TW200843772A - Compounds with a combination of cannabinoid-CB1 antagonism and acetylcholinesterase inhibition - Google Patents

Info

Publication number

TW200843772A

TW200843772A TW96148210A TW96148210A TW200843772A TW 200843772 A TW200843772 A TW 200843772A TW 96148210 A TW96148210 A TW 96148210A TW 96148210 A TW96148210 A TW 96148210A TW 200843772 A TW200843772 A TW 200843772A

Authority

TW

Taiwan

Prior art keywords

compound

formula

disease

group

compounds

Prior art date

2006-12-20

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 191
• 230000008485 antagonism Effects 0.000 title abstract description 10
• 108010022752 Acetylcholinesterase Proteins 0.000 title description 14
• 229940022698 acetylcholinesterase Drugs 0.000 title description 13
• 230000005764 inhibitory process Effects 0.000 title description 13
• 102000012440 Acetylcholinesterase Human genes 0.000 title 1
• 238000000034 method Methods 0.000 claims abstract description 27
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 21
• 208000011117 substance-related disease Diseases 0.000 claims abstract description 20
• 206010013663 drug dependence Diseases 0.000 claims abstract description 16
• 206010012289 Dementia Diseases 0.000 claims abstract description 11
• 208000010877 cognitive disease Diseases 0.000 claims abstract description 11
• 208000030886 Traumatic Brain injury Diseases 0.000 claims abstract description 9
• 230000006735 deficit Effects 0.000 claims abstract description 9
• 230000009529 traumatic brain injury Effects 0.000 claims abstract description 9
• 208000026139 Memory disease Diseases 0.000 claims abstract description 5
• 201000009032 substance abuse Diseases 0.000 claims abstract description 5
• 231100000736 substance abuse Toxicity 0.000 claims abstract description 4
• -1 cyano, methyl Chemical group 0.000 claims description 56
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 55
• 201000010099 disease Diseases 0.000 claims description 41
• 150000003839 salts Chemical class 0.000 claims description 29
• 239000003814 drug Substances 0.000 claims description 26
• YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 claims description 21
• 239000005557 antagonist Substances 0.000 claims description 20
• 229960001685 tacrine Drugs 0.000 claims description 20
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 19
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
• 229930003827 cannabinoid Natural products 0.000 claims description 18
• 239000003557 cannabinoid Substances 0.000 claims description 18
• 239000012634 fragment Substances 0.000 claims description 18
• 238000002360 preparation method Methods 0.000 claims description 18
• 239000012453 solvate Substances 0.000 claims description 18
• 125000001424 substituent group Chemical group 0.000 claims description 17
• 238000006243 chemical reaction Methods 0.000 claims description 16
• 239000000126 substance Substances 0.000 claims description 16
• 239000001257 hydrogen Substances 0.000 claims description 14
• 229910052739 hydrogen Inorganic materials 0.000 claims description 14
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
• 125000005647 linker group Chemical group 0.000 claims description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
• 125000005843 halogen group Chemical group 0.000 claims description 12
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
• 208000006011 Stroke Diseases 0.000 claims description 11
• 125000000217 alkyl group Chemical group 0.000 claims description 11
• 230000002401 inhibitory effect Effects 0.000 claims description 11
• 238000012360 testing method Methods 0.000 claims description 11
• 208000035475 disorder Diseases 0.000 claims description 10
• ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 10
• 208000011580 syndromic disease Diseases 0.000 claims description 10
• 229940124596 AChE inhibitor Drugs 0.000 claims description 9
• 125000004429 atom Chemical group 0.000 claims description 9
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 9
