TW201326153A - 磷酸二酯酶第１０ａ型之新穎抑制劑化合物 - Google Patents
磷酸二酯酶第１０ａ型之新穎抑制劑化合物 Download PDFInfo
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- TW201326153A TW201326153A TW101141932A TW101141932A TW201326153A TW 201326153 A TW201326153 A TW 201326153A TW 101141932 A TW101141932 A TW 101141932A TW 101141932 A TW101141932 A TW 101141932A TW 201326153 A TW201326153 A TW 201326153A
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- Prior art keywords
- ethyl
- quinolin
- pyridin
- group
- pyridazine
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 379
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title claims abstract description 17
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title claims abstract description 17
- 239000003112 inhibitor Substances 0.000 title abstract description 5
- -1 trimethyldecyl Chemical group 0.000 claims abstract description 997
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 372
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 203
- 239000001257 hydrogen Substances 0.000 claims abstract description 180
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 110
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 107
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 107
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 99
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 79
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 55
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 50
- 150000002367 halogens Chemical class 0.000 claims abstract description 49
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 424
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 131
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 119
- 125000005842 heteroatom Chemical group 0.000 claims description 107
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 99
- 229910052731 fluorine Inorganic materials 0.000 claims description 90
- 150000003839 salts Chemical class 0.000 claims description 89
- 239000011737 fluorine Substances 0.000 claims description 88
- 229940002612 prodrug Drugs 0.000 claims description 83
- 239000000651 prodrug Substances 0.000 claims description 83
- 125000001072 heteroaryl group Chemical group 0.000 claims description 77
- 150000001204 N-oxides Chemical class 0.000 claims description 69
- 229920006395 saturated elastomer Polymers 0.000 claims description 65
- 150000004677 hydrates Chemical class 0.000 claims description 61
- 239000000126 substance Substances 0.000 claims description 59
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 46
- 125000001424 substituent group Chemical group 0.000 claims description 45
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 44
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 44
- 125000004432 carbon atom Chemical group C* 0.000 claims description 43
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 42
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 42
- 239000000460 chlorine Chemical group 0.000 claims description 38
