JP2007508290A - GSK−3阻害剤としての置換2H−[1,2,4]トリアゾロ[4,3−a]ピラジン - Google Patents
GSK−3阻害剤としての置換2H−[1,2,4]トリアゾロ[4,3−a]ピラジン Download PDFInfo
- Publication number
- JP2007508290A JP2007508290A JP2006530734A JP2006530734A JP2007508290A JP 2007508290 A JP2007508290 A JP 2007508290A JP 2006530734 A JP2006530734 A JP 2006530734A JP 2006530734 A JP2006530734 A JP 2006530734A JP 2007508290 A JP2007508290 A JP 2007508290A
- Authority
- JP
- Japan
- Prior art keywords
- independently
- alkyl
- triazolo
- substituted
- pyrazin
- 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.)
- Pending
Links
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 title claims description 24
- 239000003112 inhibitor Substances 0.000 title claims description 23
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 title description 19
- SETPVHMQKAXDMY-UHFFFAOYSA-N 2,3-dihydro-[1,2,4]triazolo[4,3-a]pyrazine Chemical class C1=NC=CN2CNN=C21 SETPVHMQKAXDMY-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 132
- 239000000651 prodrug Substances 0.000 claims abstract description 50
- 229940002612 prodrug Drugs 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims description 80
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 61
- 229910052736 halogen Inorganic materials 0.000 claims description 56
- -1 methylenedioxy Chemical group 0.000 claims description 53
- 150000002367 halogens Chemical class 0.000 claims description 47
- 125000003118 aryl group Chemical group 0.000 claims description 43
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 40
- 238000000034 method Methods 0.000 claims description 40
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 230000027455 binding Effects 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 239000002464 receptor antagonist Substances 0.000 claims description 7
- 229940044551 receptor antagonist Drugs 0.000 claims description 7
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 claims description 7
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical group O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- 201000004384 Alopecia Diseases 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 208000020925 Bipolar disease Diseases 0.000 claims description 5
- 102000001301 EGF receptor Human genes 0.000 claims description 5
- 108060006698 EGF receptor Proteins 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 5
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 5
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 208000024963 hair loss Diseases 0.000 claims description 5
- 230000003676 hair loss Effects 0.000 claims description 5
- 239000004090 neuroprotective agent Substances 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- 206010012289 Dementia Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 208000019022 Mood disease Diseases 0.000 claims description 4
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 claims description 4
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 102000004257 Potassium Channel Human genes 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 230000001028 anti-proliverative effect Effects 0.000 claims description 4
- 239000000164 antipsychotic agent Substances 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 239000000544 cholinesterase inhibitor Substances 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 230000016273 neuron death Effects 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 108020001213 potassium channel Proteins 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000007530 Essential hypertension Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 3
- 208000013016 Hypoglycemia Diseases 0.000 claims description 3
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 3
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims description 3
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
- 229940005529 antipsychotics Drugs 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 3
- 230000035558 fertility Effects 0.000 claims description 3
- 201000001421 hyperglycemia Diseases 0.000 claims description 3
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 208000028867 ischemia Diseases 0.000 claims description 3
- 210000000440 neutrophil Anatomy 0.000 claims description 3
- 208000015124 ovarian disease Diseases 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 230000011664 signaling Effects 0.000 claims description 3
- 230000019100 sperm motility Effects 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- 230000009529 traumatic brain injury Effects 0.000 claims description 3
- 239000002525 vasculotropin inhibitor Substances 0.000 claims description 3
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 claims description 2
- CYENWPOUSLGVMZ-UHFFFAOYSA-N 6-tert-butyl-8-(pyridin-3-ylmethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NCC1=CC=CN=C1 CYENWPOUSLGVMZ-UHFFFAOYSA-N 0.000 claims description 2
- HYQVWXMXOTZEPD-UHFFFAOYSA-N 6-tert-butyl-8-[2-(4-methoxyphenoxy)ethylamino]-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C1=CC(OC)=CC=C1OCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 HYQVWXMXOTZEPD-UHFFFAOYSA-N 0.000 claims description 2
- SXHAFJZKPXLKGL-UHFFFAOYSA-N 6-tert-butyl-8-[2-(6-methoxypyridin-3-yl)ethylamino]-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C1=NC(OC)=CC=C1CCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 SXHAFJZKPXLKGL-UHFFFAOYSA-N 0.000 claims description 2
- 208000036119 Frailty Diseases 0.000 claims description 2
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 claims description 2
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 claims description 2
- 206010003549 asthenia Diseases 0.000 claims description 2
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 claims description 2
- 229960000590 celecoxib Drugs 0.000 claims description 2
- 229960003530 donepezil Drugs 0.000 claims description 2
- 229960002464 fluoxetine Drugs 0.000 claims description 2
- 229960004038 fluvoxamine Drugs 0.000 claims description 2
- CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 claims description 2
- 229960001952 metrifonate Drugs 0.000 claims description 2
- 229960002296 paroxetine Drugs 0.000 claims description 2
- 229960001697 physostigmine Drugs 0.000 claims description 2
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 claims description 2
- 230000004044 response Effects 0.000 claims description 2
- 229960004136 rivastigmine Drugs 0.000 claims description 2
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 claims description 2
- 229960000371 rofecoxib Drugs 0.000 claims description 2
- 239000004001 serotonin 1D antagonist Substances 0.000 claims description 2
- 229960002073 sertraline Drugs 0.000 claims description 2
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 claims description 2
- 229960001685 tacrine Drugs 0.000 claims description 2
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 claims description 2
- NFACJZMKEDPNKN-UHFFFAOYSA-N trichlorfon Chemical compound COP(=O)(OC)C(O)C(Cl)(Cl)Cl NFACJZMKEDPNKN-UHFFFAOYSA-N 0.000 claims description 2
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 claims description 2
- 229960002004 valdecoxib Drugs 0.000 claims description 2
- 230000003313 weakening effect Effects 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 11
- 102000001267 GSK3 Human genes 0.000 claims 4
- 125000005843 halogen group Chemical group 0.000 claims 4
- BNKVGZXDUVAYFS-UHFFFAOYSA-N ethyl 4-[(6-tert-butyl-3-oxo-2h-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1NC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 BNKVGZXDUVAYFS-UHFFFAOYSA-N 0.000 claims 2
- POLAUOGHQIDJOL-UHFFFAOYSA-N 3-[(6-tert-butyl-3-oxo-2h-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)amino]propanenitrile Chemical compound N#CCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C21 POLAUOGHQIDJOL-UHFFFAOYSA-N 0.000 claims 1
