxico conocido. Por ejemplo, la actividad citotóxica de el inhibidor de quinasa dependiente de ciclina flavopiridol se ve afectado por la secuencia de administración con agentes anticancerosos. Cancer Research, (1997) 57, 3375. Tales técnicas están dentro de las habilidades de personas con habilidad en la técnica, así como los médicos tratantes.
Cualquiera de los métodos antes mencionados puede ser aumentado por la administración de fluidos (tales como agua), diuréticos de bucle, uno o más de un agente quimioterapéutico o antineoplásico, como leucovorina y fluorouracilo, y un agente quimioterapéutico adjuntivo (tales como filgrastim y eritropoyetina), o cualquier combinación de los anteriores.
Otra realización más es un método para administrar un compuesto de la presente invención a un sujeto (por ejemplo, un humano) en necesidad del mismo mediante la administración al sujeto la formulación farmacéutica de la presente invención.
Aún otra realización es un método de preparación de una formulación farmacéutica de la presente
invención al mezclar al menos un compuesto farmacéuticamente aceptable de la presente invención, y, opcionalmente, aditivos o uno o más excipientes farmacéuticamente aceptables.
Para preparar composiciones farmacéuticas de los compuestos descritos por esta invención, los vehículos aceptables farmacéuticamente inertes, pueden ser sólidos o líquidos. Las preparaciones en forma sólida incluyen polvos, comprimidos, gránulos dispersables, cápsulas, sellos y supositorios. Los polvos y comprimidos pueden comprender ingrediente activo de aproximadamente 5 a aproximadamente 95 porciento. Los vehículos sólidos adecuados son conocidos en la técnica, por ejemplo, carbonil de magnesio, estearato de magnesio, talco, azúcar o lactosa. Los comprimidos, polvos, sellos y cápsulas pueden usarse como formas de dosificación sólidas adecuadas para administración oral. Los ejemplos de vehículos farmacéuticamente aceptables y métodos de fabricación para diversas composiciones pueden encontrar en A. Gennaro (ed.), Remington Pharmaceutical Sciences, 18a Edición, (1990), Mack Publishing Co., Easton, Pa.
Las preparaciones en forma líquida incluyen soluciones, suspensiones y emulsiones. Como ejemplo se puede mencionar agua o soluciones de glicol de agua-propileno para inyección parenteral o adición de edulcorantes y opacificantes para soluciones orales, suspensiones y emulsiones. Las preparaciones en forma líquida pueden incluir también soluciones para administración intranasal.
Las preparaciones en aerosol adecuadas para la inhalación pueden incluir soluciones y sólidos en forma de polvo, que pueden estar en combinación con un vehículo farmacéuticamente aceptable, tal como un gas comprimido inerte, por ejemplo nitrógeno.
También se incluyen preparaciones en forma sólida que están destinadas a ser convertidas, poco antes del uso, a preparaciones de forma líquida para administración oral o parenteral. Tales formas líquidas incluyen soluciones, suspensiones y emulsiones.
Los compuestos de la invención también pueden administrarse por vía transdérmica. Las composiciones transdérmicas pueden tomar la forma de cremas, lociones, aerosoles y/o emulsiones y pueden incluirse en un parche transdérmico del tipo matriz o de depósito como son convencionales en la técnica para este propósito.
Los compuestos de esta invención también se pueden administrar por vía subcutánea.
Preferiblemente, el compuesto se administra por vía oral o por vía intravenosa.
Preferiblemente, la preparación farmacéutica está en una forma de dosificación unitaria. En tal forma, la preparación se subdivide en dosis unitarias de tamaño adecuado que contienen cantidades apropiadas del componente activo, por ejemplo, una cantidad eficaz para lograr el propósito deseado.
La cantidad de compuesto activo en una dosis unitaria de preparación puede variarse o ajustarse desde aproximadamente 1 mg a aproximadamente 1 00 0 mg, preferiblemente de aproximadamente 1 mg a aproximadamente 500 mg, más preferiblemente de aproximadamente 1 mg a aproximadamente 250 mg, aún más preferiblemente de aproximadamente 1 mg a aproximadamente 25 mg, según la aplicación particular.
La dosificación real empleada puede variarse dependiendo de los requerimientos del paciente y la severidad de la afección a tratar. La determinación del régimen de dosificación apropiado para una situación particular está dentro de la experiencia de la técnica. Por conveniencia, la dosificación diaria total puede ser dividida y administrada en porciones durante el día según se requiera.
La cantidad y frecuencia de administración de los compuestos de la invención y/o las sales farmacéuticamente aceptables de los mismos se regularán de acuerdo al juicio del asistente clínico considerando tales factores como edad, condición y tamaño del paciente así como la gravedad de los síntomas que están siendo tratados. Un régimen de dosificación diaria típica recomendada para la administración oral puede variar de aproximadamente 1 mg/día a aproximadamente 500 mg/día, preferiblemente 1 mg/día a 200 mg/día, en dos a cuatro dosis divididas.
Definiciones
Tal como se usa anteriormente, y en toda esta descripción, los siguientes términos, a menos que se indique otra cosa, se entenderá que tienen los siguientes significados. Si una definición no se encuentra, controla definición de la convención como es conocido para un experto en la técnica.
"Paciente" incluye tanto seres humanos como animales.
"Mamífero" significa seres humanos y otros animales mamíferos.
El término "FASN" se refiere todas las clases, tipos, subtipos, isotipos, segmentos, variantes y formas mutantes de la sintasa de ácido graso.
El término "inhibidor" se refiere a una molécula tal como un compuesto, un fármaco, un activador enzimático o una hormona que bloquea o de otro modo interfiere con una actividad biológica particular.
Los términos "cantidad eficaz" o "cantidad terapéuticamente eficaz" se refieren a una cantidad suficiente del agente para proporcionar el resultado biológico deseado. Ese resultado puede ser la reducción y/o alivio de los signos, síntomas, o causa de una enfermedad, o cualquier otra alteración deseada de un sistema biológico. Por ejemplo, una "cantidad eficaz" para uso terapéutico es la cantidad de la composición que comprende un compuesto como se describe en la presente memoria requerida para proporcionar una disminución significativa clínicamente en una enfermedad. Una cantidad "eficaz" apropiada en cualquier caso individual puede ser determinada por alguien de habilidad normal en la técnica usando experimentación de rutina. Por lo tanto, la "cantidad eficaz" de expresión generalmente se refiere a la cantidad para la que la sustancia activa tiene efectos terapéuticos.
Tal como se utiliza aquí, los términos "tratar" o "tratamiento" son sinónimos con el término "prevenir" y se entiende para indicar un aplazamiento del desarrollo de las enfermedades, la prevención del desarrollo de las enfermedades, y/o reducir la severidad de tales síntomas que se desarrollarán o que se espera que se desarrollarán. Por lo tanto, estos términos incluyen mejorar los síntomas de la enfermedad existentes, prevenir los síntomas adicionales, mejorar o prevenir las causas metabólicas subyacentes de los síntomas, la inhibición del trastorno o enfermedad, por ejemplo, detener el desarrollo del trastorno o enfermedad, aliviar el trastorno o enfermedad, causar regresión del trastorno o enfermedad, el alivio de una condición causada por la enfermedad o trastorno, o la detención o aliviar los síntomas de la enfermedad o trastorno.
Por "farmacéuticamente aceptable" o "farmacológicamente aceptable" se entiende un material que no es indeseable biológicamente o de otra manera - el material puede administrarse a un individuo sin causar efectos biológicos indeseables o interactuar de manera perjudicial con cualquiera de los componentes de la composición en el que está contenido.