- VOIKXRQSXFJVMT-UHFFFAOYSA-N 5h-thieno[2,3-d]pyridazin-4-one Chemical compound O=C1NN=CC2=C1C=CS2 VOIKXRQSXFJVMT-UHFFFAOYSA-N 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 35
- 229910052801 chlorine Inorganic materials 0.000 claims description 35
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 34
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 34
- 125000002950 monocyclic group Chemical group 0.000 claims description 27
- 125000004076 pyridyl group Chemical group 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 125000002619 bicyclic group Chemical group 0.000 claims description 25
- 125000002541 furyl group Chemical group 0.000 claims description 25
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 25
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 24
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 23
- 125000002883 imidazolyl group Chemical group 0.000 claims description 23
- 125000002971 oxazolyl group Chemical group 0.000 claims description 23
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 23
- 125000000335 thiazolyl group Chemical group 0.000 claims description 23
- 125000001544 thienyl group Chemical group 0.000 claims description 23
- 241000124008 Mammalia Species 0.000 claims description 22
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 19
- 201000000980 schizophrenia Diseases 0.000 claims description 19
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
- 125000002837 carbocyclic group Chemical group 0.000 claims description 17
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 17
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 15
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 208000019901 Anxiety disease Diseases 0.000 claims description 14
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000004429 atom Chemical group 0.000 claims description 13
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 11
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 claims description 11
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 11
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 11
- 208000010877 cognitive disease Diseases 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 9
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 9
- 229930192474 thiophene Natural products 0.000 claims description 9
- DWHIRSWNWDXFMQ-UHFFFAOYSA-N 4h-pyridazin-5-one Chemical compound O=C1CC=NN=C1 DWHIRSWNWDXFMQ-UHFFFAOYSA-N 0.000 claims description 8
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 claims description 7
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 7
- 208000020925 Bipolar disease Diseases 0.000 claims description 7
- 230000036506 anxiety Effects 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 6
- QGFYFOHMBDMGBZ-UHFFFAOYSA-N 5-[(7-chloroquinolin-4-yl)amino]-2-(diethylaminomethyl)phenol Chemical compound C1=C(O)C(CN(CC)CC)=CC=C1NC1=CC=NC2=CC(Cl)=CC=C12 QGFYFOHMBDMGBZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 6
