JP4616831B2 - Akt活性の阻害剤 - Google Patents
Akt活性の阻害剤 Download PDFInfo
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- JP4616831B2 JP4616831B2 JP2006513160A JP2006513160A JP4616831B2 JP 4616831 B2 JP4616831 B2 JP 4616831B2 JP 2006513160 A JP2006513160 A JP 2006513160A JP 2006513160 A JP2006513160 A JP 2006513160A JP 4616831 B2 JP4616831 B2 JP 4616831B2
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- Prior art keywords
- phenyl
- piperidin
- methyl
- pyridin
- tfa
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 108091008611 Protein Kinase B Proteins 0.000 title abstract description 60
- 230000000694 effects Effects 0.000 title abstract description 20
- 239000003112 inhibitor Substances 0.000 title description 63
- 150000001875 compounds Chemical class 0.000 claims abstract description 171
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 8
- -1 pyridin-1-yl Chemical group 0.000 claims description 82
- 125000000623 heterocyclic group Chemical group 0.000 claims description 66
- 150000003839 salts Chemical class 0.000 claims description 61
- 125000003118 aryl group Chemical group 0.000 claims description 59
- 125000001424 substituent group Chemical group 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 125000000304 alkynyl group Chemical group 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 12
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 11
- SKBAKRCESRVMPS-UHFFFAOYSA-N 1-[1-[[4-[5-(1,2,4-oxadiazol-3-yl)-3-phenylpyridin-2-yl]phenyl]methyl]piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=2C(N)=NC=NC=2N1C(CC1)CCN1CC(C=C1)=CC=C1C1=NC=C(C2=NOC=N2)C=C1C1=CC=CC=C1 SKBAKRCESRVMPS-UHFFFAOYSA-N 0.000 claims description 10
- INUGOQWCVGGZKS-UHFFFAOYSA-N 3-[1-[[4-[3-phenyl-5-(2h-tetrazol-5-yl)pyridin-2-yl]phenyl]methyl]piperidin-4-yl]-1h-benzimidazol-2-one Chemical compound O=C1NC2=CC=CC=C2N1C(CC1)CCN1CC(C=C1)=CC=C1C1=NC=C(C=2NN=NN=2)C=C1C1=CC=CC=C1 INUGOQWCVGGZKS-UHFFFAOYSA-N 0.000 claims description 10
- BHRZESZXIYBZTH-UHFFFAOYSA-N 5-[5-phenyl-6-[4-[[4-(3-pyridin-4-yl-1h-pyrazol-5-yl)piperidin-1-yl]methyl]phenyl]pyridin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(C2=NNC(=C2)C=2C=CN=CC=2)CC1 BHRZESZXIYBZTH-UHFFFAOYSA-N 0.000 claims description 10
- UGUQLQRPEDJAPE-UHFFFAOYSA-N 5-[6-[4-[[4-(4-aminopyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(N2C3=NC=NC(N)=C3C=N2)CC1 UGUQLQRPEDJAPE-UHFFFAOYSA-N 0.000 claims description 10
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- XXODKQJLCQAKIT-UHFFFAOYSA-N 1-[1-[[4-(3-phenyl-5-pyrimidin-2-ylpyridin-2-yl)phenyl]methyl]piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=2C(N)=NC=NC=2N1C(CC1)CCN1CC(C=C1)=CC=C1C1=NC=C(C=2N=CC=CN=2)C=C1C1=CC=CC=C1 XXODKQJLCQAKIT-UHFFFAOYSA-N 0.000 claims description 7
- QCVUEIXWZKWEDT-UHFFFAOYSA-N 2-(methylamino)-6-[4-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound C1=C(C#N)C(NC)=NC(C=2C=CC(CN3CCC(CC3)N3C(NC4=CC=CC=C43)=O)=CC=2)=C1C1=CC=CC=C1 QCVUEIXWZKWEDT-UHFFFAOYSA-N 0.000 claims description 7
- QRHBGWSUCWMLHY-UHFFFAOYSA-N 2-[2-(dimethylamino)ethoxy]-6-[4-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound C1=C(C#N)C(OCCN(C)C)=NC(C=2C=CC(CN3CCC(CC3)N3C(NC4=CC=CC=C43)=O)=CC=2)=C1C1=CC=CC=C1 QRHBGWSUCWMLHY-UHFFFAOYSA-N 0.000 claims description 7
- ZHBADLSWYUZCCZ-UHFFFAOYSA-N 6-fluoro-2-[1-[[4-[3-phenyl-5-(2h-triazol-4-yl)pyridin-2-yl]phenyl]methyl]piperidin-4-yl]-1h-benzimidazole Chemical compound N1C2=CC(F)=CC=C2N=C1C(CC1)CCN1CC(C=C1)=CC=C1C1=NC=C(C=2N=NNC=2)C=C1C1=CC=CC=C1 ZHBADLSWYUZCCZ-UHFFFAOYSA-N 0.000 claims description 7
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- LUUUTKDUZFFBKA-UHFFFAOYSA-N 2-chloro-6-[4-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound C1=C(C#N)C(Cl)=NC(C=2C=CC(CN3CCC(CC3)N3C(NC4=CC=CC=C43)=O)=CC=2)=C1C1=CC=CC=C1 LUUUTKDUZFFBKA-UHFFFAOYSA-N 0.000 claims description 6
- GAUFULRKDWCITD-UHFFFAOYSA-N 6-[4-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound O=C1NC2=CC=CC=C2N1C(CC1)CCN1CC(C=C1)=CC=C1C1=NC=C(C#N)C=C1C1=CC=CC=C1 GAUFULRKDWCITD-UHFFFAOYSA-N 0.000 claims description 6
- UQGNXQSLAYQOLC-RUZDIDTESA-N 1-[(3r)-1-[[4-[5-(5-amino-1,3,4-thiadiazol-2-yl)-3-phenylpyridin-2-yl]phenyl]methyl]pyrrolidin-3-yl]-3-pyridin-4-ylurea Chemical compound S1C(N)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1C[C@H](NC(=O)NC=2C=CN=CC=2)CC1 UQGNXQSLAYQOLC-RUZDIDTESA-N 0.000 claims description 5
- FLLYSDWXMXBDLY-UHFFFAOYSA-N 1-[1-[[4-[5-(5-amino-1,3,4-thiadiazol-2-yl)-3-phenylpyridin-2-yl]phenyl]methyl]piperidin-4-yl]-3h-imidazo[4,5-b]pyridin-2-one Chemical compound S1C(N)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(N2C(NC3=NC=CC=C32)=O)CC1 FLLYSDWXMXBDLY-UHFFFAOYSA-N 0.000 claims description 5
- AKMOXQIBLYYHGO-UHFFFAOYSA-N 1-[3-cyano-6-[4-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridin-2-yl]-3-ethylurea Chemical compound C1=C(C#N)C(NC(=O)NCC)=NC(C=2C=CC(CN3CCC(CC3)N3C(NC4=CC=CC=C43)=O)=CC=2)=C1C1=CC=CC=C1 AKMOXQIBLYYHGO-UHFFFAOYSA-N 0.000 claims description 5
- SGVSAMKSKMVUHO-UHFFFAOYSA-N 1-ethyl-3-[5-[5-phenyl-6-[4-[[4-(3-pyridin-2-yl-1h-pyrazol-5-yl)piperidin-1-yl]methyl]phenyl]pyridin-3-yl]-1,3,4-thiadiazol-2-yl]urea Chemical compound S1C(NC(=O)NCC)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(C2=NNC(=C2)C=2N=CC=CC=2)CC1 SGVSAMKSKMVUHO-UHFFFAOYSA-N 0.000 claims description 5
- DPPPRYLSFOBUGE-UHFFFAOYSA-N 2-(2-morpholin-4-ylethoxy)-6-[4-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound O=C1NC2=CC=CC=C2N1C(CC1)CCN1CC(C=C1)=CC=C1C(C(=CC=1C#N)C=2C=CC=CC=2)=NC=1OCCN1CCOCC1 DPPPRYLSFOBUGE-UHFFFAOYSA-N 0.000 claims description 5
- ABLWOEXCHYGJNW-UHFFFAOYSA-N 2-(2-morpholin-4-ylethylamino)-6-[4-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound O=C1NC2=CC=CC=C2N1C(CC1)CCN1CC(C=C1)=CC=C1C(C(=CC=1C#N)C=2C=CC=CC=2)=NC=1NCCN1CCOCC1 ABLWOEXCHYGJNW-UHFFFAOYSA-N 0.000 claims description 5
- IIHHZZWBKMCFLK-UHFFFAOYSA-N 2-(dimethylamino)-6-[4-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound C1=C(C#N)C(N(C)C)=NC(C=2C=CC(CN3CCC(CC3)N3C(NC4=CC=CC=C43)=O)=CC=2)=C1C1=CC=CC=C1 IIHHZZWBKMCFLK-UHFFFAOYSA-N 0.000 claims description 5
- JNDZNIOMQPDXQW-UHFFFAOYSA-N 2-[2-(dimethylamino)ethylamino]-6-[4-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound C1=C(C#N)C(NCCN(C)C)=NC(C=2C=CC(CN3CCC(CC3)N3C(NC4=CC=CC=C43)=O)=CC=2)=C1C1=CC=CC=C1 JNDZNIOMQPDXQW-UHFFFAOYSA-N 0.000 claims description 5
- UHNYXVFNNZDLHF-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]-6-[4-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound C1CN(CCO)CCN1C1=NC(C=2C=CC(CN3CCC(CC3)N3C(NC4=CC=CC=C43)=O)=CC=2)=C(C=2C=CC=CC=2)C=C1C#N UHNYXVFNNZDLHF-UHFFFAOYSA-N 0.000 claims description 5
- ROJFYXCORULCGL-UHFFFAOYSA-N 2-ethoxy-6-[4-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound C1=C(C#N)C(OCC)=NC(C=2C=CC(CN3CCC(CC3)N3C(NC4=CC=CC=C43)=O)=CC=2)=C1C1=CC=CC=C1 ROJFYXCORULCGL-UHFFFAOYSA-N 0.000 claims description 5