"Materiales de portador" o lo que también se hace referencia como "excipientes" incluyen cualquiera de los excipientes utilizados habitualmente en farmacia y deberían ser seleccionados sobre la base de la compatibilidad y las propiedades del perfil de liberación de la forma de dosificación deseada. Materiales de soporte de ejemplo incluyen, por ejemplo, aglutinantes, agentes de suspensión, agentes de desintegración, agentes de relleno, agentes tensioactivos, solubilizantes, estabilizantes, lubricantes, agentes humectantes, diluyentes y similares. "Materiales portadores farmacéuticamente compatibles" pueden comprender, por ejemplo, acacia, gelatina, dióxido de silicio coloidal, glicerofosfato de calcio, lactato de calcio, maltodextrina, glicerina, silicato de magnesio, caseinato de sodio, lecitina de soja, cloruro sódico, fosfato tricálcico, fosfato dipotásico, estearoil lactilato de sodio, carragenina, monoglicérido, diglicérido, almidón pregelatinizado, y similares. Ver, p.ej. Hoover, John E., Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa. 1975.
Como se usa en el presente documento, el término "sujeto" incluye mamíferos y no mamíferos. Ejemplos de mamíferos incluyen, pero no se limitan a, cualquier miembro de la clase de mamíferos: seres humanos, primates no humanos tales como chimpancés, y otras especies de simios y monos; animales de granja tales como ganado vacuno, caballos, ovejas, Cabras, cerdos; animales domésticos tales como conejos, perros y gatos; animales de laboratorio incluyendo roedores, tales como ratas, ratones y cobayas, y similares. Ejemplos de no mamíferos incluyen, pero no se limitan a, aves, peces y similares. En una realización de la presente invención, el mamífero es un humano.
Como se usa en el presente documento, "alquilo" significa una cadena lineal o cadena saturada ramificada que tiene de 1 a 10 átomos de carbono. Grupos alquilo saturados representativos incluyen, pero no se limitan a, metilo, etilo, n-propilo, isopropilo, 2-metil-1 -propilo, 2-metil-2-propilo, 2-metil-1 -butilo, 3-metil-1 -butilo, 2-metil-3-butilo, 2,2-dimetil-1 -propilo, 2-metil-1 -pentilo, 3-metil-1 -pentilo, 4-metil-1 -pentilo, 2-metil-2-pentilo, 3-metil-2-pentilo, 4-metil-2-pentilo, 2,2-dimetil-1 -butilo, 3, 3-dimetil-1 -butilo, 2-etil-1 -butilo, butilo, isobutilo, t-butilo, n-pentilo, isopentilo, neopentilo, n-hexilo y similares, y grupos alquilo más largos, tales como heptilo, y octilo y similares. Un grupo alquilo puede estar insustituido o sustituido. Los grupos alquilo que contienen tres o más átomos de carbono pueden ser lineales, ramificados o ciclados. Como se usa en el presente documento, "alquilo inferior" significa un alquilo que tiene de 1 a 6 átomos de carbono.
Como se usa en este documento, un "alquenilo" incluye una cadena de hidrocarburo no ramificada o ramificada que tiene uno o más dobles enlaces en el mismo. El doble enlace de un grupo alquenilo puede ser conjugado o sin conjugar a otro grupo. Grupos alquenilo ilustrativos insaturados incluyen, pero no se limitan a grupos alquenilo (C2-C8), tales como etilenilo, vinilo, alilo, butenilo, pentenilo, hexenilo, butadienilo, pentadienilo, hexadienilo, 2-etilhexenil, 2-propil-2-butenilo, 4-(2-metil-3-buteno) pentenilo y similares. Un grupo alquenilo puede estar no sustituido o sustituido.
Como se usa en el presente documento, "alquinilo" incluye una cadena de hidrocarburo no ramificada o ramificada que tiene uno o más triplebonds en el mismo. El enlace triple de un grupo alquinilo puede ser conjugado o sin conjugar a otro grupo. Grupos alquinilo adecuados insaturados incluyen, pero no se limitan a, grupos alquinilo(C2-C6), tales como etinilo, propinilo, butinilo, pentinilo, hexinilo, metilopropinilo, 4-metil-1 -butinilo, 4-propil-2-pentinilo, 4-butil-2-hexinilo y similares. Un grupo alquinilo puede ser no sustituido o sustituido.
Los términos "trifluorometilo", "sulfonilo", y "carboxilo" incluyen CF3 , SO2 , y CO2 H, respectivamente.
El término "hidroxilo" significa un grupo OH;
El término hidroxilo alquilo o hidroxialquilo significa un grupo alquilo como se define anteriormente, en donde el grupo alquilo tiene un grupo OH dispuesto sobre el mismo.
El término "alcoxi" como se usa en este documento incluye -O-(alquilo), donde alquilo se define anteriormente.
El término "aminoalquilo", como se usa en este documento significa un grupo que tiene uno o más átomos de nitrógeno y uno o más grupos alquilo como se definió anteriormente en el nitrógeno.
"Aralquilo" o "arilalquilo" significa un grupo arilalquilo en donde se describen como anteriormente el arilo y alquilo. Alquilos preferidos comprenden un grupo alquilo inferior. Los ejemplos no limitantes de grupos aralquilo adecuados incluyen bencilo, 2-fenetilo y naftalenilmetilo. El enlace con el resto parental es a través del alquilo.
"Heteroarilalquilo" significa un resto heteroarilo como se define aquí unido a través de un resto alquilo (definido anteriormente) a un núcleo parenteral. Los ejemplos no limitantes de heteroarilos adecuados incluyen 2-piridinilmetil, quinolinilmetilo y similares.
"Heterociclilalquilo" significa un resto heterociclilo, ya definido antes unido a través de un resto alquilo (definido anteriormente) a un núcleo parenteral. Los ejemplos no limitantes de heterociclilalquilos adecuados incluyen piperidinilmetilo, piperazinlmetilo y similares.
También debe observarse que cualquier carbono así como heteroátomo con valencias no satisfechas en el texto, esquemas, ejemplos y Tablas en este documento se asume que tiene el número suficiente de átomo(s) de hidrógeno para satisfacer las valencias.
Cuando cualquier variable (por ejemplo, arilo, heterociclo, R2, etc.) aparece más de una vez en cualquier constituyente o en las Fórmulas, su definición en cada ocasión es independiente de su definición en cualquier otra aparición.
Tal como se utiliza aquí, el término "composición" pretende abarcar un producto que comprende los ingredientes especificados sin las cantidades especificadas, así como cualquier producto que resulte, directa o indirectamente, de la combinación de los ingredientes especificados en las cantidades especificadas.
El término "deuterio" como se usa en este documento significa un isótopo estable del hidrógeno con un número impar de protones y neutrones.
El término "halo" como se usa en este documento significa un sustituyente que tiene al menos un halógeno seleccionado de flúor, cloro, bromo, y yodo.
El término "ciano", como se usa en este documento significa un sustituyente que tiene un átomo de carbono unido a un átomo de nitrógeno por un triple enlace.
El término "amino" como se usa en este documento significa un sustituyente que contiene al menos un átomo de nitrógeno.
El término "(amino)alcoxi" como se usa en este documento significa un sustituyente que tiene al menos un grupo amino y al menos un grupo alcoxi.
El término "ariloxi" como se usa en este documento significa un sustituyente de la forma Ar-O- en donde Ar es un grupo arilo como se ha definido aquí.
El término "metilendioxi", como se usa en este documento significa un grupo funcional con la fórmula estructural -O-CH2-O- que está conectado a la molécula mediante dos enlaces químicos a través de los oxígenos.
Como se usa en este documento, "alcoxialquilo" se refiere a -(alquil)-O-(alquilo), en donde cada "alquilo" es
independientemente un grupo alquilo definido anteriormente.
