TWI457333B - 嗒酮化合物 - Google Patents
嗒酮化合物 Download PDFInfo
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- TWI457333B TWI457333B TW099103286A TW99103286A TWI457333B TW I457333 B TWI457333 B TW I457333B TW 099103286 A TW099103286 A TW 099103286A TW 99103286 A TW99103286 A TW 99103286A TW I457333 B TWI457333 B TW I457333B
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- substituted
- alkoxy
- ring
- compound
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- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title description 2
- -1 benzimidazol-2-yloxy Chemical group 0.000 claims description 488
- 150000001875 compounds Chemical class 0.000 claims description 434
- 125000001424 substituent group Chemical group 0.000 claims description 244
- 125000005843 halogen group Chemical group 0.000 claims description 240
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 121
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 116
- 150000003839 salts Chemical class 0.000 claims description 113
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 101
- 125000005842 heteroatom Chemical group 0.000 claims description 87
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 80
- 125000000623 heterocyclic group Chemical group 0.000 claims description 79
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 75
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 72
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 61
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 125000003118 aryl group Chemical group 0.000 claims description 54
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 53
- 239000003814 drug Substances 0.000 claims description 52
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 52
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 50
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims description 45
- 125000003545 alkoxy group Chemical group 0.000 claims description 44
- 229910052717 sulfur Inorganic materials 0.000 claims description 43
- 238000004519 manufacturing process Methods 0.000 claims description 41
- 239000011593 sulfur Substances 0.000 claims description 40
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 39
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 39
- 229910052760 oxygen Inorganic materials 0.000 claims description 39
- 239000001301 oxygen Substances 0.000 claims description 39
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 36
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 125000000468 ketone group Chemical group 0.000 claims description 36
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 36
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 35
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 33
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 32
- 239000003795 chemical substances by application Substances 0.000 claims description 32
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 27
- 150000001412 amines Chemical class 0.000 claims description 27
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
- 125000004414 alkyl thio group Chemical group 0.000 claims description 23
- 201000000980 schizophrenia Diseases 0.000 claims description 23
- 125000002883 imidazolyl group Chemical group 0.000 claims description 22
- 125000003282 alkyl amino group Chemical group 0.000 claims description 18
- 229930194542 Keto Natural products 0.000 claims description 17
- 125000003386 piperidinyl group Chemical group 0.000 claims description 17
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 17
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 15
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 15
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 15
- 150000003536 tetrazoles Chemical group 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 150000003852 triazoles Chemical group 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- 101001072037 Homo sapiens cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Proteins 0.000 claims description 13
- 125000002393 azetidinyl group Chemical group 0.000 claims description 13
- 102100036377 cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Human genes 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 12
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 11
- 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 claims description 11
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 10
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 229960005286 carbaryl Drugs 0.000 claims description 9
- CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical compound C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
- 125000002912 morpholin-4-ylsulfonyl group Chemical group O1C([H])([H])C([H])([H])N(S(=O)(=O)[*])C([H])([H])C1([H])[H] 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 208000017194 Affective disease Diseases 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 208000019022 Mood disease Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 claims description 3
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical group NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 3
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 3
- 206010003805 Autism Diseases 0.000 claims description 3
- 208000020706 Autistic disease Diseases 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 3
- 206010013663 drug dependence Diseases 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 4
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 claims 4
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims 2
- 125000005936 piperidyl group Chemical group 0.000 claims 2
- 206010008748 Chorea Diseases 0.000 claims 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 1
- 150000001555 benzenes Chemical group 0.000 claims 1
- 208000012601 choreatic disease Diseases 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 196
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 156
- 239000000203 mixture Substances 0.000 description 135
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 115
- 239000002904 solvent Substances 0.000 description 107
- 239000000243 solution Substances 0.000 description 81
- 235000002639 sodium chloride Nutrition 0.000 description 79
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 75
- 238000000034 method Methods 0.000 description 70
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 68
- 239000002585 base Substances 0.000 description 65
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 58
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- 229940079593 drug Drugs 0.000 description 42
- 230000035484 reaction time Effects 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 35
- 238000005481 NMR spectroscopy Methods 0.000 description 34
- 238000000746 purification Methods 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 230000002829 reductive effect Effects 0.000 description 30
- 235000010288 sodium nitrite Nutrition 0.000 description 29
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 27
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 27
- 239000001632 sodium acetate Substances 0.000 description 27
- 235000017281 sodium acetate Nutrition 0.000 description 27
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 25
- 235000011054 acetic acid Nutrition 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000010438 heat treatment Methods 0.000 description 24
- 239000000047 product Substances 0.000 description 23
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
- 125000003277 amino group Chemical group 0.000 description 22
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 19
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 19
- MJXUFBUYCLOLBZ-UHFFFAOYSA-N C(C)(=N)N.CC(=O)C Chemical compound C(C)(=N)N.CC(=O)C MJXUFBUYCLOLBZ-UHFFFAOYSA-N 0.000 description 18
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 229910052731 fluorine Inorganic materials 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 239000003054 catalyst Substances 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 description 15
- 125000000732 arylene group Chemical group 0.000 description 15
- 125000000547 substituted alkyl group Chemical group 0.000 description 15
- 125000005974 C6-C14 arylcarbonyl group Chemical group 0.000 description 14
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- 150000002367 halogens Chemical class 0.000 description 14
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 13
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 description 13
- 150000007524 organic acids Chemical class 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 12
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 12
- 125000001769 aryl amino group Chemical group 0.000 description 12
- 238000007796 conventional method Methods 0.000 description 12
- 125000005415 substituted alkoxy group Chemical group 0.000 description 12
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 11
- 125000001691 aryl alkyl amino group Chemical group 0.000 description 11
- 239000011737 fluorine Substances 0.000 description 11
- 229910052763 palladium Inorganic materials 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 229940002612 prodrug Drugs 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 10
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 9
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 9
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 8
- 206010012289 Dementia Diseases 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 230000002378 acidificating effect Effects 0.000 description 8
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 8
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 239000007810 chemical reaction solvent Substances 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 229910052802 copper Inorganic materials 0.000 description 8
- 239000010949 copper Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 7
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 7
- 229940123773 Phosphodiesterase 10A inhibitor Drugs 0.000 description 7
- 230000005856 abnormality Effects 0.000 description 7
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 125000001153 fluoro group Chemical group F* 0.000 description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 229910017604 nitric acid Inorganic materials 0.000 description 7
- 150000002825 nitriles Chemical class 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
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Classifications
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| WO2015006689A1 (en) | 2013-07-12 | 2015-01-15 | University Of South Alabama | Treatment and diagnosis of cancer and precancerous conditions using pde10a inhibitors and methods to measure pde10a expression |
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| CN108498868B (zh) * | 2018-04-03 | 2020-09-15 | 北京大学口腔医学院 | 具有细胞外基质电学拓扑特征的带电复合膜及其制备方法 |
| CN110407806B (zh) * | 2018-04-28 | 2021-08-17 | 深圳微芯生物科技股份有限公司 | 甲酰胺类化合物、其制备方法及其应用 |
| WO2019241787A1 (en) * | 2018-06-15 | 2019-12-19 | The Regents Of The University Of Colorado A Body Corporate | Novel cyclic gmp-amp synthase (cgas) inhibitors and their method of use |
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