- RROZJMWKQNSJOL-OXJNMPFZSA-N 3-pyrimidin-5-yl-5-[(1R,2R)-2-quinolin-2-ylcyclopropyl]thieno[3,2-c]pyridin-4-one Chemical compound N1=CN=CC(=C1)C1=CSC2=C1C(N(C=C2)[C@H]2[C@@H](C2)C2=NC1=CC=CC=C1C=C2)=O RROZJMWKQNSJOL-OXJNMPFZSA-N 0.000 claims description 5
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 5
- DHLCTHXZKHGREA-UHFFFAOYSA-N 6h-pyrido[2,3-d]pyridazin-5-one Chemical compound C1=CC=C2C(=O)NN=CC2=N1 DHLCTHXZKHGREA-UHFFFAOYSA-N 0.000 claims description 5
- LCSGWIUZBNBGDL-UHFFFAOYSA-N 8-(2-fluoropyridin-4-yl)-2-(2-quinolin-2-ylcyclopropyl)isoquinolin-1-one Chemical compound C1=NC(F)=CC(C=2C=3C(=O)N(C4C(C4)C=4N=C5C=CC=CC5=CC=4)C=CC=3C=CC=2)=C1 LCSGWIUZBNBGDL-UHFFFAOYSA-N 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- ASNUDELVENWRMB-LAUBAEHRSA-N 3-pyridin-4-yl-5-[(1R,2R)-2-quinolin-2-ylcyclopropyl]thieno[3,2-c]pyridin-4-one Chemical compound C1[C@H]([C@@H]1N2C=CC3=C(C2=O)C(=CS3)C4=CC=NC=C4)C5=NC6=CC=CC=C6C=C5 ASNUDELVENWRMB-LAUBAEHRSA-N 0.000 claims description 4
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 235000005911 diet Nutrition 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- OELZFJUWWFRWLC-UHFFFAOYSA-N oxazine-1 Chemical compound C1=CC(N(CC)CC)=CC2=[O+]C3=CC(N(CC)CC)=CC=C3N=C21 OELZFJUWWFRWLC-UHFFFAOYSA-N 0.000 claims description 4
- 230000036961 partial effect Effects 0.000 claims description 4
- FSDNTQSJGHSJBG-UHFFFAOYSA-N piperidine-4-carbonitrile Chemical compound N#CC1CCNCC1 FSDNTQSJGHSJBG-UHFFFAOYSA-N 0.000 claims description 4
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 4
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 4
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- 125000003003 spiro group Chemical group 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- ASNUDELVENWRMB-UHFFFAOYSA-N 3-pyridin-4-yl-5-(2-quinolin-2-ylcyclopropyl)thieno[3,2-c]pyridin-4-one Chemical compound C1=2C(=O)N(C3C(C3)C=3N=C4C=CC=CC4=CC=3)C=CC=2SC=C1C1=CC=NC=C1 ASNUDELVENWRMB-UHFFFAOYSA-N 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- RROZJMWKQNSJOL-UHFFFAOYSA-N 3-pyrimidin-5-yl-5-(2-quinolin-2-ylcyclopropyl)thieno[3,2-c]pyridin-4-one Chemical compound C1=2C(=O)N(C3C(C3)C=3N=C4C=CC=CC4=CC=3)C=CC=2SC=C1C1=CN=CN=C1 RROZJMWKQNSJOL-UHFFFAOYSA-N 0.000 claims description 3
- MPOYBFYHRQBZPM-UHFFFAOYSA-N 3h-pyridin-4-one Chemical compound O=C1CC=NC=C1 MPOYBFYHRQBZPM-UHFFFAOYSA-N 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 3
- 230000000378 dietary effect Effects 0.000 claims description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- OJEOJUQOECNDND-UHFFFAOYSA-N oxetan-3-amine Chemical compound NC1COC1 OJEOJUQOECNDND-UHFFFAOYSA-N 0.000 claims description 3
- VXPLXMJHHKHSOA-UHFFFAOYSA-N propham Chemical compound CC(C)OC(=O)NC1=CC=CC=C1 VXPLXMJHHKHSOA-UHFFFAOYSA-N 0.000 claims description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- PCVUPNNIMVDXTJ-UHFFFAOYSA-N 2-[2-(1,3-benzothiazol-2-yl)ethyl]-8-pyridin-4-ylisoquinolin-1-one Chemical compound C=12C(=O)N(CCC=3SC4=CC=CC=C4N=3)C=CC2=CC=CC=1C1=CC=NC=C1 PCVUPNNIMVDXTJ-UHFFFAOYSA-N 0.000 claims description 2
- RNZOPJWJVAXPFR-UHFFFAOYSA-N 2-[2-(3-methylquinolin-2-yl)ethyl]-8-pyridin-4-ylisoquinolin-1-one Chemical compound CC1=CC2=CC=CC=C2N=C1CCN(C(C1=2)=O)C=CC1=CC=CC=2C1=CC=NC=C1 RNZOPJWJVAXPFR-UHFFFAOYSA-N 0.000 claims description 2
