TW200817400A - Pyrido [3,2-e] pyrazines, their use as inhibitors of phosphodiesterase 10, and processes for preparing them - Google Patents

Info

Publication number

TW200817400A

TW200817400A TW096117906A TW96117906A TW200817400A TW 200817400 A TW200817400 A TW 200817400A TW 096117906 A TW096117906 A TW 096117906A TW 96117906 A TW96117906 A TW 96117906A TW 200817400 A TW200817400 A TW 200817400A

Authority

TW

Taiwan

Prior art keywords

pyrazine

methoxy

methyl

imidazo

pyrido

Prior art date

2006-05-30

Links

• Espacenet
• Global Dossier
• Discuss

• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title claims abstract description 37
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title claims abstract description 37
• 238000000034 method Methods 0.000 title claims abstract description 27
• 239000003112 inhibitor Substances 0.000 title claims abstract description 14
• YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical class N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 title claims abstract description 14
• 150000001875 compounds Chemical class 0.000 claims abstract description 137
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 82
• 201000010099 disease Diseases 0.000 claims abstract description 49
• 208000028017 Psychotic disease Diseases 0.000 claims abstract description 48
• 208000020016 psychiatric disease Diseases 0.000 claims abstract description 37
• 208000035475 disorder Diseases 0.000 claims abstract description 33
• 208000012902 Nervous system disease Diseases 0.000 claims abstract description 9
• 241000124008 Mammalia Species 0.000 claims abstract description 7
• 208000024891 symptom Diseases 0.000 claims abstract description 5
• 210000003169 central nervous system Anatomy 0.000 claims abstract description 4
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 252
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 128
• 125000000217 alkyl group Chemical group 0.000 claims description 76
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 70
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 42
• -1 Cl_3 Chemical class 0.000 claims description 41
• 125000004122 cyclic group Chemical group 0.000 claims description 34
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 31
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
• 229910052736 halogen Inorganic materials 0.000 claims description 27
• 150000002367 halogens Chemical class 0.000 claims description 27
• 229910052739 hydrogen Inorganic materials 0.000 claims description 27
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 25
• 238000006243 chemical reaction Methods 0.000 claims description 24
• 201000000980 schizophrenia Diseases 0.000 claims description 24
• 239000002904 solvent Substances 0.000 claims description 22
• 239000001257 hydrogen Substances 0.000 claims description 20
• 238000002360 preparation method Methods 0.000 claims description 19
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 18
• 239000013067 intermediate product Substances 0.000 claims description 17
• 150000003839 salts Chemical class 0.000 claims description 17
• 125000003282 alkyl amino group Chemical group 0.000 claims description 15
• 150000001412 amines Chemical class 0.000 claims description 15
• 208000013403 hyperactivity Diseases 0.000 claims description 15
• 230000007547 defect Effects 0.000 claims description 14
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 13
• 230000003542 behavioural effect Effects 0.000 claims description 13
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 229920006395 saturated elastomer Polymers 0.000 claims description 10
• 208000019901 Anxiety disease Diseases 0.000 claims description 9
• 206010026749 Mania Diseases 0.000 claims description 9
• 125000005842 heteroatom Chemical group 0.000 claims description 9
• 230000002085 persistent effect Effects 0.000 claims description 9
• 241000700199 Cavia porcellus Species 0.000 claims description 8
• 150000003973 alkyl amines Chemical class 0.000 claims description 8
• 125000003118 aryl group Chemical group 0.000 claims description 8
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
• 230000000698 schizophrenic effect Effects 0.000 claims description 8
• 208000014094 Dystonic disease Diseases 0.000 claims description 7
• 244000294411 Mirabilis expansa Species 0.000 claims description 7
• 235000015429 Mirabilis expansa Nutrition 0.000 claims description 7
• 125000003342 alkenyl group Chemical group 0.000 claims description 7
• 235000013536 miso Nutrition 0.000 claims description 7
• 210000000056 organ Anatomy 0.000 claims description 7
• 208000022821 personality disease Diseases 0.000 claims description 7
• 206010012289 Dementia Diseases 0.000 claims description 6
• 150000001204 N-oxides Chemical class 0.000 claims description 6
• 208000025966 Neurological disease Diseases 0.000 claims description 6
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 6
• 239000003795 chemical substances by application Substances 0.000 claims description 6
• 230000002996 emotional effect Effects 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• 230000036651 mood Effects 0.000 claims description 6
• 229910052763 palladium Inorganic materials 0.000 claims description 6
• 206010012239 Delusion Diseases 0.000 claims description 5
• 241000282412 Homo Species 0.000 claims description 5
• 208000019430 Motor disease Diseases 0.000 claims description 5
• 208000018737 Parkinson disease Diseases 0.000 claims description 5
• 230000004913 activation Effects 0.000 claims description 5
• 230000001154 acute effect Effects 0.000 claims description 5
• 125000000304 alkynyl group Chemical group 0.000 claims description 5
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 5
• 239000003153 chemical reaction reagent Substances 0.000 claims description 5
• 231100000868 delusion Toxicity 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 230000004064 dysfunction Effects 0.000 claims description 5
• 150000002431 hydrogen Chemical group 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 4
• 208000020925 Bipolar disease Diseases 0.000 claims description 4
• 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