• 208000028698 Cognitive impairment Diseases 0.000 claims description 8
• 150000001204 N-oxides Chemical class 0.000 claims description 8
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 8
• 125000003118 aryl group Chemical group 0.000 claims description 8
• 239000000460 chlorine Substances 0.000 claims description 8
• 239000000544 cholinesterase inhibitor Substances 0.000 claims description 8
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
• 229940124597 therapeutic agent Drugs 0.000 claims description 8
• 208000002193 Pain Diseases 0.000 claims description 7
• 239000003795 chemical substances by application Substances 0.000 claims description 7
• 230000004770 neurodegeneration Effects 0.000 claims description 7
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
• 206010028980 Neoplasm Diseases 0.000 claims description 6
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 201000011510 cancer Diseases 0.000 claims description 6
• 206010015037 epilepsy Diseases 0.000 claims description 6
• 230000000968 intestinal effect Effects 0.000 claims description 6
• 239000003960 organic solvent Substances 0.000 claims description 6
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
• 239000000651 prodrug Substances 0.000 claims description 6
• 229940002612 prodrug Drugs 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 208000007848 Alcoholism Diseases 0.000 claims description 5
• 208000000044 Amnesia Diseases 0.000 claims description 5
• 208000031091 Amnestic disease Diseases 0.000 claims description 5
• 208000019901 Anxiety disease Diseases 0.000 claims description 5
• 208000027559 Appetite disease Diseases 0.000 claims description 5
• 201000006474 Brain Ischemia Diseases 0.000 claims description 5
• 206010008120 Cerebral ischaemia Diseases 0.000 claims description 5
• 206010008190 Cerebrovascular accident Diseases 0.000 claims description 5
• 206010010774 Constipation Diseases 0.000 claims description 5
• 208000014094 Dystonic disease Diseases 0.000 claims description 5
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 5
• 208000010412 Glaucoma Diseases 0.000 claims description 5
• 235000014647 Lens culinaris subsp culinaris Nutrition 0.000 claims description 5
• 208000019695 Migraine disease Diseases 0.000 claims description 5
• 208000021642 Muscular disease Diseases 0.000 claims description 5
• 201000009623 Myopathy Diseases 0.000 claims description 5
• 206010057852 Nicotine dependence Diseases 0.000 claims description 5
• 208000008589 Obesity Diseases 0.000 claims description 5
• 208000018737 Parkinson disease Diseases 0.000 claims description 5
• 208000034189 Sclerosis Diseases 0.000 claims description 5
• 208000007107 Stomach Ulcer Diseases 0.000 claims description 5
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 5
• 208000025569 Tobacco Use disease Diseases 0.000 claims description 5
• 206010044565 Tremor Diseases 0.000 claims description 5
• 206010047700 Vomiting Diseases 0.000 claims description 5
• 201000007930 alcohol dependence Diseases 0.000 claims description 5
• 230000006986 amnesia Effects 0.000 claims description 5
• 230000036506 anxiety Effects 0.000 claims description 5
• 206010003246 arthritis Diseases 0.000 claims description 5
• 230000002490 cerebral effect Effects 0.000 claims description 5
• 206010008118 cerebral infarction Diseases 0.000 claims description 5
• 229910052801 chlorine Inorganic materials 0.000 claims description 5
• 206010012601 diabetes mellitus Diseases 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 206010013781 dry mouth Diseases 0.000 claims description 5
• 230000004064 dysfunction Effects 0.000 claims description 5
• 208000010118 dystonia Diseases 0.000 claims description 5
• ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims description 5
• 125000001072 heteroaryl group Chemical group 0.000 claims description 5
• 208000015181 infectious disease Diseases 0.000 claims description 5
• 206010027599 migraine Diseases 0.000 claims description 5
