KR20160116054A - 트리아졸로〔4,5-ｄ〕피리미딘 유도체들 및 이들의 퓨린 수용체 안타고니스트로서의 용도 - Google Patents
트리아졸로〔4,5-ｄ〕피리미딘 유도체들 및 이들의 퓨린 수용체 안타고니스트로서의 용도 Download PDFInfo
- Publication number
- KR20160116054A KR20160116054A KR1020167026831A KR20167026831A KR20160116054A KR 20160116054 A KR20160116054 A KR 20160116054A KR 1020167026831 A KR1020167026831 A KR 1020167026831A KR 20167026831 A KR20167026831 A KR 20167026831A KR 20160116054 A KR20160116054 A KR 20160116054A
- Authority
- KR
- South Korea
- Prior art keywords
- pyrimidin
- amine
- triazolo
- ylmethyl
- methyl
- 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.)
- Ceased
Links
- 102000000033 Purinergic Receptors Human genes 0.000 title claims abstract description 14
- 108010080192 Purinergic Receptors Proteins 0.000 title claims abstract description 14
- 229940044551 receptor antagonist Drugs 0.000 title description 3
- 239000002464 receptor antagonist Substances 0.000 title description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 182
- 238000000034 method Methods 0.000 claims abstract description 54
- 238000011282 treatment Methods 0.000 claims abstract description 39
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- -1 5-methyl-furan-2-yl Chemical group 0.000 claims description 136
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 104
- FVLAYJRLBLHIPV-UHFFFAOYSA-N pyrimidin-5-amine Chemical compound NC1=CN=CN=C1 FVLAYJRLBLHIPV-UHFFFAOYSA-N 0.000 claims description 62
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 53
- 229960005305 adenosine Drugs 0.000 claims description 53
- 102000005962 receptors Human genes 0.000 claims description 51
- 108020003175 receptors Proteins 0.000 claims description 51
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 34
- 208000018737 Parkinson disease Diseases 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 28
- 229940079593 drug Drugs 0.000 claims description 24
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 24
- 208000035475 disorder Diseases 0.000 claims description 22
- 125000004429 atom Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- 239000012453 solvate Substances 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 12
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 11
- 206010034010 Parkinsonism Diseases 0.000 claims description 11
- 208000002193 Pain Diseases 0.000 claims description 10
- 208000027089 Parkinsonian disease Diseases 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 8
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 6
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 6
- 230000007074 memory dysfunction Effects 0.000 claims description 6
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 5
- 208000016285 Movement disease Diseases 0.000 claims description 5
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 5
- 230000003920 cognitive function Effects 0.000 claims description 5
- 239000003136 dopamine receptor stimulating agent Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 201000003631 narcolepsy Diseases 0.000 claims description 5
- 230000000750 progressive effect Effects 0.000 claims description 5
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 208000000094 Chronic Pain Diseases 0.000 claims description 4
- 208000003098 Ganglion Cysts Diseases 0.000 claims description 4
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 claims description 4
- 208000005793 Restless legs syndrome Diseases 0.000 claims description 4
- 208000005400 Synovial Cyst Diseases 0.000 claims description 4
- 208000018839 Wilson disease Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 230000000386 athletic effect Effects 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 208000005298 acute pain Diseases 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 230000007850 degeneration Effects 0.000 claims description 3
- 206010014599 encephalitis Diseases 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- LZJBVOMKJQWHML-UHFFFAOYSA-N 3-[[6-(methoxymethyl)pyridin-2-yl]methyl]-7-phenyltriazolo[4,5-d]pyrimidin-5-amine Chemical compound COCC1=CC=CC(CN2C3=NC(N)=NC(=C3N=N2)C=2C=CC=CC=2)=N1 LZJBVOMKJQWHML-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 230000001054 cortical effect Effects 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 231100000572 poisoning Toxicity 0.000 claims description 2
- 230000000607 poisoning effect Effects 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 206010011224 Cough Diseases 0.000 claims 1
- 206010033799 Paralysis Diseases 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 47
- 230000002265 prevention Effects 0.000 abstract description 3
- 239000000018 receptor agonist Substances 0.000 abstract 1
- 229940044601 receptor agonist Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 92
- 239000000243 solution Substances 0.000 description 79
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
- 239000007787 solid Substances 0.000 description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 44
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 230000027455 binding Effects 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 23
- 238000010561 standard procedure Methods 0.000 description 19
- QMHIMXFNBOYPND-UHFFFAOYSA-N 4-methylthiazole Chemical compound CC1=CSC=N1 QMHIMXFNBOYPND-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 16
- 108050000203 Adenosine receptors Proteins 0.000 description 16
- 102000009346 Adenosine receptors Human genes 0.000 description 16
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 230000014759 maintenance of location Effects 0.000 description 15
- 239000000284 extract Substances 0.000 description 14
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 13
- 239000002467 adenosine A2a receptor antagonist Substances 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 12
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 12
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 238000007792 addition Methods 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000005557 antagonist Substances 0.000 description 9
- 239000012230 colorless oil Substances 0.000 description 9
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 8
- 206010012289 Dementia Diseases 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 229960003878 haloperidol Drugs 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- VQKFNUFAXTZWDK-UHFFFAOYSA-N 2-Methylfuran Chemical compound CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 230000029936 alkylation Effects 0.000 description 7
- 238000005804 alkylation reaction Methods 0.000 description 7
- 239000000939 antiparkinson agent Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 210000003169 central nervous system Anatomy 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 150000002430 hydrocarbons Chemical group 0.000 description 7
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 7
- 235000010288 sodium nitrite Nutrition 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 7
- VJCQEPWQSBKWTE-UHFFFAOYSA-N 2h-triazolo[4,5-d]pyrimidin-5-amine Chemical compound N1=C(N)N=CC2=NNN=C21 VJCQEPWQSBKWTE-UHFFFAOYSA-N 0.000 description 6
- HXZSXRIRQLDGTG-UHFFFAOYSA-N 4-nitropyrimidin-2-amine Chemical compound NC1=NC=CC([N+]([O-])=O)=N1 HXZSXRIRQLDGTG-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 6
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 6
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 230000000648 anti-parkinson Effects 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 6
- 229960001948 caffeine Drugs 0.000 description 6
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 6
- 208000015122 neurodegenerative disease Diseases 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 5
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 5
- FFBDFADSZUINTG-UHFFFAOYSA-N DPCPX Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1CCCC1 FFBDFADSZUINTG-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 229910004298 SiO 2 Inorganic materials 0.000 description 5
- 229960004046 apomorphine Drugs 0.000 description 5