• 208000027534 Emotional disease Diseases 0.000 claims description 4
• 208000023105 Huntington disease Diseases 0.000 claims description 4
• 150000008064 anhydrides Chemical class 0.000 claims description 4
• 125000004429 atom Chemical group 0.000 claims description 4
• 208000029028 brain injury Diseases 0.000 claims description 4
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 4
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 4
• 208000010118 dystonia Diseases 0.000 claims description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 208000019899 phobic disease Diseases 0.000 claims description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 4
• 125000006413 ring segment Chemical group 0.000 claims description 4
• 208000015891 sexual disease Diseases 0.000 claims description 4
• SUUZQBPJXAPCMG-UHFFFAOYSA-N C(C)OC(=O)[Mg]C(F)F Chemical compound C(C)OC(=O)[Mg]C(F)F SUUZQBPJXAPCMG-UHFFFAOYSA-N 0.000 claims description 3
• 206010010904 Convulsion Diseases 0.000 claims description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 3
• 208000019022 Mood disease Diseases 0.000 claims description 3
• 239000007868 Raney catalyst Substances 0.000 claims description 3
• 229910000564 Raney nickel Inorganic materials 0.000 claims description 3
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 3
• 206010038743 Restlessness Diseases 0.000 claims description 3
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 3
• 206010041250 Social phobia Diseases 0.000 claims description 3
• 239000013543 active substance Substances 0.000 claims description 3
• 239000002671 adjuvant Substances 0.000 claims description 3
• 230000006399 behavior Effects 0.000 claims description 3
• 229910052802 copper Chemical group 0.000 claims description 3
• 239000000796 flavoring agent Substances 0.000 claims description 3
• 201000002904 focal dystonia Diseases 0.000 claims description 3
• FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 claims description 3
• 230000003340 mental effect Effects 0.000 claims description 3
• 230000000926 neurological effect Effects 0.000 claims description 3
• 229910052707 ruthenium Inorganic materials 0.000 claims description 3
• 230000001568 sexual effect Effects 0.000 claims description 3
• 208000011580 syndromic disease Diseases 0.000 claims description 3
• BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
• 208000024827 Alzheimer disease Diseases 0.000 claims description 2
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 2
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 2
• 208000014644 Brain disease Diseases 0.000 claims description 2
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 2
• 101100079984 Caenorhabditis elegans nhr-9 gene Proteins 0.000 claims description 2
• MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims description 2
• 206010012559 Developmental delay Diseases 0.000 claims description 2
• 101001117086 Dictyostelium discoideum cAMP/cGMP-dependent 3',5'-cAMP/cGMP phosphodiesterase A Proteins 0.000 claims description 2
• 206010013654 Drug abuse Diseases 0.000 claims description 2
• 208000012661 Dyskinesia Diseases 0.000 claims description 2
• 208000030814 Eating disease Diseases 0.000 claims description 2
• 208000008967 Enuresis Diseases 0.000 claims description 2
• 206010015605 Excessive masturbation Diseases 0.000 claims description 2
• 208000034347 Faecal incontinence Diseases 0.000 claims description 2
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 2
• 208000001836 Firesetting Behavior Diseases 0.000 claims description 2
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 2
• 238000003747 Grignard reaction Methods 0.000 claims description 2
• 208000031886 HIV Infections Diseases 0.000 claims description 2
• 101100477978 Hypocrea jecorina (strain QM6a) sor6 gene Proteins 0.000 claims description 2
• 206010021030 Hypomania Diseases 0.000 claims description 2
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 2
• 208000036626 Mental retardation Diseases 0.000 claims description 2
• 208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 2
• 206010034912 Phobia Diseases 0.000 claims description 2
• 101710122057 Phospholemman-like protein Proteins 0.000 claims description 2
• 201000009916 Postpartum depression Diseases 0.000 claims description 2
• 206010037180 Psychiatric symptoms Diseases 0.000 claims description 2
• 208000001431 Psychomotor Agitation Diseases 0.000 claims description 2
• 206010061921 Psychotic disorder due to a general medical condition Diseases 0.000 claims description 2
• 101100017604 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HOR7 gene Proteins 0.000 claims description 2
• 206010039897 Sedation Diseases 0.000 claims description 2
• 206010039987 Senile psychosis Diseases 0.000 claims description 2
• 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
• 208000006011 Stroke Diseases 0.000 claims description 2
• 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 2
• 201000004810 Vascular dementia Diseases 0.000 claims description 2
• 230000006978 adaptation Effects 0.000 claims description 2
• 230000003044 adaptive effect Effects 0.000 claims description 2
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 2
• 230000009286 beneficial effect Effects 0.000 claims description 2
• 230000006931 brain damage Effects 0.000 claims description 2
• 231100000874 brain damage Toxicity 0.000 claims description 2
• 229960001948 caffeine Drugs 0.000 claims description 2
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 2
• 229930003827 cannabinoid Natural products 0.000 claims description 2
• 239000003557 cannabinoid Substances 0.000 claims description 2
• 229940065144 cannabinoids Drugs 0.000 claims description 2
• 208000015114 central nervous system disease Diseases 0.000 claims description 2
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims description 2
• 229960003920 cocaine Drugs 0.000 claims description 2
• 230000006378 damage Effects 0.000 claims description 2
• 238000011161 development Methods 0.000 claims description 2
• 230000018109 developmental process Effects 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 235000014632 disordered eating Nutrition 0.000 claims description 2