• 235000020824 obesity Nutrition 0.000 claims description 5
• JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 claims description 5
• 229960003015 rimonabant Drugs 0.000 claims description 5
• 201000004409 schistosomiasis Diseases 0.000 claims description 5
• 208000020431 spinal cord injury Diseases 0.000 claims description 5
• 229910021653 sulphate ion Inorganic materials 0.000 claims description 5
• 230000001225 therapeutic effect Effects 0.000 claims description 5
• 230000002485 urinary effect Effects 0.000 claims description 5
• 230000008673 vomiting Effects 0.000 claims description 5
• HMXDWDSNPRNUKI-UHFFFAOYSA-N 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-N-(1-piperidinyl)-3-pyrazolecarboxamide Chemical compound CCC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Br)C=C1 HMXDWDSNPRNUKI-UHFFFAOYSA-N 0.000 claims description 4
• APQPVVOYBLOJDY-UHFFFAOYSA-N 7-methoxy-1,2,3,4-tetrahydroacridin-9-amine Chemical compound C1CCCC2=C(N)C3=CC(OC)=CC=C3N=C21 APQPVVOYBLOJDY-UHFFFAOYSA-N 0.000 claims description 4
• 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 claims description 4
• 208000016192 Demyelinating disease Diseases 0.000 claims description 4
• 206010012335 Dependence Diseases 0.000 claims description 4
• 206010014612 Encephalitis viral Diseases 0.000 claims description 4
• 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
• 206010021518 Impaired gastric emptying Diseases 0.000 claims description 4
• 206010028289 Muscle atrophy Diseases 0.000 claims description 4
• 206010028813 Nausea Diseases 0.000 claims description 4
• 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 4
• 206010039966 Senile dementia Diseases 0.000 claims description 4
• 201000001880 Sexual dysfunction Diseases 0.000 claims description 4
• 125000003277 amino group Chemical group 0.000 claims description 4
• 208000015114 central nervous system disease Diseases 0.000 claims description 4
• 229960003530 donepezil Drugs 0.000 claims description 4
• 201000005917 gastric ulcer Diseases 0.000 claims description 4
• 208000001288 gastroparesis Diseases 0.000 claims description 4
• 150000004677 hydrates Chemical class 0.000 claims description 4
• 201000006417 multiple sclerosis Diseases 0.000 claims description 4
• 230000020763 muscle atrophy Effects 0.000 claims description 4
• 201000000585 muscular atrophy Diseases 0.000 claims description 4
• 230000008693 nausea Effects 0.000 claims description 4
• 208000004296 neuralgia Diseases 0.000 claims description 4
• 208000021722 neuropathic pain Diseases 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 239000001301 oxygen Substances 0.000 claims description 4
• 231100000572 poisoning Toxicity 0.000 claims description 4
• 230000000607 poisoning effect Effects 0.000 claims description 4
• 208000020016 psychiatric disease Diseases 0.000 claims description 4
• 231100000872 sexual dysfunction Toxicity 0.000 claims description 4
• 230000035882 stress Effects 0.000 claims description 4
• 125000004434 sulfur atom Chemical group 0.000 claims description 4
• 210000002435 tendon Anatomy 0.000 claims description 4
• 201000002498 viral encephalitis Diseases 0.000 claims description 4
• AXJQVVLKUYCICH-OAQYLSRUSA-N (4s)-5-(4-chlorophenyl)-n-(4-chlorophenyl)sulfonyl-n'-methyl-4-phenyl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C=1C=C(Cl)C=CC=1C([C@H](C1)C=2C=CC=CC=2)=NN1C(=NC)NS(=O)(=O)C1=CC=C(Cl)C=C1 AXJQVVLKUYCICH-OAQYLSRUSA-N 0.000 claims description 3
• RXBYRTSOWREATF-UHFFFAOYSA-N 1,2,3,4-tetrahydroacridine Chemical compound C1=CC=C2C=C(CCCC3)C3=NC2=C1 RXBYRTSOWREATF-UHFFFAOYSA-N 0.000 claims description 3
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
• 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 3
• 206010036790 Productive cough Diseases 0.000 claims description 3
• 208000028017 Psychotic disease Diseases 0.000 claims description 3
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
• 208000000323 Tourette Syndrome Diseases 0.000 claims description 3
• 208000016620 Tourette disease Diseases 0.000 claims description 3