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 208000010877 cognitive disease Diseases 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 229960003638 dopamine Drugs 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 208000031225 myocardial ischemia Diseases 0.000 description 5
- XYWHZUCZNRMJGO-UHFFFAOYSA-N n-(2-amino-4,6-dichloropyrimidin-5-yl)formamide Chemical compound NC1=NC(Cl)=C(NC=O)C(Cl)=N1 XYWHZUCZNRMJGO-UHFFFAOYSA-N 0.000 description 5
- 230000004112 neuroprotection Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 5
- 239000002287 radioligand Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- LQBVARDGLYXGHF-UHFFFAOYSA-N triazolo[4,5-d]pyrimidin-2-amine Chemical compound C1=NC=NC2=NN(N)N=C21 LQBVARDGLYXGHF-UHFFFAOYSA-N 0.000 description 5
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 5
- XDBHWPLGGBLUHH-UHFFFAOYSA-N (3-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C#N)=C1 XDBHWPLGGBLUHH-UHFFFAOYSA-N 0.000 description 4
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 4
- QUTSYCOAZVHGGT-UHFFFAOYSA-N 2,6-bis(bromomethyl)pyridine Chemical compound BrCC1=CC=CC(CBr)=N1 QUTSYCOAZVHGGT-UHFFFAOYSA-N 0.000 description 4
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 4
- 206010008120 Cerebral ischaemia Diseases 0.000 description 4
- 229920002873 Polyethylenimine Polymers 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- 208000024248 Vascular System injury Diseases 0.000 description 4
- 208000012339 Vascular injury Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000013024 dilution buffer Substances 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 208000013403 hyperactivity Diseases 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- 230000009871 nonspecific binding Effects 0.000 description 4
- LMYJGUNNJIDROI-UHFFFAOYSA-N oxan-4-ol Chemical compound OC1CCOCC1 LMYJGUNNJIDROI-UHFFFAOYSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
- LOGOEBMHHXYBID-WBKNRDRNSA-N (2s,3s,4r,5r)-5-[6-[(4-amino-3-iodanylphenyl)methylamino]purin-9-yl]-3,4-dihydroxy-n-methyloxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NC)O[C@H]1N1C2=NC=NC(NCC=3C=C([125I])C(N)=CC=3)=C2N=C1 LOGOEBMHHXYBID-WBKNRDRNSA-N 0.000 description 3
- LMJIDBVSSSPRII-UHFFFAOYSA-N (5-methylfuran-2-yl)boronic acid Chemical compound CC1=CC=C(B(O)O)O1 LMJIDBVSSSPRII-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- OFPWMRMIFDHXFE-UHFFFAOYSA-N 2-(bromomethyl)pyridine Chemical compound BrCC1=CC=CC=N1 OFPWMRMIFDHXFE-UHFFFAOYSA-N 0.000 description 3
- XYZUUYCGBQQGRC-UHFFFAOYSA-N 2-[6-(hydroxymethyl)pyridin-2-yl]propan-2-ol Chemical compound CC(C)(O)C1=CC=CC(CO)=N1 XYZUUYCGBQQGRC-UHFFFAOYSA-N 0.000 description 3
- JBKVXVOEFRYZMV-UHFFFAOYSA-N 2-amino-6-(5-methylfuran-2-yl)-5-nitro-1h-pyrimidin-4-one Chemical compound O1C(C)=CC=C1C1=NC(N)=NC(O)=C1[N+]([O-])=O JBKVXVOEFRYZMV-UHFFFAOYSA-N 0.000 description 3
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- PWTBZOIUWZOPFT-XHHURNKPSA-N 4-[2-[[7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl]amino]ethyl]-2-tritiophenol Chemical compound C1=C(O)C([3H])=CC(CCNC2=NC3=NC(=NN3C(N)=N2)C=2OC=CC=2)=C1 PWTBZOIUWZOPFT-XHHURNKPSA-N 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 3
- MLACDGUOKDOLGC-UHFFFAOYSA-N 5-(2-aminoethyl)benzene-1,2,4-triol;hydron;bromide Chemical compound Br.NCCC1=CC(O)=C(O)C=C1O MLACDGUOKDOLGC-UHFFFAOYSA-N 0.000 description 3
- WZHJDCUWKLWQRC-UHFFFAOYSA-N 7-(5-methylfuran-2-yl)-2h-triazolo[4,5-d]pyrimidin-5-amine Chemical compound O1C(C)=CC=C1C1=NC(N)=NC2=C1NN=N2 WZHJDCUWKLWQRC-UHFFFAOYSA-N 0.000 description 3
- 102000055025 Adenosine deaminases Human genes 0.000 description 3
- 206010003694 Atrophy Diseases 0.000 description 3
- 201000006474 Brain Ischemia Diseases 0.000 description 3
- PAOANWZGLPPROA-RQXXJAGISA-N CGS-21680 Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(NCCC=3C=CC(CCC(O)=O)=CC=3)=NC(N)=C2N=C1 PAOANWZGLPPROA-RQXXJAGISA-N 0.000 description 3
- 208000009132 Catalepsy Diseases 0.000 description 3
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 3
- YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 3
- 208000012661 Dyskinesia Diseases 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010047853 Waxy flexibility Diseases 0.000 description 3
- 230000006978 adaptation Effects 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 230000008485 antagonism Effects 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 150000001543 aryl boronic acids Chemical class 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 230000037444 atrophy Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- 229960003914 desipramine Drugs 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 229940052760 dopamine agonists Drugs 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 208000001286 intracranial vasospasm Diseases 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 210000001577 neostriatum Anatomy 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 229960000278 theophylline Drugs 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 3
- 208000019553 vascular disease Diseases 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- XDPCNPCKDGQBAN-BYPYZUCNSA-N (3s)-oxolan-3-ol Chemical compound O[C@H]1CCOC1 XDPCNPCKDGQBAN-BYPYZUCNSA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- JARXILKNCSJPKM-UHFFFAOYSA-N 1-(1-oxidopyridin-1-ium-2-yl)cyclobutan-1-ol Chemical compound C=1C=CC=[N+]([O-])C=1C1(O)CCC1 JARXILKNCSJPKM-UHFFFAOYSA-N 0.000 description 2
- MVMBHNHVCKMIPK-UHFFFAOYSA-N 1-(1-oxidopyridin-1-ium-2-yl)cyclopentan-1-ol Chemical compound C=1C=CC=[N+]([O-])C=1C1(O)CCCC1 MVMBHNHVCKMIPK-UHFFFAOYSA-N 0.000 description 2
- ZOGWPVWEMBRPGW-UHFFFAOYSA-N 1-[6-(aminomethyl)pyridin-2-yl]cyclobutan-1-ol Chemical compound NCC1=CC=CC(C2(O)CCC2)=N1 ZOGWPVWEMBRPGW-UHFFFAOYSA-N 0.000 description 2
- VQIKFXCDAHZGQT-UHFFFAOYSA-N 1-[6-(aminomethyl)pyridin-2-yl]cyclopentan-1-ol Chemical compound NCC1=CC=CC(C2(O)CCCC2)=N1 VQIKFXCDAHZGQT-UHFFFAOYSA-N 0.000 description 2
- KMJZWCDFXHFBQD-UHFFFAOYSA-N 1-pyridin-2-ylcyclobutan-1-ol Chemical compound C=1C=CC=NC=1C1(O)CCC1 KMJZWCDFXHFBQD-UHFFFAOYSA-N 0.000 description 2
- QSVMFIDDAPYMRD-UHFFFAOYSA-N 1-pyridin-2-ylcyclopentan-1-ol Chemical compound C=1C=CC=NC=1C1(O)CCCC1 QSVMFIDDAPYMRD-UHFFFAOYSA-N 0.000 description 2
- SVFGOOOWKUXAPZ-UHFFFAOYSA-N 2-(bromomethyl)-6-(2-propan-2-yloxyethoxymethyl)pyridine Chemical compound CC(C)OCCOCC1=CC=CC(CBr)=N1 SVFGOOOWKUXAPZ-UHFFFAOYSA-N 0.000 description 2
- NBZAQPCYHYHLJO-UHFFFAOYSA-N 2-(bromomethyl)-6-(oxolan-2-ylmethoxymethyl)pyridine Chemical compound BrCC1=CC=CC(COCC2OCCC2)=N1 NBZAQPCYHYHLJO-UHFFFAOYSA-N 0.000 description 2
- NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 2
- AXWKZUIWQFZIRF-UHFFFAOYSA-N 2-[6-(aminomethyl)pyridin-2-yl]propan-2-ol Chemical compound CC(C)(O)C1=CC=CC(CN)=N1 AXWKZUIWQFZIRF-UHFFFAOYSA-N 0.000 description 2
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- SLANLHXGWSJIHY-UHFFFAOYSA-N 6-(1-hydroxycyclobutyl)pyridine-2-carbonitrile Chemical compound C=1C=CC(C#N)=NC=1C1(O)CCC1 SLANLHXGWSJIHY-UHFFFAOYSA-N 0.000 description 2
- MJGSUEJOMZHWSF-UHFFFAOYSA-N 6-(1-hydroxycyclopentyl)pyridine-2-carbonitrile Chemical compound C=1C=CC(C#N)=NC=1C1(O)CCCC1 MJGSUEJOMZHWSF-UHFFFAOYSA-N 0.000 description 2
- DEUADSNQWDJUOX-UHFFFAOYSA-N 7-chloro-3-[[6-(methoxymethyl)pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound COCC1=CC=CC(CN2C3=NC(N)=NC(Cl)=C3N=N2)=N1 DEUADSNQWDJUOX-UHFFFAOYSA-N 0.000 description 2
- WBWFIUAVMCNYPG-BQYQJAHWSA-N 8-(3-chlorostyryl)caffeine Chemical group N=1C=2N(C)C(=O)N(C)C(=O)C=2N(C)C=1\C=C\C1=CC=CC(Cl)=C1 WBWFIUAVMCNYPG-BQYQJAHWSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 208000027534 Emotional disease Diseases 0.000 description 2
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000004454 Hyperalgesia Diseases 0.000 description 2
- 208000032382 Ischaemic stroke Diseases 0.000 description 2