- AKHDKRSBRGGAGE-UHFFFAOYSA-N 5-[1-[[4-[5-(5-amino-1,3,4-thiadiazol-2-yl)-3-phenylpyridin-2-yl]phenyl]methyl]piperidin-4-yl]-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C1CCN(CC=2C=CC(=CC=2)C=2C(=CC(=CN=2)C=2SC(N)=NN=2)C=2C=CC=CC=2)CC1 AKHDKRSBRGGAGE-UHFFFAOYSA-N 0.000 claims description 5
- XWBOPVSUCCBXHQ-UHFFFAOYSA-N 5-[5-phenyl-6-[4-[(4-pyrazolo[3,4-b]pyridin-1-ylpiperidin-1-yl)methyl]phenyl]pyridin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(N2C3=NC=CC=C3C=N2)CC1 XWBOPVSUCCBXHQ-UHFFFAOYSA-N 0.000 claims description 5
- IOTHDTICZAKUMW-UHFFFAOYSA-N 5-[5-phenyl-6-[4-[[4-(3-pyridin-2-yl-1h-pyrazol-5-yl)piperidin-1-yl]methyl]phenyl]pyridin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(C2=NNC(=C2)C=2N=CC=CC=2)CC1 IOTHDTICZAKUMW-UHFFFAOYSA-N 0.000 claims description 5
- JEBHQRKVJAFLBR-UHFFFAOYSA-N 5-[5-phenyl-6-[4-[[4-(4-pyrazin-2-ylpyrazol-1-yl)piperidin-1-yl]methyl]phenyl]pyridin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(N2N=CC(=C2)C=2N=CC=NC=2)CC1 JEBHQRKVJAFLBR-UHFFFAOYSA-N 0.000 claims description 5
- FHJUGOOSLGTUSW-UHFFFAOYSA-N 5-[5-phenyl-6-[4-[[4-(4-pyridin-2-ylpyrazol-1-yl)piperidin-1-yl]methyl]phenyl]pyridin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(N2N=CC(=C2)C=2N=CC=CC=2)CC1 FHJUGOOSLGTUSW-UHFFFAOYSA-N 0.000 claims description 5
- VSMLLGUVRXYZHS-UHFFFAOYSA-N 5-[5-phenyl-6-[4-[[4-(4-pyrimidin-2-ylpyrazol-1-yl)piperidin-1-yl]methyl]phenyl]pyridin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(N2N=CC(=C2)C=2N=CC=CN=2)CC1 VSMLLGUVRXYZHS-UHFFFAOYSA-N 0.000 claims description 5
- RTJIFUCOACUUGD-UHFFFAOYSA-N 5-[5-phenyl-6-[4-[[4-[4-(1,3-thiazol-4-yl)pyrazol-1-yl]piperidin-1-yl]methyl]phenyl]pyridin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(N2N=CC(=C2)C=2N=CSC=2)CC1 RTJIFUCOACUUGD-UHFFFAOYSA-N 0.000 claims description 5
- PWAUOLDGQBXWQW-UHFFFAOYSA-N 5-phenyl-6-[4-[[4-(3-pyridin-4-yl-1h-pyrazol-5-yl)piperidin-1-yl]methyl]phenyl]pyridine-3-carbonitrile Chemical compound C=1C=CC=CC=1C1=CC(C#N)=CN=C1C(C=C1)=CC=C1CN(CC1)CCC1C(=NN1)C=C1C1=CC=NC=C1 PWAUOLDGQBXWQW-UHFFFAOYSA-N 0.000 claims description 5
- LCXALGPBRIZAIK-UHFFFAOYSA-N 6-fluoro-2-[1-[[4-[5-(1h-imidazol-2-yl)-3-phenylpyridin-2-yl]phenyl]methyl]piperidin-4-yl]-1h-benzimidazole Chemical compound N1C2=CC(F)=CC=C2N=C1C(CC1)CCN1CC(C=C1)=CC=C1C1=NC=C(C=2NC=CN=2)C=C1C1=CC=CC=C1 LCXALGPBRIZAIK-UHFFFAOYSA-N 0.000 claims description 5
- KSZMTQBTJXCFKF-UHFFFAOYSA-N 6-fluoro-2-[1-[[4-[5-(5-methyl-1h-imidazol-2-yl)-3-phenylpyridin-2-yl]phenyl]methyl]piperidin-4-yl]-1h-benzimidazole Chemical compound N1C(C)=CN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(C=2NC3=CC(F)=CC=C3N=2)CC1 KSZMTQBTJXCFKF-UHFFFAOYSA-N 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- GJTDWTDYXNLZFY-UHFFFAOYSA-N 1-[1-[[4-(3-phenyl-5-pyridin-2-ylpyridin-2-yl)phenyl]methyl]piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=2C(N)=NC=NC=2N1C(CC1)CCN1CC(C=C1)=CC=C1C1=NC=C(C=2N=CC=CC=2)C=C1C1=CC=CC=C1 GJTDWTDYXNLZFY-UHFFFAOYSA-N 0.000 claims description 4
- WPQHLIPHCCADRU-UHFFFAOYSA-N 1-[1-[[4-[3-phenyl-5-(1h-1,2,4-triazol-5-yl)pyridin-2-yl]phenyl]methyl]piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=2C(N)=NC=NC=2N1C(CC1)CCN1CC(C=C1)=CC=C1C1=NC=C(C=2NN=CN=2)C=C1C1=CC=CC=C1 WPQHLIPHCCADRU-UHFFFAOYSA-N 0.000 claims description 4
- BUDCDMBOPKDELH-UHFFFAOYSA-N 1-[1-[[4-[3-phenyl-5-(2h-tetrazol-5-yl)pyridin-2-yl]phenyl]methyl]piperidin-4-yl]benzimidazole Chemical compound C1CC(N2C3=CC=CC=C3N=C2)CCN1CC(C=C1)=CC=C1C1=NC=C(C=2NN=NN=2)C=C1C1=CC=CC=C1 BUDCDMBOPKDELH-UHFFFAOYSA-N 0.000 claims description 4
- PUURNEUEBMDYQT-JOCHJYFZSA-N 1-ethyl-3-[(3r)-1-[[4-[3-phenyl-5-(2h-tetrazol-5-yl)pyridin-2-yl]phenyl]methyl]pyrrolidin-3-yl]urea Chemical compound C1[C@H](NC(=O)NCC)CCN1CC1=CC=C(C=2C(=CC(=CN=2)C2=NNN=N2)C=2C=CC=CC=2)C=C1 PUURNEUEBMDYQT-JOCHJYFZSA-N 0.000 claims description 4
- HYOQFFBLOLYSDU-UHFFFAOYSA-N 2-[1-[[4-[3-phenyl-5-(2h-tetrazol-5-yl)pyridin-2-yl]phenyl]methyl]piperidin-4-yl]-1h-benzimidazole Chemical compound C1CC(C=2NC3=CC=CC=C3N=2)CCN1CC(C=C1)=CC=C1C1=NC=C(C=2NN=NN=2)C=C1C1=CC=CC=C1 HYOQFFBLOLYSDU-UHFFFAOYSA-N 0.000 claims description 4
- WFJPPVPRGHMBFH-UHFFFAOYSA-N 2-[6-[4-[[4-(6-fluoro-1h-benzimidazol-2-yl)piperidin-1-yl]methyl]phenyl]-5-phenylpyridin-3-yl]-4,5-dihydro-1h-imidazole-5-carboxamide Chemical compound N1C(C(=O)N)CN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(C=2NC3=CC(F)=CC=C3N=2)CC1 WFJPPVPRGHMBFH-UHFFFAOYSA-N 0.000 claims description 4
- NKDVYWMSYQSYCC-UHFFFAOYSA-N 4-chloro-n-[1-[[4-(5-cyano-3-phenylpyridin-2-yl)phenyl]methyl]piperidin-4-yl]-n-cyclopropylbenzenesulfonamide Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N(C1CCN(CC=2C=CC(=CC=2)C=2C(=CC(=CN=2)C#N)C=2C=CC=CC=2)CC1)C1CC1 NKDVYWMSYQSYCC-UHFFFAOYSA-N 0.000 claims description 4
- QMWBUFQWRWCLHE-UHFFFAOYSA-N 5-[5-phenyl-6-[4-[[4-(3-pyridin-2-yl-1h-1,2,4-triazol-5-yl)piperidin-1-yl]methyl]phenyl]pyridin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C(C=C1C=2C=CC=CC=2)=CN=C1C(C=C1)=CC=C1CN1CCC(C=2NC(=NN=2)C=2N=CC=CC=2)CC1 QMWBUFQWRWCLHE-UHFFFAOYSA-N 0.000 claims description 4
- VJVCNMHTTOTNFL-UHFFFAOYSA-N 5-phenyl-6-[4-[(4-phenylpiperidin-1-yl)methyl]phenyl]pyridine-3-carbonitrile Chemical compound C=1C=CC=CC=1C1=CC(C#N)=CN=C1C(C=C1)=CC=C1CN(CC1)CCC1C1=CC=CC=C1 VJVCNMHTTOTNFL-UHFFFAOYSA-N 0.000 claims description 4
- UPGFHLCWVCRHIN-UHFFFAOYSA-N 5-phenyl-6-[4-[[4-(3-pyridin-3-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methyl]phenyl]pyridine-3-carbonitrile Chemical compound C=1C=CC=CC=1C1=CC(C#N)=CN=C1C(C=C1)=CC=C1CN(CC1)CCC1C(ON=1)=NC=1C1=CC=CN=C1 UPGFHLCWVCRHIN-UHFFFAOYSA-N 0.000 claims description 4
- WSCDOEHSMMTRLK-UHFFFAOYSA-N 6-[4-(morpholin-4-ylmethyl)phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound C=1C=CC=CC=1C1=CC(C#N)=CN=C1C(C=C1)=CC=C1CN1CCOCC1 WSCDOEHSMMTRLK-UHFFFAOYSA-N 0.000 claims description 4
- RIWGPPXCSDKFLO-UHFFFAOYSA-N 6-[4-[(4-fluoropiperidin-1-yl)methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound C1CC(F)CCN1CC1=CC=C(C=2C(=CC(=CN=2)C#N)C=2C=CC=CC=2)C=C1 RIWGPPXCSDKFLO-UHFFFAOYSA-N 0.000 claims description 4
- PFPKUQQCAAMMCP-UHFFFAOYSA-N 6-[4-[(4-isoquinolin-1-ylpiperazin-1-yl)methyl]phenyl]-5-phenylpyridine-3-carbonitrile Chemical compound C=1C(C#N)=CN=C(C=2C=CC(CN3CCN(CC3)C=3C4=CC=CC=C4C=CN=3)=CC=2)C=1C1=CC=CC=C1 PFPKUQQCAAMMCP-UHFFFAOYSA-N 0.000 claims description 4
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Classifications
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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Description
aは、0または1であり;bは、0または1であり;mは、0、1または2であり;nは、0、1、2または3であり;pは、0、1または2であり;qは、0、1、2または3であり;rは、0または1であり;sは、0または1であり;tは、2、3、4、5または6であり;
Qは、C1〜C6アルキル、ハロゲン、−NR6R7、アリールおよびヘテロシクリルから選択され、前記アルキル、アリールおよびヘテロシクリルは、1つから3つのRzにより場合によっては置換されており;