• 208000036142 Viral infection Diseases 0.000 claims description 3
• 125000006309 butyl amino group Chemical group 0.000 claims description 3
• 125000006612 decyloxy group Chemical group 0.000 claims description 3
• 208000010643 digestive system disease Diseases 0.000 claims description 3
• 201000006549 dyspepsia Diseases 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 208000018685 gastrointestinal system disease Diseases 0.000 claims description 3
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 206010027175 memory impairment Diseases 0.000 claims description 3
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• IIFRKALDATVOJE-GGAORHGYSA-N quilostigmine Chemical compound C1CC2=CC=CC=C2CN1C(=O)OC(C=C12)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C IIFRKALDATVOJE-GGAORHGYSA-N 0.000 claims description 3
• 229910052707 ruthenium Inorganic materials 0.000 claims description 3
• 208000024794 sputum Diseases 0.000 claims description 3
• 210000003802 sputum Anatomy 0.000 claims description 3
• 239000011593 sulfur Substances 0.000 claims description 3
• 231100000331 toxic Toxicity 0.000 claims description 3
• 230000002588 toxic effect Effects 0.000 claims description 3
• 230000009385 viral infection Effects 0.000 claims description 3
• ULJCVCIVEVXIKD-WLHGVMLRSA-N (e)-but-2-enedioic acid;2-[1-[2-[[5-(piperidin-1-ylmethyl)furan-2-yl]methylamino]ethyl]imidazolidin-2-ylidene]propanedinitrile Chemical compound OC(=O)\C=C\C(O)=O.N#CC(C#N)=C1NCCN1CCNCC(O1)=CC=C1CN1CCCCC1 ULJCVCIVEVXIKD-WLHGVMLRSA-N 0.000 claims description 2
• RCEDCOCCCMIKCY-ZVCJTHDASA-N (e)-but-2-enedioic acid;octyl (2s,3as,6as)-1-[(2s)-2-[[(2s)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrole-2-carboxylate Chemical compound OC(=O)\C=C\C(O)=O.C([C@H](N[C@@H](C)C(=O)N1[C@H]2CCC[C@H]2C[C@H]1C(=O)OCCCCCCCC)C(=O)OCC)CC1=CC=CC=C1 RCEDCOCCCMIKCY-ZVCJTHDASA-N 0.000 claims description 2
• FXBXWJPMXQHOGD-UVTIVQHFSA-N (z,4r)-n-[3-(3-methoxyphenyl)prop-2-ynoxy]-1-azabicyclo[2.2.1]heptan-3-imine Chemical compound COC1=CC=CC(C#CCO\N=C/2[C@@H]3CCN(C3)C\2)=C1 FXBXWJPMXQHOGD-UVTIVQHFSA-N 0.000 claims description 2
• KWDBQJRWPWTGPF-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-4-methyl-n-piperidin-1-ylpyrazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl KWDBQJRWPWTGPF-UHFFFAOYSA-N 0.000 claims description 2
• CNEWKIDCGDXBDE-UHFFFAOYSA-N 1-[2-(4-phenylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=CC=CC=3)CC=2)=C1 CNEWKIDCGDXBDE-UHFFFAOYSA-N 0.000 claims description 2
• VPXVPJQOPRBXPO-UHFFFAOYSA-N 2,5-bis[6-[ethyl-[(2-methoxyphenyl)methyl]amino]hexylamino]cyclohexa-2,5-diene-1,4-dione Chemical compound C=1C=CC=C(OC)C=1CN(CC)CCCCCCNC(C(C=1)=O)=CC(=O)C=1NCCCCCCN(CC)CC1=CC=CC=C1OC VPXVPJQOPRBXPO-UHFFFAOYSA-N 0.000 claims description 2
• KZAJTVRKNKAXAG-UHFFFAOYSA-N 2-[4-[3-(3-chlorophenothiazin-10-yl)propyl]piperazin-1-yl]ethyl 3,4,5-trimethoxybenzoate Chemical compound COC1=C(OC)C(OC)=CC(C(=O)OCCN2CCN(CCCN3C4=CC=C(Cl)C=C4SC4=CC=CC=C43)CC2)=C1 KZAJTVRKNKAXAG-UHFFFAOYSA-N 0.000 claims description 2
• LGIURFWBBUZISG-UHFFFAOYSA-N 3-[2-[1-(1,3-dioxolan-2-ylmethyl)piperidin-4-yl]ethyl]-1,3-benzoxazine-2,4-dione;hydrochloride Chemical compound Cl.O=C1OC=2C=CC=CC=2C(=O)N1CCC(CC1)CCN1CC1OCCO1 LGIURFWBBUZISG-UHFFFAOYSA-N 0.000 claims description 2
• ONNMDRQRSGKZCN-UHFFFAOYSA-N 3-aminopropyl(butyl)phosphinic acid Chemical compound CCCCP(O)(=O)CCCN ONNMDRQRSGKZCN-UHFFFAOYSA-N 0.000 claims description 2
• SAURKKOJWIFYSR-UHFFFAOYSA-N 4-(2-fluorophenyl)-6-methyl-2-piperazin-1-ylthieno[2,3-d]pyrimidine;hydrate;hydrochloride Chemical compound O.Cl.N1=C2SC(C)=CC2=C(C=2C(=CC=CC=2)F)N=C1N1CCNCC1 SAURKKOJWIFYSR-UHFFFAOYSA-N 0.000 claims description 2
• MCNQUWLLXZZZAC-BJUDXGSMSA-N 4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-n-piperidin-1-ylpyrazole-3-carboxamide Chemical compound C1=CC(O[11CH3])=CC=C1C1=C(C#N)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl MCNQUWLLXZZZAC-BJUDXGSMSA-N 0.000 claims description 2