- ZVICCLKJAFIQPK-UHFFFAOYSA-N 5-methyl-6-propan-2-yl-8-(2-pyridin-3-ylethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C12=NNC(=O)N2C(C)=C(C(C)C)N=C1NCCC1=CC=CN=C1 ZVICCLKJAFIQPK-UHFFFAOYSA-N 0.000 claims 1
- AGKIGFGRCKEUIU-UHFFFAOYSA-N 6-tert-butyl-8-(1-hydroxypropan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound OCC(C)NC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 AGKIGFGRCKEUIU-UHFFFAOYSA-N 0.000 claims 1
- BDHXUVFUQBVLKW-UHFFFAOYSA-N 6-tert-butyl-8-(2-ethylsulfanylethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CCSCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 BDHXUVFUQBVLKW-UHFFFAOYSA-N 0.000 claims 1
- RGSWWBAMGAFCQA-UHFFFAOYSA-N 6-tert-butyl-8-(2-methoxyethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound COCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 RGSWWBAMGAFCQA-UHFFFAOYSA-N 0.000 claims 1
- QXUHWSNAOLAIHF-UHFFFAOYSA-N 6-tert-butyl-8-(2-pyridin-3-yloxyethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NCCOC1=CC=CN=C1 QXUHWSNAOLAIHF-UHFFFAOYSA-N 0.000 claims 1
- OCDKRJXMBSTSLF-UHFFFAOYSA-N 6-tert-butyl-8-(2-pyridin-4-yloxyethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NCCOC1=CC=NC=C1 OCDKRJXMBSTSLF-UHFFFAOYSA-N 0.000 claims 1
- MADZBIDQNUJHGS-UHFFFAOYSA-N 6-tert-butyl-8-(3-imidazol-1-ylpropylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NCCCN1C=CN=C1 MADZBIDQNUJHGS-UHFFFAOYSA-N 0.000 claims 1
- OVWGZKPAZNUTCZ-UHFFFAOYSA-N 6-tert-butyl-8-(3-methoxypropylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound COCCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 OVWGZKPAZNUTCZ-UHFFFAOYSA-N 0.000 claims 1
- NSRHZPWFEUPBDQ-UHFFFAOYSA-N 6-tert-butyl-8-(3-morpholin-4-ylpropylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NCCCN1CCOCC1 NSRHZPWFEUPBDQ-UHFFFAOYSA-N 0.000 claims 1
- KXZONCXHEBLIPF-UHFFFAOYSA-N 6-tert-butyl-8-(6-hydroxyhexylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound OCCCCCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C21 KXZONCXHEBLIPF-UHFFFAOYSA-N 0.000 claims 1
- GYXFKTYCDZYNGD-UHFFFAOYSA-N 6-tert-butyl-8-(oxolan-2-ylmethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NCC1CCCO1 GYXFKTYCDZYNGD-UHFFFAOYSA-N 0.000 claims 1
- QUHBCBXUVIHAIR-UHFFFAOYSA-N 6-tert-butyl-8-(pyridin-4-ylmethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NCC1=CC=NC=C1 QUHBCBXUVIHAIR-UHFFFAOYSA-N 0.000 claims 1
- BGUMMDJJAIJMCP-UHFFFAOYSA-N 6-tert-butyl-8-[(4-nitrophenyl)methylamino]-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NCC1=CC=C([N+]([O-])=O)C=C1 BGUMMDJJAIJMCP-UHFFFAOYSA-N 0.000 claims 1
- PLJTUDBAKXBITC-UHFFFAOYSA-N 6-tert-butyl-8-[2-(2-methylpyridin-3-yl)ethylamino]-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CC1=NC=CC=C1CCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 PLJTUDBAKXBITC-UHFFFAOYSA-N 0.000 claims 1
- HIWMBFPGVAHHPE-UHFFFAOYSA-N 6-tert-butyl-8-[2-(2-methylpyridin-3-yl)oxyethylamino]-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CC1=NC=CC=C1OCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 HIWMBFPGVAHHPE-UHFFFAOYSA-N 0.000 claims 1
- JWOZTMKXSCELPG-UHFFFAOYSA-N 6-tert-butyl-8-[2-(4-methyl-1h-benzimidazol-2-yl)ethylamino]-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CC(C)(C)C1=CN2C(=O)NN=C2C(NCCC2=NC=3C=CC=C(C=3N2)C)=N1 JWOZTMKXSCELPG-UHFFFAOYSA-N 0.000 claims 1
- HXZQTJWJZWAEFZ-UHFFFAOYSA-N 6-tert-butyl-8-[2-(6-methylpyridin-3-yl)ethylamino]-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C1=NC(C)=CC=C1CCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 HXZQTJWJZWAEFZ-UHFFFAOYSA-N 0.000 claims 1
- KYWIRYJDXDTYTP-UHFFFAOYSA-N 6-tert-butyl-8-[3-(2-oxopyrrolidin-1-yl)propylamino]-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NCCCN1CCCC1=O KYWIRYJDXDTYTP-UHFFFAOYSA-N 0.000 claims 1
- RJFYCUAWRSFYHY-UHFFFAOYSA-N 6-tert-butyl-8-[3-(3,5-dimethylpyrazol-1-yl)propylamino]-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N1=C(C)C=C(C)N1CCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 RJFYCUAWRSFYHY-UHFFFAOYSA-N 0.000 claims 1
- IMRPZUHUKOZYAK-UHFFFAOYSA-N 8-[2-(1,3-benzothiazol-2-ylamino)ethylamino]-6-tert-butyl-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C1=CC=C2SC(NCCNC=3C=4N(C(NN=4)=O)C=C(N=3)C(C)(C)C)=NC2=C1 IMRPZUHUKOZYAK-UHFFFAOYSA-N 0.000 claims 1
- WVLKZLVPJXMADI-UHFFFAOYSA-N 8-[2-(3-aminopyridin-2-yl)oxyethylamino]-6-tert-butyl-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NCCOC1=NC=CC=C1N WVLKZLVPJXMADI-UHFFFAOYSA-N 0.000 claims 1
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 claims 1
- 102000001938 Plasminogen Activators Human genes 0.000 claims 1
- 108010001014 Plasminogen Activators Proteins 0.000 claims 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 1
- 229960001058 bupropion Drugs 0.000 claims 1
- 229960001800 nefazodone Drugs 0.000 claims 1
- VRBKIVRKKCLPHA-UHFFFAOYSA-N nefazodone Chemical compound O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 VRBKIVRKKCLPHA-UHFFFAOYSA-N 0.000 claims 1
- 229940127126 plasminogen activator Drugs 0.000 claims 1
- 229960004688 venlafaxine Drugs 0.000 claims 1
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 94
- 239000000243 solution Substances 0.000 description 78
- 239000007787 solid Substances 0.000 description 72
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
- 238000006243 chemical reaction Methods 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 48
- 235000019439 ethyl acetate Nutrition 0.000 description 46
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- 239000000047 product Substances 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 36
- 229910052938 sodium sulfate Inorganic materials 0.000 description 36
- 235000011152 sodium sulphate Nutrition 0.000 description 36
- 238000010898 silica gel chromatography Methods 0.000 description 35
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- 239000012044 organic layer Substances 0.000 description 32
- 239000011541 reaction mixture Substances 0.000 description 29
- 239000012047 saturated solution Substances 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000002904 solvent Substances 0.000 description 27
- 238000002360 preparation method Methods 0.000 description 26
- 238000010992 reflux Methods 0.000 description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 23
- 239000007858 starting material Substances 0.000 description 23
- 239000011780 sodium chloride Substances 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- 239000000284 extract Substances 0.000 description 19
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
- 235000019341 magnesium sulphate Nutrition 0.000 description 19
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 239000000758 substrate Substances 0.000 description 15
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- JSYGRUBHOCKMGQ-UHFFFAOYSA-N dichloramine Chemical compound ClNCl JSYGRUBHOCKMGQ-UHFFFAOYSA-N 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 238000010791 quenching Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical class O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 description 8
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
- 239000005909 Kieselgur Substances 0.000 description 6
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 description 6
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 6
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 239000003586 protic polar solvent Substances 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 5
- UAYGJWQHKHNZLS-UHFFFAOYSA-N 6-tert-butyl-8-chloro-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound ClC1=NC(C(C)(C)C)=CN2C(=O)NN=C21 UAYGJWQHKHNZLS-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 4
- HLVSDKPLSJGCPD-UHFFFAOYSA-N 3-bromo-5-phenyl-1h-pyrazin-2-one Chemical compound N1=C(Br)C(O)=NC=C1C1=CC=CC=C1 HLVSDKPLSJGCPD-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 4
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 4
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 229960000187 tissue plasminogen activator Drugs 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 3