• 206010013932 dyslexia Diseases 0.000 claims description 2
• 206010015037 epilepsy Diseases 0.000 claims description 2
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 2
• 230000002650 habitual effect Effects 0.000 claims description 2
• 239000000380 hallucinogen Substances 0.000 claims description 2
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 2
• 208000015181 infectious disease Diseases 0.000 claims description 2
• 230000002458 infectious effect Effects 0.000 claims description 2
• 201000003723 learning disability Diseases 0.000 claims description 2
• 208000024714 major depressive disease Diseases 0.000 claims description 2
• 230000007087 memory ability Effects 0.000 claims description 2
• 206010027175 memory impairment Diseases 0.000 claims description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000001624 naphthyl group Chemical group 0.000 claims description 2
• 230000009251 neurologic dysfunction Effects 0.000 claims description 2
• 208000015015 neurological dysfunction Diseases 0.000 claims description 2
• 150000002825 nitriles Chemical class 0.000 claims description 2
• 208000030459 obsessive-compulsive personality disease Diseases 0.000 claims description 2
• 229940005483 opioid analgesics Drugs 0.000 claims description 2
• 150000002923 oximes Chemical class 0.000 claims description 2
• 230000001314 paroxysmal effect Effects 0.000 claims description 2
• 208000028173 post-traumatic stress disease Diseases 0.000 claims description 2
• 230000002028 premature Effects 0.000 claims description 2
• 230000002265 prevention Effects 0.000 claims description 2
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 2
• 229940001470 psychoactive drug Drugs 0.000 claims description 2
• 239000004089 psychotropic agent Substances 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 230000004044 response Effects 0.000 claims description 2
• 230000036280 sedation Effects 0.000 claims description 2
• 208000012201 sexual and gender identity disease Diseases 0.000 claims description 2
• 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
• 239000000021 stimulant Substances 0.000 claims description 2
• 208000011117 substance-related disease Diseases 0.000 claims description 2
• 229940124530 sulfonamide Drugs 0.000 claims description 2
• 150000003456 sulfonamides Chemical class 0.000 claims description 2
• 230000009885 systemic effect Effects 0.000 claims description 2
• XDLNRRRJZOJTRW-UHFFFAOYSA-N thiohypochlorous acid Chemical compound ClS XDLNRRRJZOJTRW-UHFFFAOYSA-N 0.000 claims description 2
• 150000003573 thiols Chemical class 0.000 claims description 2
• 210000003813 thumb Anatomy 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• 208000017194 Affective disease Diseases 0.000 claims 2
• 208000024254 Delusional disease Diseases 0.000 claims 2
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
• 125000003277 amino group Chemical group 0.000 claims 2
• 238000004519 manufacturing process Methods 0.000 claims 2
• 208000002851 paranoid schizophrenia Diseases 0.000 claims 2
• NHIWSXUIUANKOJ-UHFFFAOYSA-N 13-ethyl-4-methoxy-11-methyl-10-methylsulfanyl-2,4,8,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5,7,10-tetraene Chemical compound N12CN(OC)C=C2C=NC2=C1N(CC)CC(C)=C2SC NHIWSXUIUANKOJ-UHFFFAOYSA-N 0.000 claims 1
• JERLPGDWXNOQLS-UHFFFAOYSA-N 13-hexyl-4-methoxy-10,11-dimethyl-2,4,8,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5,7,10-tetraene Chemical compound N12CN(OC)C=C2C=NC2=C1N(CCCCCC)CC(C)=C2C JERLPGDWXNOQLS-UHFFFAOYSA-N 0.000 claims 1
• BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims 1
• OPDPWGAWFLFVGQ-UHFFFAOYSA-N 4-azido-8-methoxy-3-methyl-1-propyl-imidazo[1,5-a]pyrido[3,2-e]pyrazine Chemical compound N12CN(OC)C=C2C=NC2=C1N(CCC)CC(C)=C2N=[N+]=[N-] OPDPWGAWFLFVGQ-UHFFFAOYSA-N 0.000 claims 1
• RNDJPOPVHIKKIQ-UHFFFAOYSA-N 4-methoxy-11,13-dimethyl-10-(2-phenylethoxy)-2,4,8,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5,7,10-tetraene Chemical compound C=1N(OC)CN2C=1C=NC1=C2N(C)CC(C)=C1OCCC1=CC=CC=C1 RNDJPOPVHIKKIQ-UHFFFAOYSA-N 0.000 claims 1
• 206010000117 Abnormal behaviour Diseases 0.000 claims 1
• 206010054196 Affect lability Diseases 0.000 claims 1
• 208000036640 Asperger disease Diseases 0.000 claims 1
• 201000006062 Asperger syndrome Diseases 0.000 claims 1
• LHNATZYLTDLSPL-UHFFFAOYSA-N C1=CC(=NC2=C1N=CC3=CN=CN32)N Chemical compound C1=CC(=NC2=C1N=CC3=CN=CN32)N LHNATZYLTDLSPL-UHFFFAOYSA-N 0.000 claims 1
• GJNBAHWMXFEVEJ-UHFFFAOYSA-N CON1CN2C(C=NC3=C2N=CC(=C3SC)C)=C1.CN1CC(=C(C=3N=CC=2N(C31)CN(C2)OC)SC)C Chemical compound CON1CN2C(C=NC3=C2N=CC(=C3SC)C)=C1.CN1CC(=C(C=3N=CC=2N(C31)CN(C2)OC)SC)C GJNBAHWMXFEVEJ-UHFFFAOYSA-N 0.000 claims 1
• 108010051152 Carboxylesterase Proteins 0.000 claims 1
• 102000013392 Carboxylesterase Human genes 0.000 claims 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 1
• WBLQQGDEQLAWNM-UHFFFAOYSA-N FC1=CC=C(C=C1)N1CC(=C(C=2N=CC=3N(C21)CN(C3)OC)NS(=O)(=O)C)C.N3=CC=NC2=C3C=CC=N2 Chemical compound FC1=CC=C(C=C1)N1CC(=C(C=2N=CC=3N(C21)CN(C3)OC)NS(=O)(=O)C)C.N3=CC=NC2=C3C=CC=N2 WBLQQGDEQLAWNM-UHFFFAOYSA-N 0.000 claims 1
• 208000003098 Ganglion Cysts Diseases 0.000 claims 1
• 206010057342 Onychophagia Diseases 0.000 claims 1
• 229910019142 PO4 Inorganic materials 0.000 claims 1
• 240000007643 Phytolacca americana Species 0.000 claims 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
• 208000005400 Synovial Cyst Diseases 0.000 claims 1
• 230000036506 anxiety Effects 0.000 claims 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
• 230000000994 depressogenic effect Effects 0.000 claims 1
• 229910052805 deuterium Inorganic materials 0.000 claims 1
• 230000006806 disease prevention Effects 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 1
• 229960002182 imipenem Drugs 0.000 claims 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
• 230000008140 language development Effects 0.000 claims 1
• 125000002950 monocyclic group Chemical group 0.000 claims 1
• 239000007800 oxidant agent Substances 0.000 claims 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
• 239000010452 phosphate Substances 0.000 claims 1
• 208000021011 postpartum psychosis Diseases 0.000 claims 1
• 239000001294 propane Substances 0.000 claims 1