• CJMJXTWMGXRFOM-FKTURHEWSA-N 5-O-[8-(cis-2,6-dimethylmorpholino)octylcarbamoyl]eseroline Chemical compound C1[C@@H](C)O[C@@H](C)CN1CCCCCCCCNC(=O)OC1=CC=C(N(C)[C@@H]2[C@@]3(C)CCN2C)C3=C1 CJMJXTWMGXRFOM-FKTURHEWSA-N 0.000 claims description 2
• 241000218645 Cedrus Species 0.000 claims description 2
• 239000005944 Chlorpyrifos Substances 0.000 claims description 2
• MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims description 2
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 2
• 229920000877 Melamine resin Polymers 0.000 claims description 2
• 208000005374 Poisoning Diseases 0.000 claims description 2
• 206010040070 Septic Shock Diseases 0.000 claims description 2
• QLYKJCMUNUWAGO-GAJHUEQPSA-N Taranabant Chemical compound N([C@@H](C)[C@@H](CC=1C=CC(Cl)=CC=1)C=1C=C(C=CC=1)C#N)C(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 QLYKJCMUNUWAGO-GAJHUEQPSA-N 0.000 claims description 2
• 101000693961 Trachemys scripta 68 kDa serum albumin Proteins 0.000 claims description 2
• 208000005946 Xerostomia Diseases 0.000 claims description 2
• JGAGHIIOCADQOV-CTNGQTDRSA-N [(3ar,8bs)-3,4,8b-trimethyl-2,3a-dihydro-1h-pyrrolo[2,3-b]indol-7-yl] n-(2-methylphenyl)carbamate Chemical compound CN([C@@H]1[C@@](C2=C3)(C)CCN1C)C2=CC=C3OC(=O)NC1=CC=CC=C1C JGAGHIIOCADQOV-CTNGQTDRSA-N 0.000 claims description 2
• ZIGIADNCAWZUAB-CTNGQTDRSA-N [(3ar,8bs)-8b-methyl-2,3,3a,4-tetrahydro-1h-pyrrolo[2,3-b]indol-7-yl] n-(4-propan-2-ylphenyl)carbamate Chemical compound C1=CC(C(C)C)=CC=C1NC(=O)OC1=CC=C(N[C@@H]2[C@@]3(C)CCN2)C3=C1 ZIGIADNCAWZUAB-CTNGQTDRSA-N 0.000 claims description 2
• MCOVMZDBWGMPGM-UHFFFAOYSA-N [1-methyl-2-[(phenylcarbamoylhydrazinylidene)methyl]pyridin-1-ium-3-yl] n,n-dimethylcarbamate;chloride Chemical compound [Cl-].CN(C)C(=O)OC1=CC=C[N+](C)=C1C=NNC(=O)NC1=CC=CC=C1 MCOVMZDBWGMPGM-UHFFFAOYSA-N 0.000 claims description 2
• JHOTYHDSLIUKCJ-UHFFFAOYSA-N [6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-3-indolyl]-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)C(C1=CC=C(I)C=C11)=C(C)N1CCN1CCOCC1 JHOTYHDSLIUKCJ-UHFFFAOYSA-N 0.000 claims description 2
• ZCFHOMLAFTWDFM-UHFFFAOYSA-N a-796,260 Chemical compound CC1(C)C(C)(C)C1C(=O)C(C1=CC=CC=C11)=CN1CCN1CCOCC1 ZCFHOMLAFTWDFM-UHFFFAOYSA-N 0.000 claims description 2
• AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims description 2
• 229960000723 ampicillin Drugs 0.000 claims description 2
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 2
• DUEPRVBVGDRKAG-UHFFFAOYSA-N carbofuran Chemical compound CNC(=O)OC1=CC=CC2=C1OC(C)(C)C2 DUEPRVBVGDRKAG-UHFFFAOYSA-N 0.000 claims description 2
• SBPBAQFWLVIOKP-UHFFFAOYSA-N chlorpyrifos Chemical compound CCOP(=S)(OCC)OC1=NC(Cl)=C(Cl)C=C1Cl SBPBAQFWLVIOKP-UHFFFAOYSA-N 0.000 claims description 2
• 230000029087 digestion Effects 0.000 claims description 2
• IQQBRKLVEALROM-UHFFFAOYSA-N drinabant Chemical compound C=1C(F)=CC(F)=CC=1N(S(=O)(=O)C)C(C1)CN1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 IQQBRKLVEALROM-UHFFFAOYSA-N 0.000 claims description 2
• 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 2
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
• 229960003980 galantamine Drugs 0.000 claims description 2
• ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims description 2
• 230000002496 gastric effect Effects 0.000 claims description 2
• 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
• 230000007794 irritation Effects 0.000 claims description 2
• JDSHMPZPIAZGSV-UHFFFAOYSA-N melamine Chemical compound NC1=NC(N)=NC(N)=N1 JDSHMPZPIAZGSV-UHFFFAOYSA-N 0.000 claims description 2
• 229960004640 memantine Drugs 0.000 claims description 2
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
• VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 claims description 2
• 229960003248 mifepristone Drugs 0.000 claims description 2
• 229960002362 neostigmine Drugs 0.000 claims description 2
• LULNWZDBKTWDGK-UHFFFAOYSA-M neostigmine bromide Chemical compound [Br-].CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 LULNWZDBKTWDGK-UHFFFAOYSA-M 0.000 claims description 2