El término "(alcoxialquilo)amino" como se usa en este documento significa un sustituyente que tiene al menos un grupo alcoxialquilo tal como se define anteriormente y al menos un grupo amino como se define anteriormente.
Tal como se utiliza aquí, el término "arilo" se refiere a un anillo monocíclico o policíclico condensado, carbociclo aromático (estructura de anillo que tiene átomos en el anillo que son todos de carbono) que tiene de 3 a 24 átomos de anillo por anillo. Los ejemplos ilustrativos de grupos arilo incluyen, pero no se limitan a los siguientes restos:
Arilos sustituidos ilustrativos incluyen:
Claims (15)
2. Un compuesto de acuerdo con la reivindicación 1, en donde el compuesto se selecciona de los enumerados en la Tabla 2-1, Tabla 2-2, y la Tabla 2-3 o una sal farmacéuticamente aceptable de los mismos,
en donde los compuestos enumerados en la Tabla 2-1 son:
5-[4-({4-[(1 -hidroxiciclopropil)carbonil]piperazin-1 -il}carbonil)fenil]-1 -(propan-2-il)-1 H-indol-3-carbonitrilo 1 -[(4-{[4-(4-cloro-3-fluorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-[(4-{[4-(6-metoxi-4-metilquinolin-2-il)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1 -[(4-{[3-metil-4-(quinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 -metil-1 H-indol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2-metoxiquinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -({4-[(4-{imidazo[1,2-a]piridin-2-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -{[4-({3-cloro-4-[1 -(trifluorometil)-1 H-indol-5-il]fenil}carbonil)piperazin-1 -il]carbonil}ciclopropan-1 -ol
1 -[(4-{[5-(1 -metil-1 H-indol-5-il)pirazin-2-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzotiazol-5-il)-2-clorofenil]carbonil }piperazin-1 -il)carbonil]ciclopropan-1 -ol
3-[3-fluoro-4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]quinolin-2-ol
5-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-1 H-indol-2-carbonitrilo
1 -[(4-{[4-(5-cloro-1,3-benzoxazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2,4-diclorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
3-[4-({4-[(oxetan-2-il)carbonil]piperazin-1-il}carbonil)fenil]quinolina
1 -[(4-{[4-(1,3-benzoxazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[2-cloro-4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 -metil-1 H-1,3-benzodiazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 H-indazol-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 -metil-1 H-indol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 -benzofuran-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 H-1,3-benzodiazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-dimetil-1 H-indazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2,1,3-benzotiadiazol-4-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(6-metoxiquinolin-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -({4-[(2-fenil-1,3-benzotiazol-6-il)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzotiazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[3-metil-4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[2-fluoro-4-(quinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(6-fluoroquinolin-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 H-1,3-benzodiazol-4-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzotiazol-5-il)-3-metilfenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzotiazol-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(4-clorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(6-cloro-1,3-benzoxazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(4-cloro-2-fluorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzotiazol-5-il)-3-clorofenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[2-fluoro-4-(7-fluoro-1 H-indol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzotiazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(4-cloroquinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(isoquinolin-1 -il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(5-cloro-1 H-1,3-benzodiazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzoxazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzoxazol-4-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[3-fluoro-4-(quinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(3,4-diclorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[6-(1 -metil-1 H-indol-5-il)piridin-3-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2,1,3-benzotiadiazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[2-fluoro-4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
5-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-1 H-indol-2-carboxamida
1 -[(4-{[4-(2-metil-2H-indazol-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-1,2-dihidroquinolin-2-ona
1 -[(4-{[4-(3-cloro-4-fluorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -{[4-({4-[2-metoxi-4-(1 H-pirazol-1 -il)fenil]fenil}carbonil)piperazin-1 -il]carbonil}ciclopropan-1 -ol
1 -[(4-{[2-cloro-4-(quinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2-metil-2H-indazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(5-cloro-2-fluorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
5-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-1 H-indol-3-carbonitrilo
5-[4-({4-[(oxetan-2-il)carbonil]piperazin-1-il}carbonil)fenil]-1 H-indol
1 -[(4-{[4-(quinolin-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
N-{3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]fenil}metanosulfonamida 1 -[(4-{[5-(1 -metil-1 H-indol-5-il)piridin-2-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-[(4-{[2-fluoro-4-(2-metoxiquinolin-3-il)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1 -({4-[(4-fenilfenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -[(4-{[4-(7-fluoro-1 H-indol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-[(4-{[2,3-difluoro-4-(6-metoxiquinolin-2-il)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol N-{3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]fenil}ciclopropanosulfonamida 1 -[(4-{[4-(3-ciclopropoxifenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2,5-diclorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
5- [3-cloro-4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-1 H-indol-3-carbonitrilo 1 -[(4-{[4-(2H-1,2,3-benzotriazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(3-cloro-2-metoxifenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-[(4-{[2,3-difluoro-4-(quinolin-2-il)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1 -[(4-{[4-(1 H-indol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
3-[3-cloro-4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-N-ciclopropilbenceno-1-sulfonamida
1 -[(4-{[3-cloro-4-(quinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(5-fluoro-1,3-benzoxazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 -metil-1 H-indol-5-il)-2-(trifluorometil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol 1 -[(4-{[4-(1 -metil-1 H-indazol-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
N-ciclopropil-3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]benzamida
1 -[(4-{[4-(4-cloro-2-metoxifenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 -metil-1 H-indazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-[(4-{[2-fluoro-4-(6-fluoroquinolin-2-il)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1- {[4-({4-[3-(ciclopropilmetoxi)fenil]fenil}carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol
2- [4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-1,3-benzoxazol-5-carbonitrilo 1 -({4-[(4-{imidazo[1,2-b]piridazin-6-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -({4-[(4-{-1 H-pirrolo[3,2-b]piridin-5-il}fenil)carbonil]piperazin-1 il}carbonil)ciclopropan-1 -ol