• 150000003254 radicals Chemical class 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 21
• 239000000825 pharmaceutical preparation Substances 0.000 abstract description 3
• 230000007278 cognition impairment Effects 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
• 239000000203 mixture Substances 0.000 description 50
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
• 239000000243 solution Substances 0.000 description 28
• 241000700159 Rattus Species 0.000 description 24
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• 239000000543 intermediate Substances 0.000 description 19
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
• 239000000047 product Substances 0.000 description 16
• 238000012360 testing method Methods 0.000 description 16
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
• 239000011541 reaction mixture Substances 0.000 description 13
• 102000004190 Enzymes Human genes 0.000 description 12
• 108090000790 Enzymes Proteins 0.000 description 12
• 210000001577 neostriatum Anatomy 0.000 description 12
• 238000003756 stirring Methods 0.000 description 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• 239000012043 crude product Substances 0.000 description 11
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
• ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 10
• LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 10
• 239000012044 organic layer Substances 0.000 description 10
• 108090000623 proteins and genes Proteins 0.000 description 10
• 239000007787 solid Substances 0.000 description 10
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 241000282887 Suidae Species 0.000 description 9
• 238000009472 formulation Methods 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
• 241000700198 Cavia Species 0.000 description 8
• 235000014113 dietary fatty acids Nutrition 0.000 description 8
• 239000000194 fatty acid Substances 0.000 description 8
• 229930195729 fatty acid Natural products 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 230000005764 inhibitory process Effects 0.000 description 8
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
• 239000000164 antipsychotic agent Substances 0.000 description 7
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 7
• 235000018102 proteins Nutrition 0.000 description 7
• 102000004169 proteins and genes Human genes 0.000 description 7
• 108020003175 receptors Proteins 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• 229910052938 sodium sulfate Inorganic materials 0.000 description 7
• 235000011152 sodium sulphate Nutrition 0.000 description 7
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 6
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 6
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• 101001072037 Homo sapiens cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Proteins 0.000 description 6
• 239000005642 Oleic acid Substances 0.000 description 6
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 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
• 102100036377 cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Human genes 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 235000019439 ethyl acetate Nutrition 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 239000002858 neurotransmitter agent Substances 0.000 description 6
• 239000003921 oil Substances 0.000 description 6
• 235000019198 oils Nutrition 0.000 description 6
• XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 6
• 238000002953 preparative HPLC Methods 0.000 description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
• 230000003291 dopaminomimetic effect Effects 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 238000001704 evaporation Methods 0.000 description 5
• 229960003878 haloperidol Drugs 0.000 description 5
• 239000010410 layer Substances 0.000 description 5
• 210000002569 neuron Anatomy 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• LENLQGBLVGGAMF-UHFFFAOYSA-N tributyl([1,2,4]triazolo[1,5-a]pyridin-6-yl)stannane Chemical compound C1=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=NN21 LENLQGBLVGGAMF-UHFFFAOYSA-N 0.000 description 5
• 102000004980 Dopamine D2 Receptors Human genes 0.000 description 4
• 108090001111 Dopamine D2 Receptors Proteins 0.000 description 4
• 108010010803 Gelatin Proteins 0.000 description 4
• 229940123773 Phosphodiesterase 10A inhibitor Drugs 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• 239000002202 Polyethylene glycol Substances 0.000 description 4
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
• 238000010171 animal model Methods 0.000 description 4
• 239000005557 antagonist Substances 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
• 210000004556 brain Anatomy 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 230000003197 catalytic effect Effects 0.000 description 4
• 210000000170 cell membrane Anatomy 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 125000000753 cycloalkyl group Chemical group 0.000 description 4
• 230000006735 deficit Effects 0.000 description 4
• 150000004665 fatty acids Chemical class 0.000 description 4
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical group C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 4
• 239000008273 gelatin Substances 0.000 description 4
• 229920000159 gelatin Polymers 0.000 description 4
• 235000019322 gelatine Nutrition 0.000 description 4
• 235000011852 gelatine desserts Nutrition 0.000 description 4
• 238000010438 heat treatment Methods 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 239000012074 organic phase Substances 0.000 description 4
• 230000008506 pathogenesis Effects 0.000 description 4
• JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 4
• 229950010883 phencyclidine Drugs 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 238000004237 preparative chromatography Methods 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 4
• 239000012453 solvate Substances 0.000 description 4
• 229930008281 A03AD01 - Papaverine Natural products 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
• 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 3
• 241001465754 Metazoa Species 0.000 description 3