R1は、1)(C=O)aObC1〜C10アルキル、2)(C=O)aObアリール、3)C2〜C10アルケニル、4)C2〜C10アルキニル、5)(C=O)aObヘテロシクリル、6)(C=O)aObC3〜C8シクロアルキル、7)CO2H、8)ハロ、9)CN、10)OH、11)ObC1〜C6ペルフルオロアルキル、12)Oa(C=O)bNR6R7、13)NRc(C=O)bNR6R7、14)S(O)mRa、15)S(O)2NR6R7、16)NRcS(O)mRa、17)オキソ、18)CHO、19)NO2、20)NRc(C=O)ObRa、21)O(C=O)ObC1〜C10アルキル、22)O(C=O)ObC3〜C8シクロアルキル、23)O(C=O)Obアリール、24)C0〜C6アルキル(C=NRb)N(Rb)2、25)O(C=O)Ob−複素環、26)Oa−P=O(OH)2および27)−N=CHN(Rb)2から独立して選択され、前記アルキル、アリール、アルケニル、アルキニル、ヘテロシクリル、およびシクロアルキルは、Rzから選択される1つ以上の置換基により場合によっては置換されており;
R2は、1)(C=O)aObC1〜C10アルキル、2)(C=O)aObアリール、3)C2〜C10アルケニル、4)C2〜C10アルキニル、5)(C=O)aObヘテロシクリル、6)(C=O)aObC3〜C8シクロアルキル、7)CO2H、8)ハロ、9)CN、10)OH、11)ObC1〜C6ペルフルオロアルキル、12)Oa(C=O)bNR6R7、13)NRc(C=O)NR6R7、14)S(O)mRa、15)S(O)2NR6R7、16)NRcS(O)mRa、17)CHO、18)NO2、19)NRc(C=O)ObRa、20)O(C=O)ObC1〜C10アルキル、21)O(C=O)ObC3〜C8シクロアルキル、22)O(C=O)Obアリール、23)O(C=O)Ob−複素環、および24)Oa−P=O(OH)2から独立して選択され、前記アルキル、アリール、アルケニル、アルキニル、ヘテロシクリル、およびシクロアルキルは、Rzから選択される1つ、2つまたは3つの置換基により場合によっては置換されており;
R3およびR4は、H、C1〜C6−アルキルおよびC1〜C6−ペルフルオロアルキルから独立して選択されるか、またはR3とR4は組み合わされて、−(CH2)t−を形成し、ここで炭素原子の1つは、O、S(O)m、−N(Rb)C(O)−、および−N(CORa)−から選択される部分により場合によっては入替されており;
R5は、1)(C=O)aObC1〜C10アルキル、2)(C=O)aObアリール、3)C2〜C10アルケニル、4)C2〜C10アルキニル、5)(C=O)aObヘテロシクリル、6)(C=O)aObC3〜C8シクロアルキル、7)CO2H、8)ハロ、9)CN、10)OH、11)ObC1〜C6ペルフルオロアルキル、12)Oa(C=O)bNR6R7、13)NRc(C=O)NR6R7、14)S(O)mRa、15)S(O)2NR6R7、16)NRcS(O)mRa、17)オキソ、18)CHO、19)NO2、20)O(C=O)ObC1〜C10アルキル、21)O(C=O)ObC3〜C8シクロアルキル、および22)Oa−P=O(OH)2から独立して選択され、前記アルキル、アリール、アルケニル、アルキニル、ヘテロシクリル、およびシクロアルキルは、Rzから選択される1つ以上の置換基により場合によっては置換されており;
R6およびR7は、1)H、2)(C=O)ObRa、3)C1〜C10アルキル、4)アリール、5)C2〜C10アルケニル、6)C2〜C10アルキニル、7)ヘテロシクリル、8)C3〜C8シクロアルキル、9)SO2Ra、10)(C=O)NRb 2、11)OH、および12)Oa−P=O(OH)2から独立して選択され、前記アルキル、シクロアルキル、アリール、ヘテロシクリル、アルケニル、およびアルキニルは、Rzから選択される1つ以上の置換基により場合によっては置換されており;またはR6とR7は、それらが結合している窒素と一緒になって、各環が4〜7員環で、前記窒素に加えて、N、OおよびSから選択される1個以上のヘテロ原子を場合によっては含有する単環式または二環式複素環を形成することができ、前記単環式または二環式複素環は、Rzから選択される1つ以上の置換基により場合によっては置換されており;
Rzは、1)(C=O)rOs(C1〜C10)アルキル、2)Or(C1〜C3)ペルフルオロアルキル、3)(C0〜C6)アルキレン−S(O)mRa、4)オキソ、5)OH、6)ハロ、7)CN、8)(C=O)rOs(C2〜C10)アルケニル、9)(C=O)rOs(C2〜C10)アルキニル、10)(C=O)rOs(C3〜C6)シクロアルキル、11)(C=O)rOs(C0〜C6)アルキレン−アリール、12)(C=O)rOs(C0〜C6)アルキレン−ヘテロシクリル、13)(C=O)rOs(C0〜C6)アルキレン−N(Rb)2、14)C(O)Ra、15)(C0〜C6)アルキレン−CO2Ra、16)C(O)H、17)(C0〜C6)アルキレン−CO2H、18)C(O)N(Rb)2、19)S(O)mRa、20)S(O)2N(Rb)2、21)NRc(C=O)ObRa、22)O(C=O)ObC1〜C10アルキル、23)O(C=O)ObC3〜C8シクロアルキル、24)O(C=O)Obアリール、25)O(C=O)Ob−複素環、および26)Oa−P=O(OH)2から独立して選択され、前記アルキル、アルケニル、アルキニル、シクロアルキル、アリール、およびヘテロシクリルは、Rb、OH、(C1〜C6)アルコキシ、ハロゲン、CO2H、CN、O(C=O)C1〜C6アルキル、オキソ、N(Rb)2およびOa−P=O(OH)2から選択される3つまでの置換基により場合によっては置換されており;
Raは、置換または非置換(C1〜C6)アルキル、置換または非置換(C2〜C6)アルケニル、置換または非置換(C2〜C6)アルキニル、置換または非置換(C3〜C6)シクロアルキル、置換または非置換アリール、(C1〜C6)ペルフルオロアルキル、2,2,2−トリフルオロエチル、または置換または非置換ヘテロシクリルであり;
Rbは、H、(C1〜C6)アルキル、置換または非置換アリール、置換または非置換ベンジル、置換または非置換ヘテロシクリル、(C3〜C6)シクロアルキル、(C=O)OC1〜C6アルキル、(C=O)C1〜C6アルキルまたはS(O)2Raであり;
Rcは、1)H、2)C1〜C10アルキル、3)アリール、4)C2〜C10アルケニル、5)C2〜C10アルキニル、6)ヘテロシクリル、7)C3〜C8シクロアルキル、および8)C1〜C6ペルフルオロアルキルから選択され、前記アルキル、シクロアルキル、アリール、ヘテロシクリル、アルケニル、およびアルキニルは、Rzから選択される1つ以上の置換基により場合によっては置換されている。]または製薬的に許容できるその塩もしくはその立体異性体によって例示される。
[式中:
Qは、−NR6R7、1つから3つのRzにより場合によっては置換されているフェニルおよびヘテロシクリルから選択され;
Raは、(C1〜C6)アルキル、(C3〜C6)シクロアルキル、アリール、またはヘテロシクリルであり;
Rbは、H、(C1〜C6)アルキル、アリール、ヘテロシクリル、(C3〜C6)シクロアルキル、(C=O)OC1〜C6アルキル、(C=O)C1〜C6アルキルまたはS(O)2Raであり;すべての他の置換基および可変部分は、第2の実施形態に定義されているとおりである。]または製薬的に許容できるその塩もしくはその立体異性体である。
[式中:
qは、0であり;
R2が、1)C1〜C6アルキル、2)アリール、3)ヘテロシクリル、4)CO2H、5)ハロ、6)CN、7)OH、8)S(O)2NR6R7、および9)Oa−P=O(OH)2から独立して選択され、前記アルキル、アリール、およびヘテロシクリルは、Rzから選択される1つ、2つまたは3つの置換基により場合によっては置換されており、すべての他の置換基および可変部分は、第3の実施形態に定義されているとおりである。]または製薬的に許容できるその塩もしくはその立体異性体である。
[式中:
nは、0、1または2であり;
Qは、1つから3つのRzにより場合によっては置換されているヘテロシクリルから選択され;すべての他の置換基および可変部分は、第4の実施形態に定義されているとおりである。]または製薬的に許容できるその塩もしくはその立体異性体である。
6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(2−メチル−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(6−メチル−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(2−オキソ−4−フェニル−2,3−ジヒドロ−1H−イミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(ベンジルアミノ)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−{4−[(4−イソキノリン−1−イルピペラジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル;
6−(4−{[4−(4−メチル−4H−1,2,4−トリアゾール−3−イル)ピペラジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(1,2−ベンゾイソチアゾール−3−イル)ピペラジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[5−(4−フルオロフェニル)−2,5−ジアザビシクロ[2.2.1]ヘプタ−2−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(2−オキソ−3,4−ジヒドロキノリン−1(2H)−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
5−フェニル−6−{4−[(4−フェニルピペリジン−1−イル)メチル]フェニル}ニコチノニトリル;
6−{4−[(4−フルオロピペリジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル;
6−{4−[(4−メチルピペラジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル;
6−[4−(モルホリン−4−イルメチル)フェニル]−5−フェニルニコチノニトリル;
6−(4−{[4−(2−オキソ−2H−3,1−ベンゾオキサジン−1(4H)−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
4−クロロ−N−{1−[4−(5−シアノ−3−フェニルピリジン−2−イル)ベンジル]ピペリジン−4−イル}−N−シクロプロピルベンゼンスルホンアミド;
5−フェニル−6−(4−{[4−(3−ピリジン−3−イル−1,2,4−オキサジアゾール−5−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル;
1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3−ジヒドロ−2H−ベンゾイミダゾール−2−オン(1−6);
6−(4−{[4−(1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
2−メチル−1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
5−メチル−2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
5−フルオロ−2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
N−ベンジル−1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−アミン;
N−{(3R)−1−[4−(5−シアノ−3−フェニルピリジン−2−イル)ベンジル]ピロリジン−3−イル}−N’−エチル尿素;
N−エチル−N’−((3R)−1−{4−[3−フェニル−5−(2H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピロリジン−3−イル)尿素;
6−(4−{[4−(6−アミノ−9H−プリン−9−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
9−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−9H−プリン−6−アミン;
5−フェニル−6−(4−{[4−(5−ピリジン−4−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル;
N−{(3R)−1−[4−(5−シアノ−3−フェニルピリジン−2−イル)ベンジル]ピロリジン−3−イル}−N’−ピリジン−4−イル尿素;
6−(4−{[4−(4−ヒドロキシ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(4−アミノ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−4H−1,2,4−トリアゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル;
5−フェニル−6−(4−{[4−(4−ピリジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル;
2−クロロ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル]−5−フェニルニコチノニトリル(2−6);
2−クロロ−6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(2−7);
6−(4−{[4−(6−アミノ−9H−プリン−9−イル)ピペリジン−1−イル]メチル}フェニル)−2−クロロ−5−フェニルニコチノニトリル(2−8);
2−クロロ−6−(4−{[4−(2−メチル−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(2−9);
2−クロロ−6−(4−{[4−(4−オキシド−2−オキソ−2,3−ジヒドロ−1H−イミダゾ[4,5−b]ピリジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(2−10);
2−クロロ−5−フェニル−6−(4−{[4−(5−ピリジン−4−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル(2−11);
6−(4−{[4−(4−アミノ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−2−クロロ−5−フェニルニコチノニトリル(2−12);
2−フルオロ−6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(2−13);
6−(4−{[4−(6−アミノ−9H−プリン−9−イル)ピペリジン−1−イル]メチル}フェニル)−2−クロロ−5−フェニルニコチンアミド(2−14);
2−クロロ−6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチンアミド(2−15);
2−クロロ−6−(4−{[4−(2−メチル−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチンアミド(2−16);
6−フルオロ−2−(1−{4−[5−(1H−イミダゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(3−3);