1 -[(4-{[3-fluoro-4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-[(4-{[2-fluoro-4-(6-metoxiquinolin-2-il)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1 -[(4-{[4-(2,3-diclorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-[(4-{[2,3-difluoro-4-(6-fluoroquinolin-2-il)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol N-ciclopropil-3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]benceno-1-sulfonamida 1 -({4-[(4-{furo[3,2-b]piridin-5-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -({4-[(4-{3-cloroimidazo[1,2-a]piridin-2-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol 1 -[(4-{[4-(1,3-benzotiazol-5-il)-3-fluorofenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
N-{3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]fenil}propano-2-sulfonamida 6- [4-({4-[(oxetan-2-il)carbonil]piperazin-1-il}carbonil)fenil]isoquinolina
N-{3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]fenil}bencenosulfonamida 1- {[4-({4-[2-metoxi-5-(trifluorometoxi)fenil]fenil}carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol 1 -[(4-{[4-(2-cloro-4-fluorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(3-clorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclobutan-1 -ol
1 -({4-[(2-cloro-4-{imidazo[1,2-a]piridin-2-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol 1 -[(4-{[4-(1 H-indol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(isoquinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclobutan-1 -ol
1 -[(4-{[4-(6-fluoro-1,3-benzoxazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
N-{3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]fenil}ciclopropanocarboxamida 1 -({4-[(4-{pirazolo[1,5-a]piridin-2-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
6-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-1,2-dihidroquinolin-2-ona
2- [4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-1,3-benzoxazol-6-carbonitrilo 1 -{[4-({3-cloro-4-[1 -(propan-2-il)-1 H-indol-5-il]fenil}carbonil)piperazin-1 -il]carbonil}ciclopropan-1 -ol 1 -[(4-{[4-(6-metoxinaftalen-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
N-(3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)ciclopentanocarboxamida 1 -(4-{4-[4-(1 H-pirazol-4-il)fenil]benzoil}piperazina-1 -carbonil)ciclopropan-1 -ol
1 -{4-[4-(1,2,3,4-tetrahidroisoquinolin-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(1,3-dimetil-1 H-indazol-5-il)-2-fluorobenzoil]piperazina-1 -carbonil}ciclopropan-1 -amina 1 -(4-{4-[4-(1 -metil-1 H-pirazol-4-il)fenil]benzoil}piperazina-1 -carbonil)ciclopropan-1 -ol
1 -[(2S)-4-[2-fluoro-4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]-2-metilpiperazina-1 -carbonil]ciclopropan-1 -ol
1 -{4-[3-cloro-4-(1 -metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil }ciclopropan-1 -ol
1 -{4-[3-cloro-4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-ol 1 -[4-(4-{pirazolo[1,5-a]piridin-6-il}benzoil)piperazina-1 -carbonil]ciclopropan-1 -ol
1 -{4-[4-(4-fluoro-2,3-dihidro-1 H-indol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol 1 -{4-[4-(3-metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[2-fluoro-4-(3-metil-1 H-indazol-7-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -[(2S)-2-metil-4-[4-(1 -metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil]ciclopropan-1 -ol
1 -{4-[3-cloro-4-(2-metil-2H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-ol
3.3.3- trifluoro-N-(3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)propano-1-sulfonamida
1 -{4-[2-fluoro-4-(1 -metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-ol
1 -{3,3-dimetil-4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol 1 -{4-[2,6-difluoro-4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol 1 -{4-[2-fluoro-4-(1 -metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclobutan-1 -amina
1 -{4-[3-cloro-4-(6-cloro-1,3-benzoxazol-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(1,3-dimetil-1 H-indazol-5-il)-2-fluorobenzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
N-(3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)ciclobutanosulfonamida 1 -{4-[4-(2,3-dihidro-1 H-indol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[3-cloro-4-(1,3-dimetil-1 H-indazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -[(2S)-2-metil-4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil]ciclopropan-1 -ol 1-{4-[2,6-difluoro-4-(2-metil-2H-indazol-6-il)benzoil]piperazina-1-carbonil}ciclopropan-1-ol
1 -(4-{4-[3-(5-amino-1,2-oxazol-3-il)fenil]-2-fluorobenzoil}piperazina-1 -carbonil)ciclopropan-1-ol
1-[(2S)-2-metil-4-[4-(2-metil-2H-indazol-6-il)benzoil]piperazina-1-carbonil]ciclopropan-1-ol
1- ciclobutil-N-(3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)metanosulfonamida 1 -{4-[2-fluoro-4-(7-fluoro-1 H-indazol-3-il)benzoil]piperazina-1-carbonil}ciclopropan-1 -ol
1 -[(2S)-4-[4-(6-cloro-1,3-benzoxazol-2-il)benzoil]-2-metilpiperazina-1 -carbonil]ciclopropan-1-ol
1 -{4-[4-(1 H-indol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(7-fluoro-1 H-indazol-3-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(7-fluoro-1,2,3,4-tetrahidroisoquinolin-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol 1 -{4-[2-fluoro-4-(2-metil-2H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-ol
1 -{4-[4-(3-amino-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(3-amino-1,2-benzoxazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(1,3-dimetil-1 H-indazol-5-il)-2-fluorobenzoil]piperazina-1 -carbonil}ciclobutan-1 -amina
1 -{4-[2-fluoro-4-(3-metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
etil N-(3-{4-[4-(4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)carbamato
1 -{4-[4-(5-cloro-2-metil-1 H-1,3-benzodiazol-7-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-ol
1 -[4-(4-{1 H,2H,3H,4H,9H-pirido[3,4-b]indol-2-il}benzoil)piperazina-1 -carbonil]ciclopropan-1 -ol
1 -[(2R,6S)-2,6-dimetil-4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil]ciclopropan-1 -ol
1 -[4-(2-cloro-4-{3-cloroimidazo[1,2-a]piridin-2-il}benzoil)piperazina-1 -carbonil]ciclopropan-1-ol
1 -{4-[4-(4-cloro-2-fluorofenil)benzoil]-3,3-dimetilpiperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[2-cloro-4-(1 -metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-ol
1 -[(2S)-4-[4-(4-cloro-2-fluorofenil)benzoil]-2-metilpiperazina-1 -carbonil]ciclopropan-1 -ol
1 -[(2S)-4-[4-(1,3-dimetil-1 H-indazol-5-il)benzoil]-2-metilpiperazina-1 -carbonil]ciclopropan-1-ol
1 -(4-{4-[3-(5-amino-1,2-oxazol-3-il)fenil]benzoil}piperazina-1 -carbonil)ciclopropan-1 -ol
2- (3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)acetonitrilo
N-(3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)ciclopentanosulfonamida 1 -[(3S)-3-metil-4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil] ciclopropan-1 -ol 1-ciclopropil-N-(3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)metanosulfonamida 1 -{4-[3-cloro-4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[2-cloro-4-(2-metil-2H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-ol
1 -{4-[2,6-difluoro-4-(1 -metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -[(3R)-3-metil-4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil]ciclopropan-1 -ol N-(6-{4-[4-(1 -hidroxiciclopropanocarbonil)piperazina-1 -carbonil]fenil}-1,2-benzoxazol-3-il)ciclopropanocarboxamida
1 -[(3R,5S)-3,5-dimetil-4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil]ciclopropan-1 -ol
propan-2-il N-(3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)carbamato 1 -{4-[4-(3-amino-1 H-indazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -[(2R)-2-metil-4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil]ciclopropan-1 -ol 3.3- difluoro-N-(3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)ciclobutano-1-carboxamida