• 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 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 235000021355 Stearic acid Nutrition 0.000 description 3
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
• 229960000583 acetic acid Drugs 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 150000001335 aliphatic alkanes Chemical class 0.000 description 3
• 230000000561 anti-psychotic effect Effects 0.000 description 3
• 150000001721 carbon Chemical group 0.000 description 3
• 239000012876 carrier material Substances 0.000 description 3
• 238000002648 combination therapy Methods 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 230000008020 evaporation Effects 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 150000002191 fatty alcohols Chemical class 0.000 description 3
• 229920006158 high molecular weight polymer Polymers 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 230000003434 inspiratory effect Effects 0.000 description 3
• 230000003834 intracellular effect Effects 0.000 description 3
• 239000007928 intraperitoneal injection Substances 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 230000015654 memory Effects 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
• 229960001789 papaverine Drugs 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 238000001262 western blot Methods 0.000 description 3
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
• BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
• LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 2
• ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
• LYDISBKIGPKQMB-UHFFFAOYSA-N 8-methoxy-3-methyl-1-propyl-imidazo[1,5-a]pyrido[3,2-e]pyrazine Chemical compound N12CN(OC)C=C2C=NC2=C1N(CCC)CC(C)=C2 LYDISBKIGPKQMB-UHFFFAOYSA-N 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-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
• 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 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• 101001098806 Dictyostelium discoideum cGMP-specific 3',5'-cGMP phosphodiesterase 3 Proteins 0.000 description 2
• 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 description 2
• 208000010228 Erectile Dysfunction Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
• 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 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
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
• AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• 101150098694 PDE5A gene Proteins 0.000 description 2
• 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 2
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• 241000700157 Rattus norvegicus Species 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• 235000011054 acetic acid Nutrition 0.000 description 2
• 239000008272 agar Substances 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 239000007795 chemical reaction product Substances 0.000 description 2
• 239000002299 complementary DNA Substances 0.000 description 2
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 238000004821 distillation Methods 0.000 description 2
• UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 2
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
• 239000012467 final product Substances 0.000 description 2
• GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 2
• QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 2
• 239000003349 gelling agent Substances 0.000 description 2
• 229930195712 glutamate Natural products 0.000 description 2
• KEMQGTRYUADPNZ-UHFFFAOYSA-N heptadecanoic acid Chemical compound CCCCCCCCCCCCCCCCC(O)=O KEMQGTRYUADPNZ-UHFFFAOYSA-N 0.000 description 2
• 238000005984 hydrogenation reaction Methods 0.000 description 2
• 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
• VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
• 201000001881 impotence Diseases 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 150000002576 ketones Chemical class 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 239000003550 marker Substances 0.000 description 2
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical class O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
• 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 2
• 230000003472 neutralizing effect Effects 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 2
• XNGIFLGASWRNHJ-UHFFFAOYSA-N o-dicarboxybenzene Natural products OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
• WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 229910052698 phosphorus Inorganic materials 0.000 description 2
• 229920000136 polysorbate Polymers 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000037452 priming Effects 0.000 description 2
• SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 239000000932 sedative agent Substances 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 230000004936 stimulating effect Effects 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 150000005846 sugar alcohols Chemical class 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 229920001864 tannin Polymers 0.000 description 2
• 239000001648 tannin Substances 0.000 description 2
• 235000018553 tannin Nutrition 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 210000001519 tissue Anatomy 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
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
• JCMVPOVHKWWBAU-UHFFFAOYSA-N 1,2-dichlorohydrazine Chemical compound ClNNCl JCMVPOVHKWWBAU-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
• CXBDYQVECUFKRK-UHFFFAOYSA-N 1-methoxybutane Chemical compound CCCCOC CXBDYQVECUFKRK-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
• XUJLWPFSUCHPQL-UHFFFAOYSA-N 11-methyldodecan-1-ol Chemical compound CC(C)CCCCCCCCCCO XUJLWPFSUCHPQL-UHFFFAOYSA-N 0.000 description 1
• WSYQXFIKLITSBF-UHFFFAOYSA-N 13-ethyl-4-methoxy-11-methyl-2,4,8,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5,7,10-tetraene Chemical compound N12CN(OC)C=C2C=NC2=C1N(CC)CC(C)=C2 WSYQXFIKLITSBF-UHFFFAOYSA-N 0.000 description 1
• DCBOUXKSNFDXER-UHFFFAOYSA-N 1h-pyrido[2,3-b]pyrazin-2-one Chemical class C1=CC=C2NC(=O)C=NC2=N1 DCBOUXKSNFDXER-UHFFFAOYSA-N 0.000 description 1
• LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
• YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-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
• OAWAZQITIZDJRB-UHFFFAOYSA-N 2-chloro-2,2-difluoroacetic acid Chemical compound OC(=O)C(F)(F)Cl OAWAZQITIZDJRB-UHFFFAOYSA-N 0.000 description 1
• XDZMPRGFOOFSBL-UHFFFAOYSA-N 2-ethoxybenzoic acid Chemical compound CCOC1=CC=CC=C1C(O)=O XDZMPRGFOOFSBL-UHFFFAOYSA-N 0.000 description 1
• ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
• PKRSYEPBQPFNRB-UHFFFAOYSA-N 2-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=CC=C1 PKRSYEPBQPFNRB-UHFFFAOYSA-N 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• QHYJQIFBULBQBV-UHFFFAOYSA-N 3,4-dimethyl-8-methoxy-1-propyl-imidazo[1,5-a]-pyrido[3,2-e]-pyrazine hydrochloride Chemical compound Cl.N12CN(OC)C=C2C=NC2=C1N(CCC)CC(C)=C2C QHYJQIFBULBQBV-UHFFFAOYSA-N 0.000 description 1
• IQGMRVWUTCYCST-UHFFFAOYSA-N 3-Aminosalicylic acid Chemical compound NC1=CC=CC(C(O)=O)=C1O IQGMRVWUTCYCST-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• ZRKIDSSAOZPBCY-UHFFFAOYSA-N 4-(difluoromethoxy)-3-methyl-1-propyl-2H-imidazole Chemical compound FC(OC=1N(CN(C1)CCC)C)F ZRKIDSSAOZPBCY-UHFFFAOYSA-N 0.000 description 1
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
• HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 1
• HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
• MDKNGSXTDJJWHH-UHFFFAOYSA-N 4-methoxy-11-methyl-10-(2-phenylethoxy)-2,4,8,13-tetrazatricyclo[7.4.0.02,6]trideca-1(13),5,7,9,11-pentaene Chemical compound C=1N(OC)CN(C2=NC=C3C)C=1C=NC2=C3OCCC1=CC=CC=C1 MDKNGSXTDJJWHH-UHFFFAOYSA-N 0.000 description 1
• QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical group CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
• FHZALEJIENDROK-UHFFFAOYSA-N 5-bromo-1h-imidazole Chemical compound BrC1=CN=CN1 FHZALEJIENDROK-UHFFFAOYSA-N 0.000 description 1
• VGUCJSBVDMSYSU-UHFFFAOYSA-N 5-methyl-2-propan-2-yl-1h-imidazole Chemical compound CC(C)C1=NC(C)=CN1 VGUCJSBVDMSYSU-UHFFFAOYSA-N 0.000 description 1
• 125000004070 6 membered heterocyclic group Chemical group 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
• MCHCDFBUXBUKMG-UHFFFAOYSA-N 8-methoxy-3-methyl-1-propyl-imidazo[1,5-a]-pyrido[3,2-e]-pyrazinone Chemical compound N12CN(OC)C=C2C=NC2=C1N(CCC)C(=O)C(C)=C2 MCHCDFBUXBUKMG-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 229920000936 Agarose Polymers 0.000 description 1
• POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• 229920000945 Amylopectin Polymers 0.000 description 1
• 241000272525 Anas platyrhynchos Species 0.000 description 1
• 235000019737 Animal fat Nutrition 0.000 description 1
• 206010002942 Apathy Diseases 0.000 description 1
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
• 206010003591 Ataxia Diseases 0.000 description 1
• 235000021357 Behenic acid Nutrition 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• QFXVNNDYGQECAB-UHFFFAOYSA-N C(C)N1CC(=C(C=2N=CC=3N(C21)CN(C3)OC)OCCC)C.C(C)N3CC(=C(C=2N=CC=1N(C23)CN(C1)OC)OC(C)C)C Chemical compound C(C)N1CC(=C(C=2N=CC=3N(C21)CN(C3)OC)OCCC)C.C(C)N3CC(=C(C=2N=CC=1N(C23)CN(C1)OC)OC(C)C)C QFXVNNDYGQECAB-UHFFFAOYSA-N 0.000 description 1
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 1
• 101100243082 Caenorhabditis elegans pde-1 gene Proteins 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 208000009132 Catalepsy Diseases 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 244000060011 Cocos nucifera Species 0.000 description 1
• 235000013162 Cocos nucifera Nutrition 0.000 description 1
• 108091026890 Coding region Proteins 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 description 1
• QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
• 102000004076 Dopamine D1 Receptors Human genes 0.000 description 1
• 108090000511 Dopamine D1 Receptors Proteins 0.000 description 1
• 101001117089 Drosophila melanogaster Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1 Proteins 0.000 description 1
• 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 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• 108700024394 Exon Proteins 0.000 description 1
• 239000001263 FEMA 3042 Substances 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
• 108091006027 G proteins Proteins 0.000 description 1
• 102000030782 GTP binding Human genes 0.000 description 1
• 108091000058 GTP-Binding Proteins 0.000 description 1
• 108091006101 Gi proteins Proteins 0.000 description 1
• 102000034354 Gi proteins Human genes 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 108091006065 Gs proteins Proteins 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 208000004547 Hallucinations Diseases 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 206010020651 Hyperkinesia Diseases 0.000 description 1
• 208000000269 Hyperkinesis Diseases 0.000 description 1
• 206010020852 Hypertonia Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical compound C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 description 1
• 108010044467 Isoenzymes Proteins 0.000 description 1
• YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
• 208000030979 Language Development disease Diseases 0.000 description 1
• 102000003960 Ligases Human genes 0.000 description 1
• 108090000364 Ligases Proteins 0.000 description 1
• QXKHYNVANLEOEG-UHFFFAOYSA-N Methoxsalen Chemical group C1=CC(=O)OC2=C1C=C1C=COC1=C2OC QXKHYNVANLEOEG-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 206010027940 Mood altered Diseases 0.000 description 1
• 208000016285 Movement disease Diseases 0.000 description 1
• VYQHVJLYCVBMPP-UHFFFAOYSA-N N-(4-methoxy-11-methyl-13-phenyl-2,4,8,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5,7,10-tetraen-10-yl)methanesulfonamide Chemical compound C=1N(OC)CN2C=1C=NC(C(=C(C)C1)NS(C)(=O)=O)=C2N1C1=CC=CC=C1 VYQHVJLYCVBMPP-UHFFFAOYSA-N 0.000 description 1
• NAXIXAPHUQGPPU-UHFFFAOYSA-N N1=CC2=CN=CN2C2=C1C=CC(=O)N2 Chemical compound N1=CC2=CN=CN2C2=C1C=CC(=O)N2 NAXIXAPHUQGPPU-UHFFFAOYSA-N 0.000 description 1
• 229910020667 PBr3 Inorganic materials 0.000 description 1
• 229910020656 PBr5 Inorganic materials 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 description 1