6−フルオロ−2−(1−{4−[5−(5−メチル−1H−イミダゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(3−4);
{2−[6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−イル]−1H−イミダゾール−5−イル}メタノール(3−5);
2−[6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−イル]−4,5−ジヒドロ−1H−イミダゾール−5−カルボキサミド(3−6);
2−クロロ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−カルボキシイミドアミド(3−7);
1−(1−{4−[6−クロロ−5−(1H−イミダゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3−ジヒドロ−2H−ベンゾイミダゾール−2−オン(3−8);
6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−3−(1H−イミダゾール−2−イル)−5−フェニルピリジン−2−カルボニトリル(3−9);
6−フルオロ−2−(1−{4−[6−フルオロ−5−(1H−イミダゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(3−10);
1−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(4A−5);
5−[5−フェニル−6−(4−{[4−(5−ピリジン−4−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(4B−6);
5−[6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(4−1);
5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(4−2);
5−[5−フェニル−6−(4−{[4−(1H−ピラゾロ[3,4−b]ピリジン−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(4−3);
5−[5−フェニル−6−(4−{[4−(1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(4−4);
5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−4H−1,2,4−トリアゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(4−5);
5−[5−フェニル−6−(4−{[4−(4−ピリジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(4−6);
5−[5−フェニル−6−(4−{[4−(4−ピリミジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(4−7);
5−[5−フェニル−6−(4−{[4−(4−ピラジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(4−8);
5−{5−フェニル−6−[4−({4−[4−(1,3−チアゾール−4−イル)−1H−ピラゾール−1−イル]ピペリジン−1−イル}メチル)フェニル]ピリジン−3−イル}−1,3,4−チアジアゾール−2−アミン(4−9);
1−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3−ジヒドロ−2H−イミダゾ[4,5−b]ピリジン−2−オン(4−10);
5−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3,4−チアジアゾール−2−アミン(4−11);
N−((3R)−1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピロリジン−3−イル)−N’−ピリジン−4−イル尿素(4−12);
N−エチル−N’−{5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−イル}尿素(4−13);
2−[2−(ジメチルアミノ)エトキシ]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(5−1);
2−メトキシ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(5−2);
2−エトキシ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(5−3);
2−(2−モルホリン−4−イルエトキシ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(5−4);
2−(メチルアミノ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(6−1);
2−(ジメチルアミノ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(6−2);
2−アミノ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(6−3);
2−[(2−モルホリン−4−イルエチル)アミノ]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(6−4);
2−{[2−(ジメチルアミノ)エチル]アミノ}−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(6−5);
2−[4−(2−ヒドロキシエチル)ピペラジン−1−イル]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(6−6);
2−[(4−メトキシベンジル)アミノ]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(6−7);
N−[3−シアノ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−2−イル]−N’−エチル尿素(7−1);
N−[3−シアノ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−2−イル]アセトアミド(7−2);
N’−[3−シアノ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−2−イル]−N,N−ジメチルイミドホルムアミド(7−3);
6−フルオロ−2−(1−{4−[3−フェニル−5−(1H−1,2,3−トリアゾール−4−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(8−1);
9−(1−{4−[6−クロロ−3−フェニル−5−(1H−1,2,3−トリアゾール−4−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−9H−プリン−6−アミン(8−2);
1−(1−{4−[5−(1,2,4−オキサジアゾール−3−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(9−3);
1−(1−{4−[3−フェニル−5−(1H−1,2,4−トリアゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(9−4);
1−{1−[4−(3−フェニル−5−ピリミジン−2−イルピリジン−2−イル)ベンジル]ピペリジン−4−イル}−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(10−5);
1−{1−[4−(5’−フェニル−2,3’−ビピリジン−6’−イル)ベンジル]ピペリジン−4−イル}−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(10−6);および
5−[2−({4−[2−(メチルチオ)−6−フェニルピリド[2,3−d]ピリミジン−7−イル]ベンジル}アミノ)エチル]−1,3,4−チアジアゾール−2−アミン(10−7);または製薬的に許容できるその塩もしくはその立体異性体が挙げられる。
6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(2−メチル−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(6−メチル−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(2−オキソ−4−フェニル−2,3−ジヒドロ−1H−イミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(ベンジルアミノ)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−{4−[(4−イソキノリン−1−イルピペラジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(4−メチル−4H−1,2,4−トリアゾール−3−イル)ピペラジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(1,2−ベンゾイソチアゾール−3−イル)ピペラジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[5−(4−フルオロフェニル)−2,5−ジアザビシクロ[2.2.1]ヘプタ−2−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(2−オキソ−3,4−ジヒドロキノリン−1(2H)−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
5−フェニル−6−{4−[(4−フェニルピペリジン−1−イル)メチル]フェニル}ニコチノニトリル(TFA);
6−{4−[(4−フルオロピペリジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル(TFA);
6−{4−[(4−メチルピペラジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル(TFA);
6−[4−(モルホリン−4−イルメチル)フェニル]−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(2−オキソ−2H−3,1−ベンゾオキサジン−1(4H)−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
4−クロロ−N−{1−[4−(5−シアノ−3−フェニルピリジン−2−イル)ベンジル]ピペリジン−4−イル}−N−シクロプロピルベンゼンスルホンアミド(TFA);
5−フェニル−6−(4−{[4−(3−ピリジン−3−イル−1,2,4−オキサジアゾール−5−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル(TFA);
1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3−ジヒドロ−2H−ベンゾイミダゾール−2−オン(TFA、1−6);
6−(4−{[4−(1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
2−メチル−1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
5−メチル−2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
5−フルオロ−2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
N−ベンジル−1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−アミン(TFA);
N−エチル−N’−((3R)−1−{4−[3−フェニル−5−(2H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピロリジン−3−イル)尿素(TFA);
9−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−9H−プリン−6−アミン(TFA);
6−(4−{[4−(4−ヒドロキシ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(HCl);
6−フルオロ−2−(1−{4−[5−(5−メチル−1H−イミダゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA、3−4);
{2−[6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−イル]−1H−イミダゾール−5−イル}メタノール(TFA、3−5);
2−[6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−イル]−4,5−ジヒドロ−1H−イミダゾール−5−カルボキサミド(TFA、3−6);
1−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(TFA、4A−5);
5−[5−フェニル−6−(4−{[4−(5−ピリジン−4−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA、4B−6);
5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA、4−2);
5−[5−フェニル−6−(4−{[4−(1H−ピラゾロ[3,4−b]ピリジン−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA、4−3);
5−[5−フェニル−6−(4−{[4−(1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA、4−4);
5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−4H−1,2,4−トリアゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA、4−5);
5−[5−フェニル−6−(4−{[4−(4−ピリジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA、4−6);
5−[5−フェニル−6−(4−{[4−(4−ピリミジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA、4−7);
5−[5−フェニル−6−(4−{[4−(4−ピラジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA、4−8);
5−{5−フェニル−6−[4−({4−[4−(1,3−チアゾール−4−イル)−1H−ピラゾール−1−イル]ピペリジン−1−イル}メチル)フェニル]ピリジン−3−イル}−1,3,4−チアジアゾール−2−アミン(TFA、4−9);