1 -[(2S,6R)-4-[4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]-2,6-dimetilpiperazina-1 -carbonil]ciclopropan-1 -ol 1 -(4-{4-[1 -(2-hidroxietil)-1 H-1,3-benzodiazol-6-il]benzoil}piperazina-1 -carbonil)ciclopropan-1 -ol
1 -{4-[4-(1 H-1,3-benzodiazol-4-il)-2-clorobenzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(5-fluoro-2,3-dihidro-1 H-indol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -[4-(4-{3-cloroimidazo[1,2-a]piridin-2-il}-2-fluorobenzoil)piperazina-1 -carbonil] ciclopropan-1 -ol 1 -{4-[4-(4-cloro-2-fluorofenil)-2-fluorobenzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[3-cloro-4-(4-cloro-2-fluorofenil)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[2-cloro-4-(6-cloro-1,3-benzoxazol-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(5-fluoro-2,3-dihidro-1 H-isoindol-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(3-metil-1 H-indazol-4-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(6-metoxi-1,3-benzoxazol-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(3-metil-1 H-indazol-7-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -[(2R)-4-[4-(4-cloro-2-fluorofenil)benzoil]-2-metilpiperazina-1 -carbonil]ciclopropan-1 -ol
1 -(3-{4-[4-(1 -hidroxiciclopropanocarbonil)piperazina-1 -carbonil]fenil}fenil)ciclobutano-1 -carbonitrilo
1 -{4-[2-fluoro-4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1-[4-(4-{1 H,2H,3H,4H,5H-pirido[4,3-b]indol-2-il}benzoil)piperazina-1-carbonil]ciclopropan-1-ol
1 -{4-[4-(2-metil-1 H-indol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -[(2S)-2-metil-4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil]ciclopropan-1 -amina 1 -{4-[3-fluoro-4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[2-fluoro-4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil}ciclobutan-1 -amina
1 -{4-[3-fluoro-4-(1 -metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-ol
1 -[(2S)-4-[4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]-2-metilpiperazina-1 -carbonil]ciclopropan-1 -ol
1 -{4-[4-(4-fluoro-2,3 -dihidro-1 H-isoindol-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1-(4-{3-cloro-4-[3-(ciclopropanosulfonil)fenil]benzoil}piperazina-1-carbonil)ciclopropan-1-ol
1 -{4-[4-(7-fluoro-2,3-dihidro-1 H-indol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(3-ciclopropil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]-3,3-dimetilpiperazina-1 -carbonil}ciclopropan-1-ol
1 -{4-[4-(3-metil-1 H-indazol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[2-fluoro-4-(3-metil-1 H-indazol-7-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-amina
1 -{4-[4-(1 -metanosulfonil-1 H-indol-6-il)benzoil]piperazina-1 -carbonil }ciclopropan-1 -ol
1 -{4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -amina
1 -{4-[4-(2-metil-2,3-dihidro-1 H-indol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(5-fluoro-1 H-1,2,3-benzotriazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[3-cloro-4-(5-cloro-2-fluorofenil)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1- [(2S,6R)-4-[4-(4-cloro-2-fluorofenil)benzoil]-2,6-dimetilpiperazina-1-carbonil]ciclopropan-1-ol
N-(3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)oxano-4-sulfonamida
1 -{4-[4-(1 -metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -amina
1 -{4-[4-(7-metoxi-1,2,3,4-tetrahidroisoquinolin-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -(3-{3-fluoro-4-[4-(1 -hidroxiciclopropanocarbonil)piperazina-1 -carbonil]fenil}fenil)ciclopropano-1 -carbonitrilo
1 -{4-[2-fluoro-4-(2-metil-1 H-indol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(1 H-1,3-benzodiazol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -(3-{4-[4-(1 -hidroxiciclopropanocarbonil)piperazina-1 -carbonil]fenil}fenil)ciclopropano-1 -carbonitrilo
1 -{4-[2-fluoro-4-(3-metil-1 H-indazol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1-ol
1 -{4-[2-fluoro-4-(1 -metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-amina
2- {4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}-1,2,3,4-tetrahidroisoquinolina-7-carbonitrilo 1 -(4-{4-[1 -(2-hidroxietil)-1 H-1,3-benzodiazol-5-il]benzoil}piperazina-1 -carbonil)ciclopropan-1-ol
1 -[(2R)-4-[4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]-2-metilpiperazina-1 -carbonil]ciclopropan-1 -ol
1 -{4-[4-(1 H-indazol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[2-cloro-4-(5-cloro-2-fluorofenil)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(1,3 -dimetil-1 H-indazol-5-il)-3-fluorobenzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1-{4-[4-(4-cloro-2-fluorofenil)benzoil]-4,7-diazaspiro[2.5]octano-7-carbonil}ciclopropan-1-ol
1 -{4-[2-fluoro-4-(7-fluoro-1 H-indazol-3-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -amina
6-{1-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]piperidin-4-il}naftalene-2-carbonitrilo
1-(3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)imidazolidin-2-ona
1-{4-[2,6-difluoro-4-(2-metil-2H-indazol-6-il)benzoil]piperazina-1-carbonil}ciclopropan-1-amina
1,3-dimetil-5-{4-[4-(oxetano-2-carbonil)piperazina-1 -carbonil]fenil}-1 H-indazol
1 -{4-[2-fluoro-4-(2-metil-2H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-amina
1 -(4-{4-[3-(5-amino-1 H-1,2,4-triazol-3-il)fenil]benzoil}piperazina-1 -carbonil)ciclopropan-1 -ol
1 -{4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]-4,7-diazaspiro[2.5]octano-7-carbonil}ciclopropan-1 -ol 1 -{4-[4-(2-metil-1 H-indol-3-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(2-metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1- {4-[4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]-4,7-diazaspiro[2.5]octano-7-carbonil}ciclopropan-1-ol 1 -{ 4-[4-(6-fluoro-1 -metil-1 H-1,2,3-benzotriazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil}ciclobutan-1 -ol
6-cloro-4-{4-[4-(1 -hidroxiciclopropanocarbonil)piperazina-1 -carbonil]fenil}-2,3-dihidro-1 H-1,3-benzodiazol-2- ona
1 -(4-{4-[2-(hidroximetil)-1 H-1,3-benzodiazol-5-il]benzoil}piperazina-1 -carbonil)ciclopropan-1-ol
5-{4-[4-(1 -aminociclopropanocarbonil)piperazina-1 -carbonil]fenil}-1,2-benzoxazol-3-amina
1 -{4-[4-(2-ciclopropil-2H-indazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[2-fluoro-4-(5,6,7,8-tetrahidro-1,7-naftiridin-7-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(3-metil-1,2,3,4-tetrahidroisoquinolin-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol 1 -{4-[4-(2,3-dihidro-1 H-isoindol-2-il)benzoil]piperazina-1 -carbonil4-(1ciclopropan-1 -ol
1 -[(3R)-4-[4-(4-cloro-2-fluorofenil)benzoil]-3-metilpiperazina-1 -carbonil]ciclopropan-1 -ol
1 -[4-(4-{3-metil-1 H-pirazolo[3,4-b]piridin-5-il}benzoil)piperazina-1 -carbonil] ciclopropan-1 -ol
1 -{4-[4-(3-metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -amina
1 -{4-[2-fluoro-4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -amina 6-{4-[4-(1 -hidroxiciclopropanocarbonil)piperazina-1 -carbonil]fenil}-1 -metil-1 H-indazol-3-ol
1 -{4-[4-(1,2,3,4-tetrahidroquinolin-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(3-metil-1 H-indazol-7-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -amina
1-[4-(4-{4H,5H,6H,7H-tieno[3,2-c]piridin-5-il}benzoil)piperazina-1-carbonil]ciclopropan-1-ol
1 -{4-[4-(1 -metil-1 H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclobutan-1 -amina
1 -(4-{4-[3-(2-amino-1,3-tiazol-4-il)fenil]benzoil}piperazina-1 -carbonil)ciclopropan-1 -ol
1 -{4-[4-(1,3-dimetil-1 H-indazol-5-il)benzoil]piperazina-1 -carbonil}ciclobutan-1 -amina
1- (4-{4-[3-(ciclopropanosulfonil)fenil]-2-fluorobenzoil}piperazina-1-carbonil)ciclopropan-1-ol 1 -{4-[4-(6-fluoroquinazolin-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
