CA2981055A1 - Spirocyclic compounds - Google Patents
Spirocyclic compounds Download PDFInfo
- Publication number
- CA2981055A1 CA2981055A1 CA2981055A CA2981055A CA2981055A1 CA 2981055 A1 CA2981055 A1 CA 2981055A1 CA 2981055 A CA2981055 A CA 2981055A CA 2981055 A CA2981055 A CA 2981055A CA 2981055 A1 CA2981055 A1 CA 2981055A1
- Authority
- CA
- Canada
- Prior art keywords
- optionally substituted
- compound
- alkyl
- cancer
- diazaspiro
- 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.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 482
- 201000011510 cancer Diseases 0.000 claims abstract description 117
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 107
- 238000000034 method Methods 0.000 claims abstract description 68
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 287
- 125000001072 heteroaryl group Chemical group 0.000 claims description 145
- 125000003107 substituted aryl group Chemical group 0.000 claims description 103
- 150000003839 salts Chemical class 0.000 claims description 98
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 97
- 125000000623 heterocyclic group Chemical group 0.000 claims description 96
- 229910052739 hydrogen Inorganic materials 0.000 claims description 93
- 239000001257 hydrogen Substances 0.000 claims description 93
- -1 mono-substituted amino group Chemical group 0.000 claims description 92
- 150000002431 hydrogen Chemical group 0.000 claims description 72
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 43
- 229910052736 halogen Inorganic materials 0.000 claims description 40
- 150000002367 halogens Chemical class 0.000 claims description 40
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 36
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 claims description 35
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 30
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 27
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 230000000694 effects Effects 0.000 claims description 25
- 230000002401 inhibitory effect Effects 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 108040008097 MAP kinase activity proteins Proteins 0.000 claims description 19
- 102000019149 MAP kinase activity proteins Human genes 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 claims description 18
- 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 claims description 18
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 12
- 201000005202 lung cancer Diseases 0.000 claims description 12
- 208000020816 lung neoplasm Diseases 0.000 claims description 12
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims description 12
- 206010009944 Colon cancer Diseases 0.000 claims description 11
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 208000029742 colonic neoplasm Diseases 0.000 claims description 11
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 11
- 201000001441 melanoma Diseases 0.000 claims description 11
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 11
- 208000001446 Anaplastic Thyroid Carcinoma Diseases 0.000 claims description 10
- 206010005003 Bladder cancer Diseases 0.000 claims description 10
- 208000034578 Multiple myelomas Diseases 0.000 claims description 10
- 206010029260 Neuroblastoma Diseases 0.000 claims description 10
- 206010033128 Ovarian cancer Diseases 0.000 claims description 10
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 10