- LAQJGAKLLZAETL-UHFFFAOYSA-N 2h-pyrazin-3-one Chemical compound O=C1CN=CC=N1 LAQJGAKLLZAETL-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 3
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 3
- 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 3
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- MSMGXWFHBSCQFB-UHFFFAOYSA-N ethyl cyanoformate Chemical compound CCOC(=O)C#N MSMGXWFHBSCQFB-UHFFFAOYSA-N 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 210000002027 skeletal muscle Anatomy 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000007909 solid dosage form Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 3
- MUQNAPSBHXFMHT-UHFFFAOYSA-N tert-butylhydrazine Chemical compound CC(C)(C)NN MUQNAPSBHXFMHT-UHFFFAOYSA-N 0.000 description 3
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 3
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- ZLCOWUKVVFVVKA-WDSKDSINSA-N (2r)-3-[[(2r)-2-acetamido-2-carboxyethyl]disulfanyl]-2-aminopropanoic acid Chemical compound CC(=O)N[C@H](C(O)=O)CSSC[C@H](N)C(O)=O ZLCOWUKVVFVVKA-WDSKDSINSA-N 0.000 description 2
- QORTVAZDQKELRP-UHFFFAOYSA-N (3-chloro-6-phenylpyrazin-2-yl)hydrazine Chemical compound N1=C(Cl)C(NN)=NC(C=2C=CC=CC=2)=C1 QORTVAZDQKELRP-UHFFFAOYSA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical compound CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 description 2
- DTUVZWILXLSUTQ-UHFFFAOYSA-N 2-[2-tert-butyl-3-oxo-8-(propan-2-ylamino)-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]-2-methylpropanoic acid Chemical compound CC(C)NC1=NC(C(C)(C)C(O)=O)=CN2C(=O)N(C(C)(C)C)N=C12 DTUVZWILXLSUTQ-UHFFFAOYSA-N 0.000 description 2
- LRLQQERNMXHASR-UHFFFAOYSA-N 2-diphenylphosphanylpropan-2-yl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 LRLQQERNMXHASR-UHFFFAOYSA-N 0.000 description 2
- NAHHNSMHYCLMON-UHFFFAOYSA-N 2-pyridin-3-ylethanamine Chemical compound NCCC1=CC=CN=C1 NAHHNSMHYCLMON-UHFFFAOYSA-N 0.000 description 2
- XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- LNCBWVSOZHPVNU-UHFFFAOYSA-N 6-bromo-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CC(C)NC1=NC(Br)=CN2C(=O)NN=C12 LNCBWVSOZHPVNU-UHFFFAOYSA-N 0.000 description 2
- BDAVCSXONVNHIM-UHFFFAOYSA-N 6-tert-butyl-5-(1-hydroxy-3-methylbutyl)-8-(2-pyridin-3-ylethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C12=NNC(=O)N2C(C(O)CC(C)C)=C(C(C)(C)C)N=C1NCCC1=CC=CN=C1 BDAVCSXONVNHIM-UHFFFAOYSA-N 0.000 description 2
- HFJGLKPSDDTDOR-UHFFFAOYSA-N 6-tert-butyl-8-(2-ethylsulfinylethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CCS(=O)CCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 HFJGLKPSDDTDOR-UHFFFAOYSA-N 0.000 description 2
- CKMZJBNPOJOLLH-UHFFFAOYSA-N 6-tert-butyl-8-(2-ethylsulfonylethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CCS(=O)(=O)CCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 CKMZJBNPOJOLLH-UHFFFAOYSA-N 0.000 description 2
- LTSQSRVUOKUVNG-UHFFFAOYSA-N 6-tert-butyl-8-(piperidin-4-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NC1CCNCC1 LTSQSRVUOKUVNG-UHFFFAOYSA-N 0.000 description 2
- JRLQVERYPYUZRK-UHFFFAOYSA-N 8-(2-aminoethylamino)-6-tert-butyl-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound NCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C21 JRLQVERYPYUZRK-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229920001817 Agar Polymers 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 2
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920002527 Glycogen Polymers 0.000 description 2
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 2
- 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 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 2
- VGIGHGMPMUCLIQ-UHFFFAOYSA-N LSM-2183 Chemical compound C1=CC(F)=CC=C1N1CCN(CCCN2S(C=3C=CC=C4C=CC=C2C=34)(=O)=O)CC1 VGIGHGMPMUCLIQ-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
- 229940124761 MMP inhibitor Drugs 0.000 description 2
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 2
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical compound BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000005879 dioxolanyl group Chemical group 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 229940121647 egfr inhibitor Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229940096919 glycogen Drugs 0.000 description 2
- 108010049611 glycogen synthase kinase 3 alpha Proteins 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000002429 hydrazines Chemical class 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 239000011777 magnesium Substances 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
- 230000002503 metabolic effect Effects 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- DYCKFEBIOUQECE-UHFFFAOYSA-N nefazodone hydrochloride Chemical compound [H+].[Cl-].O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 DYCKFEBIOUQECE-UHFFFAOYSA-N 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000003495 polar organic solvent Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000001453 quaternary ammonium group Chemical group 0.000 description 2
- 208000001076 sarcopenia Diseases 0.000 description 2
- 238000003345 scintillation counting Methods 0.000 description 2
- 102000034285 signal transducing proteins Human genes 0.000 description 2
- 108091006024 signal transducing proteins Proteins 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical group [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000001665 trituration Methods 0.000 description 2
- QYRYFNHXARDNFZ-UHFFFAOYSA-N venlafaxine hydrochloride Chemical compound [H+].[Cl-].C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 QYRYFNHXARDNFZ-UHFFFAOYSA-N 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 2
- LTVIJEFEZVFIST-AZUAARDMSA-N (2r,3r)-1-[4-[(2-chloro-4-fluorophenyl)methoxy]phenyl]sulfonyl-n,3-dihydroxy-3-methylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1[C@](C)(O)CCCN1S(=O)(=O)C(C=C1)=CC=C1OCC1=CC=C(F)C=C1Cl LTVIJEFEZVFIST-AZUAARDMSA-N 0.000 description 1
- ZHCXOELPVFPGHI-PZJWPPBQSA-N (2r,3r)-1-[4-[(4-fluoro-2-methylphenyl)methoxy]phenyl]sulfonyl-n,3-dihydroxy-3-methylpiperidine-2-carboxamide Chemical compound CC1=CC(F)=CC=C1COC1=CC=C(S(=O)(=O)N2[C@H]([C@](C)(O)CCC2)C(=O)NO)C=C1 ZHCXOELPVFPGHI-PZJWPPBQSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- OITFLUYJTYSKAD-UHFFFAOYSA-N (3-bromo-5-phenylpyrazin-2-yl)hydrazine Chemical compound N1=C(Br)C(NN)=NC=C1C1=CC=CC=C1 OITFLUYJTYSKAD-UHFFFAOYSA-N 0.000 description 1
- LLKSEOZHRKKEQF-UHFFFAOYSA-N (3-bromo-5-phenylpyrazin-2-yl)hydrazine;trifluoromethanesulfonic acid Chemical compound OS(=O)(=O)C(F)(F)F.N1=C(Br)C(NN)=NC=C1C1=CC=CC=C1 LLKSEOZHRKKEQF-UHFFFAOYSA-N 0.000 description 1
- BCRAZIIZSYYKBB-UHFFFAOYSA-N (3-chloro-5-phenylpyrazin-2-yl)hydrazine Chemical compound N1=C(Cl)C(NN)=NC=C1C1=CC=CC=C1 BCRAZIIZSYYKBB-UHFFFAOYSA-N 0.000 description 1
- PLDFODLZWKXMGG-UHFFFAOYSA-N (3-chloropyrazin-2-yl)hydrazine;hydrochloride Chemical compound Cl.NNC1=NC=CN=C1Cl PLDFODLZWKXMGG-UHFFFAOYSA-N 0.000 description 1
- JJSAEDOMTCNEQL-GOSISDBHSA-N (3r)-3-[[4-(4-chlorophenoxy)phenyl]sulfonylamino]-n-hydroxyoxane-3-carboxamide Chemical compound C=1C=C(OC=2C=CC(Cl)=CC=2)C=CC=1S(=O)(=O)N[C@]1(C(=O)NO)CCCOC1 JJSAEDOMTCNEQL-GOSISDBHSA-N 0.000 description 1
- YZIGEYGKVJNXSU-QGZVFWFLSA-N (3r)-3-[[4-(4-fluorophenoxy)phenyl]sulfonylamino]-n-hydroxyoxolane-3-carboxamide Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N[C@]1(C(=O)NO)CCOC1 YZIGEYGKVJNXSU-QGZVFWFLSA-N 0.000 description 1
- ULYONBAOIMCNEH-HNNXBMFYSA-N (3s)-3-(5-chloro-2-methoxyphenyl)-3-fluoro-6-(trifluoromethyl)-1h-indol-2-one Chemical compound COC1=CC=C(Cl)C=C1[C@@]1(F)C2=CC=C(C(F)(F)F)C=C2NC1=O ULYONBAOIMCNEH-HNNXBMFYSA-N 0.000 description 1
- LDSVTELDHUQWGO-UHFFFAOYSA-N (5-bromo-3-chloropyrazin-2-yl)hydrazine Chemical compound NNC1=NC=C(Br)N=C1Cl LDSVTELDHUQWGO-UHFFFAOYSA-N 0.000 description 1