N-(5-{4-[4-(1 -hidroxiciclopropanocarbonil)piperazina-1 -carbonil]fenil}-1,2-benzoxazol-3-il)ciclopropanocarboxamida
4-{4-[4-(1 -hidroxiciclopropanocarbonil)piperazina-1 -carbonil]fenil}-1 -metil-2,3-dihidro-1 H-indol-2-ona 1 -[(3R)-4-[4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]-3-metilpiperazina-1 -carbonil]ciclopropan-1 -ol 1 -{4-[4-(2-metil-1 H-1,3-benzodiazol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(5-cloro-2-fluorofenil)benzoil]piperazina-1 -carbonil}ciclopropan-1 -amina
1 -{4-[3-fluoro-4-(2-metil-2H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1-ol
3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}-N-metilbenzamida
1 -(4-{4-[3-(5-amino-1 H-pirazol-3-il)fenil]benzoil}piperazina-1 -carbonil)ciclopropan-1 -ol
1 -[(2S)-2-metil-4-[4-(5,6,7,8-tetrahidro-1,7-naftiridin-7-il)benzoil]piperazina-1 -carbonil]ciclopropan-1 -ol
1 -[(3S)-4-[4-(4-cloro-2-fluorofenil)benzoil]-3-metilpiperazina-1 -carbonil]ciclopropan-1 -ol
2- (3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenoxi)-N-metilacetamida 1 -{4-[4-(1 -ciclopropil-1 H-indazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -metil-5-{4-[4-(oxetano-2-carbonil)piperazina-1 -carbonil]fenil}-1 H-1,3-benzodiazol
(1 -{4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropil)metanol
1 -{4-[4-( 1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil}ciclobutan-1 -amina
1 -[4-(3-cloro-4-{3-cloroimidazo[1,2-a]piridin-2-il}benzoil)piperazina-1 -carbonil]ciclopropan-1 -ol 1 -[(2R)-2-(hidroximetil)-4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil]ciclopropan-1 -ol
1 -{4-[4-(2,3,4,5-tetrahidro-1 H-3-benzazepin-3-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol 1 -[(2S,6R)-4-[4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]-2,6-dimetilpiperazina-1 -carbonil]ciclopropan-1 -amina
1 -[(2S)-4-[4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]-2-metilpiperazina-1 -carbonil]ciclopropan-1 -amina 1 -(4-{4-[3-(5-metil-1,3,4-tiadiazol-2-il)fenil]benzoil}piperazina-1 -carbonil)ciclopropan-1 -ol
1 -{4-[4-(3-metil-2H-indazol-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
2- (3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)-2-metilpropanonitrilo 1-[(2S)-4-{4-[3-(ciclopropanosulfonil)fenil]benzoil}-2-metilpiperazina-1-carbonil]ciclopropan-1-ol 1- (3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)pirrolidin-2-ona
3- (3-{4-[4-(1-aminociclopropanocarbonil)piperazina-1-carbonil]-3-fluorofenil}fenil)-1,2-oxazol-5-amina 6-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}-N-metilpiridina-2-carboxamida 1 -[(3S)-4-[4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]-3-metilpiperazina-1 -carbonil]ciclopropan-1 -ol 4- (3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)oxano-4-carbonitrilo 1 -(4-{4-[3-(5-metil-1,2,4-oxadiazol-3-il)fenil]benzoil}piperazina-1 -carbonil)ciclopropan-1 -ol
5- (3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)-5-metilimidazolidina-2,4-diona
1 -{4-[2-fluoro-4-(2-metil-1 H-indol-1 -il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -amina
1 -{4-[4-(3-amino-1,2-benzoxazol-6-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[2-fluoro-4-(2-metil-2H-indazol-6-il)benzoil]piperazina-1 -carbonil}ciclobutan-1 -amina
2- (3-{4-[4-(1-hidroxiciclopropanocarbonil)piperazina-1-carbonil]fenil}fenil)-1 A6,2-tiazolidina-1,1-diona 1 -{4-[4-(6-cloro-1,3-benzoxazol-2-il)-3-fluorobenzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(2,3,4,5-tetrahidro-1 H-2-benzazepin-2-il)benzoil]piperazina-1 -carbonil} ciclopropan-1 -ol 1-[4-(4-{3-cloroimidazo[1,2-a]piridin-2-il}-3-fluorobenzoil)piperazina-1-carbonil]ciclopropan-1-ol 1 -(3-{4-[4-(1 -aminociclopropanocarbonil)piperazina-1 -carbonil]fenil}fenil)ciclopropano-1 -carbonitrilo 1 -{4-[3-fluoro-4-(6-fluoro-1,3-benzoxazol-2-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -{4-[4-(2-metil-2H-1,2,3-benzotriazol-5-il)benzoil]piperazina-1 -carbonil}ciclopropan-1 -ol
1 -[(3S)-3-metil-4-[4-(1 -metil-1 H-1,3-benzodiazol-5-il)benzoil]piperazina-1 -carbonil]ciclopropan-1 -amina;
en donde los compuestos enumerados en la Tabla 2-2 son:
1 -[(4-{[4-(2-fluoro-3-metoxifenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol 1-{[4-({4-[2-fluoro-3-(trifluorometoxi)fenil]fenil}carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol 1 -({4-[(4-{6-cloroimidazo[1,2-a]piridin-3-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol 1 -({4-[(4-{furo[3,2-c]piridin-4-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -[(4-{[4-metil-2-(quinolin-3-il)-1,3-tiazol-5-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol 1 -({4-[(4-{imidazo[1,2-a]pirazin-6-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
4-fluoro-3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-N-(propan-2-il)benzamida 1-{[(3S)-4-{[4-(4-cloro-2-fluorofenil)fenil]carbonil}-3-(hidroximetil)piperazin-1-il]carbonil}ciclopropan-1 -ol
1 -{[4-({4-[1 -(trifluorometil)-1 H-indol-5-il]fenil}carbonil)piperazin-1 -il]carbonil}ciclopropan-1 -ol 1 -{[4-({4-[2-(trifluorometil)imidazo[1,2-a]piridin-6-il]fenil}carbonil)piperazin-1 -il]carbonil}ciclopropan-1 -ol
1 -({4-[(4-{imidazo[1,2-a]pirimidin-7-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -[(4-{[2-metoxi-4-(quinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(5-metoxi-1 H-1,3-benzodiazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol 1 -[(4-{[4-(4-cloro-1 H-1,3-benzodiazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol 1-[(4-{[6-(2-metoxiquinolin-6-il)piridin-3-il]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1-[(4-{[5-(2-metoxiquinolin-6-il)piridin-2-il]carbonil)piperazin-1-il)carbonil]ciclopropan-1-ol
1 -[(4-{[2-(4-fluorofenil)-1,3-benzotiazol-6-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol 1 -[(4-{[4-(2-fluoro-5-metilfenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzotiazol-5-il)-2-metoxifenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol 1 -[(4-{[4-metil-2-(1 -metil-1 H-indol-5-il)-1,3-tiazol-5-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol 6-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-2,3-dihidro-1,3-benzoxazol-2-ona 1-[(4-{[5-(4-cloro-2-fluorofenil)piridin-2-il]carbonil)piperazin-1-il)carbonil]ciclopropan-1-ol
1 -[(4-{[4-(1 H-1,3-benzodiazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-{[4-({4-[2-cloro-5-(trifluorometil)fenil]fenil}carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol 1 -[(4-{[5-(quinolin-6-il)pirazin-2-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[6-(quinolin-6-il)piridin-3-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-{[4-({4-[2-fluoro-3-(trifluorometil)fenil]fenil}carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol 1 -[(4-{[4-(quinolin-6-il)-2-(trifluorometil)fenil]carbonil)piperazin-1 -il)carbonil]ciclopropan-1 -ol 1-{[4-({4-[3-fluoro-5-(trifluorometil)fenil]fenil)carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol 1 -[(4-{[4-(5-fluoro-1 H-1,3-benzodiazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol 4- fluoro-3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-N-metilbenzamida 1 -[(4-{[4-(3-metil-1,2-benzoxazol-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