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 10
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 10
- 201000010536 head and neck cancer Diseases 0.000 claims description 10
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 10
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 10
- 201000002528 pancreatic cancer Diseases 0.000 claims description 10
- 201000002510 thyroid cancer Diseases 0.000 claims description 10
- 201000008440 thyroid gland anaplastic carcinoma Diseases 0.000 claims description 10
- 208000019179 thyroid gland undifferentiated (anaplastic) carcinoma Diseases 0.000 claims description 10
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 9
- 206010006187 Breast cancer Diseases 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 9
- 201000009030 Carcinoma Diseases 0.000 claims description 9
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 9
- 208000009905 Neurofibromatoses Diseases 0.000 claims description 9
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 9
- 206010060862 Prostate cancer Diseases 0.000 claims description 9
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 9
- 206010038389 Renal cancer Diseases 0.000 claims description 9
- 206010039491 Sarcoma Diseases 0.000 claims description 9
- 201000001531 bladder carcinoma Diseases 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 208000025113 myeloid leukemia Diseases 0.000 claims description 9
- 201000004931 neurofibromatosis Diseases 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 201000010174 renal carcinoma Diseases 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 208000010570 urinary bladder carcinoma Diseases 0.000 claims description 9
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 8
- 230000012010 growth Effects 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 230000010076 replication Effects 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- 239000004202 carbamide Substances 0.000 claims description 7
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 6
- 229910052805 deuterium Inorganic materials 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- 150000003672 ureas Chemical class 0.000 claims description 6
- 125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 claims description 5
- 150000002923 oximes Chemical class 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 7
- OBKRRKAUHSPXPC-QNGWXLTQSA-N (5S)-2-[3-(1-acetylpiperidin-4-yl)-2H-indazol-5-yl]-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound CN1C=NC(=N1)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3CCN(CC3)C(C)=O)C=C2)C1 OBKRRKAUHSPXPC-QNGWXLTQSA-N 0.000 claims 1
- GTZJXZZYRIMYEL-LHEWISCISA-N (5S)-2-[3-(2-methyl-1,3-benzoxazol-5-yl)-1H-indazol-5-yl]-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound CN1N=C(N=C1)C1=CC=C(C=C1)C=1CCN(CC=1)C(CN1C[C@@]2(CCN(C2=O)C=2C=C3C(=NNC3=CC=2)C=2C=CC3=C(N=C(O3)C)C=2)CC1)=O GTZJXZZYRIMYEL-LHEWISCISA-N 0.000 claims 1
- NWPDFALVYJWUJA-DHUJRADRSA-N (5S)-2-[3-(3,6-dihydro-2H-pyran-4-yl)-1H-indazol-5-yl]-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound CN1C=NC(=N1)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3=CCOCC3)C=C2)C1 NWPDFALVYJWUJA-DHUJRADRSA-N 0.000 claims 1
- RSOAEEGYFGFBCE-QNGWXLTQSA-N (5S)-2-[3-(4-methoxyphenyl)-1H-indazol-5-yl]-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound COC1=CC=C(C=C1)C1=NNC2=C1C=C(C=C2)N1CC[C@]2(CCN(CC(=O)N3CCC(=CC3)C3=CC=C(C=C3)C3=NN(C)C=N3)C2)C1=O RSOAEEGYFGFBCE-QNGWXLTQSA-N 0.000 claims 1