- GUSZZCFDFJEHQY-UHFFFAOYSA-N 2-[2-(5-methylpyridin-2-yl)ethyl]-8-pyridin-4-ylisoquinolin-1-one Chemical compound N1=CC(C)=CC=C1CCN1C(=O)C2=C(C=3C=CN=CC=3)C=CC=C2C=C1 GUSZZCFDFJEHQY-UHFFFAOYSA-N 0.000 claims description 2
- SIXKYHRABSUILN-UHFFFAOYSA-N 2-[2-(6-fluoroquinolin-2-yl)cyclopropyl]-8-morpholin-4-ylisoquinolin-1-one Chemical compound C1=CC2=CC(F)=CC=C2N=C1C1CC1N(C(C1=2)=O)C=CC1=CC=CC=2N1CCOCC1 SIXKYHRABSUILN-UHFFFAOYSA-N 0.000 claims description 2
- YYKZVHXBOVKANS-UHFFFAOYSA-N 2-[2-(6-fluoroquinolin-2-yl)cyclopropyl]-8-pyrimidin-5-ylisoquinolin-1-one Chemical compound C1=CC2=CC(F)=CC=C2N=C1C1CC1N(C(C1=2)=O)C=CC1=CC=CC=2C1=CN=CN=C1 YYKZVHXBOVKANS-UHFFFAOYSA-N 0.000 claims description 2
- GBLUIIINCIVDDD-UHFFFAOYSA-N 2-[2-(8-fluoroquinolin-2-yl)ethyl]-8-pyridin-4-ylisoquinolin-1-one Chemical compound N1=C2C(F)=CC=CC2=CC=C1CCN(C(C1=2)=O)C=CC1=CC=CC=2C1=CC=NC=C1 GBLUIIINCIVDDD-UHFFFAOYSA-N 0.000 claims description 2
- ULMDVRBWINKKKT-UHFFFAOYSA-N 3-(1-benzofuran-2-yl)-5-(2-quinolin-2-ylethyl)thieno[2,3-d]pyridazin-4-one Chemical compound C1=CC=C2OC(C3=CSC=4C=NN(CCC=5N=C6C=CC=CC6=CC=5)C(C3=4)=O)=CC2=C1 ULMDVRBWINKKKT-UHFFFAOYSA-N 0.000 claims description 2
- HRAMAKGPDRKFFD-UHFFFAOYSA-N 3-(1h-pyrazol-5-yl)-5-(2-quinolin-2-ylethyl)thieno[2,3-d]pyridazin-4-one Chemical compound C1=2C(=O)N(CCC=3N=C4C=CC=CC4=CC=3)N=CC=2SC=C1C=1C=CNN=1 HRAMAKGPDRKFFD-UHFFFAOYSA-N 0.000 claims description 2
- FVDXMNXFJQEXSP-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-5-yl)-5-(2-quinolin-2-ylethyl)thieno[2,3-d]pyridazin-4-one Chemical compound C1=C2OCCC2=CC(C2=CSC=3C=NN(CCC=4N=C5C=CC=CC5=CC=4)C(C2=3)=O)=C1 FVDXMNXFJQEXSP-UHFFFAOYSA-N 0.000 claims description 2
- PUCCFQQFKJXEIK-UHFFFAOYSA-N 3-(2,5-dichlorophenyl)-5-(2-quinolin-2-ylethyl)thieno[2,3-d]pyridazin-4-one Chemical compound ClC1=CC=C(Cl)C(C=2C=3C(=O)N(CCC=4N=C5C=CC=CC5=CC=4)N=CC=3SC=2)=C1 PUCCFQQFKJXEIK-UHFFFAOYSA-N 0.000 claims description 2
- DNGAPPWFPQYXHZ-UHFFFAOYSA-N 3-(2-chloro-4-fluorophenyl)-5-(2-quinolin-2-ylethyl)thieno[2,3-d]pyridazin-4-one Chemical compound ClC1=CC(F)=CC=C1C1=CSC2=C1C(=O)N(CCC=1N=C3C=CC=CC3=CC=1)N=C2 DNGAPPWFPQYXHZ-UHFFFAOYSA-N 0.000 claims description 2
- XUPANYHEJOSCDA-UHFFFAOYSA-N 3-(2-ethylphenyl)-5-(2-quinolin-2-ylethyl)thieno[2,3-d]pyridazin-4-one Chemical compound CCC1=CC=CC=C1C1=CSC2=C1C(=O)N(CCC=1N=C3C=CC=CC3=CC=1)N=C2 XUPANYHEJOSCDA-UHFFFAOYSA-N 0.000 claims description 2
- RYORFSMHEDEJPU-UHFFFAOYSA-N 3-(2-fluoro-4-methylphenyl)-5-(2-quinolin-2-ylethyl)thieno[2,3-d]pyridazin-4-one Chemical compound FC1=CC(C)=CC=C1C1=CSC2=C1C(=O)N(CCC=1N=C3C=CC=CC3=CC=1)N=C2 RYORFSMHEDEJPU-UHFFFAOYSA-N 0.000 claims description 2
- FVHHUOKOJFNQHF-UHFFFAOYSA-N 3-(2-fluoro-5-methoxyphenyl)-5-(2-quinolin-2-ylethyl)thieno[2,3-d]pyridazin-4-one Chemical compound COC1=CC=C(F)C(C=2C=3C(=O)N(CCC=4N=C5C=CC=CC5=CC=4)N=CC=3SC=2)=C1 FVHHUOKOJFNQHF-UHFFFAOYSA-N 0.000 claims description 2