5- [4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-2,3-dihidro-1,3-benzoxazol-2-ona 1 -({4-[(4-{[1,2,4]triazolo[4,3-b]piridazin-6-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol 1-{[4-({4-[7-(trifluorometil)quinolin-4-il]fenil}carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol 1-{[4-({4-[4-cloro-2-(trifluorometil)fenil]fenil)carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol 1 -{[4-({4-[1 -(propan-2-il)-1 H-indazol-5-il]fenil}carbonil)piperazin-1 -il]carbonil}ciclopropan-1 -ol 1 -[(4-{[5-(quinolin-3-il)pirazin-2-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[3-metoxi-4-(quinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(5,6-difluoro-1 H-1,3-benzodiazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol 1 -[(4-{[4-(1 -metil-1 H-1,3-benzodiazol-2-il)fenil]carbonil)piperazin-1 -il)carbonil]ciclopropan-1 -ol 1 -[(4-{[4-(2-fluoro-3-metilfenil)fenil]carbonil)piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -({4-[(4-{6-metoxiimidazo[1,2-a]piridin-2-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol 1 -[(4-{[4-(2-fluoro-4-metoxifenil)fenil]carbonil)piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[5-(quinolin-6-il)pirimidin-2-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -({4-[(4-{imidazo[1,2-a]piridin-6-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -({4-[(4-fenilfenil)carbonil]piperazin-1 -il}carbonil)ciclobutan-1-ol
1-{[4-({4-[4-fluoro-2-(trifluorometil)fenil]fenil}carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol 1 -[(4-{[4-(3-fluoro-4-metilfenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2,1,3-benzoxadiazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[2-metoxi-4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-[(4-{[5-(4-cloro-2-fluorofenil)pirimidin-2-il]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol; y
en donde los compuestos enumerados en la Tabla 2-3 son:
1 -{[4-({4-[6-(trifluorometil)piridin-3-il]fenil}carbonil)piperazin-1 -il]carbonil} ciclopropan-1 -ol
1 -{[4-({4-[2-fluoro-3-(propan-2-iloxi)fenil]fenil}carbonil)piperazin-1 -il]carbonil} ciclopropan-1 -ol 1 -({4-[(4-{6-fluoroifnidazo[1,2-a]piridin-2-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol 1 -[(4-{[6-(4-fluorofenil)imidazo[1,2-a]piridin-2-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol 1 -[(4-{[4-(2-cloro-5-fluorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2,3-difluorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(3-fluoro-2-metoxifenil)fenil]carbonil)piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,5-naftiridin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2-fluoro-5-metoxifenil)fenil]carbonil)piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-{[(2S,,5R)-4-{[4-(isoquinolin-6-il)fenil]carbonil}-2,5-dimetilpiperazin-1-il]carbonil}ciclopropan-1-ol
1 -{[4-({6-fenilimidazo[1,2-a]piridin-2-il}carbonil)piperazin-1 -il]carbonil}ciclopropan-1 -ol
1-[(4-{[4-(4,5-difluoro-2-metoxifenil)fenil]carbonil)piperazin-1-il)carbonil]ciclopropan-1-ol
1- {[(2S)-4-{[4-(4-cloro-2-fluorofenil)fenil]carbonil}-2-(hidroximetil)piperazin-1-il]carbonil}ciclopropan-1 -ol
1 -({4-[(4-fenoxifenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
5-fluoro-2-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]benzonitrilo
2- metoxi-2-metil-1 -{4-[(4-fenilfenil)carbonil]piperazin-1 -il}propan-1 -ona
3,3,3-trifluoro-2-hidroxi-2-metil-1 -{4-[(4-fenilfenil)carbonil]piperazin-1 -il}propan-1 -ona
1 -[(4-{[4-(2-cloro-4-metoxifenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
2-hidroxi-2-metil-1 -{4-[(4-fenilfenil)carbonil]piperazin-1 -il}propan-1 -ona
1 -[(4-{[4-(4-metilfenil)fenil]carbonil)piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-{[4-({4-[2-cloro-5-(hidroximetil)fenil]fenil}carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol
1 -[(4-{[2-(1,3-benzotiazol-5-il)-4-metil-1,3-tiazol-5-il]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -({4-[(3-fenoxifenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 [(4-{[4-(3-metilfenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(3-metoxipiridin-4-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -({4-[(4-fenilfenil)carbonil]piperazin-1 -il}carbonil)ciclopentan-1 -ol
1 -[(4-{[4-(1 -metil-1 H-indazol-7-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(6-metilpiridin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
(2S)-2-hidroxi-1 -{4-[(4-fenilfenil)carbonil]piperazin-1 -il}propan-1 -ona
1-{[4-({4-[5-cloro-2-(propan-2-iloxi)fenil]fenil}carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol
1- [(4-{[6-(4-cloro-2-fluorofenil)piridin-3-il]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1 -[(4-{[4-(5-fluoropiridin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2,5-difluorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
2- hidroxi-1 -{4-[(4-fenilfenil)carbonil]piperazin-1 -il}etan-1 -ona
1 -[(4-{[4-(2-fluoro-4-metilfenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2,6-dimetoxipiridin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-[(4-{[4-(2,4-dicloro-3-metoxifenil)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1 -[(4-{[4-(5-fluoro-2-metilfenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol.
3. Un compuesto de acuerdo con la reivindicación 2, en donde el compuesto se selecciona de los enumerados en la Tabla 2-1 y la Tabla 2-2 o una sal farmacéuticamente aceptable de los mismos.
4. Un compuesto de acuerdo con la reivindicación 2, en donde el compuesto se selecciona de los enumerados en la Tabla 2-1 o una sal farmacéuticamente aceptable de los mismos.
5. Un compuesto de acuerdo con cualquier reivindicación anterior, en donde el compuesto se selecciona de los enumerados en la Tabla 3-1 y la Tabla 3-2 o una sal farmacéuticamente aceptable de los mismos,
en donde los compuestos enumerados en la Tabla 3-1 son:
1 -[(4-{[4-(1 -benzofuran-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
5-[4-({4-[(1 -hidroxiciclopropil)carbonil]piperazin-1 -il}carbonil)fenil]-1 H-indol-2-carbonitrilo
1 -({4-[(4-{imidazo[1,2-b]piridazin-6-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -[(4-{[4-(1 H-indol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 -metil-1 H-1,3-benzodiazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
5-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-1 H-indol-3-carbonitrilo
1 -[(4-{[4-(1,3-benzotiazol-5-il)-3-clorofenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1- [(4-{[2-fluoro-4-(6-metoxiquinolin-2-il)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1 -[(4-{[2-cloro-4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[3-metil-4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[2-fluoro-4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[3-cloro-4-(quinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(6-metoxinaftalen-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[2-fluoro-4-(7-fluoro-1 H-indol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -({4-[(4-{pirazolo[1,5-a]piridin-2-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -[(4-{[3-fluoro-4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 -metil-1 H-indazol-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[2-fluoro-4-(quinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil}ciclopropan-1 -ol
1 -[(4-{[4-(2-metil-2H-indazol-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(quinolin-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
2- [4-({4-[(1 -hidroxiciclopropil)carbonil]piperazin-1 -il}carbonil)fenil]-1,3-benzoxazol-6-carbonitrilo
1 -[(4-{[4-(1,3-benzotiazol-6-il)fenil]carbonil)piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzotiazol-5-il)fenil]carbonil)piperazin-1 -il)carbonil]ciclopropan-1 -ol
N-{3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]fenil}ciclopropanosulfonamida
1 -({4-[(4-{1 H-pirrolo[3,2-b]piridin-5-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -[(4-{[4-(1 H-indazol-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-[(4-{[2-fluoro-4-(2-metoxiquinolin-3-il)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1 -{[4-({3-cloro-4-[1 -(trifluorometil)-1 H-indol-5-il]fenil}carbonil)piperazin-1 -il]carbonil}ciclopropan-1 -ol
1-[(4-{[2,3-difluoro-4-(quinolin-2-il)fenil]carbonil)piperazin-1-il)carbonil]ciclopropan-1-ol