- UTLPKQYUXOEJIL-UHFFFAOYSA-N LSM-3822 Chemical compound N1=CC=2C3=NC(C=4OC=CC=4)=NN3C(N)=NC=2N1CCC1=CC=CC=C1 UTLPKQYUXOEJIL-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- VYTJENNDCVVQEU-UHFFFAOYSA-N [6-(difluoromethoxymethyl)pyridin-2-yl]methanol Chemical compound OCC1=CC=CC(COC(F)F)=N1 VYTJENNDCVVQEU-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 125000006466 alkoxy alkyl cycloalkyl group Chemical group 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 229940072107 ascorbate Drugs 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 230000006999 cognitive decline Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 210000005064 dopaminergic neuron Anatomy 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000006742 locomotor activity Effects 0.000 description 2
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 208000024714 major depressive disease Diseases 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 239000002581 neurotoxin Substances 0.000 description 2
- 231100000618 neurotoxin Toxicity 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 230000001314 paroxysmal effect Effects 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 2
- FUXJMHXHGDAHPD-UHFFFAOYSA-N pyrimidine-2-carboxamide Chemical compound NC(=O)C1=NC=CC=N1 FUXJMHXHGDAHPD-UHFFFAOYSA-N 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 2
- 210000003625 skull Anatomy 0.000 description 2
- 230000007958 sleep Effects 0.000 description 2
- 208000019116 sleep disease Diseases 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 208000002025 tabes dorsalis Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- SZBULDQSDUXAPJ-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[6-(cyclohexylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(NC3CCCCC3)=C2N=C1 SZBULDQSDUXAPJ-XNIJJKJLSA-N 0.000 description 1
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- XDDGKNRSCDEWBR-UHFFFAOYSA-N (6-bromopyridin-2-yl)methanol Chemical compound OCC1=CC=CC(Br)=N1 XDDGKNRSCDEWBR-UHFFFAOYSA-N 0.000 description 1
- LXRCSRYYCAEDRJ-UHFFFAOYSA-N (6-bromopyridin-2-yl)methoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCC1=CC=CC(Br)=N1 LXRCSRYYCAEDRJ-UHFFFAOYSA-N 0.000 description 1
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- 0 *C(*)(c1nc(C[n]2nnc3c2nc(N)nc3*)ccc1)O* Chemical compound *C(*)(c1nc(C[n]2nnc3c2nc(N)nc3*)ccc1)O* 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- KOCZAVMDAZLYBJ-UHFFFAOYSA-N 1-[6-(bromomethyl)-4-methylpyridin-2-yl]propan-2-ol Chemical compound CC1=CC(=NC(=C1)CBr)CC(C)O KOCZAVMDAZLYBJ-UHFFFAOYSA-N 0.000 description 1
- WTYPJWMERVGLHE-UHFFFAOYSA-N 1-[6-(bromomethyl)pyridin-2-yl]cyclohexan-1-ol Chemical compound C=1C=CC(CBr)=NC=1C1(O)CCCCC1 WTYPJWMERVGLHE-UHFFFAOYSA-N 0.000 description 1
- YPMZGKUPRMFLFO-UHFFFAOYSA-N 1-[6-[(2-amino-7-chloro-1h-triazolo[4,5-d]pyrimidin-3-yl)methyl]pyridin-2-yl]cyclopentan-1-ol Chemical compound NN1NC(C(=NC=N2)Cl)=C2N1CC(N=1)=CC=CC=1C1(O)CCCC1 YPMZGKUPRMFLFO-UHFFFAOYSA-N 0.000 description 1
- XNXGMIGCARIDKO-UHFFFAOYSA-N 1-[6-[(5-amino-7-phenyltriazolo[4,5-d]pyrimidin-3-yl)methyl]pyridin-2-yl]cyclopentan-1-ol Chemical compound C=12N=NN(CC=3N=C(C=CC=3)C3(O)CCCC3)C2=NC(N)=NC=1C1=CC=CC=C1 XNXGMIGCARIDKO-UHFFFAOYSA-N 0.000 description 1
- FYDHMWHJZDBADJ-UHFFFAOYSA-N 1-[6-[(5-amino-7-phenyltriazolo[4,5-d]pyrimidin-3-yl)methyl]pyridin-2-yl]pyrrolidin-2-one Chemical compound C=12N=NN(CC=3N=C(C=CC=3)N3C(CCC3)=O)C2=NC(N)=NC=1C1=CC=CC=C1 FYDHMWHJZDBADJ-UHFFFAOYSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- MIGAMSKMVLYMHY-UHFFFAOYSA-N 1-[6-[[(2-amino-6-chloropyrimidin-4-yl)amino]methyl]pyridin-2-yl]pyrrolidin-2-one Chemical compound C1CC(=O)N(C1)C2=CC=CC(=N2)CNC3=CC(=NC(=N3)N)Cl MIGAMSKMVLYMHY-UHFFFAOYSA-N 0.000 description 1
- IENFLCUMMJPJQN-UHFFFAOYSA-N 1-[6-[[5-(chloroamino)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]cyclobutan-1-ol Chemical compound ClNC=1N=CC2=C(N=1)N(N=N2)CC1=NC(=CC=C1)C1(CCC1)O IENFLCUMMJPJQN-UHFFFAOYSA-N 0.000 description 1
- ZCIMLPGZYISKTM-UHFFFAOYSA-N 1-[6-[[5-amino-7-(3-methoxyphenyl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]cyclobutan-1-ol Chemical compound COC1=CC=CC(C=2C=3N=NN(CC=4N=C(C=CC=4)C4(O)CCC4)C=3N=C(N)N=2)=C1 ZCIMLPGZYISKTM-UHFFFAOYSA-N 0.000 description 1
- XPQLAYQODILNNG-UHFFFAOYSA-N 1-[6-[[5-amino-7-(3-methoxyphenyl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]cyclopentan-1-ol Chemical compound COC1=CC=CC(C=2C=3N=NN(CC=4N=C(C=CC=4)C4(O)CCCC4)C=3N=C(N)N=2)=C1 XPQLAYQODILNNG-UHFFFAOYSA-N 0.000 description 1
- NCBRBZZVSUEOFQ-UHFFFAOYSA-N 1-[6-[[5-amino-7-(4-methyl-1,3-thiazol-2-yl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]cyclopentan-1-ol Chemical compound CC1=CSC(C=2C=3N=NN(CC=4N=C(C=CC=4)C4(O)CCCC4)C=3N=C(N)N=2)=N1 NCBRBZZVSUEOFQ-UHFFFAOYSA-N 0.000 description 1
- PGCTZXXIHHZPHM-UHFFFAOYSA-N 1-[6-[[5-amino-7-(5-methylfuran-2-yl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]cyclobutan-1-ol Chemical compound O1C(C)=CC=C1C1=NC(N)=NC2=C1N=NN2CC1=CC=CC(C2(O)CCC2)=N1 PGCTZXXIHHZPHM-UHFFFAOYSA-N 0.000 description 1
- WRQYDKYVNGEQCW-UHFFFAOYSA-N 1-[6-[[5-amino-7-(5-methylfuran-2-yl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]cyclopentan-1-ol Chemical compound O1C(C)=CC=C1C1=NC(N)=NC2=C1N=NN2CC1=CC=CC(C2(O)CCCC2)=N1 WRQYDKYVNGEQCW-UHFFFAOYSA-N 0.000 description 1
- WHNUSOAQELOMAE-UHFFFAOYSA-N 1-[6-[[tert-butyl(dimethyl)silyl]oxymethyl]pyridin-2-yl]cyclohexan-1-ol Chemical compound CC(C)(C)[Si](C)(C)OCC1=CC=CC(C2(O)CCCCC2)=N1 WHNUSOAQELOMAE-UHFFFAOYSA-N 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 1
- VESFYGOXGYREOK-JTQLQIEISA-N 1-oxido-2-[[(3s)-oxolan-3-yl]oxymethyl]pyridin-1-ium Chemical compound [O-][N+]1=CC=CC=C1CO[C@@H]1COCC1 VESFYGOXGYREOK-JTQLQIEISA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- VYDQUABHDFWIIX-UHFFFAOYSA-N 2,2-difluoro-2-fluorosulfonylacetic acid Chemical compound OC(=O)C(F)(F)S(F)(=O)=O VYDQUABHDFWIIX-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- CETSXNCIBVRWEC-UHFFFAOYSA-N 2-(azidomethyl)pyridine Chemical compound [N-]=[N+]=NCC1=CC=CC=N1 CETSXNCIBVRWEC-UHFFFAOYSA-N 0.000 description 1
- WCKXISHTUWEIMQ-UHFFFAOYSA-N 2-(bromomethyl)-6-(2-methoxypropan-2-yl)pyridine Chemical compound COC(C)(C)C1=CC=CC(CBr)=N1 WCKXISHTUWEIMQ-UHFFFAOYSA-N 0.000 description 1
- QEUIVJQJSCVCFV-UHFFFAOYSA-N 2-(bromomethyl)-6-(difluoromethoxymethyl)pyridine Chemical compound FC(F)OCC1=CC=CC(CBr)=N1 QEUIVJQJSCVCFV-UHFFFAOYSA-N 0.000 description 1
- VXVYDSVTWUSLNY-UHFFFAOYSA-N 2-(bromomethyl)-6-(oxolan-3-ylmethoxymethyl)pyridine Chemical compound BrCC1=CC=CC(COCC2COCC2)=N1 VXVYDSVTWUSLNY-UHFFFAOYSA-N 0.000 description 1
- OEMHVRVTVJOLFI-NSHDSACASA-N 2-(bromomethyl)-6-[[(3s)-oxolan-3-yl]oxymethyl]pyridine Chemical compound BrCC1=CC=CC(CO[C@@H]2COCC2)=N1 OEMHVRVTVJOLFI-NSHDSACASA-N 0.000 description 1
- JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 1
- AVDUKUCLMGVSRK-UHFFFAOYSA-N 2-(difluoromethoxymethyl)-6-methylpyridine Chemical compound CC1=NC(=CC=C1)COC(F)F AVDUKUCLMGVSRK-UHFFFAOYSA-N 0.000 description 1
- QDTSINVSGKAPBV-UHFFFAOYSA-N 2-(methoxymethyl)pyridine Chemical compound COCC1=CC=CC=N1 QDTSINVSGKAPBV-UHFFFAOYSA-N 0.000 description 1
- IVVPYTQBOKXDHC-UHFFFAOYSA-N 2-[6-(azidomethyl)pyridin-2-yl]propan-2-ol Chemical compound CC(C)(O)C1=CC=CC(CN=[N+]=[N-])=N1 IVVPYTQBOKXDHC-UHFFFAOYSA-N 0.000 description 1
- QWNXNHDKTIUGQB-UHFFFAOYSA-N 2-[6-(bromomethyl)pyridin-2-yl]propan-2-ol Chemical compound CC(C)(O)C1=CC=CC(CBr)=N1 QWNXNHDKTIUGQB-UHFFFAOYSA-N 0.000 description 1
- RYRFIQRWORDCKZ-UHFFFAOYSA-N 2-[6-[(2-amino-5-chloro-1H-triazolo[4,5-d]pyrimidin-3-yl)methyl]pyridin-2-yl]propan-2-ol Chemical compound ClC=1N=CC2=C(N=1)N(N(N2)N)CC1=NC(=CC=C1)C(C)(C)O RYRFIQRWORDCKZ-UHFFFAOYSA-N 0.000 description 1
- WBQDITDDICQDQQ-UHFFFAOYSA-N 2-[6-[[5-amino-7-(3-methoxyphenyl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]propan-2-ol Chemical compound COC1=CC=CC(C=2C=3N=NN(CC=4N=C(C=CC=4)C(C)(C)O)C=3N=C(N)N=2)=C1 WBQDITDDICQDQQ-UHFFFAOYSA-N 0.000 description 1
- YQYKENUCSZTMJE-UHFFFAOYSA-N 2-[6-[[5-amino-7-(4-methyl-1,3-thiazol-2-yl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]propan-2-ol Chemical compound CC1=CSC(C=2C=3N=NN(CC=4N=C(C=CC=4)C(C)(C)O)C=3N=C(N)N=2)=N1 YQYKENUCSZTMJE-UHFFFAOYSA-N 0.000 description 1
- XPZYUVLLSFGKPS-UHFFFAOYSA-N 2-[6-[[5-amino-7-(5-methylfuran-2-yl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]propan-2-ol Chemical compound O1C(C)=CC=C1C1=NC(N)=NC2=C1N=NN2CC1=CC=CC(C(C)(C)O)=N1 XPZYUVLLSFGKPS-UHFFFAOYSA-N 0.000 description 1