- KMPLYESDOZJASB-PAHRJMAXSA-N (6s,8r,9s,10r,13s,14s,17r)-17-acetyl-17-hydroxy-6-methoxy-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-3-one;(z)-n-carbamoyl-2-ethylbut-2-enamide;6-ethoxy-1,3-benzothiazole-2-sulfonamide Chemical compound CC\C(=C\C)C(=O)NC(N)=O.CCOC1=CC=C2N=C(S(N)(=O)=O)SC2=C1.C([C@@]12C)CC(=O)C=C1[C@@H](OC)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 KMPLYESDOZJASB-PAHRJMAXSA-N 0.000 description 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- GGUSQTSTQSHJAH-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanol Chemical compound C=1C=C(Cl)C=CC=1C(O)CN(CC1)CCC1CC1=CC=C(F)C=C1 GGUSQTSTQSHJAH-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- QEMSVZNTSXPFJA-HNAYVOBHSA-N 1-[(1s,2s)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]-4-phenylpiperidin-4-ol Chemical compound C1([C@H](O)[C@H](C)N2CCC(O)(CC2)C=2C=CC=CC=2)=CC=C(O)C=C1 QEMSVZNTSXPFJA-HNAYVOBHSA-N 0.000 description 1
- QHMBUPFFCCEMDC-UHFFFAOYSA-N 1-[2-tert-butyl-3-oxo-8-(propan-2-ylamino)-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]cyclopentane-1-carboxylic acid Chemical compound C=1N(C(N(N=2)C(C)(C)C)=O)C=2C(NC(C)C)=NC=1C1(C(O)=O)CCCC1 QHMBUPFFCCEMDC-UHFFFAOYSA-N 0.000 description 1
- RBPMBICXIBHHEQ-UHFFFAOYSA-N 1-[3-oxo-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]cyclopentane-1-carboxylic acid Chemical compound C=1N(C(NN=2)=O)C=2C(NC(C)C)=NC=1C1(C(O)=O)CCCC1 RBPMBICXIBHHEQ-UHFFFAOYSA-N 0.000 description 1
- BPIPYQZVAXMQRR-UHFFFAOYSA-N 1-[4-(morpholin-4-ylmethyl)pyridin-2-yl]ethane-1,2-diamine Chemical compound C1=NC(C(N)CN)=CC(CN2CCOCC2)=C1 BPIPYQZVAXMQRR-UHFFFAOYSA-N 0.000 description 1
- ZUTXIUQCVJBLSM-UHFFFAOYSA-N 1-[4-(trifluoromethyl)pyridin-2-yl]ethane-1,2-diamine Chemical compound NCC(N)C1=CC(C(F)(F)F)=CC=N1 ZUTXIUQCVJBLSM-UHFFFAOYSA-N 0.000 description 1
- CGKYFPNWHRRUQJ-UHFFFAOYSA-N 1-bromo-1-(3,5-dimethoxyphenyl)-3-methylbutan-2-one Chemical compound COC1=CC(OC)=CC(C(Br)C(=O)C(C)C)=C1 CGKYFPNWHRRUQJ-UHFFFAOYSA-N 0.000 description 1
- SAIRZMWXVJEBMO-UHFFFAOYSA-N 1-bromo-3,3-dimethylbutan-2-one Chemical compound CC(C)(C)C(=O)CBr SAIRZMWXVJEBMO-UHFFFAOYSA-N 0.000 description 1
- WIIIQFYNZMQEQS-UHFFFAOYSA-N 1-bromo-3-methyl-1-phenylbutan-2-one Chemical compound CC(C)C(=O)C(Br)C1=CC=CC=C1 WIIIQFYNZMQEQS-UHFFFAOYSA-N 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- WYTPKWXHHZJJPY-UHFFFAOYSA-N 1-hydroxy-3-methyl-1-phenylbutan-2-one Chemical compound CC(C)C(=O)C(O)C1=CC=CC=C1 WYTPKWXHHZJJPY-UHFFFAOYSA-N 0.000 description 1
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-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
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- ZWWZVUJIUBEFTN-UHFFFAOYSA-N 2,3-dichloro-5-phenylpyrazine Chemical compound N1=C(Cl)C(Cl)=NC=C1C1=CC=CC=C1 ZWWZVUJIUBEFTN-UHFFFAOYSA-N 0.000 description 1
- UMPSXRYVXUPCOS-UHFFFAOYSA-N 2,3-dichlorophenol Chemical compound OC1=CC=CC(Cl)=C1Cl UMPSXRYVXUPCOS-UHFFFAOYSA-N 0.000 description 1
- MLCNOCRGSBCAGH-UHFFFAOYSA-N 2,3-dichloropyrazine Chemical compound ClC1=NC=CN=C1Cl MLCNOCRGSBCAGH-UHFFFAOYSA-N 0.000 description 1
- KDECKWVEFNMXLO-UHFFFAOYSA-N 2,6-ditert-butyl-7h-[1,2,4]triazolo[4,3-a]pyrazine-3,8-dione Chemical compound O=C1NC(C(C)(C)C)=CN2C(=O)N(C(C)(C)C)N=C21 KDECKWVEFNMXLO-UHFFFAOYSA-N 0.000 description 1
- ZAQQXCDMMKHUPE-UHFFFAOYSA-N 2,6-ditert-butyl-8-chloro-5-(2-methylphenyl)-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CC1=CC=CC=C1C1=C(C(C)(C)C)N=C(Cl)C2=NN(C(C)(C)C)C(=O)N12 ZAQQXCDMMKHUPE-UHFFFAOYSA-N 0.000 description 1
- LWAKORUFSFPXAK-UHFFFAOYSA-N 2,6-ditert-butyl-8-chloro-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound ClC1=NC(C(C)(C)C)=CN2C(=O)N(C(C)(C)C)N=C21 LWAKORUFSFPXAK-UHFFFAOYSA-N 0.000 description 1
- HLTRQIYNHRBUNW-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)ethanamine Chemical compound C1=CC=C2SC(CCN)=NC2=C1 HLTRQIYNHRBUNW-UHFFFAOYSA-N 0.000 description 1
- RHDSEUDGLHITHP-UHFFFAOYSA-N 2-(2,3-dichlorophenyl)-6-phenylpyrazine Chemical compound ClC1=CC=CC(C=2N=C(C=NC=2)C=2C=CC=CC=2)=C1Cl RHDSEUDGLHITHP-UHFFFAOYSA-N 0.000 description 1
- RXPLSUNVXZROEH-UHFFFAOYSA-N 2-(3,4-dichlorophenoxy)ethanamine Chemical compound NCCOC1=CC=C(Cl)C(Cl)=C1 RXPLSUNVXZROEH-UHFFFAOYSA-N 0.000 description 1
- JTEJMGHPAYJBTA-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)ethanamine Chemical compound C1=CC=C2CN(CCN)CCC2=C1 JTEJMGHPAYJBTA-UHFFFAOYSA-N 0.000 description 1
- GOWUDHPKGOIDIX-UHFFFAOYSA-N 2-(4-methyl-1-piperazinyl)ethanamine Chemical compound CN1CCN(CCN)CC1 GOWUDHPKGOIDIX-UHFFFAOYSA-N 0.000 description 1
- AGYSILLANCXWQW-UHFFFAOYSA-N 2-(4-methylphenoxy)ethanamine;hydrochloride Chemical compound Cl.CC1=CC=C(OCCN)C=C1 AGYSILLANCXWQW-UHFFFAOYSA-N 0.000 description 1
- SZOCPFOWWXFMLF-UHFFFAOYSA-N 2-(aminohydrazinylidene)acetic acid Chemical class NNN=CC(O)=O SZOCPFOWWXFMLF-UHFFFAOYSA-N 0.000 description 1
- XPBHPXODAUHISM-UHFFFAOYSA-N 2-(phenylmethoxycarbonylamino)ethyl methanesulfonate Chemical compound CS(=O)(=O)OCCNC(=O)OCC1=CC=CC=C1 XPBHPXODAUHISM-UHFFFAOYSA-N 0.000 description 1
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 1
- BDWCPCICKGFAFA-UHFFFAOYSA-N 2-amino-1-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)ethanone Chemical compound C1=CC=C2CN(C(=O)CN)CCC2=N1 BDWCPCICKGFAFA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 description 1
- MLYRFDXHQSQCKA-UHFFFAOYSA-N 2-bromo-4-methylpentan-3-one Chemical compound CC(C)C(=O)C(C)Br MLYRFDXHQSQCKA-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- HXJWAHBPGVXWBB-UHFFFAOYSA-N 2-chloro-1-methyl-2h-1,8-naphthyridine Chemical compound C1=CN=C2N(C)C(Cl)C=CC2=C1 HXJWAHBPGVXWBB-UHFFFAOYSA-N 0.000 description 1
- CQDMQOQCJRLUQN-UHFFFAOYSA-N 2-chloro-5,6,7,8-tetrahydro-1,6-naphthyridine Chemical compound C1NCCC2=NC(Cl)=CC=C21 CQDMQOQCJRLUQN-UHFFFAOYSA-N 0.000 description 1
- FRACHJCOMOVESL-UHFFFAOYSA-N 2-chloro-5,6,7,8-tetrahydro-1,6-naphthyridine;hydrochloride Chemical compound Cl.C1NCCC2=NC(Cl)=CC=C21 FRACHJCOMOVESL-UHFFFAOYSA-N 0.000 description 1
- JFZJMSDDOOAOIV-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(Cl)N=C1 JFZJMSDDOOAOIV-UHFFFAOYSA-N 0.000 description 1
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
- QXCOHSRHFCHCHN-UHFFFAOYSA-N 2-chloropyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(Cl)=C1 QXCOHSRHFCHCHN-UHFFFAOYSA-N 0.000 description 1
- SBPQKRFVOHEWRY-UHFFFAOYSA-N 2-methyl-2-[3-oxo-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]-n-(2-phenylethyl)propanamide Chemical compound C=1N(C(NN=2)=O)C=2C(NC(C)C)=NC=1C(C)(C)C(=O)NCCC1=CC=CC=C1 SBPQKRFVOHEWRY-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- TUVONOFKFDJHBJ-UHFFFAOYSA-N 2-pyridin-2-yloxyethanamine Chemical compound NCCOC1=CC=CC=N1 TUVONOFKFDJHBJ-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- XPYKJFYQGVTSIP-UHFFFAOYSA-N 2-tert-butyl-6-propan-2-yl-8-(propan-2-ylamino)-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CC(C)NC1=NC(C(C)C)=CN2C(=O)N(C(C)(C)C)N=C12 XPYKJFYQGVTSIP-UHFFFAOYSA-N 0.000 description 1
- OZWNFLFNOOOUFK-UHFFFAOYSA-N 2-tert-butyl-8-chloro-6-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C=1N2C(=O)N(C(C)(C)C)N=C2C(Cl)=NC=1C1=CC=C(Cl)C=C1 OZWNFLFNOOOUFK-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- WGTASENVNYJZBK-UHFFFAOYSA-N 3,4,5-trimethoxyamphetamine Chemical compound COC1=CC(CC(C)N)=CC(OC)=C1OC WGTASENVNYJZBK-UHFFFAOYSA-N 0.000 description 1
- DNFGPFRQSJOKEZ-UHFFFAOYSA-N 3-[2-(1-benzylpiperidin-4-yl)ethyl]-2,5-dihydropyrrolo[3,2-f][1,2]benzoxazol-6-one Chemical compound N1OC2=CC3=NC(=O)CC3=CC2=C1CCC(CC1)CCN1CC1=CC=CC=C1 DNFGPFRQSJOKEZ-UHFFFAOYSA-N 0.000 description 1
- XLJWJFKYRFPJSD-LZQZEXGQSA-N 3-[2-[(1s,5r,6s)-6-(4-fluorophenyl)-3-azabicyclo[3.2.0]heptan-3-yl]ethyl]-1h-quinazoline-2,4-dione Chemical compound C1=CC(F)=CC=C1[C@@H]1[C@H]2CN(CCN3C(C4=CC=CC=C4NC3=O)=O)C[C@H]2C1 XLJWJFKYRFPJSD-LZQZEXGQSA-N 0.000 description 1
- QDJSRGYYSLITSA-UHFFFAOYSA-N 3-[2-tert-butyl-3-oxo-8-(propan-2-ylamino)-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]benzoic acid Chemical compound C=1N(C(N(N=2)C(C)(C)C)=O)C=2C(NC(C)C)=NC=1C1=CC=CC(C(O)=O)=C1 QDJSRGYYSLITSA-UHFFFAOYSA-N 0.000 description 1