1−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3−ジヒドロ−2H−イミダゾ[4,5−b]ピリジン−2−オン(TFA、4−10);
5−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3,4−チアジアゾール−2−アミン(TFA、4−11);
N−((3R)−1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピロリジン−3−イル)−N’−ピリジン−4−イル尿素(TFA、4−12);
N−エチル−N’−{5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−イル}尿素(TFA、4−13);
2−[2−(ジメチルアミノ)エトキシ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA、5−1);
2−エトキシ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA、5−3);
2−(2−モルホリン−4−イルエトキシ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA、5−4);
2−(メチルアミノ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA、6−1);
2−(ジメチルアミノ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA、6−2);
2−[(2−モルホリン−4−イルエチル)アミノ]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA、6−4);
2−{[2−(ジメチルアミノ)エチル]アミノ}−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA、6−5);
2−[4−(2−ヒドロキシエチル)ピペラジン−1−イル]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA、6−6);
6−フルオロ−2−(1−{4−[3−フェニル−5−(1H−1,2,3−トリアゾール−4−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA、8−1);
9−(1−{4−[6−クロロ−3−フェニル−5−(1H−1,2,3−トリアゾール−4−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−9H−プリン−6−アミン(TFA、8−2);
1−(1−{4−[5−(1,2,4−オキサジアゾール−3−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(TFA、9−3);および
1−(1−{4−[3−フェニル−5−(1H−1,2,4−トリアゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(TFA、9−4);
1−{1−[4−(3−フェニル−5−ピリミジン−2−イルピリジン−2−イル)ベンジル]ピペリジン−4−イル}−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(TFA、10−5);
1−{1−[4−(5’−フェニル−2,3’−ビピリジン−6’−イル)ベンジル]ピペリジン−4−イル}−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(TFA、10−6);および
5−[2−({4−[2−(メチルチオ)−6−フェニルピリド[2,3−d]ピリミジン−7−イル]ベンジル}アミノ)エチル]−1,3,4−チアジアゾール−2−アミン(TFA、10−7);またはそれらの立体異性体が挙げられる。
1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3−ジヒドロ−2H−ベンゾイミダゾール−2−オン(1−6):
6−フルオロ−2−(1−{4−[5−(1H−イミダゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(3−3):
5−[5−フェニル−6−(4−{[4−(5−ピリジン−4−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(4B−6):
1−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(4A−5):
6−フルオロ−2−(1−{4−[3−フェニル−5−(1H−1,2,3−トリアゾール−4−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(8−1):
1−(1−{4−[5−(1,2,4−オキサジアゾール−3−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(9−3):
1−{1−[4−(3−フェニル−5−ピリミジン−2−イルピリジン−2−イル)ベンジル]ピペリジン−4−イル}−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(10−4):
提供された実施例は、本発明のさらなる理解の助けとなるように意図されている。使用される特定の物質、種類および条件は、本発明のさらなる例示のために意図されており、その妥当な範囲を限定はしていない。以下の表に描写された化合物を合成するのに利用される試薬は、商品として入手できるか、または通常の当業者により容易に調製される。
2−クロロ−6−(4−メチルフェニル)−5−フェニルニコチノニトリル(2−4;0.066g、0.217mmol)、NBS(0.046g、0.26mmol)およびベンゾイルペルオキシド(0.010g、0.043mmol)のCDCl3(2mL)溶液を、一晩加熱還流した。この混合物を濃縮して6−[4−(ブロモメチル)フェニル]−2−クロロ−5−フェニルニコチノニトリル(2−5)を得、さらに精製することなく用いた。LRMS m/z(M+H)計算値:383.7、実測値:383.1。
6−[4−(ブロモメチル)フェニル]−2−クロロ−5−フェニルニコチノニトリル(2−5;0.078g、0.203mmol)のMeOH(1mL)およびTHF(1mL)溶液に、4−(2−ケト−1−ベンゾイミダゾリニル)−ピリジン(0.066g、0.305mmol;商品として入手できる)およびDIEPA(0.131g、1.02mmol)を加えた。この混合物を室温で一晩攪拌し、濃縮した。残渣を、Na2CO3水溶液(5mL、2M)で処理し、CH2Cl2(3×10mL)により抽出した。有機層を合わせて乾燥し、ろ過し、濃縮した。残渣をシリカゲルクロマトグラフィー(CH2Cl2中3〜5%MeOH)により精製して2−クロロ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル]−5−フェニルニコチノニトリル(2−6)を得た。1H−NMR(500MHz,CDCl3)δ7.98(s,1H)、7.31〜7.37(m,4H)、7.25〜7.29(m,4H)、7.17〜7.19(m,2H)、7.05〜7.09(m,3H)、4.31〜4.36(m,1H)、3.54(s,2H)、2.97〜2.99(m,2H)、2.41〜2.47(m,2H)、2.12〜2.17(m,2H)、1.78〜1.80(m,2H)。LRMS m/z(M+H)計算値:520.0、実測値:520.0。
N2下、火炎乾燥丸底フラスコに、無水THF(200mL)中、4−クロロピラゾロ(3,4−d)ピリミジン(J.Am.Chem.Soc.1956年、78、784ページ)(1.80g、11.65mmol)、t−ブチル4−ヒドロキシ−1−ピペリジンカルボキシレート(2.46g、12.23mol)、およびPS−PPh3(9.211g、1.77mmol/g)を加えた。この混合物を0℃に冷却し、THF(20mL)中のDEAD(2.20mL、13.98mmol)を滴下により加えた。混合物を室温に温め、一晩攪拌した。次に前記反応液をろ過し、CH2Cl2に溶かした。不溶物をろ過して除いた。ろ液を濃縮し、再度CH2Cl2に溶かし、フリーザーに5時間入れた。形成した結晶をろ過して除き、ろ液をシリカゲルクロマトグラフィー(CH2Cl2中0〜2%MeOH)により精製した。1H−NMR(500MHz,CDCl3)δ8.76(s,1H)、8.16(s,1H)、4.92〜5.02(m,1H)、4.32(bs,2H)、2.97(bs,2H)、2.20〜2.31(m,2H)、1.96〜2.05(m,2H)。LRMS m/z(M+H)計算値:337.13、実測値:338.09。
EtOH−飽和NH3(1mL)中、t−ブチル4−(4−クロロ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−カルボキシレート(4A−1;0.050g、0.148mmol)の混合物を、マイクロ波中80℃に30分間加熱した。この混合物を冷却し、濃縮して減圧乾燥した。さらに精製せずに用いた。1H−NMR(500MHz,CDCl3)δ8.38(s,1H)、7.93(s,1H)、5.60(bs,2H)、4.84〜4.95(m,1H)、4.29(bs,2H)、2.95(bs,2H)、2.13〜2.28(m,2H)、1.92〜2.03(m,2H)。LRMS m/z(M+H)計算値:319.1、実測値:319.1。
4M HClジオキサン(12mL)中、t−ブチル4−(4−アミノ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−カルボキシレート(4A−2;1.30g、4.08mmol)の混合物を1時間攪拌した。反応液を濃縮してエーテルで粉砕して二塩化4−アミノ−1−ピペリジニウム−4−イル−1H−ピラゾロ[3,4−d]ピリミジン−2−イウムを得た。遊離塩基に関して:上記塩をH2Oに溶解して、Dowex 1X2−400、イオン交換樹脂(−OH体)に通過させた。この樹脂を水に次いでMeOHで洗浄した。ろ液を濃縮し、減圧乾燥して純粋な遊離塩基を得た。1H−NMR(500MHz,d6 DMSO)δ8.14(s,1H)、8.07(s,1H)、7.64(bs,2H)、4.57〜4.67(m,1H)、3.05(d,J=12.46 2H)、2.55〜2.67(m,2H)、2.06(bs,1H)、1.90〜2.12(m,2H)、1.73〜1.80(m,2H)。LRMS m/z(M+H)計算値:219.1、実測値:219.1。
N2下、火炎乾燥丸底フラスコに、5% AcOH:DMF(2mL)中、二塩化4−アミノ−1−ピペリジニウム−4−イル−1H−ピラゾロ[3,4−d]ピリミジン−2−イウム(0.183g、0.901mmol)、6−(4−ホルミルフェニル)−5−フェニルニコチノニトリル(1−3;0.170g、0.598mmol)、およびEt3N(0.163mL、1.20mmol)を加えた。この混合物を1時間攪拌し、NaBH(OAc)3(0.191g、0.658mmol)を加えた。この反応液を、飽和水性NaHCO3とCH2Cl2とに分配する際、1時間攪拌した。水層を、CH2Cl2でさらに2回抽出し、有機層を合わせて乾燥し(無水Na2SO4)、ろ過し、濃縮した。残渣をシリカゲルに乗せ、シリカゲルクロマトグラフィー(CH2Cl2中2〜4%MeOH)により精製した。1H−NMR(500MHz,CDCl3)δ8.92(d,J=1.96,1H)、8.36(s,1H)、7.97(d,J=1.96,1H)、7.91(s,1H)、7.12〜7.40(m,9H)、5.51(bs,2H)、4.65〜4.80(m,1H)、3.56(s,2H)、3.00(d,J=9.77,2H)、2.15〜2.45(m,4H)、1.95(d,J=10.74,2H)HRMS(ES)m/z(M+H)計算値:487.2353、実測値:487.2335。
6−(4−{[4−(4−アミノ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(4A−4;0.035g、0.072mmol)およびチオセミカルバジド(0.010g、0.108mmol)のTFA(2mL)溶液を60℃に16時間加熱した。次に反応液を冷却し、氷に注ぎ、飽和重炭酸ナトリウム水で塩基性にした。生じた沈殿物をろ過し、DMFに溶かし、逆相HPLC(5% CH3CN:95% H2O+0.1% TFAから95% CH3CN:5% H2O+0.1% TFA)により精製した。1H−NMR(500MHz,d6 DMSO)δ9.72(bs,1H)、9.07(d,J=2.19,1H)、8.93(bs,1H)、8.42(bs,1H)、8.36(s,1H)、8.29(s,1H)、8.10(d,J=1.96,1H)、7.65(bs,2H)、7.22〜7.49(m,9H)、4.93〜5.03(m,1H)、4.34(s,2H)、3.49(d,J=12.21,2H)、3.19〜3.35(m,2H)、2.32〜2.56(m,2H)、2.15(d,J=11.96,2H)。HRMS m/z(M+H)計算値:561.2292、実測値:561.2256。
塩酸4−アセチルピペリジン(4B−1、5.0g、30.55mmol)をCH2Cl2(150mL)に溶かした。これに、Et3N(9.8mL、70.27mmol)を加えて懸濁液溶液にした。混合物を0℃に冷却し、クロロギ酸ベンジル(5.2mL、36.66mmol)を加えた。添加が完了後、混合物を室温に温めた。18時間後、混合物をH2Oで希釈した。層を分離して、CH2Cl2で抽出(3×)した。有機層を合わせて乾燥し(MgSO4)、ろ過し、濃縮して4−アセチルピペリジン−1−カルボキシレートを灰白色固体(4B−2)として得た:1H−NMR(500MHz,CDCl3)δ7.35(m,5H)、5.13(s,2H)、4,18(bs,2H)、2.88(bs,2H)、2.49(m,1H)、2.17(s,3H)、1.86(bs,2H)、1.55(m,2H)。
標題化合物を、化合物(4A−4)と同じ方法で調製した。HRMS(ES)m/z(M+H)計算値:497.2448、実測値:497.2429。
5−フェニル−6−(4−{[4−(5−ピリジン−4−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル(4B−5;0.030g、0.060mmol)およびチオセミカルバジド(0.006g、0.066mmol)のTFA(1.5mL)溶液を、60℃に16時間加熱した。次に反応液を冷却し、氷に注ぎ、飽和重炭酸ナトリウム水で塩基性にした。生じた沈殿物(4B−6)をろ過し、DMFに溶かし、逆相HPLC(5% CH3CN:95% H2O+0.1% TFAから95% CH3CN:5% H2O+0.01% TFA)により精製した。1H−NMR(500MHz,d6 DMSO)δ13.54(bs,1H)、9.64(s,1H)、9.07(d,J=1.96,1H)、8.81(d,J=6.11,2H)、8.21(s,2H)、8.10(d,J=2.2,1H)、7.65(s,2H)、7.23〜7.49(m,9H)、7.00(s,1H)、4.33(d,2H)、3.45(d,J=10.5,2H)、2.95〜3.15(m,3H)、2.21(d,J=12.69,2H)、1.76〜1.90(m 2H)。HRMS m/z(M+H)計算値:571.2387、実測値:571.2359。