- IRWUZWXIWRVNSS-UHFFFAOYSA-N 2-[6-tert-butyl-5-(dimethylsilyloxymethyl)pyridin-2-yl]propan-2-ol Chemical compound C(C)(C)(C)C1=NC(=CC=C1CO[SiH](C)C)C(C)(C)O IRWUZWXIWRVNSS-UHFFFAOYSA-N 0.000 description 1
- XPBMPKIFSUBHDG-JTQLQIEISA-N 2-[[(3s)-oxolan-3-yl]oxymethyl]pyridine Chemical compound C=1C=CC=NC=1CO[C@H]1CCOC1 XPBMPKIFSUBHDG-JTQLQIEISA-N 0.000 description 1
- UTTPUMOOQSNOHH-UHFFFAOYSA-N 2-amino-6-chloro-5-nitro-1h-pyrimidin-4-one Chemical compound NC1=NC(=O)C([N+]([O-])=O)=C(Cl)N1 UTTPUMOOQSNOHH-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- 229940093475 2-ethoxyethanol Drugs 0.000 description 1
- ZPHQQAXECGSBSE-UHFFFAOYSA-N 2-methyl-6-(oxolan-3-ylmethoxymethyl)pyridine Chemical compound CC1=NC(=CC=C1)COCC1COCC1 ZPHQQAXECGSBSE-UHFFFAOYSA-N 0.000 description 1
- UQOKRDJILZMZKU-UHFFFAOYSA-N 2-nitropyrimidine Chemical class [O-][N+](=O)C1=NC=CC=N1 UQOKRDJILZMZKU-UHFFFAOYSA-N 0.000 description 1
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
- HCGFUIQPSOCUHI-UHFFFAOYSA-N 2-propan-2-yloxyethanol Chemical compound CC(C)OCCO HCGFUIQPSOCUHI-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- VRYWJDIBTLUMCG-UHFFFAOYSA-N 3-[(3-aminophenyl)methyl]-7-phenyltriazolo[4,5-d]pyrimidin-5-amine Chemical compound NC1=CC=CC(CN2C3=NC(N)=NC(=C3N=N2)C=2C=CC=CC=2)=C1 VRYWJDIBTLUMCG-UHFFFAOYSA-N 0.000 description 1
- KTHGZVWUNCZBEI-UHFFFAOYSA-N 3-[(6-methoxypyridin-2-yl)methyl]-7-(5-methylfuran-2-yl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound COC1=CC=CC(=N1)CN1N=NC2=C1N=C(N=C2C=1OC(=CC=1)C)N KTHGZVWUNCZBEI-UHFFFAOYSA-N 0.000 description 1
- ONCBSTLSMMBXHX-UHFFFAOYSA-N 3-[5-amino-3-[[6-(1-hydroxycyclopentyl)pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-7-yl]benzonitrile Chemical compound C=12N=NN(CC=3N=C(C=CC=3)C3(O)CCCC3)C2=NC(N)=NC=1C1=CC=CC(C#N)=C1 ONCBSTLSMMBXHX-UHFFFAOYSA-N 0.000 description 1
- BCQRGFUTGJBNKT-UHFFFAOYSA-N 3-[5-amino-3-[[6-(2-hydroxypropan-2-yl)pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-7-yl]benzonitrile Chemical compound CC(C)(O)C1=CC=CC(CN2C3=NC(N)=NC(=C3N=N2)C=2C=C(C=CC=2)C#N)=N1 BCQRGFUTGJBNKT-UHFFFAOYSA-N 0.000 description 1
- VAYVTDPINUWJKZ-UHFFFAOYSA-N 3-[5-amino-3-[[6-(4-hydroxyoxan-4-yl)pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-7-yl]benzonitrile Chemical compound C=12N=NN(CC=3N=C(C=CC=3)C3(O)CCOCC3)C2=NC(N)=NC=1C1=CC=CC(C#N)=C1 VAYVTDPINUWJKZ-UHFFFAOYSA-N 0.000 description 1
- IJPKWTVYFLHMFF-UHFFFAOYSA-N 3-[5-amino-3-[[6-(methoxymethyl)pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-7-yl]benzonitrile Chemical compound COCC1=CC=CC(CN2C3=NC(N)=NC(=C3N=N2)C=2C=C(C=CC=2)C#N)=N1 IJPKWTVYFLHMFF-UHFFFAOYSA-N 0.000 description 1
- BWALWLVVBBIGCY-UHFFFAOYSA-N 3-[[6-(bromomethyl)pyridin-2-yl]methyl]-7-(5-methylfuran-2-yl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound O1C(C)=CC=C1C1=NC(N)=NC2=C1N=NN2CC1=CC=CC(CBr)=N1 BWALWLVVBBIGCY-UHFFFAOYSA-N 0.000 description 1
- UESWRCOBJTWHIX-UHFFFAOYSA-N 3-[[6-(methoxymethyl)pyridin-2-yl]methyl]-7-(3-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound COCC1=CC=CC(CN2C3=NC(N)=NC(=C3N=N2)C=2C=C(OC)C=CC=2)=N1 UESWRCOBJTWHIX-UHFFFAOYSA-N 0.000 description 1
- WRUJOLSNCOGBCD-UHFFFAOYSA-N 3-[[6-(methoxymethyl)pyridin-2-yl]methyl]-7-(4-methyl-1,3-thiazol-2-yl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound COCC1=CC=CC(CN2C3=NC(N)=NC(=C3N=N2)C=2SC=C(C)N=2)=N1 WRUJOLSNCOGBCD-UHFFFAOYSA-N 0.000 description 1
- HUJXGQILHAUCCV-MOROJQBDSA-N 3-iodobenzyl-5'-N-methylcarboxamidoadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NC)O[C@H]1N1C2=NC=NC(NCC=3C=C(I)C=CC=3)=C2N=C1 HUJXGQILHAUCCV-MOROJQBDSA-N 0.000 description 1
- XCIHFQLCPXHFCW-UHFFFAOYSA-N 3-phenylpropanoic acid;hydrochloride Chemical compound Cl.OC(=O)CCC1=CC=CC=C1 XCIHFQLCPXHFCW-UHFFFAOYSA-N 0.000 description 1
- SWJAIWACFQMNLR-UHFFFAOYSA-N 4-(1-oxidopyridin-1-ium-2-yl)oxan-4-ol Chemical compound C=1C=CC=[N+]([O-])C=1C1(O)CCOCC1 SWJAIWACFQMNLR-UHFFFAOYSA-N 0.000 description 1
- PWTBZOIUWZOPFT-UHFFFAOYSA-N 4-[2-[[7-amino-2-(2-furanyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl]amino]ethyl]phenol Chemical compound N=1C2=NC(C=3OC=CC=3)=NN2C(N)=NC=1NCCC1=CC=C(O)C=C1 PWTBZOIUWZOPFT-UHFFFAOYSA-N 0.000 description 1
- ODKBCWZLCXMXRB-UHFFFAOYSA-N 4-[6-(aminomethyl)pyridin-2-yl]oxan-4-ol Chemical compound NCC1=CC=CC(C2(O)CCOCC2)=N1 ODKBCWZLCXMXRB-UHFFFAOYSA-N 0.000 description 1
- YNRLREZIGIVCIG-UHFFFAOYSA-N 4-[6-[(5-amino-7-phenyltriazolo[4,5-d]pyrimidin-3-yl)methyl]pyridin-2-yl]oxan-4-ol Chemical compound C=12N=NN(CC=3N=C(C=CC=3)C3(O)CCOCC3)C2=NC(N)=NC=1C1=CC=CC=C1 YNRLREZIGIVCIG-UHFFFAOYSA-N 0.000 description 1
- DLIYMAPNSDNKEQ-UHFFFAOYSA-N 4-[6-[[5-amino-7-(3-methoxyphenyl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]oxan-4-ol Chemical compound COC1=CC=CC(C=2C=3N=NN(CC=4N=C(C=CC=4)C4(O)CCOCC4)C=3N=C(N)N=2)=C1 DLIYMAPNSDNKEQ-UHFFFAOYSA-N 0.000 description 1
- JHHCMMVKLXZUPL-UHFFFAOYSA-N 4-[6-[[5-amino-7-(4-methyl-1,3-thiazol-2-yl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]oxan-4-ol Chemical compound CC1=CSC(C=2C=3N=NN(CC=4N=C(C=CC=4)C4(O)CCOCC4)C=3N=C(N)N=2)=N1 JHHCMMVKLXZUPL-UHFFFAOYSA-N 0.000 description 1
- COENJCHOYLKDNG-UHFFFAOYSA-N 4-[6-[[5-amino-7-(5-methylfuran-2-yl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]oxan-4-ol Chemical compound O1C(C)=CC=C1C1=NC(N)=NC2=C1N=NN2CC1=CC=CC(C2(O)CCOCC2)=N1 COENJCHOYLKDNG-UHFFFAOYSA-N 0.000 description 1
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
- MXACUJBXYCTSEN-UHFFFAOYSA-N 4-pyridin-2-yloxan-4-ol Chemical compound C=1C=CC=NC=1C1(O)CCOCC1 MXACUJBXYCTSEN-UHFFFAOYSA-N 0.000 description 1
- QWFHFNGMCPMOCD-UHFFFAOYSA-N 6-bromopyridine-2-carbaldehyde Chemical compound BrC1=CC=CC(C=O)=N1 QWFHFNGMCPMOCD-UHFFFAOYSA-N 0.000 description 1
- ICJNEMFLACIDTD-UHFFFAOYSA-N 6-chloro-4-N-[(6-pyrrolidin-1-ylpyridin-2-yl)methyl]pyrimidine-2,4,5-triamine Chemical compound NC1=NC(=C(C(=N1)NCC1=CC=CC(=N1)N1CCCC1)N)Cl ICJNEMFLACIDTD-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- YLNSHGGWPGMGFA-UHFFFAOYSA-N 7-(4-methyl-1,3-thiazol-2-yl)-3-[[6-(1-trimethylsilyloxycyclopentyl)pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound CC1=CSC(C=2C=3N=NN(CC=4N=C(C=CC=4)C4(CCCC4)O[Si](C)(C)C)C=3N=C(N)N=2)=N1 YLNSHGGWPGMGFA-UHFFFAOYSA-N 0.000 description 1
- QOASHFYQMZOHPI-UHFFFAOYSA-N 7-(5-methylfuran-2-yl)-3-[[6-(2,2,2-trifluoroethoxymethyl)pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound O1C(C)=CC=C1C1=NC(N)=NC2=C1N=NN2CC1=CC=CC(COCC(F)(F)F)=N1 QOASHFYQMZOHPI-UHFFFAOYSA-N 0.000 description 1
- KCILAWKAHWFBDN-UHFFFAOYSA-N 7-(5-methylfuran-2-yl)-3-[[6-(oxolan-2-ylmethoxymethyl)pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound O1C(C)=CC=C1C1=NC(N)=NC2=C1N=NN2CC1=CC=CC(COCC2OCCC2)=N1 KCILAWKAHWFBDN-UHFFFAOYSA-N 0.000 description 1
- VEDXQMZUZASSKU-UHFFFAOYSA-N 7-(5-methylfuran-2-yl)-3-[[6-(oxolan-3-ylmethoxymethyl)pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound O1C(C)=CC=C1C1=NC(N)=NC2=C1N=NN2CC1=CC=CC(COCC2COCC2)=N1 VEDXQMZUZASSKU-UHFFFAOYSA-N 0.000 description 1
- BSGJTDIJLQJQHR-UHFFFAOYSA-N 7-(furan-2-yl)-3-[(6-propan-2-yloxypyridin-2-yl)methyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound O1C(=CC=C1)C=1C2=C(N=C(N=1)N)N(N=N2)CC1=NC(=CC=C1)OC(C)C BSGJTDIJLQJQHR-UHFFFAOYSA-N 0.000 description 1
- KJQJMBQXTWYQEI-UHFFFAOYSA-N 7-(furan-2-yl)-3-[[6-(2-methylpropoxy)pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound O1C(=CC=C1)C=1C2=C(N=C(N=1)N)N(N=N2)CC1=NC(=CC=C1)OCC(C)C KJQJMBQXTWYQEI-UHFFFAOYSA-N 0.000 description 1
- HHVGSGWNKPENEQ-UHFFFAOYSA-N 7-chloro-2h-triazolo[4,5-d]pyrimidin-5-amine Chemical compound N1=C(N)N=C(Cl)C2=NNN=C21 HHVGSGWNKPENEQ-UHFFFAOYSA-N 0.000 description 1
- WDEHMCKFQQVGLL-NSHDSACASA-N 7-chloro-3-[[6-[[(3s)-oxolan-3-yl]oxymethyl]pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C12=NC(N)=NC(Cl)=C2N=NN1CC(N=1)=CC=CC=1CO[C@H]1CCOC1 WDEHMCKFQQVGLL-NSHDSACASA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 125000005330 8 membered heterocyclic group Chemical group 0.000 description 1