- ZGRFUHPMVBFGGU-UHFFFAOYSA-N 3-[3-oxo-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]-n-(2-phenylethyl)benzamide Chemical compound C=1N(C(NN=2)=O)C=2C(NC(C)C)=NC=1C(C=1)=CC=CC=1C(=O)NCCC1=CC=CC=C1 ZGRFUHPMVBFGGU-UHFFFAOYSA-N 0.000 description 1
- NMDUJEUWNLCXSB-UHFFFAOYSA-N 3-[[4-(4-fluorophenoxy)phenyl]sulfonyl-[1-(hydroxyamino)-2-methyl-1-oxopropan-2-yl]amino]propanoic acid Chemical compound C1=CC(S(=O)(=O)N(CCC(O)=O)C(C)(C)C(=O)NO)=CC=C1OC1=CC=C(F)C=C1 NMDUJEUWNLCXSB-UHFFFAOYSA-N 0.000 description 1
- PDCBVHDMAFCHPK-UHFFFAOYSA-N 3-[[4-(4-fluorophenoxy)phenyl]sulfonyl-[1-(hydroxycarbamoyl)cyclobutyl]amino]propanoic acid Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(O)=O)C1(C(=O)NO)CCC1 PDCBVHDMAFCHPK-UHFFFAOYSA-N 0.000 description 1
- WARXYAHFCARUNH-UHFFFAOYSA-N 3-[[4-(4-fluorophenoxy)phenyl]sulfonyl-[4-(hydroxycarbamoyl)oxan-4-yl]amino]propanoic acid Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(O)=O)C1(C(=O)NO)CCOCC1 WARXYAHFCARUNH-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- PWRBCZZQRRPXAB-UHFFFAOYSA-N 3-chloropyridine Chemical compound ClC1=CC=CN=C1 PWRBCZZQRRPXAB-UHFFFAOYSA-N 0.000 description 1
- KGAJQOIQFADGAX-UHFFFAOYSA-N 3-oxo-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazine-6-carboxylic acid Chemical compound CC(C)NC1=NC(C(O)=O)=CN2C(=O)NN=C12 KGAJQOIQFADGAX-UHFFFAOYSA-N 0.000 description 1
- PFFNURQSGRAIJD-UHFFFAOYSA-N 3-oxo-n-(2-phenylethyl)-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazine-6-carboxamide Chemical compound C=1N(C(NN=2)=O)C=2C(NC(C)C)=NC=1C(=O)NCCC1=CC=CC=C1 PFFNURQSGRAIJD-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- CYZMUIMLRBJSRO-UHFFFAOYSA-N 4-[[4-(4-chlorophenoxy)phenyl]sulfonylamino]-n-hydroxyoxane-4-carboxamide Chemical compound C=1C=C(OC=2C=CC(Cl)=CC=2)C=CC=1S(=O)(=O)NC1(C(=O)NO)CCOCC1 CYZMUIMLRBJSRO-UHFFFAOYSA-N 0.000 description 1
- ZBRHTUMWSDPCMI-UHFFFAOYSA-N 4-[[4-(4-fluorophenoxy)phenyl]sulfonylamino]-n-hydroxyoxane-4-carboxamide Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)NC1(C(=O)NO)CCOCC1 ZBRHTUMWSDPCMI-UHFFFAOYSA-N 0.000 description 1
- LLRQVSZVVAKRJA-UHFFFAOYSA-N 4-chloro-7-(trifluoromethyl)quinoline Chemical compound ClC1=CC=NC2=CC(C(F)(F)F)=CC=C21 LLRQVSZVVAKRJA-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- JAYKYPXVHLUMOR-UHFFFAOYSA-N 5-(3-methylbut-1-enyl)-6-propan-2-yl-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CC(C)NC1=NC(C(C)C)=C(C=CC(C)C)N2C(=O)NN=C12 JAYKYPXVHLUMOR-UHFFFAOYSA-N 0.000 description 1
- PAMFCOWZPWXWRR-UHFFFAOYSA-N 5-(3-methylbutyl)-6-propan-2-yl-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CC(C)CCC1=C(C(C)C)N=C(NC(C)C)C2=NNC(=O)N12 PAMFCOWZPWXWRR-UHFFFAOYSA-N 0.000 description 1
- IKBZAUYPBWFMDI-UHFFFAOYSA-N 5-bromo-4-methoxy-7-methyl-2,3-dihydro-1h-indene Chemical compound C1=C(Br)C(OC)=C2CCCC2=C1C IKBZAUYPBWFMDI-UHFFFAOYSA-N 0.000 description 1
- FUARLYRXLXDKDZ-UHFFFAOYSA-N 5-phenyl-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1NC(=O)N2C=1C(NC(C)C)=NC=C2C1=CC=CC=C1 FUARLYRXLXDKDZ-UHFFFAOYSA-N 0.000 description 1
- CGJQYTSOGSBQRD-UHFFFAOYSA-N 6-(3-bromophenyl)-2-tert-butyl-8-[2-[[4-(trifluoromethyl)pyridin-2-yl]amino]ethylamino]-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1C(C=2C=C(Br)C=CC=2)=CN2C(=O)N(C(C)(C)C)N=C2C=1NCCNC1=CC(C(F)(F)F)=CC=N1 CGJQYTSOGSBQRD-UHFFFAOYSA-N 0.000 description 1
- RZGFXXLUDXODLN-UHFFFAOYSA-N 6-(3-bromophenyl)-2-tert-butyl-8-chloro-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C=1N2C(=O)N(C(C)(C)C)N=C2C(Cl)=NC=1C1=CC=CC(Br)=C1 RZGFXXLUDXODLN-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- DCKSRAQFOPDGNV-UHFFFAOYSA-N 6-bromo-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical class C1=NC(Br)=CN2C(=O)NN=C12 DCKSRAQFOPDGNV-UHFFFAOYSA-N 0.000 description 1
- ASQNCWLIXYHZSI-UHFFFAOYSA-N 6-cyclopentyl-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C=1N(C(NN=2)=O)C=2C(NC(C)C)=NC=1C1CCCC1 ASQNCWLIXYHZSI-UHFFFAOYSA-N 0.000 description 1
- YLTQDJSDJRPGEV-UHFFFAOYSA-N 6-phenyl-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C=1N(C(NN=2)=O)C=2C(NC(C)C)=NC=1C1=CC=CC=C1 YLTQDJSDJRPGEV-UHFFFAOYSA-N 0.000 description 1
- QBLKYVFJHUDDQM-UHFFFAOYSA-N 6-propan-2-yl-8-(propan-2-ylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CC(C)NC1=NC(C(C)C)=CN2C(=O)NN=C12 QBLKYVFJHUDDQM-UHFFFAOYSA-N 0.000 description 1
- PMIKLZQHQIFURW-UHFFFAOYSA-N 6-tert-butyl-5-(3-methylphenyl)-8-(2-pyridin-3-ylethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CC1=CC=CC(C=2N3C(=O)NN=C3C(NCCC=3C=NC=CC=3)=NC=2C(C)(C)C)=C1 PMIKLZQHQIFURW-UHFFFAOYSA-N 0.000 description 1
- ZSBHAJGXGRIWGZ-UHFFFAOYSA-N 6-tert-butyl-8-(2-hydroxyethylamino)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound OCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C21 ZSBHAJGXGRIWGZ-UHFFFAOYSA-N 0.000 description 1
- MXOAQTLGMCIWIW-UHFFFAOYSA-N 6-tert-butyl-8-[2-(4-methylphenoxy)ethylamino]-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C1=CC(C)=CC=C1OCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 MXOAQTLGMCIWIW-UHFFFAOYSA-N 0.000 description 1
- NQRGRSAVQURSLF-UHFFFAOYSA-N 6-tert-butyl-8-[3-(dimethylamino)propylamino]-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CN(C)CCCNC1=NC(C(C)(C)C)=CN2C(=O)NN=C12 NQRGRSAVQURSLF-UHFFFAOYSA-N 0.000 description 1
- RNIXHGKLICEFDK-UHFFFAOYSA-N 6-tert-butyl-8-chloro-5-(2-methylphenyl)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound CC1=CC=CC=C1C1=C(C(C)(C)C)N=C(Cl)C2=NNC(=O)N12 RNIXHGKLICEFDK-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
- BPSDKERHEQFIAS-UHFFFAOYSA-N 8-[2-(1,3-benzothiazol-2-ylamino)ethylamino]-6-(4-chlorophenyl)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C1=CC(Cl)=CC=C1C1=CN2C(=O)NN=C2C(NCCNC=2SC3=CC=CC=C3N=2)=N1 BPSDKERHEQFIAS-UHFFFAOYSA-N 0.000 description 1
- NIDQZCFMAQPHSJ-UHFFFAOYSA-N 8-amino-6-tert-butyl-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical class NC1=NC(C(C)(C)C)=CN2C(=O)NN=C21 NIDQZCFMAQPHSJ-UHFFFAOYSA-N 0.000 description 1
- CPELXKRGGOWABA-UHFFFAOYSA-N 8-bromo-6-(4-chlorophenyl)-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C1=CC(Cl)=CC=C1C1=CN2C(=O)NN=C2C(Br)=N1 CPELXKRGGOWABA-UHFFFAOYSA-N 0.000 description 1
- OFFYTXZHDKYCEP-UHFFFAOYSA-N 8-bromo-6-phenyl-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C=1N(C(NN=2)=O)C=2C(Br)=NC=1C1=CC=CC=C1 OFFYTXZHDKYCEP-UHFFFAOYSA-N 0.000 description 1
- WTTAHSBJCVTMQO-UHFFFAOYSA-N 8-chloro-5-phenyl-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound N=1NC(=O)N2C=1C(Cl)=NC=C2C1=CC=CC=C1 WTTAHSBJCVTMQO-UHFFFAOYSA-N 0.000 description 1
- XGBJWBJIOZVLIZ-UHFFFAOYSA-N 8-chloro-6-phenyl-2h-[1,2,4]triazolo[4,3-a]pyrazin-3-one Chemical compound C=1N(C(NN=2)=O)C=2C(Cl)=NC=1C1=CC=CC=C1 XGBJWBJIOZVLIZ-UHFFFAOYSA-N 0.000 description 1
- FHCSBLWRGCOVPT-UHFFFAOYSA-N AZD2858 Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C(=O)NC=2C=NC=CC=2)C=C1 FHCSBLWRGCOVPT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 108090000644 Angiozyme Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 102000015735 Beta-catenin Human genes 0.000 description 1
- 108060000903 Beta-catenin Proteins 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- DFDKKVDXQOCERU-UHFFFAOYSA-N CC(C)(C)N1C(=O)N2C=C(N=C(C2=N1)Cl)C3(CCCC3)C(=O)O Chemical compound CC(C)(C)N1C(=O)N2C=C(N=C(C2=N1)Cl)C3(CCCC3)C(=O)O DFDKKVDXQOCERU-UHFFFAOYSA-N 0.000 description 1
- PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 1
- 239000012275 CTLA-4 inhibitor Substances 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 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
- 102100027995 Collagenase 3 Human genes 0.000 description 1
- 108050005238 Collagenase 3 Proteins 0.000 description 1
- VHHGUBHZBLPTKL-UHFFFAOYSA-N Cp-471358 Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(O)=O)C1(C(=O)NO)CCCC1 VHHGUBHZBLPTKL-UHFFFAOYSA-N 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 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