• UNAZAADNBYXMIV-UHFFFAOYSA-N otenabant Chemical compound C1CC(NCC)(C(N)=O)CCN1C1=NC=NC2=C1N=C(C=1C(=CC=CC=1)Cl)N2C1=CC=C(Cl)C=C1 UNAZAADNBYXMIV-UHFFFAOYSA-N 0.000 claims description 2
• 229950007398 paliroden Drugs 0.000 claims description 2
• JUOSGGQXEBBCJB-GORDUTHDSA-N rivanicline Chemical compound CNCC\C=C\C1=CC=CN=C1 JUOSGGQXEBBCJB-GORDUTHDSA-N 0.000 claims description 2
• 229950004279 rivanicline Drugs 0.000 claims description 2
• 230000036303 septic shock Effects 0.000 claims description 2
• 230000035939 shock Effects 0.000 claims description 2
• 229940124530 sulfonamide Drugs 0.000 claims description 2
• 150000003456 sulfonamides Chemical class 0.000 claims description 2
• 229950003174 surinabant Drugs 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
• DUYGSAPQVOBOCS-UHFFFAOYSA-N win 54,461 Chemical compound C1=CC(OC)=CC=C1C(=O)C(C1=CC=C(Br)C=C11)=C(C)N1CCN1CCOCC1 DUYGSAPQVOBOCS-UHFFFAOYSA-N 0.000 claims description 2
• PMBLXLOXUGVTGB-UHFFFAOYSA-N zanapezil Chemical compound C=1C=C2CCCCNC2=CC=1C(=O)CCC(CC1)CCN1CC1=CC=CC=C1 PMBLXLOXUGVTGB-UHFFFAOYSA-N 0.000 claims description 2
• 229950010696 zanapezil Drugs 0.000 claims description 2
• 241000219739 Lens Species 0.000 claims 3
• 206010028417 myasthenia gravis Diseases 0.000 claims 2
• FDOXPBJQDCKVOB-ZETCQYMHSA-N (2s)-2-(n-hydroxyanilino)propanoic acid Chemical compound OC(=O)[C@H](C)N(O)C1=CC=CC=C1 FDOXPBJQDCKVOB-ZETCQYMHSA-N 0.000 claims 1
• LVKSHCMUMKNPFN-UHFFFAOYSA-N 3-hydroxy-2,4-dioxa-3lambda5-phosphabicyclo[3.2.2]nona-1(7),5,8-triene 3-oxide Chemical compound C1=CC2=CC=C1OP(=O)(O2)O LVKSHCMUMKNPFN-UHFFFAOYSA-N 0.000 claims 1
• 244000046038 Ehretia acuminata Species 0.000 claims 1
• 235000009300 Ehretia acuminata Nutrition 0.000 claims 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 claims 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims 1
• QQQIECGTIMUVDS-UHFFFAOYSA-N N-[[4-[2-(dimethylamino)ethoxy]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=C(OCCN(C)C)C=C1 QQQIECGTIMUVDS-UHFFFAOYSA-N 0.000 claims 1
• 229940124815 NXX-066 Drugs 0.000 claims 1
• 241000517307 Pediculus humanus Species 0.000 claims 1
• 208000037063 Thinness Diseases 0.000 claims 1
• 241000700605 Viruses Species 0.000 claims 1
• GUHMRCCRDRBMHO-UHFFFAOYSA-N [1-[(3-fluoropyridin-4-yl)amino]-3-methylindol-5-yl] n-methylcarbamate Chemical compound C1=C(C)C2=CC(OC(=O)NC)=CC=C2N1NC1=CC=NC=C1F GUHMRCCRDRBMHO-UHFFFAOYSA-N 0.000 claims 1
• XPVDRMQXBMGFBP-UHFFFAOYSA-N [Cl-].[NH4+].OC1=CC=CC=C1 Chemical compound [Cl-].[NH4+].OC1=CC=CC=C1 XPVDRMQXBMGFBP-UHFFFAOYSA-N 0.000 claims 1
• 210000001015 abdomen Anatomy 0.000 claims 1
• 230000003187 abdominal effect Effects 0.000 claims 1
• YGCFIWIQZPHFLU-UHFFFAOYSA-N acesulfame Chemical compound CC1=CC(=O)NS(=O)(=O)O1 YGCFIWIQZPHFLU-UHFFFAOYSA-N 0.000 claims 1
• 229960005164 acesulfame Drugs 0.000 claims 1
• 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims 1
• 229960005286 carbaryl Drugs 0.000 claims 1
• CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical compound C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 claims 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims 1
• 229960003957 dexamethasone Drugs 0.000 claims 1
• FHIVAFMUCKRCQO-UHFFFAOYSA-N diazinon Chemical compound CCOP(=S)(OCC)OC1=CC(C)=NC(C(C)C)=N1 FHIVAFMUCKRCQO-UHFFFAOYSA-N 0.000 claims 1
• 230000002526 effect on cardiovascular system Effects 0.000 claims 1
• 206010014599 encephalitis Diseases 0.000 claims 1
• YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 claims 1
• 229960003667 flupirtine Drugs 0.000 claims 1
• 229960002725 isoflurane Drugs 0.000 claims 1
• 229960005302 itopride Drugs 0.000 claims 1
• 208000028454 lice infestation Diseases 0.000 claims 1
• BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 claims 1
• 229930182817 methionine Natural products 0.000 claims 1
• 210000003205 muscle Anatomy 0.000 claims 1
• 229940028444 muse Drugs 0.000 claims 1