- UQGGPCQNHJCOPS-PKNBQFBNSA-N 8-[(e)-2-(3,4-dimethoxyphenyl)ethenyl]-7-methyl-1,3-dipropylpurine-2,6-dione Chemical compound CN1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1\C=C\C1=CC=C(OC)C(OC)=C1 UQGGPCQNHJCOPS-PKNBQFBNSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108010060263 Adenosine A1 Receptor Proteins 0.000 description 1
- 102000030814 Adenosine A1 receptor Human genes 0.000 description 1
- 108010060261 Adenosine A3 Receptor Proteins 0.000 description 1
- 102000008161 Adenosine A3 Receptor Human genes 0.000 description 1
- 101150078577 Adora2b gene Proteins 0.000 description 1
- 206010001541 Akinesia Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000009017 Athetosis Diseases 0.000 description 1
- 208000000412 Avitaminosis Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- XAVYRNYYKJNPSI-UHFFFAOYSA-N C1CC(C1)(C2=CC=CC(=N2)CN3C4=NC=NC(=C4N=N3)C5=CC=CC=C5)O Chemical compound C1CC(C1)(C2=CC=CC(=N2)CN3C4=NC=NC(=C4N=N3)C5=CC=CC=C5)O XAVYRNYYKJNPSI-UHFFFAOYSA-N 0.000 description 1
- OERULFWTYBEYHA-UHFFFAOYSA-N C1CC(C1)(C2=CC=CC(=N2)CNC3=NC4=NNN=C4C=N3)O Chemical compound C1CC(C1)(C2=CC=CC(=N2)CNC3=NC4=NNN=C4C=N3)O OERULFWTYBEYHA-UHFFFAOYSA-N 0.000 description 1
- FNQRCPDCLXUHSM-UHFFFAOYSA-N C1CCC(C1)(C2=CC=CC(=N2)CNC3=NC4=NNN=C4C=N3)O Chemical compound C1CCC(C1)(C2=CC=CC(=N2)CNC3=NC4=NNN=C4C=N3)O FNQRCPDCLXUHSM-UHFFFAOYSA-N 0.000 description 1
- YMZVJYGDQVYPLA-UHFFFAOYSA-N CC1=CC=C(O1)C2=C3C(=NC(=N2)N)N(N=N3)C(C)C4=NC(=CC=C4)OC(C)(C)OC Chemical compound CC1=CC=C(O1)C2=C3C(=NC(=N2)N)N(N=N3)C(C)C4=NC(=CC=C4)OC(C)(C)OC YMZVJYGDQVYPLA-UHFFFAOYSA-N 0.000 description 1
- 208000025480 CHILD syndrome Diseases 0.000 description 1
- REFDUNMBLGZNRV-UHFFFAOYSA-N C[Si](C)(C)OC1(CCCC1)C2=CC=CC(=N2)CNC3=NC4=NNN=C4C=N3 Chemical compound C[Si](C)(C)OC1(CCCC1)C2=CC=CC(=N2)CNC3=NC4=NNN=C4C=N3 REFDUNMBLGZNRV-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 244000132059 Carica parviflora Species 0.000 description 1
- 235000014653 Carica parviflora Nutrition 0.000 description 1
- 206010051290 Central nervous system lesion Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010008748 Chorea Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 208000002603 Dopa-responsive dystonia Diseases 0.000 description 1
- 206010013647 Drowning Diseases 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000016988 Hemorrhagic Stroke Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010021135 Hypovitaminosis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 208000028603 Interstitial lung disease specific to childhood Diseases 0.000 description 1
- 208000015592 Involuntary movements Diseases 0.000 description 1
- OWYWGLHRNBIFJP-UHFFFAOYSA-N Ipazine Chemical compound CCN(CC)C1=NC(Cl)=NC(NC(C)C)=N1 OWYWGLHRNBIFJP-UHFFFAOYSA-N 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 208000004552 Lacunar Stroke Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 206010027374 Mental impairment Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000002740 Muscle Rigidity Diseases 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- AGLPQNDHZLCOSY-LBPRGKRZSA-N N-chloro-3-[[6-[[(3S)-oxolan-3-yl]oxymethyl]pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound ClNC=1N=CC2=C(N=1)N(N=N2)CC1=NC(=CC=C1)CO[C@@H]1COCC1 AGLPQNDHZLCOSY-LBPRGKRZSA-N 0.000 description 1
- 206010028923 Neonatal asphyxia Diseases 0.000 description 1
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000001738 Nervous System Trauma Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 101710138657 Neurotoxin Proteins 0.000 description 1
- 208000001294 Nociceptive Pain Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920005439 Perspex® Polymers 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 208000004983 Phantom Limb Diseases 0.000 description 1
- 206010056238 Phantom pain Diseases 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 208000010340 Sleep Deprivation Diseases 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 208000002667 Subdural Hematoma Diseases 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 206010043647 Thrombotic Stroke Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- BANZCXOYWVVTPC-UHFFFAOYSA-N [6-(2-methoxypropan-2-yl)pyridin-2-yl]methanol Chemical compound COC(C)(C)C1=CC=CC(CO)=N1 BANZCXOYWVVTPC-UHFFFAOYSA-N 0.000 description 1
- FQNCHEXECHBQLT-UHFFFAOYSA-N [6-(5-methylfuran-2-yl)-5-nitropyrimidin-4-yl] 4-methylbenzenesulfonate Chemical compound CC1=CC=C(O1)C1=NC=NC(=C1[N+](=O)[O-])OS(=O)(=O)C1=CC=C(C)C=C1 FQNCHEXECHBQLT-UHFFFAOYSA-N 0.000 description 1
- LEYOQGZGDPIVMN-UHFFFAOYSA-N [6-(methoxymethyl)pyridin-2-yl]methanamine Chemical compound COCC1=CC=CC(CN)=N1 LEYOQGZGDPIVMN-UHFFFAOYSA-N 0.000 description 1
- LSWFUJBECFGHFC-UHFFFAOYSA-N [6-[[5-amino-7-(furan-2-yl)triazolo[4,5-d]pyrimidin-3-yl]methyl]pyridin-2-yl]methanol;hydrochloride Chemical compound Cl.C=12N=NN(CC=3N=C(CO)C=CC=3)C2=NC(N)=NC=1C1=CC=CO1 LSWFUJBECFGHFC-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002465 adenosine A2a receptor agonist Substances 0.000 description 1
- 229940121359 adenosine receptor antagonist Drugs 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 229940035678 anti-parkinson drug Drugs 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000012223 aqueous fraction Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000025748 atypical depressive disease Diseases 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 238000002725 brachytherapy Methods 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000005961 cardioprotection Effects 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 229940081733 cetearyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 208000012601 choreatic disease Diseases 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 1
- BALGDZWGNCXXES-UHFFFAOYSA-N cyclopentane;propanoic acid Chemical compound CCC(O)=O.C1CCCC1 BALGDZWGNCXXES-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 208000017004 dementia pugilistica Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- GJJQGADUEUTUGR-UHFFFAOYSA-N diazonio-[[6-(2-oxopyrrolidin-1-yl)pyridin-2-yl]methyl]azanide Chemical compound [N-]=[N+]=NCC1=CC=CC(N2C(CCC2)=O)=N1 GJJQGADUEUTUGR-UHFFFAOYSA-N 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 230000010249 dopaminergic function Effects 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000008387 emulsifying waxe Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- NRSYCKPMRLULMV-UHFFFAOYSA-N ethyl 6-(difluoromethoxymethyl)pyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC(COC(F)F)=N1 NRSYCKPMRLULMV-UHFFFAOYSA-N 0.000 description 1
- CDFOARSBQKJGNL-UHFFFAOYSA-N ethyl 6-(hydroxymethyl)pyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC(CO)=N1 CDFOARSBQKJGNL-UHFFFAOYSA-N 0.000 description 1
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 208000003906 hydrocephalus Diseases 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000003483 hypokinetic effect Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 201000009941 intracranial hypertension Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 229940042472 mineral oil Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- MRWXACSTFXYYMV-FDDDBJFASA-N nebularine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC=C2N=C1 MRWXACSTFXYYMV-FDDDBJFASA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 208000028412 nervous system injury Diseases 0.000 description 1
- 230000007971 neurological deficit Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 208000002040 neurosyphilis Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000002474 noradrenergic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 208000031237 olivopontocerebellar atrophy Diseases 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229960003941 orphenadrine Drugs 0.000 description 1
- QVYRGXJJSLMXQH-UHFFFAOYSA-N orphenadrine Chemical compound C=1C=CC=C(C)C=1C(OCCN(C)C)C1=CC=CC=C1 QVYRGXJJSLMXQH-UHFFFAOYSA-N 0.000 description 1
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- PCPUMGYALMOCHF-UHFFFAOYSA-N oxolan-3-ylmethanol Chemical compound OCC1CCOC1 PCPUMGYALMOCHF-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 230000001898 pallidal effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 208000033300 perinatal asphyxia Diseases 0.000 description 1