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102100031547 HLA class II histocompatibility antigen, DO alpha chain Human genes 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 101001032567 Homo sapiens Glycogen synthase kinase-3 beta Proteins 0.000 description 1
- 101000866278 Homo sapiens HLA class II histocompatibility antigen, DO alpha chain Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 1
- ZQPQGKQTIZYFEF-WCVJEAGWSA-N Huperzine Natural products C1([C@H]2[C@H](O)C(=O)N[C@H]2[C@@H](O)C=2C=CC=CC=2)=CC=CC=C1 ZQPQGKQTIZYFEF-WCVJEAGWSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- 102100027998 Macrophage metalloelastase Human genes 0.000 description 1
- 101710187853 Macrophage metalloelastase Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102100030417 Matrilysin Human genes 0.000 description 1
- 108090000855 Matrilysin Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- CJUMAFVKTCBCJK-UHFFFAOYSA-N N-benzyloxycarbonylglycine Chemical compound OC(=O)CNC(=O)OCC1=CC=CC=C1 CJUMAFVKTCBCJK-UHFFFAOYSA-N 0.000 description 1
- FTFRZXFNZVCRSK-UHFFFAOYSA-N N4-(3-chloro-4-fluorophenyl)-N6-(1-methyl-4-piperidinyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CN(C)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 FTFRZXFNZVCRSK-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 102100030411 Neutrophil collagenase Human genes 0.000 description 1
- 101710118230 Neutrophil collagenase Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- CEFBXMNJODPQHJ-SPIKMXEPSA-N OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C=1N=C(C=2C=CC=CC=2)NC=1CN(CC1)CCN1C1=NC=CC=N1 Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C=1N=C(C=2C=CC=CC=2)NC=1CN(CC1)CCN1C1=NC=CC=N1 CEFBXMNJODPQHJ-SPIKMXEPSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 108010087776 Proto-Oncogene Proteins c-myb Proteins 0.000 description 1
- 102000009096 Proto-Oncogene Proteins c-myb Human genes 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 208000026214 Skeletal muscle atrophy Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
- 102100030416 Stromelysin-1 Human genes 0.000 description 1
- 101710108790 Stromelysin-1 Proteins 0.000 description 1
- 102100028848 Stromelysin-2 Human genes 0.000 description 1
- 101710108792 Stromelysin-2 Proteins 0.000 description 1
- 102100028847 Stromelysin-3 Human genes 0.000 description 1
- 108050005271 Stromelysin-3 Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001411 amidrazones Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 229940039856 aricept Drugs 0.000 description 1
- 125000002393 azetidinyl group Chemical group 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
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- AGSPXMVUFBBBMO-UHFFFAOYSA-N beta-aminopropionitrile Chemical compound NCCC#N AGSPXMVUFBBBMO-UHFFFAOYSA-N 0.000 description 1
- 150000005347 biaryls Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- 229960004367 bupropion hydrochloride Drugs 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229940047495 celebrex Drugs 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 108010044165 crotoxin drug combination cardiotoxin Proteins 0.000 description 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 125000005883 dithianyl group Chemical group 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 229940098766 effexor Drugs 0.000 description 1
- 229950005455 eliprodil Drugs 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- CRLVPDZDXUHTLQ-UHFFFAOYSA-N ethyl 1-[2-tert-butyl-3-oxo-8-(propan-2-ylamino)-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]cyclopentane-1-carboxylate Chemical compound C=1N(C(N(N=2)C(C)(C)C)=O)C=2C(NC(C)C)=NC=1C1(C(=O)OCC)CCCC1 CRLVPDZDXUHTLQ-UHFFFAOYSA-N 0.000 description 1
- MJAAERXSVQAQJR-UHFFFAOYSA-N ethyl 1-tert-butyl-4-(3,3-dimethyl-2-oxobutyl)-5-oxo-1,2,4-triazole-3-carboxylate Chemical compound CCOC(=O)C1=NN(C(C)(C)C)C(=O)N1CC(=O)C(C)(C)C MJAAERXSVQAQJR-UHFFFAOYSA-N 0.000 description 1
- RZMZBHSKPLVQCP-UHFFFAOYSA-N ethyl 2-amino-2-oxoacetate Chemical compound CCOC(=O)C(N)=O RZMZBHSKPLVQCP-UHFFFAOYSA-N 0.000 description 1
- IZTSGBXNCQUHFZ-UHFFFAOYSA-N ethyl 2-tert-butyl-3-oxo-1h-1,2,4-triazole-5-carboxylate Chemical compound CCOC(=O)C1=NN(C(C)(C)C)C(=O)N1 IZTSGBXNCQUHFZ-UHFFFAOYSA-N 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 229940108366 exelon Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 229950002951 fananserin Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- NYSDRDDQELAVKP-SFHVURJKSA-N flesinoxan Chemical compound C([C@@H](O1)CO)OC2=C1C=CC=C2N(CC1)CCN1CCNC(=O)C1=CC=C(F)C=C1 NYSDRDDQELAVKP-SFHVURJKSA-N 0.000 description 1
- 229950003678 flesinoxan Drugs 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229940003380 geodon Drugs 0.000 description 1
- 229960000647 gepirone Drugs 0.000 description 1
- QOIGKGMMAGJZNZ-UHFFFAOYSA-N gepirone Chemical compound O=C1CC(C)(C)CC(=O)N1CCCCN1CCN(C=2N=CC=CN=2)CC1 QOIGKGMMAGJZNZ-UHFFFAOYSA-N 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 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
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical class OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 229950010480 icopezil Drugs 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 229940070765 laurate Drugs 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
- 150000007517 lewis acids Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- JCIVHYBIFRUGKO-UHFFFAOYSA-N lithium;2,2,6,6-tetramethylpiperidine Chemical compound [Li].CC1(C)CCCC(C)(C)N1 JCIVHYBIFRUGKO-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- IOZLFEPCLZZJIF-UHFFFAOYSA-N methyl 2-[2-tert-butyl-3-oxo-8-(propan-2-ylamino)-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]-2-methylpropanoate Chemical compound CC(C)NC1=NC(C(C)(C)C(=O)OC)=CN2C(=O)N(C(C)(C)C)N=C21 IOZLFEPCLZZJIF-UHFFFAOYSA-N 0.000 description 1
- FYKUMNRBXCMTTD-UHFFFAOYSA-N methyl 3-(2-tert-butyl-8-chloro-3-oxo-[1,2,4]triazolo[4,3-a]pyrazin-6-yl)benzoate Chemical compound COC(=O)C1=CC=CC(C=2N=C(Cl)C=3N(C(N(N=3)C(C)(C)C)=O)C=2)=C1 FYKUMNRBXCMTTD-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- TWIIRMSFZNYMQE-UHFFFAOYSA-N methyl pyrazine-2-carboxylate Chemical compound COC(=O)C1=CN=CC=N1 TWIIRMSFZNYMQE-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- ZKWFSTHEYLJLEL-UHFFFAOYSA-N morpholine-4-carboxamide Chemical compound NC(=O)N1CCOCC1 ZKWFSTHEYLJLEL-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- KDAQFKLDHWSEHK-UHFFFAOYSA-N n'-(1,3-benzothiazol-2-yl)ethane-1,2-diamine Chemical compound C1=CC=C2SC(NCCN)=NC2=C1 KDAQFKLDHWSEHK-UHFFFAOYSA-N 0.000 description 1
- SINGLPBIGBATOH-UHFFFAOYSA-N n'-(1-methylpiperidin-4-yl)ethane-1,2-diamine Chemical compound CN1CCC(NCCN)CC1 SINGLPBIGBATOH-UHFFFAOYSA-N 0.000 description 1
- KJNDLGHBEZARBJ-UHFFFAOYSA-N n'-(6-methyl-7,8-dihydro-5h-1,6-naphthyridin-2-yl)ethane-1,2-diamine Chemical compound NCCNC1=CC=C2CN(C)CCC2=N1 KJNDLGHBEZARBJ-UHFFFAOYSA-N 0.000 description 1
- KFIGICHILYTCJF-UHFFFAOYSA-N n'-methylethane-1,2-diamine Chemical compound CNCCN KFIGICHILYTCJF-UHFFFAOYSA-N 0.000 description 1
- VPTHSIHGLIRODH-UHFFFAOYSA-N n'-pyridin-3-ylethane-1,2-diamine Chemical compound NCCNC1=CC=CN=C1 VPTHSIHGLIRODH-UHFFFAOYSA-N 0.000 description 1
- PTEMOGKSEXPRTP-UHFFFAOYSA-N n-[2-[(6-tert-butyl-3-oxo-2h-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)amino]ethyl]benzenesulfonamide Chemical compound N=1C(C(C)(C)C)=CN(C(NN=2)=O)C=2C=1NCCNS(=O)(=O)C1=CC=CC=C1 PTEMOGKSEXPRTP-UHFFFAOYSA-N 0.000 description 1
- SLIJTYPFHHQROI-UHFFFAOYSA-N n-methyl-n'-pyrimidin-2-ylethane-1,2-diamine Chemical compound CNCCNC1=NC=CC=N1 SLIJTYPFHHQROI-UHFFFAOYSA-N 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 229960002441 nefazodone hydrochloride Drugs 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000005593 norbornanyl group Chemical group 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229960005017 olanzapine Drugs 0.000 description 1