• 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• HDSBZMRLPLPFLQ-UHFFFAOYSA-N Propylene glycol alginate Chemical compound OC1C(O)C(OC)OC(C(O)=O)C1OC1C(O)C(O)C(C)C(C(=O)OCC(C)O)O1 HDSBZMRLPLPFLQ-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 229910006124 SOCl2 Inorganic materials 0.000 description 1
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 229920002125 Sokalan® Polymers 0.000 description 1
• HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 108010006785 Taq Polymerase Proteins 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 238000010162 Tukey test Methods 0.000 description 1
• 206010047141 Vasodilatation Diseases 0.000 description 1
• 206010047853 Waxy flexibility Diseases 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 102000030621 adenylate cyclase Human genes 0.000 description 1
• 108060000200 adenylate cyclase Proteins 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 150000001299 aldehydes Chemical class 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
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 229960000458 allantoin Drugs 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 229940025084 amphetamine Drugs 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 125000005577 anthracene group Chemical group 0.000 description 1
• RJGDLRCDCYRQOQ-UHFFFAOYSA-N anthrone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3CC2=C1 RJGDLRCDCYRQOQ-UHFFFAOYSA-N 0.000 description 1
• 230000003266 anti-allergic effect Effects 0.000 description 1
• 230000001088 anti-asthma Effects 0.000 description 1
• 230000000845 anti-microbial effect Effects 0.000 description 1
• 239000000924 antiasthmatic agent Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 229940005529 antipsychotics Drugs 0.000 description 1
• 239000002249 anxiolytic agent Substances 0.000 description 1
• 230000000949 anxiolytic effect Effects 0.000 description 1
• 229940005530 anxiolytics Drugs 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 230000002238 attenuated effect Effects 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 229940116226 behenic acid Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 229960004365 benzoic acid Drugs 0.000 description 1
• KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
• 229940073608 benzyl chloride Drugs 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000036770 blood supply Effects 0.000 description 1
• LKXYJYDRLBPHRS-UHFFFAOYSA-N bromocyclopropane Chemical compound BrC1CC1 LKXYJYDRLBPHRS-UHFFFAOYSA-N 0.000 description 1
• RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
• 230000003139 buffering effect Effects 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 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
• CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920003086 cellulose ether Polymers 0.000 description 1
• WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• OQCOTUFOPUUTPJ-UHFFFAOYSA-N chembl1083399 Chemical compound C1=C(OC)N=C2N3C(CCC)=NC(C)=C3C(S(C)(=O)=O)=NC2=C1 OQCOTUFOPUUTPJ-UHFFFAOYSA-N 0.000 description 1
• ZRRFTWBRZKCVAY-UHFFFAOYSA-N chembl1083460 Chemical compound C1=C(OC)N=C2N3C(CCC)=NC(C)=C3C(N(C)C(=O)OC)=NC2=C1 ZRRFTWBRZKCVAY-UHFFFAOYSA-N 0.000 description 1
• NEIMIIAEFGYPPD-UHFFFAOYSA-N chembl1085404 Chemical compound C1=C(OC(F)F)N=C2N3C(CCC)=NC(C)=C3C(C)=NC2=C1 NEIMIIAEFGYPPD-UHFFFAOYSA-N 0.000 description 1
• MFMGRWBSTBLPCH-UHFFFAOYSA-N chembl1085646 Chemical compound C1=C(OC)N=C2N3C(CCCCC)=NC(C)=C3C(C)=NC2=C1 MFMGRWBSTBLPCH-UHFFFAOYSA-N 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 239000007979 citrate buffer Substances 0.000 description 1
• 229960004106 citric acid Drugs 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 230000009194 climbing Effects 0.000 description 1
• 229960004170 clozapine Drugs 0.000 description 1
• QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
• 230000001149 cognitive effect Effects 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 238000004590 computer program Methods 0.000 description 1
• 230000003750 conditioning effect Effects 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000000392 cycloalkenyl group Chemical group 0.000 description 1
• 125000001316 cycloalkyl alkyl 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
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 1
• 229960002380 dibutyl phthalate Drugs 0.000 description 1
• 125000003963 dichloro group Chemical group Cl* 0.000 description 1
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
• 229940031578 diisopropyl adipate Drugs 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• LBOJYSIDWZQNJS-CVEARBPZSA-N dizocilpine Chemical compound C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 LBOJYSIDWZQNJS-CVEARBPZSA-N 0.000 description 1
• 229950004794 dizocilpine Drugs 0.000 description 1
• 229960003638 dopamine Drugs 0.000 description 1
• 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 229940116333 ethyl lactate Drugs 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
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 235000012631 food intake Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000003205 fragrance Substances 0.000 description 1
• 210000005153 frontal cortex Anatomy 0.000 description 1
• 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
• 239000000451 gelidium spp. gum Substances 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 210000004907 gland Anatomy 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 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
• 239000008187 granular material Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 238000005658 halogenation reaction Methods 0.000 description 1
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
• 210000001320 hippocampus Anatomy 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
• 239000003326 hypnotic agent Substances 0.000 description 1
• 230000000147 hypnotic effect Effects 0.000 description 1
• WGYMXASRWCYKQR-UHFFFAOYSA-N imidazo[1,5-a]quinoxaline Chemical class C1=CC=C2N3C=NC=C3C=NC2=C1 WGYMXASRWCYKQR-UHFFFAOYSA-N 0.000 description 1
• HOFSPGAYXKNFAM-UHFFFAOYSA-N imidazo[4,5-f]quinoxalin-2-one Chemical class C1=CN=C2C3=NC(=O)N=C3C=CC2=N1 HOFSPGAYXKNFAM-UHFFFAOYSA-N 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 150000005235 imidazopyrazines Chemical class 0.000 description 1