- IJVFXZRAODURBL-UHFFFAOYSA-N 3-(2-fluoropyridin-4-yl)-5-[2-(6-fluoroquinolin-2-yl)cyclopropyl]thieno[3,2-c]pyridin-4-one Chemical compound C1=CC2=CC(F)=CC=C2N=C1C1CC1N(C(C=12)=O)C=CC=1SC=C2C1=CC=NC(F)=C1 IJVFXZRAODURBL-UHFFFAOYSA-N 0.000 claims description 2
- ZYXIVTZVKLFZKM-UHFFFAOYSA-N 3-(2-methylphenyl)-5-(2-quinolin-2-ylethyl)thieno[2,3-d]pyridazin-4-one Chemical compound CC1=CC=CC=C1C1=CSC2=C1C(=O)N(CCC=1N=C3C=CC=CC3=CC=1)N=C2 ZYXIVTZVKLFZKM-UHFFFAOYSA-N 0.000 claims description 2
- ZGDQKGYAOYVOIH-UHFFFAOYSA-N 3-(2-methylpyrimidin-5-yl)-5-(2-quinolin-2-ylcyclopropyl)thieno[3,2-c]pyridin-4-one Chemical compound C1=NC(C)=NC=C1C1=CSC2=C1C(=O)N(C1C(C1)C=1N=C3C=CC=CC3=CC=1)C=C2 ZGDQKGYAOYVOIH-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- 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
- C07D471/04—Ortho-condensed systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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| EP2994141A4 (en) | 2013-05-10 | 2016-11-23 | Nimbus Apollo Inc | ACC-HEMMER AND USES THEREOF |
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| US9988399B2 (en) | 2013-05-10 | 2018-06-05 | Gilead Apollo, Llc | Bicyclic compounds as ACC inhibitors and uses thereof |
| US9249163B2 (en) | 2013-06-11 | 2016-02-02 | Janssen Pharmaceutica Nv. | PDE10a inhibitors for the treatment of type II diabetes |
| US9193736B2 (en) | 2013-06-11 | 2015-11-24 | Janssen Pharmaceutica, Nv | PDE 10a inhibitors for the treatment of type II diabetes |
| US9453002B2 (en) | 2013-08-16 | 2016-09-27 | Janssen Pharmaceutica Nv | Substituted imidazoles as N-type calcium channel blockers |
| EP3126354B1 (en) * | 2014-04-04 | 2020-01-22 | H. Lundbeck A/S | Halogenated quinazolin-thf-amines as pde1 inhibitors |
| PT3597649T (pt) * | 2014-04-23 | 2022-01-21 | Dart Neuroscience Llc | Composições contendo compostos substituidos de [1,2,4]triazolo[1,5-a] pirimidin-7il como inibidores de pde2 |
| GB201416352D0 (en) * | 2014-09-16 | 2014-10-29 | Shire Internat Gmbh | Spirocyclic derivatives |
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| MA41291A (fr) | 2014-12-30 | 2017-11-07 | Forma Therapeutics Inc | Dérivés de la pyrrolotriazinone et de l'imidazotriazinone en tant qu'inhibiteurs de la protéase spécifique de l'ubiquitine n° 7 (usp7) pour le traitement d'un cancer |
| WO2016126926A1 (en) | 2015-02-05 | 2016-08-11 | Forma Therapeutics, Inc. | Quinazolinones and azaquinazolinones as ubiquitin-specific protease 7 inhibitors |
| HK1248221A1 (zh) | 2015-02-05 | 2018-10-12 | Forma Therapeutics, Inc. | 异噻唑啉酮类，吡唑并嘧啶酮类和吡咯并嘧啶酮作为泛蛋白特异性蛋白酶7抑制剂 |
| JP2018504431A (ja) | 2015-02-05 | 2018-02-15 | フォーマ セラピューティクス，インコーポレイテッド | ユビキチン特異的プロテアーゼ７阻害物質としてのチエノピリミジノン |
| WO2017003723A1 (en) | 2015-07-01 | 2017-01-05 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators and uses thereof |
| CN105669680B (zh) * | 2016-03-24 | 2018-02-23 | 南京药捷安康生物科技有限公司 | 吡咯并[2,1‑f][1,2,4]三嗪‑4(1H)‑酮衍生物类PDE9A抑制剂 |
| RU2750935C2 (ru) | 2016-06-22 | 2021-07-06 | Вандербильт Юниверсити | Положительные аллостерические модуляторы мускаринового ацетилхолинового рецептора m4 |