- KJEOBKKNJGKUMR-BHVANESWSA-N (5S)-2-[3-(4-methoxypiperidin-1-yl)-1H-indazol-5-yl]-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound COC1CCN(CC1)C1=NNC2=C1C=C(C=C2)N1CC[C@]2(CCN(CC(=O)N3CCC(=CC3)C3=CC=C(C=C3)C3=NN(C)C=N3)C2)C1=O KJEOBKKNJGKUMR-BHVANESWSA-N 0.000 claims 1
- ZWMCBHQQIARLIE-QNGWXLTQSA-N (5S)-2-[3-[1-(2-hydroxyacetyl)piperidin-4-yl]-2H-indazol-5-yl]-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound CN1C=NC(=N1)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3CCN(CC3)C(=O)CO)C=C2)C1 ZWMCBHQQIARLIE-QNGWXLTQSA-N 0.000 claims 1
- GEORDXNJIBHRFW-DHUJRADRSA-N (5S)-2-[3-[2-(difluoromethyl)pyrimidin-5-yl]-1H-indazol-5-yl]-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound CN1C=NC(=N1)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3=CN=C(N=C3)C(F)F)C=C2)C1 GEORDXNJIBHRFW-DHUJRADRSA-N 0.000 claims 1
- HNVBYPHCKMNORJ-DNUYPZOSSA-N (5S)-2-[3-[6-(1-hydroxypropan-2-yl)pyridin-3-yl]-1H-indazol-5-yl]-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound CC(CO)C1=CC=C(C=N1)C1=NNC2=C1C=C(C=C2)N1CC[C@]2(CCN(CC(=O)N3CCC(=CC3)C3=CC=C(C=C3)C3=NN(C)C=N3)C2)C1=O HNVBYPHCKMNORJ-DNUYPZOSSA-N 0.000 claims 1
- YNIJUTINJJMWKK-BHVANESWSA-N (5S)-2-[3-[6-(difluoromethyl)pyridin-3-yl]-1H-indazol-5-yl]-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound CN1C=NC(=N1)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3=CC=C(N=C3)C(F)F)C=C2)C1 YNIJUTINJJMWKK-BHVANESWSA-N 0.000 claims 1
- DFLXRQAIQUAIFJ-KDXMTYKHSA-N (5S)-7-[2-[4-[4-(1-cyclopropyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2-[3-(6-propan-2-yloxypyridin-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound CC(C)OC1=CC=C(C=N1)C1=NNC2=C1N=C(C=C2)N1CC[C@]2(CCN(CC(=O)N3CCC(=CC3)C3=CC=C(C=C3)C3=NN(C=N3)C3CC3)C2)C1=O DFLXRQAIQUAIFJ-KDXMTYKHSA-N 0.000 claims 1
- BPGVSQWUBDBBAJ-DHUJRADRSA-N (5S)-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2-[3-(oxan-4-yl)-2H-indazol-5-yl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound CN1C=NC(=N1)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3CCOCC3)C=C2)C1 BPGVSQWUBDBBAJ-DHUJRADRSA-N 0.000 claims 1
- AQZWQCDSFJRAEJ-DHUJRADRSA-N (5S)-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2-[3-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-5-yl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound CN1C=NC(=N1)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3=CC=C(N=C3)C(F)(F)F)C=C2)C1 AQZWQCDSFJRAEJ-DHUJRADRSA-N 0.000 claims 1
- XHFIEJBGBYWSDA-DHUJRADRSA-N (5S)-7-[2-[4-[5-(1-methyl-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-2-[3-(6-propan-2-yloxypyridin-3-yl)-1H-indazol-5-yl]-2,7-diazaspiro[4.4]nonan-1-one Chemical compound CC(C)OC1=CC=C(C=N1)C1=NNC2=C1C=C(C=C2)N1CC[C@]2(CCN(CC(=O)N3CCC(=CC3)C3=NC=C(S3)C3=NN(C)C=N3)C2)C1=O XHFIEJBGBYWSDA-DHUJRADRSA-N 0.000 claims 1
- GAXAFTQHTHBBPG-LHEWISCISA-N 2-methoxy-4-[5-[(5S)-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-1-oxo-2,7-diazaspiro[4.4]nonan-2-yl]-1H-indazol-3-yl]benzonitrile Chemical compound COC1=C(C=CC(=C1)C1=NNC2=C1C=C(C=C2)N1CC[C@]2(CCN(CC(=O)N3CCC(=CC3)C3=CC=C(C=C3)C3=NN(C)C=N3)C2)C1=O)C#N GAXAFTQHTHBBPG-LHEWISCISA-N 0.000 claims 1
- VGKFRMVABBXTKV-LHEWISCISA-N 2-methoxy-4-[5-[(5S)-7-[2-[4-[4-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-1-oxo-2,7-diazaspiro[4.4]nonan-2-yl]-1H-indazol-3-yl]benzonitrile Chemical compound COC1=C(C=CC(=C1)C1=NNC2=C1C=C(C=C2)N1CC[C@]2(CCN(CC(=O)N3CCC(=CC3)C3=CC=C(C=C3)C3=NN(C)C(=O)O3)C2)C1=O)C#N VGKFRMVABBXTKV-LHEWISCISA-N 0.000 claims 1