• 208000026278 immune system disease Diseases 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 229940060367 inert ingredients Drugs 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 206010022437 insomnia Diseases 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• YAQXGBBDJYBXKL-UHFFFAOYSA-N iron(2+);1,10-phenanthroline;dicyanide Chemical compound [Fe+2].N#[C-].N#[C-].C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CN=C2C3=NC=CC=C3C=CC2=C1 YAQXGBBDJYBXKL-UHFFFAOYSA-N 0.000 description 1
• XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
• 239000000644 isotonic solution Substances 0.000 description 1
• 229960003299 ketamine Drugs 0.000 description 1
• TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 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
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229940099690 malic acid Drugs 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 229910052901 montmorillonite Inorganic materials 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 230000037023 motor activity Effects 0.000 description 1
• 230000007659 motor function Effects 0.000 description 1
• WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
• SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 230000005015 neuronal process Effects 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 150000002829 nitrogen Chemical class 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 210000001009 nucleus accumben Anatomy 0.000 description 1
• VHEKHNHKXIJIHM-UHFFFAOYSA-N octadecane;propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCCCC VHEKHNHKXIJIHM-UHFFFAOYSA-N 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• 229940055577 oleyl alcohol Drugs 0.000 description 1
• XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 235000019809 paraffin wax Nutrition 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
• 235000019271 petrolatum Nutrition 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
• XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
• 125000005498 phthalate group Chemical class 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000004584 polyacrylic acid Substances 0.000 description 1
• 239000008389 polyethoxylated castor oil Substances 0.000 description 1
• 229920000151 polyglycol Polymers 0.000 description 1
• 239000010695 polyglycol Substances 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229950008882 polysorbate Drugs 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 230000001242 postsynaptic effect Effects 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 210000002442 prefrontal cortex Anatomy 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• ZPWFUIUNWDIYCJ-UHFFFAOYSA-N propan-2-yl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(C)C ZPWFUIUNWDIYCJ-UHFFFAOYSA-N 0.000 description 1
• 235000010409 propane-1,2-diol alginate Nutrition 0.000 description 1
• 239000000770 propane-1,2-diol alginate Substances 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 230000002294 pubertal effect Effects 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 210000002637 putamen Anatomy 0.000 description 1
• 150000003216 pyrazines Chemical class 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 238000003757 reverse transcription PCR Methods 0.000 description 1
• YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 208000022610 schizoaffective disease Diseases 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 229940125723 sedative agent Drugs 0.000 description 1
• 230000001624 sedative effect Effects 0.000 description 1
• 239000013049 sediment Substances 0.000 description 1
• 201000002899 segmental dystonia Diseases 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 239000003352 sequestering agent Substances 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 210000001013 sinoatrial node Anatomy 0.000 description 1
• 230000003997 social interaction Effects 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 235000011069 sorbitan monooleate Nutrition 0.000 description 1
• 239000001593 sorbitan monooleate Substances 0.000 description 1
• 229940035049 sorbitan monooleate Drugs 0.000 description 1
• 235000011076 sorbitan monostearate Nutrition 0.000 description 1
• 239000001587 sorbitan monostearate Substances 0.000 description 1
• 229940035048 sorbitan monostearate Drugs 0.000 description 1
• VIDRYROWYFWGSY-UHFFFAOYSA-N sotalol hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 VIDRYROWYFWGSY-UHFFFAOYSA-N 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 208000027765 speech disease Diseases 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 239000003760 tallow Substances 0.000 description 1
• 235000015523 tannic acid Nutrition 0.000 description 1
• 229920002258 tannic acid Polymers 0.000 description 1
• 229940033123 tannic acid Drugs 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 125000001302 tertiary amino group Chemical group 0.000 description 1
• 238000010998 test method Methods 0.000 description 1
• TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
• 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 1
• OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
• 210000001103 thalamus Anatomy 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical compound SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 description 1
• 235000010384 tocopherol Nutrition 0.000 description 1
• 229960001295 tocopherol Drugs 0.000 description 1
• 229930003799 tocopherol Natural products 0.000 description 1
• 239000011732 tocopherol Substances 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
• 150000004072 triols Chemical class 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 230000024883 vasodilation Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 235000019871 vegetable fat Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 235000013311 vegetables Nutrition 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
• 239000004034 viscosity adjusting agent Substances 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 230000003936 working memory Effects 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1