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910001392 phosphorus oxide Inorganic materials 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- GGHDAUPFEBTORZ-UHFFFAOYSA-N propane-1,1-diamine Chemical compound CCC(N)N GGHDAUPFEBTORZ-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- 229940099190 serzone Drugs 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 230000025185 skeletal muscle atrophy Effects 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 231100000469 sperm hypomotility Toxicity 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- GPTXCAZYUMDUMN-UHFFFAOYSA-N tert-butyl n-(2-hydroxyethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCO GPTXCAZYUMDUMN-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- DDPWVABNMBRBFI-UHFFFAOYSA-N tert-butylhydrazine;hydron;chloride Chemical compound Cl.CC(C)(C)NN DDPWVABNMBRBFI-UHFFFAOYSA-N 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000005888 tetrahydroindolyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- VSAISIQCTGDGPU-UHFFFAOYSA-N tetraphosphorus hexaoxide Chemical compound O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000005503 thioxanyl group Chemical group 0.000 description 1
- 238000003354 tissue distribution assay 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
- 230000000699 topical effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- YOIAWAIKYVEKMF-UHFFFAOYSA-N trifluoromethanesulfonic acid Chemical class OS(=O)(=O)C(F)(F)F.OS(=O)(=O)C(F)(F)F YOIAWAIKYVEKMF-UHFFFAOYSA-N 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229960002416 venlafaxine hydrochloride Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 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
- 229940009065 wellbutrin Drugs 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 229960000607 ziprasidone Drugs 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Reproductive Health (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US51022403P | 2003-10-10 | 2003-10-10 | |
| PCT/IB2004/003137 WO2005035532A1 (en) | 2003-10-10 | 2004-09-27 | Substituted 2h-[1,2,4]triazolo[4,3-a]pyrazines as gsk-3 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007508290A true JP2007508290A (ja) | 2007-04-05 |
| JP2007508290A5 JP2007508290A5 (enExample) | 2007-10-11 |
Family
ID=34435073
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006530734A Pending JP2007508290A (ja) | 2003-10-10 | 2004-09-27 | GSK−3阻害剤としての置換2H−[1,2,4]トリアゾロ[4,3−a]ピラジン |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US7709473B2 (enExample) |
| EP (1) | EP1678180B1 (enExample) |
| JP (1) | JP2007508290A (enExample) |
| AT (1) | ATE369370T1 (enExample) |
| BR (1) | BRPI0415185A (enExample) |
| CA (1) | CA2541832C (enExample) |
| DE (1) | DE602004008098T8 (enExample) |
| ES (1) | ES2288270T3 (enExample) |
| MX (1) | MXPA06004043A (enExample) |
| WO (1) | WO2005035532A1 (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011006404A (ja) * | 2009-05-27 | 2011-01-13 | Toyama Chem Co Ltd | 3,6−ジクロロ−2−ピラジンカルボニトリルの製造法 |
| JP2011520819A (ja) * | 2008-05-15 | 2011-07-21 | バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト | 置換イミダゾ−およびトリアゾロピリミジン類、イミダゾ−およびピラゾロピラジン類およびイミダゾトリアジン類 |
| KR20170016465A (ko) * | 2014-06-17 | 2017-02-13 | 치아타이 티안큉 파마수티컬 그룹 주식회사 | PI3K 억제제로 사용되는 피리디노[1,2-a]피리미돈 유사체 |
| JP2017518382A (ja) * | 2014-06-17 | 2017-07-06 | リーシン ファーマシューティカル カンパニー リミテッド | mTOR/PI3K阻害剤としてのピリド[1,2−a]ピリミジノン類似体 |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7728141B2 (en) | 2003-11-04 | 2010-06-01 | Merck Sharp & Dohme Corp. | Substituted naphthyridinone derivatives |
| EP2275096A3 (en) | 2005-08-26 | 2011-07-13 | Braincells, Inc. | Neurogenesis via modulation of the muscarinic receptors |
| EP2258358A3 (en) | 2005-08-26 | 2011-09-07 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
| AU2006304787A1 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by PDE inhibition |
| CA2625210A1 (en) | 2005-10-31 | 2007-05-10 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| AU2007249399A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| DE102007012645A1 (de) * | 2007-03-16 | 2008-09-18 | Bayer Healthcare Ag | Substituierte Imidazo- und Triazolopyrimidine |
| DE102007032349A1 (de) * | 2007-07-11 | 2009-01-15 | Bayer Healthcare Ag | Imidazo-, Pyrazolopyrazine und Imidazotriazine und ihre Verwendung |
| WO2009017453A1 (en) * | 2007-07-30 | 2009-02-05 | Astrazeneca Ab | New therapeutic combination of an antipsychotic and a gsk3 inhibitor 958 |
| PE20091074A1 (es) * | 2007-12-13 | 2009-07-26 | Bayer Healthcare Ag | Triazolotriazinas y triazolopirazinas y su uso |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| EP2526102B1 (en) | 2010-01-22 | 2017-03-08 | Fundación Centro Nacional de Investigaciones Oncológicas Carlos III | Inhibitors of PI3 kinase |
| WO2011141713A1 (en) | 2010-05-13 | 2011-11-17 | Centro Nacional De Investigaciones Oncologicas (Cnio) | New bicyclic compounds as pi3-k and mtor inhibitors |
| HUE048859T2 (hu) | 2010-08-10 | 2020-08-28 | Rempex Pharmaceuticals Inc | Gyûrûs bórsavészter származékok, eljárás elõállításukra, és terápiás alkalmazásuk |
| WO2013033461A1 (en) | 2011-08-31 | 2013-03-07 | Rempex Pharmaceuticals, Inc. | Heterocyclic boronic acid ester derivatives and therapeutic uses thereof |
| US9156858B2 (en) | 2012-05-23 | 2015-10-13 | Rempex Pharmaceuticals, Inc. | Boronic acid derivatives and therapeutic uses thereof |
| US10561675B2 (en) | 2012-06-06 | 2020-02-18 | Rempex Pharmaceuticals, Inc. | Cyclic boronic acid ester derivatives and therapeutic uses thereof |
| CN103121970B (zh) * | 2012-12-04 | 2015-04-29 | 中国科学院昆明植物研究所 | 苯并咪唑及其衍生物,其药物组合物及其在制备抗抑郁药物中的应用 |
| CN103121969A (zh) * | 2012-12-04 | 2013-05-29 | 中国科学院昆明植物研究所 | 苯并咪唑及其衍生物,其药物组合物及其应用 |
| EA201591003A1 (ru) | 2013-01-04 | 2015-12-30 | Ремпекс Фармасьютикалз, Инк. | Производные бороновой кислоты и их терапевтическое применение |
| US9241947B2 (en) | 2013-01-04 | 2016-01-26 | Rempex Pharmaceuticals, Inc. | Boronic acid derivatives and therapeutic uses thereof |
| US9101638B2 (en) | 2013-01-04 | 2015-08-11 | Rempex Pharmaceuticals, Inc. | Boronic acid derivatives and therapeutic uses thereof |
| AU2014204046B2 (en) | 2013-01-04 | 2017-02-23 | Rempex Pharmaceuticals, Inc. | Boronic acid derivatives and therapeutic uses thereof |
| US9493442B2 (en) | 2014-02-13 | 2016-11-15 | Incyte Corporation | Cyclopropylamines as LSD1 inhibitors |
| CN106164066B (zh) | 2014-02-13 | 2020-01-17 | 因赛特公司 | 作为lsd1抑制剂的环丙胺 |
| JP6602779B2 (ja) | 2014-02-13 | 2019-11-06 | インサイト・コーポレイション | Lsd1阻害剤としてのシクロプロピルアミン類 |
| US9527835B2 (en) | 2014-02-13 | 2016-12-27 | Incyte Corporation | Cyclopropylamines as LSD1 inhibitors |
| CA2945263A1 (en) | 2014-04-09 | 2015-10-15 | Christopher Rudd | Use of gsk-3 inhibitors or activators which modulate pd-1 or t-bet expression to modulate t cell immunity |
| WO2015171398A1 (en) | 2014-05-05 | 2015-11-12 | Rempex Pharmaceuticals, Inc. | Salts and polymorphs of cyclic boronic acid ester derivatives and therapeutic uses thereof |
| PT3140310T (pt) | 2014-05-05 | 2019-11-18 | Rempex Pharmaceuticals Inc | Síntese de sais de boronato e utilizações dos mesmos |
| BR112016026291A2 (pt) | 2014-05-19 | 2017-08-15 | Rempex Pharmaceuticals Inc | Derivados do ácido borônico e usos terapêuticos dos mesmos |
| MX2016016666A (es) | 2014-07-01 | 2017-08-08 | Rempex Pharmaceuticals Inc | Derivados de acido boronico y usos terapeuticos de los mismos. |
| US9695168B2 (en) | 2014-07-10 | 2017-07-04 | Incyte Corporation | Substituted imidazo[1,5-α]pyridines and imidazo[1,5-α]pyrazines as LSD1 inhibitors |
| WO2016007722A1 (en) | 2014-07-10 | 2016-01-14 | Incyte Corporation | Triazolopyridines and triazolopyrazines as lsd1 inhibitors |
| TW201613925A (en) | 2014-07-10 | 2016-04-16 | Incyte Corp | Imidazopyrazines as LSD1 inhibitors |
| WO2016007727A1 (en) | 2014-07-10 | 2016-01-14 | Incyte Corporation | Triazolopyridines and triazolopyrazines as lsd1 inhibitors |