- 208000023515 periodic limb movement disease Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000002212 purine nucleoside Substances 0.000 description 1
- 239000002213 purine nucleotide Substances 0.000 description 1
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 1
- 230000001696 purinergic effect Effects 0.000 description 1
- 102000008344 purinergic nucleotide receptor activity proteins Human genes 0.000 description 1
- 108040002778 purinergic nucleotide receptor activity proteins Proteins 0.000 description 1
- 239000003422 purinergic receptor affecting agent Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- CSNFMBGHUOSBFU-UHFFFAOYSA-N pyrimidine-2,4,5-triamine Chemical compound NC1=NC=C(N)C(N)=N1 CSNFMBGHUOSBFU-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229940100618 rectal suppository Drugs 0.000 description 1
- 239000006215 rectal suppository Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000015355 regulation of circadian sleep/wake cycle, sleep Effects 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 208000032253 retinal ischemia Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 208000012672 seasonal affective disease Diseases 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- PEOTZNZGNYNUIY-UHFFFAOYSA-N tert-butyl-[[6-(2-methoxypropan-2-yl)pyridin-2-yl]methoxy]-dimethylsilane Chemical compound COC(C)(C)C1=CC=CC(CO[Si](C)(C)C(C)(C)C)=N1 PEOTZNZGNYNUIY-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 210000004353 tibial menisci Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 238000007070 tosylation reaction Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 208000030401 vitamin deficiency disease Diseases 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- 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
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/131—Amines acyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/435—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
- A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/495—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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7553808P | 2008-06-25 | 2008-06-25 | |
| US61/075,538 | 2008-06-25 | ||
| GBGB0906579.8A GB0906579D0 (en) | 2009-04-16 | 2009-04-16 | Pharmaceuticals, compositions and methods of making and using the same |
| GB0906579.8 | 2009-04-16 | ||
| PCT/GB2009/001605 WO2009156737A1 (en) | 2008-06-25 | 2009-06-25 | Triazolo [4, 5-d] pyramidine derivatives and their use as purine receptor antagonists |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020117001954A Division KR101680390B1 (ko) | 2008-06-25 | 2009-06-25 | 트리아졸로〔4,5-ｄ〕피리미딘 유도체들 및 이들의 퓨린 수용체 안타고니스트로서의 용도 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020187031734A Division KR102008640B1 (ko) | 2008-06-25 | 2009-06-25 | 트리아졸로〔4,5-ｄ〕피리미딘 유도체들 및 이들의 퓨린 수용체 안타고니스트로서의 용도 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20160116054A true KR20160116054A (ko) | 2016-10-06 |
Family
ID=40750727
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020167026831A Ceased KR20160116054A (ko) | 2008-06-25 | 2009-06-25 | 트리아졸로〔4,5-ｄ〕피리미딘 유도체들 및 이들의 퓨린 수용체 안타고니스트로서의 용도 |
| KR1020187031734A Active KR102008640B1 (ko) | 2008-06-25 | 2009-06-25 | 트리아졸로〔4,5-ｄ〕피리미딘 유도체들 및 이들의 퓨린 수용체 안타고니스트로서의 용도 |
| KR1020117001954A Active KR101680390B1 (ko) | 2008-06-25 | 2009-06-25 | 트리아졸로〔4,5-ｄ〕피리미딘 유도체들 및 이들의 퓨린 수용체 안타고니스트로서의 용도 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020187031734A Active KR102008640B1 (ko) | 2008-06-25 | 2009-06-25 | 트리아졸로〔4,5-ｄ〕피리미딘 유도체들 및 이들의 퓨린 수용체 안타고니스트로서의 용도 |
| KR1020117001954A Active KR101680390B1 (ko) | 2008-06-25 | 2009-06-25 | 트리아졸로〔4,5-ｄ〕피리미딘 유도체들 및 이들의 퓨린 수용체 안타고니스트로서의 용도 |
Country Status (20)
| Country | Link |
|---|---|
| US (9) | US8450328B2 (enExample) |
| EP (1) | EP2321321B1 (enExample) |
| JP (1) | JP5559162B2 (enExample) |
| KR (3) | KR20160116054A (enExample) |
| CN (1) | CN102076692B (enExample) |
| AT (1) | ATE544767T1 (enExample) |
| AU (1) | AU2009263976B2 (enExample) |
| BR (1) | BRPI0910182B8 (enExample) |
| CA (1) | CA2727444C (enExample) |
| DK (1) | DK2321321T3 (enExample) |
| EA (1) | EA018803B1 (enExample) |
| ES (1) | ES2382154T3 (enExample) |
| GB (1) | GB0906579D0 (enExample) |
| IL (2) | IL210071A (enExample) |
| MX (1) | MX2010013841A (enExample) |
| NZ (1) | NZ590590A (enExample) |
| PL (1) | PL2321321T3 (enExample) |
| PT (1) | PT2321321E (enExample) |
| WO (1) | WO2009156737A1 (enExample) |
| ZA (1) | ZA201100526B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220104760A (ko) * | 2019-11-19 | 2022-07-26 | 일동제약(주) | 아데노신 수용체 길항제 화합물 |
Families Citing this family (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0906579D0 (en) | 2009-04-16 | 2009-05-20 | Vernalis R&D Ltd | Pharmaceuticals, compositions and methods of making and using the same |
| BRPI1009398A2 (pt) | 2009-03-13 | 2016-03-08 | Advinus Therapeutics Private Ltd | compostos de pirimidina fundida substituída |
| WO2011101861A1 (en) | 2010-01-29 | 2011-08-25 | Msn Laboratories Limited | Process for preparation of dpp-iv inhibitors |
| CN104363908B (zh) * | 2012-05-30 | 2017-12-22 | 霍夫曼-拉罗奇有限公司 | 吡咯烷基杂环类 |
| US10781178B2 (en) | 2015-08-12 | 2020-09-22 | The General Hospital Corporation | 8-hydroxyquinoline derivatives as diagnostic and therapeutic agents |
| AU2016379425B2 (en) | 2015-12-24 | 2021-11-11 | Corvus Pharmaceuticals, Inc. | Methods of treating cancer |
| EP3481869A4 (en) | 2016-07-11 | 2020-02-26 | Corvus Pharmaceuticals, Inc. | ANTI-CD73 ANTIBODIES |
| US20200078400A1 (en) | 2016-12-03 | 2020-03-12 | Juno Therapeutics, Inc. | Methods for determining car-t cells dosing |
| JP2019536460A (ja) | 2016-12-03 | 2019-12-19 | ジュノー セラピューティクス インコーポレイテッド | Ｃａｒ−ｔ細胞の調節方法 |
| MX389798B (es) * | 2017-01-20 | 2025-03-20 | Arcus Biosciences Inc | Azolopirimidina para el tratamiento de trastornos relacionados con el cáncer. |
| US10654825B2 (en) * | 2017-03-30 | 2020-05-19 | Corvus Pharmaceuticals, Inc. | Processes for making triazolo[4,5D] pyramidine derivatives and intermediates thereof |
| US20190022096A1 (en) * | 2017-04-04 | 2019-01-24 | Corvus Pharmaceuticals, Inc. | Methods of treating cancer |
| WO2018187484A1 (en) * | 2017-04-04 | 2018-10-11 | Corvus Pharmaceuticals, Inc. | Methods of treating cancer |
| MX2019012017A (es) | 2017-04-07 | 2020-02-12 | Juno Therapeutics Inc | Celulas modificadas que expresan antigeno de membrana especifico de prostata (psma) o una forma modificada del mismo y metodos relacionados. |
| IL327498A (en) | 2017-06-02 | 2026-05-01 | Juno Therapeutics Inc | Articles of manufacture and methods for treatment using adoptive cell therapy |
| US20200172628A1 (en) | 2017-06-22 | 2020-06-04 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
| MX2019015885A (es) | 2017-06-22 | 2020-09-10 | Novartis Ag | Moleculas de anticuerpo que se unen a cd73 y usos de las mismas. |
| CN111050545A (zh) | 2017-06-29 | 2020-04-21 | 朱诺治疗学股份有限公司 | 评估与免疫疗法相关的毒性的小鼠模型 |
| MA49911A (fr) | 2017-11-01 | 2020-06-24 | Juno Therapeutics Inc | Anticorps et récepteurs antigéniques chimériques spécifiques de l'antigene de maturation des lymphocytes b |
| US11066475B2 (en) | 2017-11-01 | 2021-07-20 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for B-cell maturation antigen and encoding polynucleotides |
| WO2019089858A2 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
| CA3080976A1 (en) * | 2017-11-06 | 2019-05-09 | Corvus Pharmaceuticals, Inc. | Adenosine pathway inhibitors for cancer treatment |
| MX2020004756A (es) | 2017-11-16 | 2020-08-20 | Novartis Ag | Terapias de combinacion. |
| MX2020005651A (es) | 2017-11-30 | 2020-10-28 | Novartis Ag | Receptor de antigeno quimerico dirigido a bcma y usos del mismo. |
| MA51210A (fr) | 2017-12-01 | 2020-10-07 | Juno Therapeutics Inc | Procédés de dosage et de modulation de cellules génétiquement modifiées |
| EP3724225A1 (en) | 2017-12-15 | 2020-10-21 | Juno Therapeutics, Inc. | Anti-cct5 binding molecules and methods of use thereof |
| EP3520782A3 (en) | 2018-02-01 | 2019-11-13 | Corvus Pharmaceuticals, Inc. | Pharmaceutical formulations containing adenosine a2a receptor antagonists |