- QUTCNADPXCXUDU-LHEWISCISA-N 2-methoxy-5-[5-[(5S)-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-1-oxo-2,7-diazaspiro[4.4]nonan-2-yl]-1H-indazol-3-yl]benzonitrile Chemical compound COC1=C(C=C(C=C1)C1=NNC2=C1C=C(C=C2)N1CC[C@]2(CCN(CC(=O)N3CCC(=CC3)C3=CC=C(C=C3)C3=NN(C)C=N3)C2)C1=O)C#N QUTCNADPXCXUDU-LHEWISCISA-N 0.000 claims 1
- IYSICUHAZQBAHA-LHEWISCISA-N 2-methoxy-5-[5-[(5S)-7-[2-[4-[4-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-1-oxo-2,7-diazaspiro[4.4]nonan-2-yl]-1H-indazol-3-yl]benzonitrile Chemical compound COC1=C(C=C(C=C1)C1=NNC2=C1C=C(C=C2)N1CC[C@]2(CCN(CC(=O)N3CCC(=CC3)C3=CC=C(C=C3)C3=NN(C)C(=O)O3)C2)C1=O)C#N IYSICUHAZQBAHA-LHEWISCISA-N 0.000 claims 1
- AVPCTOPEWYDAOF-QNGWXLTQSA-N 3-[5-[(5S)-7-[2-[4-[4-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-1-oxo-2,7-diazaspiro[4.4]nonan-2-yl]-1H-indazol-3-yl]benzonitrile Chemical compound CN1N=C(OC1=O)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3=CC=CC(=C3)C#N)C=C2)C1 AVPCTOPEWYDAOF-QNGWXLTQSA-N 0.000 claims 1
- UBIWVURAOAWIKD-LHEWISCISA-N 3-methyl-5-[4-[1-[2-[(5S)-1-oxo-2-[3-(6-propan-2-yloxypyridin-3-yl)-1H-indazol-5-yl]-2,7-diazaspiro[4.4]nonan-7-yl]acetyl]-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3,4-oxadiazol-2-one Chemical compound CC(C)OC1=CC=C(C=N1)C1=NNC2=C1C=C(C=C2)N1CC[C@]2(CCN(CC(=O)N3CCC(=CC3)C3=CC=C(C=C3)C3=NN(C)C(=O)O3)C2)C1=O UBIWVURAOAWIKD-LHEWISCISA-N 0.000 claims 1
- YTBBIYPNNDERSK-UMSFTDKQSA-N 3-methyl-5-[4-[1-[2-[(5S)-2-(3-morpholin-4-yl-1H-indazol-5-yl)-1-oxo-2,7-diazaspiro[4.4]nonan-7-yl]acetyl]-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3,4-oxadiazol-2-one Chemical compound CN1N=C(OC1=O)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3N3CCOCC3)C=C2)C1 YTBBIYPNNDERSK-UMSFTDKQSA-N 0.000 claims 1
- SDGQMSQBXNJHJM-LHEWISCISA-N 3-methyl-5-[4-[1-[2-[(5S)-2-[3-(2-methyl-1,3-benzoxazol-5-yl)-1H-indazol-5-yl]-1-oxo-2,7-diazaspiro[4.4]nonan-7-yl]acetyl]-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3,4-oxadiazol-2-one Chemical compound CN1N=C(OC1=O)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3=CC=C4OC(C)=NC4=C3)C=C2)C1 SDGQMSQBXNJHJM-LHEWISCISA-N 0.000 claims 1
- VOQRHOCHBNQSDK-DHUJRADRSA-N 3-methyl-5-[4-[1-[2-[(5S)-2-[3-(oxan-4-yl)-2H-indazol-5-yl]-1-oxo-2,7-diazaspiro[4.4]nonan-7-yl]acetyl]-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3,4-oxadiazol-2-one Chemical compound CN1N=C(OC1=O)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3CCOCC3)C=C2)C1 VOQRHOCHBNQSDK-DHUJRADRSA-N 0.000 claims 1
- AZRIIERYKDENHS-QNGWXLTQSA-N 4-[5-[(5S)-7-[2-[4-[4-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-1-oxo-2,7-diazaspiro[4.4]nonan-2-yl]-1H-indazol-3-yl]benzonitrile Chemical compound CN1C=NC(=N1)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3=CC=C(C=C3)C#N)C=C2)C1 AZRIIERYKDENHS-QNGWXLTQSA-N 0.000 claims 1
- CFIIXPSJXDHGHV-QNGWXLTQSA-N 4-[5-[(5S)-7-[2-[4-[4-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]-3,6-dihydro-2H-pyridin-1-yl]-2-oxoethyl]-1-oxo-2,7-diazaspiro[4.4]nonan-2-yl]-1H-indazol-3-yl]benzonitrile Chemical compound CN1N=C(OC1=O)C1=CC=C(C=C1)C1=CCN(CC1)C(=O)CN1CC[C@]2(CCN(C2=O)C2=CC3=C(NN=C3C3=CC=C(C=C3)C#N)C=C2)C1 CFIIXPSJXDHGHV-QNGWXLTQSA-N 0.000 claims 1
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A—HUMAN NECESSITIES