THF(1mL)中、2−アミノ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(6−3;0.025g、0.05mmol)およびエチルイソシアネート(0.007mg、0.100mmol)の混合物を、100℃に0.5時間加熱した。残渣を、シリカゲルクロマトグラフィー(CH2Cl2中3〜6%MeOH)により精製し、標題化合物(7−1)を得た。LRMS m/z(M+H)計算値:572.7、実測値:572.2。
6−(4−{[4−(4−アミノ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(9−1(スキーム1を用いて作製された)、0.036g、0.074mmol)のEtOH(1.5mL)溶液に、ヒドロキシルアミン(H2O中50%溶液、0.010mL、0.148mmol)を加えた。この反応液を、88℃に3時間加熱し、その時点で冷却し、濃縮した。LRMSm/z(M+H)計算値:520.1、実測値:520.09。
CDCl3(2mL)中、2−[6−(4−メチルフェニル)−5−フェニルピリジン−3−イル]ピリミジン(10−3;0.040g、0.124mmol)の混合物に、NBS(0.024g、0.134mmol)およびベンゾイルペルオキシド(0.006g、0.025mmol)を加えた。反応液を15時間加熱還流し、その時点で反応液を冷却し、濃縮して粗製の標題化合物を得た。LRMS m/z(M+H)計算値:403.9、実測値:403.9。
1:1MeOH:THF(1mL)中、粗2−{6−[4−(ブロモメチル)フェニル]−5−フェニルピリジン−3−イル}ピリミジン(0.050g、0.124mmol)、1−ピリジン−4−イル−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(0.030g、0.137mmol)、およびDIEA(0.065mL、0.373mmol)の混合物を、1時間攪拌した。反応液を濃縮し、残渣を逆相HPLC(5% CH3CN:95% H2O:0.01% TFAから95% CH3CN:5% H2O:0.01% TFA)により精製して標題化合物を得た。1H−NMR(500MHz,d6 DMSO)δ9.77(bs,1H)、9.60(d,1H,J=2.0Hz)、9.00(d,2H,J=4.9Hz)、8.70(bs,1H)、8.68(d,2H J=2.0Hz)、8.45(bs,1H)、8.37(s,1H)、8.30(s,1H)、7.58(t,1H,J=4.9Hz)、7.54〜7.37(m,9H)、5.05〜4.93(m,1H)、4.35(s,2H)、3.49(d,2H,J=11.23Hz)、3.37〜3.21(m,2H)、2.47〜2.33(m,2H)、2.15(d,2H,J=11.7Hz)HRMS m/z(M+H)計算値:540.2619、実測値:540.2616。
実施例2に記載されたS2細胞1リットルの細胞ペーストを、緩衝液A(50mMトリスpH7.4、1mM EDTA、1mM EGTA、0.2mM AEBSF、10μg/mlベンズアミジン、各5μg/mlのロイペプチン、アプロチニンおよびペプスタチン、10%グリセロールおよび1mM DTT)中、1%CHAPS50mlと共に音波処理により溶解させた。可溶性フラクションを、9mg/ml抗ミドルTモノクローナル抗体を充填したG蛋白セファロース高速(Pharmacia)カラム上で精製し、25%グリセロースを含有する緩衝液A中、75μM EYMPME(配列番号:14)ペプチドにより溶出させた。Akt含有フラクションをプールし、蛋白質純度をSDS−PAGEにより評価した。標準的なプラッドフォードプロトコルを用いて精製蛋白質を定量化した。精製蛋白質を液体窒素上で瞬間凍結させ、−70℃で保存した。
A.活性化したAktイソ酵素またはプレックストリン相同性ドメイン欠失構成体;
B.Aktペプチド基質:GSK3α(S21)ペプチド番号3928ビオチン−GGRARTSSFAEPG(配列番号:15)、Macromolecular Resources;
C.Lance標識抗ホスホGSK3αモノクローナル抗体(Cell Signaling Technology、クローン番号27);
D.SA−APC(Prozymeカタログ番号PJ25Sロット番号896067);
E.Microfluor(登録商標)BU Bottom Microtiter Plates(Dynex Technologies、カタログ番号7205);
F.Discovery(登録商標)HTRF Microplate Analyzer、Packard Instrument社;
G.100Xプロテアーゼ阻害剤カクテル(PIC):1mg/mlベンズアミジン、0.5mg/mlペプスタチン、0.5mg/mlロイペプチン、0.5mg/mlアプロチニン;
H.10Xアッセイ緩衝液:500mM HEPES、pH7.5,1%PEG、mM EDTA、1mM EGTA、1%BSA、20mM ▲θ▼−グリセロールホスフェート;
I.クエンチ緩衝液:50mM HEPES、pH7.3、16.6mM EDTA、0.1%BSA、0.1%トリトンX−100、0.17nM Lance標識モノクローナル抗体クローン番号27、0.0067mg/ml SA−APC;
J.ATP/MgCl2使用液:1Xアッセイ緩衝液、1mM DTT、1X PIC、125mM KCl、5%グリセロール、25mM MgCl2、375TM ATP;
K.酵素使用液:1Xアッセイ緩衝液、1mM DTT、1X PIC、5%グリセロール、活性Akt。アッセイが線形応答範囲にあるように、最終酵素濃度を選択した。
L.ペプチド使用液:1Xアッセイ緩衝液、1mM DTT、1X PIC、5%グリセロール、2TMGSK3ビオチニル化ペプチド番号3928。
A.5X PKAアッセイ緩衝液(200mMトリスpH7.5、100mM MgCl2、5mM ▲θ▼−メルカプトエタノール、0.5mM EDTA);
B.水で希釈したKemptide(Sigma)の50μM保存液;
C.1.0μl33P−ATP[10mCi/ml]を未標識ATPの50μM保存液200Tlに希釈することにより調製した33P−ATP;
D.0.5mg/ml BSAに希釈したPKA触媒サブユニット(UBIカタログ番号14−114)の70nM保存液10μl;
E.PKA/Kemptide使用液:5X PKAアッセイ緩衝液、Kemptide溶液およびPKA触媒サブユニットの等容量。
各PKCアッセイは、以下の成分からなる:
A.10X PKC同時発生活性化緩衝液:2.5mM EGTA、4mM CaCl2;
B.5X PKC活性化緩衝液:1.6mg/mlホスファチジルセリン、0.16mg/mlジアシルグリセロール、100mMトリスpH7.5、50mM MgCl2、5mM ▲θ▼−メルカプトエタノール;
C.1.0μl33P−ATP[10mCi/ml]を未標識ATPの100μM保存液100μlに希釈することにより調製した33P−ATP;
D.水に希釈したミエリン塩基性蛋白質(350μg/ml、UBI);
E.0.5mg/ml BSAに希釈したPKC(50μg/ml、UBIカタログ番号14−115);
F.PKC/ミエリン塩基性蛋白質使用液:PKC同時発生活性化緩衝液およびミエリン塩基性蛋白質の各5容量を、PKC活性化緩衝液およびPKCの各10容量に混合することにより調製。
細胞(例えば、活性化Aktと共にLnCaPまたはPTEN(−l−)腫瘍細胞系)を100mMディッシュにおいて平板培養した。細胞がおよそ70%から80%集密したら、細胞を5mlの新鮮培地によりレフ(refed)し、溶液に試験化合物を加えた。対照は、未処理細胞、媒体処理細胞およびそれぞれ20μMまたは200nMのLY294002(Sigma)またはwortmanin(Sigma)のいずれかで処理した細胞を含んだ。前記細胞を2時間、4時間または6時間温置し、培地を除去した。前記細胞をPBSで洗浄し、こすり落とし、遠心管へ移した。それらをペレット化し、再びPBSで洗浄した。最後に、前記細胞ペレットをリーシス緩衝液(20mMトリスpH8、140mM NaCl、2mM EDTA、1%トリトン、1mM Naピロホスフェート、10mM ▲θ▼−グリセロールホスフェート、10mM NaF、0.5mm NaVO4、1μMミクロシスチン、および1×プロテアーゼ阻害剤カクテル)に再懸濁し、氷上に15分間置き、静かに渦巻かせて細胞を溶解させた。前記細胞溶解液をBeckman卓上型超遠心分離において、4℃で20分間100,000xgで回転させた。上澄み蛋白質を標準的なBradfordプロトコル(BioRad)により定量化し、必要時まで−70℃で保存した。
Claims (14)
- 式A:
aは、0または1であり;bは、0または1であり;mは、0、1または2であり;nは、0、1、2または3であり;pは、0、1または2であり;qは、0、1、2または3であり;rは、0または1であり;sは、0または1であり;tは、2、3、4、5または6であり;
Qは、C1〜C6アルキル、ハロゲン、−NR6R7、アリールおよびヘテロシクリルから選択され、前記アルキル、アリールおよびヘテロシクリルは、1つから3つのRzにより場合によっては置換されており;
R1は、1)(C=O)aObC1〜C10アルキル、2)(C=O)aObアリール、3)C2〜C10アルケニル、4)C2〜C10アルキニル、5)(C=O)aObヘテロシクリル、6)(C=O)aObC3〜C8シクロアルキル、7)CO2H、8)ハロ、9)CN、10)OH、11)ObC1〜C6ペルフルオロアルキル、12)Oa(C=O)bNR6R7、13)NRc(C=O)bNR6R7、14)S(O)mRa、15)S(O)2NR6R7、16)NRcS(O)mRa、17)オキソ、18)CHO、19)NO2、20)NRc(C=O)ObRa、21)O(C=O)ObC1〜C10アルキル、22)O(C=O)ObC3〜C8シクロアルキル、23)O(C=O)Obアリール、24)C1〜C6アルキル(C=NRb)N(Rb)2、25)O(C=O)Ob−複素環、26)Oa−P=O(OH)2および27)−N=CHN(Rb)2から独立して選択され、前記アルキル、アリール、アルケニル、アルキニル、ヘテロシクリル、およびシクロアルキルは、Rzから選択される1つ以上の置換基により場合によっては置換されており;
R2は、1)(C=O)aObC1〜C10アルキル、2)(C=O)aObアリール、3)C2〜C10アルケニル、4)C2〜C10アルキニル、5)(C=O)aObヘテロシクリル、6)(C=O)aObC3〜C8シクロアルキル、7)CO2H、8)ハロ、9)CN、10)OH、11)ObC1〜C6ペルフルオロアルキル、12)Oa(C=O)bNR6R7、13)NRc(C=O)NR6R7、14)S(O)mRa、15)S(O)2NR6R7、16)NRcS(O)mRa、17)CHO、18)NO2、19)NRc(C=O)ObRa、20)O(C=O)ObC1〜C10アルキル、21)O(C=O)ObC3〜C8シクロアルキル、22)O(C=O)Obアリール、23)O(C=O)Ob−複素環、および24)Oa−P=O(OH)2から独立して選択され、前記アルキル、アリール、アルケニル、アルキニル、ヘテロシクリル、およびシクロアルキルは、Rzから選択される1つ、2つまたは3つの置換基により場合によっては置換されており;
R3およびR4は、H、C1〜C6アルキルおよびC1〜C6ペルフルオロアルキルから独立して選択されるか、または
R3とR4は組み合わされて、−(CH2)t−を形成し、ここで炭素原子の1つは、O、S(O)m、−N(Rb)C(O)−、および−N(CORa)−から選択される部分により場合によっては入替されており;
R5は、1)(C=O)aObC1〜C10アルキル、2)(C=O)aObアリール、3)C2〜C10アルケニル、4)C2〜C10アルキニル、5)(C=O)aObヘテロシクリル、6)(C=O)aObC3〜C8シクロアルキル、7)CO2H、8)ハロ、9)CN、10)OH、11)ObC1〜C6ペルフルオロアルキル、12)Oa(C=O)bNR6R7、13)NRc(C=O)NR6R7、14)S(O)mRa、15)S(O)2NR6R7、16)NRcS(O)mRa、17)オキソ、18)CHO、19)NO2、20)O(C=O)ObC1〜C10アルキル、21)O(C=O)ObC3〜C8シクロアルキル、および22)Oa−P=O(OH)2から独立して選択され、前記アルキル、アリール、アルケニル、アルキニル、ヘテロシクリル、およびシクロアルキルは、Rzから選択される1つ以上の置換基により場合によっては置換されており;
R6およびR7は、1)H、2)(C=O)ObRa、3)C1〜C10アルキル、4)アリール、5)C2〜C10アルケニル、6)C2〜C10アルキニル、7)ヘテロシクリル、8)C3〜C8シクロアルキル、9)SO2Ra、10)(C=O)NRb 2、11)OH、および12)Oa−P=O(OH)2から独立して選択され、前記アルキル、シクロアルキル、アリール、ヘテロシクリル、アルケニル、およびアルキニルは、Rzから選択される1つ以上の置換基により場合によっては置換されており;または
R6とR7は、それらが結合している窒素と一緒になって、各環が4〜7員環で、前記窒素に加えて、N、OおよびSから選択される1個以上のヘテロ原子を場合によっては含有する単環式または二環式複素環を形成することができ、前記単環式または二環式複素環は、Rzから選択される1つ以上の置換基により場合によっては置換されており;
Rzは、1)(C=O)rOs(C1〜C10)アルキル、2)Or(C1〜C3)ペルフルオロアルキル、3)(C0〜C6)アルキレン−S(O)mRa、4)オキソ、5)OH、6)ハロ、7)CN、8)(C=O)rOs(C2〜C10)アルケニル、9)(C=O)rOs(C2〜C10)アルキニル、10)(C=O)rOs(C3〜C6)シクロアルキル、11)(C=O)rOs(C0〜C6)アルキレン−アリール、12)(C=O)rOs(C0〜C6)アルキレン−ヘテロシクリル、13)(C=O)rOs(C0〜C6)アルキレン−N(Rb)2、14)C(O)Ra、15)(C0〜C6)アルキレン−CO2Ra、16)C(O)H、17)(C0〜C6)アルキレン−CO2H、18)C(O)N(Rb)2、19)S(O)mRa、20)S(O)2N(Rb)2、21)NRc(C=O)ObRa、22)O(C=O)ObC1〜C10アルキル、23)O(C=O)ObC3〜C8シクロアルキル、24)O(C=O)Obアリール、25)O(C=O)Ob複素環、および26)Oa−P=O(OH)2から独立して選択され、前記アルキル、アルケニル、アルキニル、シクロアルキル、アリール、およびヘテロシクリルは、Rb、OH、(C1〜C6)アルコキシ、ハロゲン、CO2H、CN、O(C=O)C1〜C6アルキル、オキソ、N(Rb)2およびOa−P=O(OH)2から選択される3つまでの置換基により場合によっては置換されており;
Raは、置換または非置換(C1〜C6)アルキル、置換または非置換(C2〜C6)アルケニル、置換または非置換(C2〜C6)アルキニル、置換または非置換(C3〜C6)シクロアルキル、置換または非置換アリール、(C1〜C6)ペルフルオロアルキル、2,2,2−トリフルオロエチル、または置換または非置換ヘテロシクリルであり;
Rbは、H、(C1〜C6)アルキル、置換または非置換アリール、置換または非置換ベンジル、置換または非置換ヘテロシクリル、(C3〜C6)シクロアルキル、(C=O)OC1〜C6アルキル、(C=O)C1〜C6アルキルまたはS(O)2Raであり;