• KGDFDVHLEYUZLN-AWEZNQCLSA-N n-[(4-chlorophenyl)methyl]-4-[(2s)-2-formylpyrrolidin-1-yl]-4-oxobutanamide Chemical compound C1=CC(Cl)=CC=C1CNC(=O)CCC(=O)N1[C@H](C=O)CCC1 KGDFDVHLEYUZLN-AWEZNQCLSA-N 0.000 claims 1
• GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 claims 1
• 229940075630 samarium oxide Drugs 0.000 claims 1
• 229910001954 samarium oxide Inorganic materials 0.000 claims 1
• FKTOIHSPIPYAPE-UHFFFAOYSA-N samarium(iii) oxide Chemical compound [O-2].[O-2].[O-2].[Sm+3].[Sm+3] FKTOIHSPIPYAPE-UHFFFAOYSA-N 0.000 claims 1
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
• 239000003981 vehicle Substances 0.000 claims 1
• 230000002861 ventricular Effects 0.000 claims 1
• 235000021419 vinegar Nutrition 0.000 claims 1
• 239000000052 vinegar Substances 0.000 claims 1
• JMOBMHYQLPPCKP-UHFFFAOYSA-N win 56,098 Chemical compound CC1=C(C(=O)C=2C3=CC=CC=C3C=C3C=CC=CC3=2)C2=CC=CC=C2N1CCN1CCOCC1 JMOBMHYQLPPCKP-UHFFFAOYSA-N 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 35
• 230000015572 biosynthetic process Effects 0.000 abstract description 11
• 238000003786 synthesis reaction Methods 0.000 abstract description 11
• 239000000543 intermediate Substances 0.000 abstract description 6
• 206010048650 Cholinesterase inhibition Diseases 0.000 abstract description 4
• 102000005962 receptors Human genes 0.000 description 17
• 108020003175 receptors Proteins 0.000 description 17
• 229940079593 drug Drugs 0.000 description 15
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
• 239000004480 active ingredient Substances 0.000 description 14
• 102100033639 Acetylcholinesterase Human genes 0.000 description 13
• 239000004615 ingredient Substances 0.000 description 13
• 238000009472 formulation Methods 0.000 description 12
• 239000002904 solvent Substances 0.000 description 11
• 239000002464 receptor antagonist Substances 0.000 description 10
• 229940044551 receptor antagonist Drugs 0.000 description 10
• 239000000243 solution Substances 0.000 description 10
• 241001465754 Metazoa Species 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 8
• 102000004190 Enzymes Human genes 0.000 description 8
• 108090000790 Enzymes Proteins 0.000 description 8
• 230000000694 effects Effects 0.000 description 8
• 229940088598 enzyme Drugs 0.000 description 8
• 239000007787 solid Substances 0.000 description 8
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
• 241000124008 Mammalia Species 0.000 description 6
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
• 229960004373 acetylcholine Drugs 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 6
• 229910052736 halogen Inorganic materials 0.000 description 6
• 238000002844 melting Methods 0.000 description 6
• 230000008018 melting Effects 0.000 description 6
• 239000012038 nucleophile Substances 0.000 description 6
• 230000000144 pharmacologic effect Effects 0.000 description 6
• 125000006850 spacer group Chemical group 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
• 230000003042 antagnostic effect Effects 0.000 description 5
• 239000013078 crystal Substances 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 238000000926 separation method Methods 0.000 description 5
• 125000003396 thiol group Chemical group [H]S* 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
• 102000003914 Cholinesterases Human genes 0.000 description 4
• 108090000322 Cholinesterases Proteins 0.000 description 4
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
• 108010010803 Gelatin Proteins 0.000 description 4
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 4
• RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 210000004027 cell Anatomy 0.000 description 4
• 229940048961 cholinesterase Drugs 0.000 description 4
• 229940125904 compound 1 Drugs 0.000 description 4
• 239000007822 coupling agent Substances 0.000 description 4
• 238000002425 crystallisation Methods 0.000 description 4
• 230000008025 crystallization Effects 0.000 description 4
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 4
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
• 238000011161 development Methods 0.000 description 4