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A—HUMAN NECESSITIES
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- 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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- A—HUMAN NECESSITIES
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
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- C—CHEMISTRY; METALLURGY
- 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
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Landscapes
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- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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| US201562142946P | 2015-04-03 | 2015-04-03 | |
| US62/142,946 | 2015-04-03 | ||
| PCT/US2016/025345 WO2016161160A1 (en) | 2015-04-03 | 2016-03-31 | Spirocyclic compounds |
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| KR20170048588A (ko) * | 2014-09-17 | 2017-05-08 | 카리라 파마슈티컬스, 아이앤씨. | 바이사이클릭 화합물 |
| DK3277690T3 (da) | 2015-04-03 | 2020-05-04 | Recurium Ip Holdings Llc | Spirocykliske forbindelser |
| BR112019005305A2 (pt) * | 2016-10-05 | 2019-07-02 | Zeno Royalties & Milestones Llc | compostos espirocíclicos |
| WO2018107072A1 (en) | 2016-12-08 | 2018-06-14 | Board Of Regents, The University Of Texas System | Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (dlk) kinase for the treatment of disease |
| SG11202007251XA (en) * | 2018-01-31 | 2020-08-28 | Aptinyx Inc | Spiro-lactam nmda receptor modulators and uses thereof |
| EP3956330A4 (en) | 2019-04-18 | 2023-01-18 | The Johns Hopkins University | SUBSTITUTED 2-AMINO-PYRAZOLYL-[1,2,4]TRIAZOLO[1,5A]PYRIDINE DERIVATIVES AND THEIR USE |
| US11560366B2 (en) | 2019-10-21 | 2023-01-24 | Board Of Regents, The University Of Texas System | Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (DLK) kinase for the treatment of disease |
| CN115124542A (zh) * | 2022-07-08 | 2022-09-30 | 河南师范大学 | 羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法 |
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| US8546404B2 (en) | 2005-12-13 | 2013-10-01 | Merck Sharp & Dohme | Compounds that are ERK inhibitors |
| EP2086974B1 (en) | 2006-11-17 | 2013-07-24 | Polyera Corporation | Diimide-based semiconductor materials and methods of preparing and using the same |
| SG188179A1 (en) | 2008-02-21 | 2013-03-28 | Merck Sharp & Dohme | Compounds that are erk inhibitors |
| US20110166124A1 (en) | 2008-07-23 | 2011-07-07 | Mccormick Kevin D | Tricyclic spirocycle derivatives and methods of use |
| WO2011041152A1 (en) | 2009-09-30 | 2011-04-07 | Schering Corporation | Novel compounds that are erk inhibitors |
| US9687550B2 (en) | 2009-12-07 | 2017-06-27 | Arbutus Biopharma Corporation | Compositions for nucleic acid delivery |
| EP2751118B1 (en) | 2011-08-29 | 2016-10-12 | Bristol-Myers Squibb Company | Spiro bicyclic diamine derivatives as hiv attachment inhibitors |
| CN103130775B (zh) * | 2011-11-22 | 2015-09-30 | 山东亨利医药科技有限责任公司 | 作为酪氨酸激酶抑制剂的吲哚满酮衍生物 |
| US8987264B2 (en) * | 2012-11-09 | 2015-03-24 | Bristol-Myers Squibb Company | 1,3,5-triazine derivatives of spiro bicyclic oxalamide-compounds for treatment of hepatitis C |
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| CN105732636B (zh) | 2014-12-30 | 2020-04-21 | 广东东阳光药业有限公司 | 杂芳化合物及其在药物中的应用 |
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