| US10662205B2 (en) | 2014-11-18 | 2020-05-26 | Qpex Biopharma, Inc. | Cyclic boronic acid ester derivatives and therapeutic uses thereof |
| WO2016149393A1 (en) | 2015-03-17 | 2016-09-22 | Rempex Pharmaceuticals, Inc. | Boronic acid derivatives and therapeutic uses thereof |
| CN107660205B (zh) | 2015-04-03 | 2021-08-27 | 因赛特公司 | 作为lsd1抑制剂的杂环化合物 |
| EA035534B1 (ru) | 2015-08-12 | 2020-06-30 | Инсайт Корпорейшн | Соли ингибитора lsd1 |
| BR112018071585B1 (pt) | 2016-04-22 | 2024-01-02 | Incyte Corporation | Formulações de um inibidor de lsd1, seus usos e método de preparação das mesmas |
| SG11201811549UA (en) | 2016-06-30 | 2019-01-30 | Qpex Biopharma Inc | Boronic acid derivatives and therapeutic uses thereof |
| CN107602446B (zh) * | 2016-07-12 | 2020-04-07 | 中国科学院上海药物研究所 | 1,4-双取代-1,2,3,6-四氢吡啶类化合物、其制备方法、药物组合物及其应用 |
| TN2019000010A1 (en) | 2016-07-12 | 2020-07-15 | Revolution Medicines Inc | 2,5-disubstituted 3-methyl pyrazines and 2,5,6-trisubstituted 3-methyl pyrazines as allosteric shp2 inhibitors |
| CA3051206A1 (en) | 2017-01-23 | 2018-07-26 | Revolution Medicines, Inc. | Bicyclic compounds as allosteric shp2 inhibitors |
| CA3051054A1 (en) | 2017-01-23 | 2018-07-26 | Revolution Medicines, Inc. | Pyridine compounds as allosteric shp2 inhibitors |
| CN111212843B (zh) | 2017-10-11 | 2025-05-16 | Qpex生物制药有限公司 | 硼酸衍生物及其合成 |
| RU2020115095A (ru) | 2017-10-12 | 2021-11-12 | Революшн Медсинз, Инк. | Пиридиновые, пиразиновые и триазиновые соединения в качестве аллостерических ингибиторов shp2 |
| MX2020006273A (es) | 2017-12-15 | 2020-09-14 | Revolution Medicines Inc | Compuestos policiclicos como inhibidores alostericos de shp2. |
| US11530220B2 (en) | 2018-02-06 | 2022-12-20 | Ideaya Biosciences, Inc. | Substituted imidazo[1,5-a]pyrazines and [1,2,4]triazolo[4,3-a]pyrazines for the modulation of AhR |
| JP7329260B2 (ja) | 2018-04-20 | 2023-08-18 | キューペックス バイオファーマ, インコーポレイテッド | ボロン酸誘導体およびその治療的使用 |
| US10968200B2 (en) | 2018-08-31 | 2021-04-06 | Incyte Corporation | Salts of an LSD1 inhibitor and processes for preparing the same |
| AR131541A1 (es) | 2023-01-07 | 2025-04-09 | Syngenta Crop Protection Ag | Compuestos de carboxamida novedosos |
| WO2025032129A1 (en) | 2023-08-08 | 2025-02-13 | Syngenta Crop Protection Ag | Novel aminoindane and aminotetraline compounds |
| WO2025109114A1 (en) | 2023-11-24 | 2025-05-30 | Syngenta Crop Protection Ag | Novel carboxamide compounds |
| WO2025149629A1 (en) | 2024-01-12 | 2025-07-17 | Syngenta Crop Protection Ag | Novel carboxamide compounds |
| WO2025149637A1 (en) | 2024-01-12 | 2025-07-17 | Syngenta Crop Protection Ag | Novel carboxamide compounds |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002080064A1 (en) * | 2001-03-28 | 2002-10-10 | Sony Computer Entertainment Inc. | Content distribution system |
| WO2002088078A2 (en) * | 2001-04-30 | 2002-11-07 | Vertex Pharmaceuticals Incorporated | INHIBITORS OF GSK-3 AND CRYSTAL STRUCTURES OF GSK-3β PROTEIN AND PROTEIN COMPLEXES |
| WO2003072580A1 (en) * | 2002-02-28 | 2003-09-04 | Sanofi-Aventis | 1-[ALKYL], 1-[HETEROARYL)ALKYL] AND 1-[ARYL)ALKYL]-7-(PYRIMIDIN-4-YL)-IMADAZO[1,2-a]PYRIMIDIN-5(1H)-ONE DERIVATIVES |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1235910A (en) | 1968-12-10 | 1971-06-16 | Ici Ltd | Pharmaceutical compositions |
| FR2662163A1 (fr) | 1990-05-16 | 1991-11-22 | Lipha | Nouvelles 8-amino-1,2,4-triazolo(4,3-a) pyrazines, procedes de preparation et medicaments les contenant. |
| JP2006521343A (ja) * | 2003-03-27 | 2006-09-21 | ファイザー・プロダクツ・インク | 置換4−アミノ[1,2,4]トリアゾロ[4,3−a]キノキサリン |
-
2004
- 2004-09-27 BR BRPI0415185-2A patent/BRPI0415185A/pt not_active IP Right Cessation
- 2004-09-27 WO PCT/IB2004/003137 patent/WO2005035532A1/en not_active Ceased
- 2004-09-27 US US10/575,395 patent/US7709473B2/en not_active Expired - Fee Related
- 2004-09-27 MX MXPA06004043A patent/MXPA06004043A/es not_active Application Discontinuation
- 2004-09-27 EP EP04769486A patent/EP1678180B1/en not_active Expired - Lifetime
- 2004-09-27 ES ES04769486T patent/ES2288270T3/es not_active Expired - Lifetime
- 2004-09-27 AT AT04769486T patent/ATE369370T1/de not_active IP Right Cessation
- 2004-09-27 CA CA002541832A patent/CA2541832C/en not_active Expired - Fee Related
- 2004-09-27 JP JP2006530734A patent/JP2007508290A/ja active Pending
- 2004-09-27 DE DE602004008098T patent/DE602004008098T8/de active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002080064A1 (en) * | 2001-03-28 | 2002-10-10 | Sony Computer Entertainment Inc. | Content distribution system |
| WO2002088078A2 (en) * | 2001-04-30 | 2002-11-07 | Vertex Pharmaceuticals Incorporated | INHIBITORS OF GSK-3 AND CRYSTAL STRUCTURES OF GSK-3β PROTEIN AND PROTEIN COMPLEXES |
| WO2003072580A1 (en) * | 2002-02-28 | 2003-09-04 | Sanofi-Aventis | 1-[ALKYL], 1-[HETEROARYL)ALKYL] AND 1-[ARYL)ALKYL]-7-(PYRIMIDIN-4-YL)-IMADAZO[1,2-a]PYRIMIDIN-5(1H)-ONE DERIVATIVES |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011520819A (ja) * | 2008-05-15 | 2011-07-21 | バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト | 置換イミダゾ−およびトリアゾロピリミジン類、イミダゾ−およびピラゾロピラジン類およびイミダゾトリアジン類 |
| JP2011006404A (ja) * | 2009-05-27 | 2011-01-13 | Toyama Chem Co Ltd | 3,6−ジクロロ−2−ピラジンカルボニトリルの製造法 |
| KR20170016465A (ko) * | 2014-06-17 | 2017-02-13 | 치아타이 티안큉 파마수티컬 그룹 주식회사 | PI3K 억제제로 사용되는 피리디노[1,2-a]피리미돈 유사체 |
| JP2017518382A (ja) * | 2014-06-17 | 2017-07-06 | リーシン ファーマシューティカル カンパニー リミテッド | mTOR/PI3K阻害剤としてのピリド[1,2−a]ピリミジノン類似体 |
| JP2017519821A (ja) * | 2014-06-17 | 2017-07-20 | チア タイ ティエンチン ファーマシューティカル グループ カンパニー リミテッド | PI3K阻害剤としてのピリド[1,2−a]ピリミドン類似体 |
| KR102495840B1 (ko) | 2014-06-17 | 2023-02-03 | 치아타이 티안큉 파마수티컬 그룹 주식회사 | PI3K 억제제로 사용되는 피리디노[1,2-a]피리미돈 유사체 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2541832C (en) | 2009-11-24 |
| MXPA06004043A (es) | 2006-06-28 |
| DE602004008098D1 (de) | 2007-09-20 |
| EP1678180B1 (en) | 2007-08-08 |
| ATE369370T1 (de) | 2007-08-15 |
| US7709473B2 (en) | 2010-05-04 |
| BRPI0415185A (pt) | 2006-11-28 |
| CA2541832A1 (en) | 2005-04-21 |
| DE602004008098T8 (de) | 2008-04-17 |
| US20070249612A1 (en) | 2007-10-25 |
| WO2005035532A1 (en) | 2005-04-21 |
| EP1678180A1 (en) | 2006-07-12 |
| DE602004008098T2 (de) | 2007-12-13 |
| ES2288270T3 (es) | 2008-01-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2007508290A (ja) | GSK−3阻害剤としての置換2H−[1,2,4]トリアゾロ[4,3−a]ピラジン | |
| US7202245B2 (en) | Substituted 4-amino[1,2,4]triazolo[4,3-a] quinoxalines | |
| KR101409727B1 (ko) | 야누스 키나제의 억제제로서 유용한 아자인돌 | |
| CN109906227B (zh) | 8,9-二氢咪唑[1,2-a]嘧啶并[5,4-e]嘧啶-5(6H)-酮类化合物 | |
| CN102753551B (zh) | 作为pde10a酶抑制剂的2-芳基咪唑衍生物 | |
| CN103068824B (zh) | 作为蛋白激酶调节剂的新型3,5‑二取代‑3h‑咪唑并[4,5‑b]吡啶和3,5‑二取代‑3h‑[1,2,3]三唑并[4,5‑b]吡啶化合物 | |
| US20100041663A1 (en) | Organic Compounds as Smo Inhibitors | |
| EP1641454B1 (en) | Pyrazolo[3,4-b]pyridin-6-ones as gsk-3 inhibitors | |
| TW200413349A (en) | Benzimidazole quinolinones and uses thereof | |
| TW201204725A (en) | Substituted imidazoquinoline derivatives as kinase inhibitors | |
| CN102459242B (zh) | 苯氧基甲基杂环化合物 | |
| US11731953B2 (en) | Methods and compounds for restoring mutant p53 function | |
| JP4637834B2 (ja) | GSK−3阻害剤としてのピラゾロ[3,4−b]ピリジン−6−オン | |
| JP2007506763A (ja) | プロテインキナーゼのインヒビターとして有用なイミダゾール組成物 | |
| EP3510030B1 (en) | 8-(azetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridinyl compounds, compositions and methods of use thereof | |
| US20190135793A1 (en) | Heterocyclic inhibitors of kdm5 for the treatment of disease | |
| HK40010367A (en) | Bicyclic bromodomain inhibitors | |
| HK40009645B (en) | 8-(azetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridinyl compounds, compositions and methods of use thereof | |
| HK40009645A (en) | 8-(azetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridinyl compounds, compositions and methods of use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070814 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070821 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110117 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20111003 |