| CN111615389A (zh) * | 2018-02-01 | 2020-09-01 | 科尔沃斯制药股份有限公司 | 药物调配物 |
| CN111511745B (zh) * | 2018-02-06 | 2022-05-27 | 江苏恒瑞医药股份有限公司 | 吡唑并[1，5-a][1，3，5]三嗪-2-胺类衍生物、其制备方法及其应用 |
| CA3090795A1 (en) | 2018-02-13 | 2019-08-22 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes (tils) with adenosine a2a receptor antagonists and therapeutic combinations of tils and adenosine a2a receptor antagonists |
| CN113754768B (zh) | 2018-03-14 | 2023-01-06 | 表面肿瘤学公司 | 结合cd39的抗体及其用途 |
| UY38247A (es) | 2018-05-30 | 2019-12-31 | Novartis Ag | Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación |
| WO2019232244A2 (en) | 2018-05-31 | 2019-12-05 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
| PE20210320A1 (es) | 2018-06-01 | 2021-02-16 | Novartis Ag | Moleculas de union contra bcma y usos de las mismas |
| AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
| KR102767594B1 (ko) | 2018-07-12 | 2025-02-12 | 코버스 파마슈티칼스, 인크. | 아데노신 경로 활성화를 갖는 암의 검출 및 치료 방법 |
| WO2020014666A1 (en) | 2018-07-12 | 2020-01-16 | Corvus Pharmaceuticals, Inc. | Methods for detecting and treating cancers having adenosine pathway activation |
| US11376255B2 (en) | 2018-09-11 | 2022-07-05 | iTeos Belgium SA | Thiocarbamate derivatives as A2A inhibitors, pharmaceutical composition thereof and combinations with anticancer agents |
| WO2020068583A1 (en) * | 2018-09-27 | 2020-04-02 | Corvus Pharmaceuticals, Inc. | Processes for making triazolo [4,5d] pyramidine derivatives and intermediates thereof |
| WO2020065036A1 (en) | 2018-09-27 | 2020-04-02 | Iteos Therapeutics S.A. | Use of an inhibitor of an ent family transporter in the treatment of cancer and combination thereof with an adenosine receptor antagonist |
| BE1026612B1 (fr) | 2018-09-27 | 2020-07-02 | Iteos Therapeutics S A | Utilisation d’un inhibiteur d’un transporteur de la famille ent dans le traitement du cancer et combinaison de celui-ci avec un antagoniste de recepteur de l’adenosine |
| US12473345B2 (en) | 2018-11-01 | 2025-11-18 | Juno Therapeutics, Inc. | Methods for treatment using chimeric antigen receptors specific for B-cell maturation antigen |
| CN119569895A (zh) | 2018-11-01 | 2025-03-07 | 朱诺治疗学股份有限公司 | G蛋白偶合受体c类5族成员d(gprc5d)特异性嵌合抗原受体 |
| BR112021009420A2 (pt) | 2018-11-16 | 2021-11-23 | Juno Therapeutics Inc | Métodos de dosagem de células t manipuladas para o tratamento de malignidades de células b |
| JP2022507734A (ja) * | 2018-11-20 | 2022-01-18 | メルク・シャープ・アンド・ドーム・コーポレーション | 置換アミノトリアゾロピリミジン及びアミノトリアゾロピラジンアデノシン受容体アンタゴニスト、医薬組成物及びそれらの使用 |
| EP4427810A3 (en) | 2018-11-30 | 2024-12-04 | Juno Therapeutics, Inc. | Methods for treatment using adoptive cell therapy |
| AU2019402189B2 (en) | 2018-12-20 | 2023-04-13 | Novartis Ag | Dosing regimen and pharmaceutical combination comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
| EA202192103A1 (ru) | 2019-01-29 | 2021-12-15 | Джуно Терапьютикс, Инк. | Антитела и химерные антигенные рецепторы, специфичные к орфанному рецептору типа рецеторной тирозинкиназы 1 (ror1) |
| CA3123519A1 (en) | 2019-02-15 | 2020-08-20 | Novartis Ag | Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
| EP3924054B1 (en) | 2019-02-15 | 2025-04-02 | Novartis AG | 3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
| KR20220062500A (ko) | 2019-09-16 | 2022-05-17 | 서피스 온콜로지, 인크. | 항-cd39 항체 조성물 및 방법 |
| TW202124446A (zh) | 2019-09-18 | 2021-07-01 | 瑞士商諾華公司 | 與ｅｎｔｐｄ２抗體之組合療法 |
| JP2022548881A (ja) | 2019-09-18 | 2022-11-22 | ノバルティス アーゲー | Ｅｎｔｐｄ２抗体、組合せ療法並びに抗体及び組合せ療法を使用する方法 |
| CA3151078A1 (en) | 2019-09-25 | 2021-04-01 | Surface Oncology, Inc. | Anti-il-27 antibodies and uses thereof |
| US20230057071A1 (en) | 2019-12-20 | 2023-02-23 | Novartis Ag | Combination of anti tim-3 antibody mbg453 and anti tgf-beta antibody nis793, with or without decitabine or the anti pd-1 antibody spartalizumab, for treating myelofibrosis and myelodysplastic syndrome |
| CN114901640A (zh) * | 2019-12-24 | 2022-08-12 | 兹杜斯生命科学有限公司 | 适用于治疗血脂异常的新型化合物 |
| WO2021170797A1 (en) | 2020-02-26 | 2021-09-02 | iTeos Belgium SA | PYRIMIDO[5,4-d]PYRIMIDINE DERIVATIVES AS ENT INHIBITORS FOR THE TREATMENT OF CANCERS, AND COMBINATION THEREOF WITH ADENOSINE RECEPTOR ANTAGONISTS |
| MX2022012558A (es) | 2020-04-07 | 2023-02-22 | iTeos Belgium SA | Derivados de diaminas macrocíclicas como inhibidores de ent para el tratamiento de cánceres y combinación de estos con antagonistas del receptor de adenosina. |
| IL297147B1 (en) | 2020-04-10 | 2026-05-01 | Juno Therapeutics Inc | Methods and uses related to engineered cell therapy with a chimeric antigen receptor directed against a B-cell maturation antigen |
| EP4168007A1 (en) | 2020-06-23 | 2023-04-26 | Novartis AG | Dosing regimen comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
| EP4188549A1 (en) | 2020-08-03 | 2023-06-07 | Novartis AG | Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
| AU2021373366A1 (en) | 2020-11-06 | 2023-06-01 | Novartis Ag | Cd19 binding molecules and uses thereof |
| EP4284510A1 (en) | 2021-01-29 | 2023-12-06 | Novartis AG | Dosage regimes for anti-cd73 and anti-entpd2 antibodies and uses thereof |
| WO2022178135A1 (en) | 2021-02-17 | 2022-08-25 | Iteos Belguim Sa | Compounds, compositions and methods of treatment thereof |
| TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗ＴＧＦβ抗體及其他治療劑用於治療增殖性疾病之用途 |
| AR125874A1 (es) | 2021-05-18 | 2023-08-23 | Novartis Ag | Terapias de combinación |
| JP2025521543A (ja) | 2022-06-22 | 2025-07-10 | ジュノー セラピューティクス インコーポレイテッド | Ｃｄ１９標的ｃａｒ ｔ細胞のセカンドライン治療のための処置方法 |
| EP4565262A2 (en) | 2022-08-05 | 2025-06-11 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for gprc5d and bcma |
| US20260207667A1 (en) | 2022-12-13 | 2026-07-23 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for baff-r and cd19 and methods and uses thereof |
| WO2024134541A1 (en) | 2022-12-20 | 2024-06-27 | iTeos Belgium SA | Heterocyclic compounds as ent inhibitors and compounds for use in the treatment of cancers |
| TW202523332A (zh) | 2023-11-14 | 2025-06-16 | 比利時商艾托斯比利時公司 | Ｅｎｔ１抑制劑與檢查點抑制劑組合 |
| WO2025170158A1 (ko) * | 2024-02-08 | 2025-08-14 | 아이리드비엠에스 주식회사 | Cxcr7 수용체 조절제 및 이의 용도 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56131587A (en) | 1980-03-18 | 1981-10-15 | Ss Pharmaceut Co Ltd | 7-substituted triazolopyrimidine derivative and its preparation |
| JPS56131586A (en) | 1980-03-18 | 1981-10-15 | Ss Pharmaceut Co Ltd | Triazolopyrimidine derivative and its preparation |
| JPS5962595A (ja) | 1982-09-30 | 1984-04-10 | Ss Pharmaceut Co Ltd | ３，５，７―トリ置換―トリアゾロピリミジン誘導体 |
| DE3304330A1 (de) | 1983-02-09 | 1984-08-09 | Basf Ag, 6700 Ludwigshafen | Neue 2h-v-triazolyl(4,5-d)-pyrimidine und deren verwendung |
| JPS60140335A (ja) | 1983-12-28 | 1985-07-25 | Konishiroku Photo Ind Co Ltd | 熱現像カラ−感光材料 |
| US5204353A (en) | 1987-04-07 | 1993-04-20 | Ciba-Geigy Corporation | 3-benzyl-3H-1,2,3-triazolo[4,5-d]pyrimidines, compositions thereof, and method of treating epilepsy therewith |
| NZ274978A (en) | 1993-10-12 | 1998-04-27 | Du Pont Merck Pharma | 1n-alkyl-n-aryl pyrimidinamine derivatives and pharmaceutical compositions thereof |
| WO1997003084A1 (en) | 1995-07-11 | 1997-01-30 | Astra Pharmaceuticals Ltd. | New inhibitors of platelet aggregation |
| ZA971896B (en) | 1996-03-26 | 1998-09-07 | Du Pont Merck Pharma | Aryloxy-and arythio-fused pyridines and pyrimidines and derivatives |
| PL332040A1 (en) | 1996-08-28 | 1999-08-16 | Pfizer | Substitution 6,5-heterobicyclic derivatives |
| EP0994860A1 (en) | 1997-07-03 | 2000-04-26 | Du Pont Pharmaceuticals Company | Aryl-and arylamino-substituted heterocycles as corticotropin releasing hormone antagonists |
| DE19736535C1 (de) | 1997-08-22 | 1999-01-28 | Basf Coatings Ag | Basislackzusammensetzung sowie Verfahren zur Herstellung von mehrschichtigen Überzügen |
| US5939432A (en) | 1997-10-29 | 1999-08-17 | Medco Research, Inc. | Thiophenes useful for modulating the adenosine receptor |
| US6197788B1 (en) | 1997-11-26 | 2001-03-06 | Vernalis Research Limited | (−)-mefloquine to block puringergic receptors and to treat movement or neurodegenerative disorders |