Rcは、1)H、2)C1〜C10アルキル、3)アリール、4)C2〜C10アルケニル、5)C2〜C10アルキニル、6)ヘテロシクリル、7)C3〜C8シクロアルキル、および8)C1〜C6ペルフルオロアルキルから選択され、前記アルキル、シクロアルキル、アリール、ヘテロシクリル、アルケニル、およびアルキニルは、Rzから選択される1つ以上の置換基により場合によっては置換されている)
の化合物または製薬的に許容できるその塩もしくはその立体異性体。 - Qは、−NR6R7、1つから3つのRzにより場合によっては置換されているフェニルおよびヘテロシクリルから選択され;
Raは、(C1〜C6)アルキル、(C3〜C6)シクロアルキル、アリール、またはヘテロシクリルであり;
Rbは、H、(C1〜C6)アルキル、アリール、ヘテロシクリル、(C3〜C6)シクロアルキル、(C=O)OC1〜C6アルキル、(C=O)C1〜C6アルキルまたはS(O)2Raである、
請求項2に記載の化合物または製薬的に許容できるその塩もしくはその立体異性体。 - qは、0であり;
R2は、1)C1〜C6アルキル、2)アリール、3)ヘテロシクリル、4)CO2H、5)ハロ、6)CN、7)OH、8)S(O)2NR6R7、および9)Oa−P=O(OH)2から独立して選択され、前記アルキル、アリール、およびヘテロシクリルは、Rzから選択される1つ、2つまたは3つの置換基により場合によっては置換されている、
請求項3に記載の化合物または製薬的に許容できるその塩もしくはその立体異性体。 - 6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(2−メチル−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(6−メチル−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(2−オキソ−4−フェニル−2,3−ジヒドロ−1H−イミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(ベンジルアミノ)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−{4−[(4−イソキノリン−1−イルピペラジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル;
6−(4−{[4−(4−メチル−4H−1,2,4−トリアゾール−3−イル)ピペラジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(1,2−ベンゾイソチアゾール−3−イル)ピペラジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[5−(4−フルオロフェニル)−2,5−ジアザビシクロ[2.2.1]ヘプタ−2−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(2−オキソ−3,4−ジヒドロキノリン−1(2H)−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
5−フェニル−6−{4−[(4−フェニルピペリジン−1−イル)メチル]フェニル}ニコチノニトリル;
6−{4−[(4−フルオロピペリジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル;
6−{4−[(4−メチルピペラジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル;
6−[4−(モルホリン−4−イルメチル)フェニル]−5−フェニルニコチノニトリル;
6−(4−{[4−(2−オキソ−2H−3,1−ベンゾオキサジン−1(4H)−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
4−クロロ−N−{1−[4−(5−シアノ−3−フェニルピリジン−2−イル)ベンジル]ピペリジン−4−イル}−N−シクロプロピルベンゼンスルホンアミド;
5−フェニル−6−(4−{[4−(3−ピリジン−3−イル−1,2,4−オキサジアゾール−5−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル;
1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3−ジヒドロ−2H−ベンゾイミダゾール−2−オン;
6−(4−{[4−(1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
2−メチル−1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
5−メチル−2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
5−フルオロ−2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
N−ベンジル−1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−アミン;
N−{(3R)−1−[4−(5−シアノ−3−フェニルピリジン−2−イル)ベンジル]ピロリジン−3−イル}−N’−エチル尿素;
N−エチル−N’−((3R)−1−{4−[3−フェニル−5−(2H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピロリジン−3−イル)尿素;
6−(4−{[4−(6−アミノ−9H−プリン−9−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
9−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−9H−プリン−6−アミン;
5−フェニル−6−(4−{[4−(5−ピリジン−4−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル;
N−{(3R)−1−[4−(5−シアノ−3−フェニルピリジン−2−イル)ベンジル]ピロリジン−3−イル}−N’−ピリジン−4−イル尿素;
6−(4−{[4−(4−ヒドロキシ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(4−アミノ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−4H−1,2,4−トリアゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル;
5−フェニル−6−(4−{[4−(4−ピリジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル;
2−クロロ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル]−5−フェニルニコチノニトリル;
2−クロロ−6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(6−アミノ−9H−プリン−9−イル)ピペリジン−1−イル]メチル}フェニル)−2−クロロ−5−フェニルニコチノニトリル;
2−クロロ−6−(4−{[4−(2−メチル−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−クロロ−6−(4−{[4−(4−オキシド−2−オキソ−2,3−ジヒドロ−1H−イミダゾ[4,5−b]ピリジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−クロロ−5−フェニル−6−(4−{[4−(5−ピリジン−4−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル;
6−(4−{[4−(4−アミノ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−2−クロロ−5−フェニルニコチノニトリル;
2−フルオロ−6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
6−(4−{[4−(6−アミノ−9H−プリン−9−イル)ピペリジン−1−イル]メチル}フェニル)−2−クロロ−5−フェニルニコチンアミド
2−クロロ−6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチンアミド;
2−クロロ−6−(4−{[4−(2−メチル−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチンアミド;
6−フルオロ−2−(1−{4−[5−(1H−イミダゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
6−フルオロ−2−(1−{4−[5−(5−メチル−1H−イミダゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
{2−[6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−イル]−1H−イミダゾール−5−イル}メタノール;
2−[6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−イル]−4,5−ジヒドロ−1H−イミダゾール−5−カルボキサミド;
2−クロロ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−カルボキシイミドアミド;
1−(1−{4−[6−クロロ−5−(1H−イミダゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3−ジヒドロ−2H−ベンゾイミダゾール−2−オン;
6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−3−(1H−イミダゾール−2−イル)−5−フェニルピリジン−2−カルボニトリル;
6−フルオロ−2−(1−{4−[6−フルオロ−5−(1H−イミダゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
1−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン;
5−[5−フェニル−6−(4−{[4−(5−ピリジン−4−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン;
5−[6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン;
5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン;
5−[5−フェニル−6−(4−{[4−(1H−ピラゾロ[3,4−b]ピリジン−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン;
5−[5−フェニル−6−(4−{[4−(1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン;
5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−4H−1,2,4−トリアゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン;
5−[5−フェニル−6−(4−{[4−(4−ピリジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン;
5−[5−フェニル−6−(4−{[4−(4−ピリミジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン;
5−[5−フェニル−6−(4−{[4−(4−ピラジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン;
5−{5−フェニル−6−[4−({4−[4−(1,3−チアゾール−4−イル)−1H−ピラゾール−1−イル]ピペリジン−1−イル}メチル)フェニル]ピリジン−3−イル}−1,3,4−チアジアゾール−2−アミン;
1−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3−ジヒドロ−2H−イミダゾ[4,5−b]ピリジン−2−オン;
5−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3,4−チアジアゾール−2−アミン;
N−((3R)−1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピロリジン−3−イル)−N’−ピリジン−4−イル尿素;
N−エチル−N’−{5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−イル}尿素;
2−[2−(ジメチルアミノ)エトキシ]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−メトキシ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−エトキシ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−(2−モルホリン−4−イルエトキシ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−(メチルアミノ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−(ジメチルアミノ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−アミノ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−[(2−モルホリン−4−イルエチル)アミノ]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−{[2−(ジメチルアミノ)エチル]アミノ}−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−[4−(2−ヒドロキシエチル)ピペラジン−1−イル]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
2−[(4−メトキシベンジル)アミノ]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル;
N−[3−シアノ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−2−イル]−N’−エチル尿素;
N−[3−シアノ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−2−イル]アセトアミド;
N’−[3−シアノ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−2−イル]−N,N−ジメチルイミドホルムアミド;
6−フルオロ−2−(1−{4−[3−フェニル−5−(1H−1,2,3−トリアゾール−4−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール;