1 -[(4-{[4-(1,3-benzotiazol-5-il)-3-metilfenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-dimetil-1 H-indazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil] ciclopropan-1 -ol
1 -[(4-{[3-metil-4-(quinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 -metil-1 H-indol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -{[4-({4-[1 -(trifluorometil)-1 H-indol-5-il]fenil}carbonil)piperazin-1 -il]carbonil}ciclopropan-1 -ol
1 -[(4-{[4-(6-cloro-1,3-benzoxazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(6-metoxiquinolin-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
N-{3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]fenil}bencenosulfonamida
1-{[4-({4-[2-metoxi-5-(trifluorometoxi)fenil]fenil}carbonil)piperazin-1-il]carbonil}ciclopropan-1-ol
1 -[(4-{[4-(6-fluoro-1,3-benzoxazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
N-{3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]fenil}propano-2-sulfonamida
1 -[(4-{[4-(isoquinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclobutan-1 -ol
1-[(4-{[4-(2,1,3-benzotiadiazol-5-il)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1 -[(4-{[4-(1,3-benzoxazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2-metil-2H-indazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
5- [3-cloro-4-({4-[(1 -hidroxiciclopropil)carbonil]piperazin-1 -il}carbonil)fenil]-1 H-indol-3-carbonitrilo
1 -[(4-{[4-(1,3-benzotiazol-5-il)-3-fluorofenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(5-fluoro-1,3-benzoxazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(5-cloro-1,3-benzoxazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzotiazol-5-il)-2-clorofenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(3-cloro-2-metoxifenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1-[(4-{[4-(6-metoxi-4-metilquinolin-2-il)fenil]carbonil}piperazin-1-il)carbonil]ciclopropan-1-ol
1 -[(4-{[4-(2-metoxiquinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 H-1,3-benzodiazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -({4-[(2-cloro-4-{imidazo[1,2-a]piridin-2-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -[(4-{[5-(1 -metil-1 H-indol-5-il)piridin-2-il]carbonil}piperazin-1 -il)carbonil] ciclopropan-1 -ol
6- [4-({4-[(oxetan-2-il)carbonil]piperazin-1-il)carbonil)fenil]isoquinolina
1 -({4-[(4-{imidazo[1,2-a]piridin-2-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -[(4-{[4-(quinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclobutan-1 -ol
1 -[(4-{[4-(isoquinolin-1 -il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -({4-[(4-{furo[3,2-b]piridin-5-il}fenil)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -[(4-{[4-(4-cloro-2-fluorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(5-cloro-2-fluorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzoxazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1 H-1,3-benzodiazol-4-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(2H-1,2,3-benzotriazol-5-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(4-cloroquinolin-3-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
3-[3-fluoro-4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]quinolin-2-ol
3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-1,2-dihidroquinolin-2-ona
N-{3-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]fenil}metanosulfonamida
6-[4-({4-[(1-hidroxiciclopropil)carbonil]piperazin-1-il}carbonil)fenil]-1,2-dihidroquinolin-2-ona
1 -[(4-{[4-(1 -metil-1 H-indol-5-il)-2-(trifluorometil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -[(4-{[4-(1,3-benzotiazol-2-il)fenil]carbonil)piperazin-1 -il)carbonil]ciclopropan-1 -ol
5-[4-({4-[(1 -hidroxiciclopropil)carbonil]piperazin-1 -il}carbonil)fenil]-1 -(propan-2-il)-1 H-indol-3-carbonitrilo
1 -[(4-{[2-cloro-4-(quinolin-6-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol
1 -({4-[(2-fenil-1,3-benzotiazol-6-il)carbonil]piperazin-1 -il}carbonil)ciclopropan-1 -ol
1 -[(4-{[4-(1 H-1,3-benzodiazol-2-il)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol; y
en donde los compuestos enumerados en la Tabla 3-2 son:
1 -{[4-({3-cloro-4-[1 -(propan-2-il)-1 H-indol-5-il]fenil}carbonil)piperazin-1 -il]carbonil}ciclopropan-1 -ol
1 -{[4-({4-[2-metoxi-4-(1 H-pirazol-1 -il)fenil]fenil}carbonil)piperazin-1 -il]carbonil}ciclopropan-1 -ol
5-[4-({4-[(oxetan-2-il)carbonil]piperazin-1-il}carbonil)fenil]-1 H-indol
3-[4-({4-[(oxetan-2-il)carbonil]piperazin-1-il}carbonil)fenil]quinolina
1 -[(4-{[4-(2,4-diclorofenil)fenil]carbonil}piperazin-1 -il)carbonil]ciclopropan-1 -ol.
6. Un compuesto de acuerdo con la reivindicación 5, en donde el compuesto se selecciona de los enumerados en la Tabla 3-1, o una sal farmacéuticamente aceptable de los mismos.
11. Una composición farmacéutica que comprende cantidades terapéuticamente eficaces de por lo menos un compuesto de cualquiera de las reivindicaciones 1 a 10, o una sal farmacéuticamente aceptable de los mismos, y por lo menos un portador farmacéuticamente aceptable.
12. Por lo menos un compuesto de cualquiera de las reivindicaciones 1 a 10, o una sal farmacéuticamente aceptable del mismo, para su uso en un método para inhibir la sintasa de ácidos grasos (“FASN”) en un paciente administrando cantidades terapéuticamente eficaces de dicho por lo menos un compuesto, o una sal farmacéuticamente aceptable del mismo.
13. Una composición farmacéutica de la reivindicación 11, para su uso en un método para inhibir FASN en un paciente administrando cantidades terapéuticamente eficaces de dicha composición farmacéutica.
14. La composición farmacéutica de la reivindicación 11, que comprende además cantidades terapéuticamente eficaces de uno o más agentes terapéuticos adicionales.
15. La composición farmacéutica de la reivindicación 14, en donde dichos uno o más agentes terapéuticos adicionales son seleccionados de grupo que consiste de agente citotóxico, cisplatino, doxorrubicina, taxotere, taxol, etopósido, irinotecán, camptostar, topotecán, paclitaxel, docetaxel, las epotilonas, tamoxifeno, 5-fluorouracilo, metotrexato, temozolomida, ciclofosfamida, s Ch 66336, tipifarnib (Zarnestra®), R115777, L778,123, BMS 214662, Iressa®, Tarceva®, C225, GLEEVEC®, Intron®, Peg-Intron®, combinaciones de aromatasa, ara-C, adriamicina, citoxano, gemcitabina, mostaza de uracilo, clormetina, ifosfamida, melfalán, clorambucilo, pipobromán, trietilenmelamina, trietilentiofosforamina, busulfán, carmustina, lomustina, estreptozocina, dacarbazina, floxuridina, citarabina, 6-mercaptopurina, 6-tioguanina, fosfato de fludarabina, leucovirina, oxaliplatino (ELOXATIN®), pentostatina, vinblastina, vincristina, vindesina, bleomicina, dactinomicina, daunorubicina, epirubicina, idarubicina, Mithramicyn™, desoxicoformicina, mitomicina-C, L-asparaginasa, tenipósido 17a-etinilestradiol, dietilestilbestrol, testosterona, prednisona, fluoximesterona, propionato de dromostanolona, testolactona, acetato de megestrol, metilprednisolona, metiltestosterona, prednisolona, triamcinolona, clorotrianiseno, hidroxiprogesterona, aminoglutetimida, estramustina, acetato de medroxiprogesterona, leuprolida, flutamida, toremifeno, goserelina, carboplatino, hidroxiurea, amsacrina, procarbazina, mitotano, mitoxantrona, levamisol, navelbeno, anastrazol, letrazol, capecitabina, reloxafina, droloxafina, hexametilmelamina, avastin, herceptin, bexxar, velcade, zevalin, trisenox, xeloda, vinorelbina, porfimer, erbitux, liposomal, tiotepa, altretamina, melfalán, trastuzumab, lerozol, fulvestrant, exemestano, rituximab, C225, campath, leucovorina, dexametasona, bicalutamida, carboplatino, clorambucilo, cisplatino, letrozol, megestrol, y valrubicina.
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