| US6579868B1 (en) | 1998-01-05 | 2003-06-17 | Eisai Co., Ltd. | Purine derivatives and adenosine A2 receptor antagonists serving as preventives/remedies for diabetes |
| US6326390B1 (en) | 1998-08-25 | 2001-12-04 | King Pharmaceuticals Reseach And Development, Inc. | Use of adenosine A3 receptor antagonists to inhibit tumor growth |
| GB9819382D0 (en) | 1998-09-04 | 1998-10-28 | Cerebrus Ltd | Chemical compounds I |
| GB9819384D0 (en) | 1998-09-04 | 1998-10-28 | Cerebrus Ltd | Chemical compounds II |
| GB9915437D0 (en) | 1999-07-01 | 1999-09-01 | Cerebrus Ltd | Chemical compounds III |
| WO2001002400A1 (en) | 1999-07-02 | 2001-01-11 | Eisai Co., Ltd. | Fused imidazole compounds and remedies for diabetes mellitus |
| GB0100624D0 (en) | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical compounds VII |
| GB0100623D0 (en) * | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical compounds IV |
| WO2007125321A2 (en) * | 2006-04-25 | 2007-11-08 | Astex Therapeutics Limited | Purine and deazapurine derivatives as pharmaceutical compounds |
| GB0906579D0 (en) * | 2009-04-16 | 2009-05-20 | Vernalis R&D Ltd | Pharmaceuticals, compositions and methods of making and using the same |
-
2009
- 2009-04-16 GB GBGB0906579.8A patent/GB0906579D0/en not_active Ceased
- 2009-06-25 US US12/997,721 patent/US8450328B2/en active Active
- 2009-06-25 NZ NZ590590A patent/NZ590590A/en unknown
- 2009-06-25 MX MX2010013841A patent/MX2010013841A/es active IP Right Grant
- 2009-06-25 EA EA201100079A patent/EA018803B1/ru not_active IP Right Cessation
- 2009-06-25 PT PT09769578T patent/PT2321321E/pt unknown
- 2009-06-25 KR KR1020167026831A patent/KR20160116054A/ko not_active Ceased
- 2009-06-25 DK DK09769578.7T patent/DK2321321T3/da active
- 2009-06-25 JP JP2011515594A patent/JP5559162B2/ja active Active
- 2009-06-25 ES ES09769578T patent/ES2382154T3/es active Active
- 2009-06-25 CA CA2727444A patent/CA2727444C/en active Active
- 2009-06-25 PL PL09769578T patent/PL2321321T3/pl unknown
- 2009-06-25 KR KR1020187031734A patent/KR102008640B1/ko active Active
- 2009-06-25 WO PCT/GB2009/001605 patent/WO2009156737A1/en not_active Ceased
- 2009-06-25 AU AU2009263976A patent/AU2009263976B2/en active Active
- 2009-06-25 AT AT09769578T patent/ATE544767T1/de active
- 2009-06-25 BR BRPI0910182A patent/BRPI0910182B8/pt active IP Right Grant
- 2009-06-25 KR KR1020117001954A patent/KR101680390B1/ko active Active
- 2009-06-25 CN CN200980124230.6A patent/CN102076692B/zh active Active
- 2009-06-25 EP EP09769578A patent/EP2321321B1/en active Active
-
2010
- 2010-12-16 IL IL210071A patent/IL210071A/en active IP Right Grant
-
2011
- 2011-01-20 ZA ZA2011/00526A patent/ZA201100526B/en unknown
-
2013
- 2013-05-08 US US13/889,921 patent/US8987279B2/en active Active
-
2015
- 2015-02-10 US US14/618,829 patent/US9376443B2/en active Active
-
2016
- 2016-01-11 IL IL243574A patent/IL243574B/en active IP Right Grant
- 2016-06-02 US US15/172,126 patent/US9765080B2/en active Active
-
2017
- 2017-08-21 US US15/682,346 patent/US10106547B2/en active Active
-
2018
- 2018-09-15 US US16/132,411 patent/US10538526B2/en active Active
-
2019
- 2019-12-02 US US16/700,160 patent/US10875868B2/en active Active
-
2020
- 2020-11-03 US US17/088,325 patent/US11466019B2/en active Active
-
2022
- 2022-08-24 US US17/895,037 patent/US20230100842A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220104760A (ko) * | 2019-11-19 | 2022-07-26 | 일동제약(주) | 아데노신 수용체 길항제 화합물 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101680390B1 (ko) | 트리아졸로〔4,5-ｄ〕피리미딘 유도체들 및 이들의 퓨린 수용체 안타고니스트로서의 용도 | |
| JP5766820B2 (ja) | Ｐｉ３キナーゼ阻害剤としての複素環化合物 | |
| EP1392312B1 (en) | TRIAZOLO 4,5-d PYRIMIDINE DERIVATIVES AND THEIR USE AS PURINERGIC RECEPTOR ANTAGONISTS | |
| JP2004517874A (ja) | プリン作動性レセプターアンタゴニストとしてのプリン誘導体 | |
| US20100173914A1 (en) | Pharmaceuticals, compositions and methods of making and using the same | |
| HK1156609A (en) | Triazolo [4, 5-d] pyramidine derivatives and their use as purine receptor antagonists | |
| HK1156609B (en) | Triazolo [4, 5-d] pyramidine derivatives and their use as purine receptor antagonists | |
| HK1061206B (en) | Triazolo 4,5-d pyrimidine derivatives and their use as purinergic receptor antagonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A107 | Divisional application of patent | ||
| A201 | Request for examination | ||
| PA0104 | Divisional application for international application |
Comment text: Divisional Application for International Patent Patent event code: PA01041R01D Patent event date: 20160928 Application number text: 1020117001954 Filing date: 20110125 |
|
| PA0201 | Request for examination | ||
| PG1501 | Laying open of application | ||
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20161201 Patent event code: PE09021S01D |
|
| AMND | Amendment | ||
| E90F | Notification of reason for final refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Final Notice of Reason for Refusal Patent event date: 20170801 Patent event code: PE09021S02D |
|
| AMND | Amendment | ||
| E601 | Decision to refuse application | ||
| E801 | Decision on dismissal of amendment | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20180702 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20170801 Comment text: Final Notice of Reason for Refusal Patent event code: PE06011S02I Patent event date: 20161201 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |
|
| PE0801 | Dismissal of amendment |
Patent event code: PE08012E01D Comment text: Decision on Dismissal of Amendment Patent event date: 20180702 Patent event code: PE08011R01I Comment text: Amendment to Specification, etc. Patent event date: 20180228 Patent event code: PE08011R01I Comment text: Amendment to Specification, etc. Patent event date: 20170601 |
|
| J201 | Request for trial against refusal decision | ||
| PJ0201 | Trial against decision of rejection |
Patent event date: 20181001 Comment text: Request for Trial against Decision on Refusal Patent event code: PJ02012R01D Patent event date: 20180702 Comment text: Decision to Refuse Application Patent event code: PJ02011S01I Appeal kind category: Appeal against decision to decline refusal Appeal identifier: 2018101004050 Request date: 20181001 |
|
| AMND | Amendment | ||
| PB0901 | Examination by re-examination before a trial |
Comment text: Amendment to Specification, etc. Patent event date: 20181031 Patent event code: PB09011R02I Comment text: Request for Trial against Decision on Refusal Patent event date: 20181001 Patent event code: PB09011R01I Comment text: Amendment to Specification, etc. Patent event date: 20180228 Patent event code: PB09011R02I Comment text: Amendment to Specification, etc. Patent event date: 20170601 Patent event code: PB09011R02I |
|
| E801 | Decision on dismissal of amendment | ||
| PE0801 | Dismissal of amendment |
Patent event code: PE08012E01D Comment text: Decision on Dismissal of Amendment Patent event date: 20181203 Patent event code: PE08011R01I Comment text: Amendment to Specification, etc. Patent event date: 20181031 Patent event code: PE08011R01I Comment text: Amendment to Specification, etc. Patent event date: 20180228 Patent event code: PE08011R01I Comment text: Amendment to Specification, etc. Patent event date: 20170601 |
|
| B601 | Maintenance of original decision after re-examination before a trial | ||
| PB0601 | Maintenance of original decision after re-examination before a trial | ||
| J301 | Trial decision |
Free format text: TRIAL NUMBER: 2018101004050; TRIAL DECISION FOR APPEAL AGAINST DECISION TO DECLINE REFUSAL REQUESTED 20181001 Effective date: 20190628 |
|
| PJ1301 | Trial decision |
Patent event code: PJ13011S01D Patent event date: 20190628 Comment text: Trial Decision on Objection to Decision on Refusal Appeal kind category: Appeal against decision to decline refusal Request date: 20181001 Decision date: 20190628 Appeal identifier: 2018101004050 |
|
| PC1202 | Submission of document of withdrawal before decision of registration |
Comment text: [Withdrawal of Procedure relating to Patent, etc.] Withdrawal (Abandonment) Patent event code: PC12021R01D Patent event date: 20190708 |
|
| WITB | Written withdrawal of application |