| MA46722A (fr) * | 2016-11-07 | 2019-09-11 | Univ Vanderbilt | Modulateurs allostériques positifs du récepteur muscarinique à l'acétylcholine m4 |
| MA46899A (fr) | 2016-11-07 | 2021-04-14 | Univ Vanderbilt | Modulateurs allostériques positifs du récepteur muscarinique de l'acétylcholine m4 |
| JP7099725B2 (ja) | 2016-11-07 | 2022-07-12 | ヴァンダービルト ユニヴァーシティ | ムスカリン性アセチルコリンレセプターｍ４のポジティブアロステリック調節因子 |
| CN108084199A (zh) * | 2017-06-13 | 2018-05-29 | 长沙理工大学 | 一种合成呋喃并[3,2-c]吡啶-4(5H)-酮衍生物的方法 |
| EP3658560A4 (en) | 2017-07-25 | 2021-01-06 | Crinetics Pharmaceuticals, Inc. | SOMATOSTAT IN MODULATORS AND USES THEREOF |
| US11833156B2 (en) | 2017-09-22 | 2023-12-05 | Jubilant Epipad LLC | Heterocyclic compounds as pad inhibitors |
| WO2019077631A1 (en) | 2017-10-18 | 2019-04-25 | Jubilant Biosys Limited | IMIDAZO-PYRIDINE COMPOUNDS FOR USE AS PAD INHIBITORS |
| KR20200085836A (ko) | 2017-11-06 | 2020-07-15 | 주빌런트 프로델 엘엘씨 | Pd1/pd-l1 활성화 억제제로서의 피리미딘 유도체 |
| BR112020010322A2 (pt) | 2017-11-24 | 2020-11-17 | Jubilant Episcribe Llc | composto da fórmula i; composto da fórmula ia; composto da fórmula ib; processo de preparação de compostos da fórmula i; composição farmacêutica; método para o tratamento e/ou prevenção de várias doenças; uso dos compostos; método para o tratamento de câncer; e método para o tratamento e/ou prevenção de uma afecção mediada por prmt5 ou um distúrbio proliferativo ou câncer |
| TW201930311A (zh) | 2017-12-05 | 2019-08-01 | 泛德比爾特大學 | 蕈毒鹼型乙醯膽鹼受體m4之正向別構調節劑 |
| US11376254B2 (en) | 2017-12-05 | 2022-07-05 | Vanderbilt University | Positive allosteric modulators of the muscarinic acetylcholine receptor M4 |
| CN112105610B (zh) | 2018-03-13 | 2024-01-26 | 朱比连特普罗德尔有限责任公司 | 作为pd1/pd-l1相互作用/活化的抑制剂的双环化合物 |
| AU2019243186A1 (en) | 2018-03-30 | 2020-10-15 | Biotheryx, Inc. | Thienopyrimidinone compounds |
| JP2024544552A (ja) * | 2021-11-09 | 2024-12-03 | ビジル・ニューロサイエンス・インコーポレイテッド | ミエロイド細胞に発現するトリガー受容体２アゴニストとしてのヘテロ環化合物 |
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| US20130116241A1 (en) | 2013-05-09 |
| JP2014534976A (ja) | 2014-12-25 |
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| BR112014011284A2 (pt) | 2017-05-02 |
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| US20160137668A1 (en) | 2016-05-19 |
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| AU2012334074A1 (en) | 2014-05-01 |
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| EP2776418B1 (en) | 2017-01-04 |
| SG11201402142VA (en) | 2014-06-27 |
| WO2013068470A1 (en) | 2013-05-16 |
| PE20141938A1 (es) | 2014-12-28 |
| NZ623727A (en) | 2016-06-24 |
| RU2014123316A (ru) | 2015-12-20 |
| CL2014001212A1 (es) | 2014-11-28 |
| US9273068B2 (en) | 2016-03-01 |
| IL232358A0 (en) | 2014-07-01 |
| GT201400089A (es) | 2015-09-30 |
| CO7030959A2 (es) | 2014-08-21 |
| AR088801A1 (es) | 2014-07-10 |
| DOP2014000097A (es) | 2014-07-15 |
| CA2852604A1 (en) | 2013-05-16 |
| US20130116233A1 (en) | 2013-05-09 |
| UY34445A (es) | 2013-06-28 |
| ZA201402966B (en) | 2017-08-30 |
| HK1201519A1 (en) | 2015-09-04 |
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