9−(1−{4−[6−クロロ−3−フェニル−5−(1H−1,2,3−トリアゾール−4−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−9H−プリン−6−アミン;
1−(1−{4−[5−(1,2,4−オキサジアゾール−3−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン;
1−(1−{4−[3−フェニル−5−(1H−1,2,4−トリアゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン;
1−{1−[4−(3−フェニル−5−ピリミジン−2−イルピリジン−2−イル)ベンジル]ピペリジン−4−イル}−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン;
1−{1−[4−(5’−フェニル−2,3’−ビピリジン−6’−イル)ベンジル]ピペリジン−4−イル}−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン;および
5−[2−({4−[2−(メチルチオ)−6−フェニルピリド[2,3−d]ピリミジン−7−イル]ベンジル}アミノ)エチル]−1,3,4−チアジアゾール−2−アミン;
から選択される、化合物または製薬的に許容できるその塩もしくはその立体異性体。 - 6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(2−メチル−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(6−メチル−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(2−オキソ−4−フェニル−2,3−ジヒドロ−1H−イミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(ベンジルアミノ)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−{4−[(4−イソキノリン−1−イルピペラジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(4−メチル−4H−1,2,4−トリアゾール−3−イル)ピペラジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(1,2−ベンゾイソチアゾール−3−イル)ピペラジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[5−(4−フルオロフェニル)−2,5−ジアザビシクロ[2.2.1]ヘプタ−2−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(2−オキソ−3,4−ジヒドロキノリン−1(2H)−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
5−フェニル−6−{4−[(4−フェニルピペリジン−1−イル)メチル]フェニル}ニコチノニトリル(TFA);
6−{4−[(4−フルオロピペリジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル(TFA);
6−{4−[(4−メチルピペラジン−1−イル)メチル]フェニル}−5−フェニルニコチノニトリル(TFA);
6−[4−(モルホリン−4−イルメチル)フェニル]−5−フェニルニコチノニトリル(TFA);
6−(4−{[4−(2−オキソ−2H−3,1−ベンゾオキサジン−1(4H)−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
4−クロロ−N−{1−[4−(5−シアノ−3−フェニルピリジン−2−イル)ベンジル]ピペリジン−4−イル}−N−シクロプロピルベンゼンスルホンアミド(TFA);
5−フェニル−6−(4−{[4−(3−ピリジン−3−イル−1,2,4−オキサジアゾール−5−イル)ピペリジン−1−イル]メチル}フェニル)ニコチノニトリル(TFA);
1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3−ジヒドロ−2H−ベンゾイミダゾール−2−オン(TFA);
6−(4−{[4−(1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
2−メチル−1−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
5−メチル−2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
5−フルオロ−2−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
N−ベンジル−1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−アミン(TFA);
N−エチル−N’−((3R)−1−{4−[3−フェニル−5−(2H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピロリジン−3−イル)尿素(TFA);
9−(1−{4−[3−フェニル−5−(1H−テトラゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−9H−プリン−6−アミン(TFA);
6−(4−{[4−(4−ヒドロキシ−1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(HCl);
6−フルオロ−2−(1−{4−[5−(5−メチル−1H−イミダゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
{2−[6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−イル]−1H−イミダゾール−5−イル}メタノール(TFA);
2−[6−(4−{[4−(6−フルオロ−1H−ベンゾイミダゾール−2−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルピリジン−3−イル]−4,5−ジヒドロ−1H−イミダゾール−5−カルボキサミド(TFA);
5−[5−フェニル−6−(4−{[4−(5−ピリジン−4−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA);
5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA);
5−[5−フェニル−6−(4−{[4−(1H−ピラゾロ[3,4−b]ピリジン−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA);
5−[5−フェニル−6−(4−{[4−(1H−ピラゾロ[3,4−d]ピリミジン−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA);
5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−4H−1,2,4−トリアゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA);
5−[5−フェニル−6−(4−{[4−(4−ピリジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA);
5−[5−フェニル−6−(4−{[4−(4−ピリミジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA);
5−[5−フェニル−6−(4−{[4−(4−ピラジン−2−イル−1H−ピラゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−アミン(TFA);
5−{5−フェニル−6−[4−({4−[4−(1,3−チアゾール−4−イル)−1H−ピラゾール−1−イル]ピペリジン−1−イル}メチル)フェニル]ピリジン−3−イル}−1,3,4−チアジアゾール−2−アミン(TFA);
1−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3−ジヒドロ−2H−イミダゾ[4,5−b]ピリジン−2−オン(TFA);
5−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1,3,4−チアジアゾール−2−アミン(TFA);
N−((3R)−1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピロリジン−3−イル)−N’−ピリジン−4−イル尿素(TFA);
N−エチル−N’−{5−[5−フェニル−6−(4−{[4−(5−ピリジン−2−イル−1H−ピラゾール−3−イル)ピペリジン−1−イル]メチル}フェニル)ピリジン−3−イル]−1,3,4−チアジアゾール−2−イル}尿素(TFA);
1−(1−{4−[5−(5−アミノ−1,3,4−チアジアゾール−2−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(TFA);
2−[2−(ジメチルアミノ)エトキシ]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
2−エトキシ−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
2−(2−モルホリン−4−イルエトキシ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
2−(メチルアミノ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
2−(ジメチルアミノ)−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
2−[(2−モルホリン−4−イルエチル)アミノ]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TEA);
2−{[2−(ジメチルアミノ)エチル]アミノ}−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
2−[4−(2−ヒドロキシエチル)ピペラジン−1−イル]−6−(4−{[4−(2−オキソ−2,3−ジヒドロ−1H−ベンゾイミダゾール−1−イル)ピペリジン−1−イル]メチル}フェニル)−5−フェニルニコチノニトリル(TFA);
6−フルオロ−2−(1−{4−[3−フェニル−5−(1H−1,2,3−トリアゾール−4−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ベンゾイミダゾール(TFA);
9−(1−{4−[6−クロロ−3−フェニル−5−(1H−1,2,3−トリアゾール−4−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−9H−プリン−6−アミン(TFA);
1−(1−{4−[5−(1,2,4−オキサジアゾール−3−イル)−3−フェニルピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(TFA);
1−(1−{4−[3−フェニル−5−(1H−1,2,4−トリアゾール−5−イル)ピリジン−2−イル]ベンジル}ピペリジン−4−イル)−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(TFA);
1−{1−[4−(3−フェニル−5−ピリミジン−2−イルピリジン−2−イル)ベンジル]ピペリジン−4−イル}−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(TFA、10−5);
1−{1−[4−(5’−フェニル−2,3’−ビピリジン−6’−イル)ベンジル]ピペリジン−4−イル}−1H−ピラゾロ[3,4−d]ピリミジン−4−アミン(TFA、10−6);および
5−[2−({4−[2−(メチルチオ)−6−フェニルピリド[2,3−d]ピリミジン−7−イル]ベンジル}アミノ)エチル]−1,3,4−チアジアゾール−2−アミン(TFA、10−7);
である請求項1に記載の化合物の塩またはその立体異性体。
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2004
- 2004-04-20 CA CA002522431A patent/CA2522431A1/en not_active Abandoned
- 2004-04-20 US US10/554,001 patent/US7579355B2/en not_active Expired - Fee Related
- 2004-04-20 WO PCT/US2004/012188 patent/WO2004096131A2/en active Application Filing
- 2004-04-20 EP EP04760294A patent/EP1622616B1/en not_active Expired - Lifetime
- 2004-04-20 AU AU2004233828A patent/AU2004233828B2/en not_active Ceased
- 2004-04-20 JP JP2006513160A patent/JP4616831B2/ja not_active Expired - Fee Related
- 2004-04-20 AT AT04760294T patent/ATE512957T1/de not_active IP Right Cessation
- 2004-04-20 CN CNA200480017118XA patent/CN1809354A/zh active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2007532551A (ja) * | 2004-04-09 | 2007-11-15 | メルク エンド カムパニー インコーポレーテッド | Akt活性の阻害剤 |
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JP2006524696A (ja) | 2006-11-02 |
WO2004096131A3 (en) | 2005-11-03 |
ATE512957T1 (de) | 2011-07-15 |
CA2522431A1 (en) | 2004-11-11 |
CN1809354A (zh) | 2006-07-26 |
AU2004233828A1 (en) | 2004-11-11 |
WO2004096131A2 (en) | 2004-11-11 |
EP1622616B1 (en) | 2011-06-15 |
AU2004233828B2 (en) | 2009-05-28 |
EP1622616A2 (en) | 2006-02-08 |
US20070043001A1 (en) | 2007-02-22 |
EP1622616A4 (en) | 2010-04-21 |
US7579355B2 (en) | 2009-08-25 |
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