• 230000018109 developmental process Effects 0.000 description 4
• 229920000159 gelatin Polymers 0.000 description 4
• 239000008273 gelatin Substances 0.000 description 4
• 239000007903 gelatin capsule Substances 0.000 description 4
• 235000019322 gelatine Nutrition 0.000 description 4
• 235000011852 gelatine desserts Nutrition 0.000 description 4
• 239000003112 inhibitor Substances 0.000 description 4
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 4
• 229960005489 paracetamol Drugs 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 150000003512 tertiary amines Chemical class 0.000 description 4
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
• 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 3
• 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 3
• 102000018208 Cannabinoid Receptor Human genes 0.000 description 3
• 108050007331 Cannabinoid receptor Proteins 0.000 description 3
• 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 3
• 206010012735 Diarrhoea Diseases 0.000 description 3
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 229930195725 Mannitol Natural products 0.000 description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
• 206010028372 Muscular weakness Diseases 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 238000009739 binding Methods 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 229910000420 cerium oxide Inorganic materials 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 125000001309 chloro group Chemical group Cl* 0.000 description 3
• 229940126214 compound 3 Drugs 0.000 description 3
• 230000009260 cross reactivity Effects 0.000 description 3
• 239000002329 esterase inhibitor Substances 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• 235000019439 ethyl acetate Nutrition 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 239000011521 glass Substances 0.000 description 3
• 150000002367 halogens Chemical class 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 230000003993 interaction Effects 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 239000000594 mannitol Substances 0.000 description 3
• 235000010355 mannitol Nutrition 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 229920006395 saturated elastomer Polymers 0.000 description 3
• 238000002603 single-photon emission computed tomography Methods 0.000 description 3
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
• 150000005846 sugar alcohols Chemical class 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 238000004809 thin layer chromatography Methods 0.000 description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
• 235000015112 vegetable and seed oil Nutrition 0.000 description 3
• 239000008158 vegetable oil Substances 0.000 description 3
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
• 101150060184 ACHE gene Proteins 0.000 description 2
• 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 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• 235000017166 Bambusa arundinacea Nutrition 0.000 description 2
• 235000017491 Bambusa tulda Nutrition 0.000 description 2
• 101150041968 CDC13 gene Proteins 0.000 description 2
• 229940119495 Cholesterol esterase inhibitor Drugs 0.000 description 2
• 229940122041 Cholinesterase inhibitor Drugs 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
• 229940122601 Esterase inhibitor Drugs 0.000 description 2
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
• 208000023105 Huntington disease Diseases 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 244000043158 Lens esculenta Species 0.000 description 2
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
• 208000010428 Muscle Weakness Diseases 0.000 description 2
• AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• 241000517308 Pediculus humanus capitis Species 0.000 description 2
• 244000082204 Phyllostachys viridis Species 0.000 description 2
• 235000015334 Phyllostachys viridis Nutrition 0.000 description 2
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
• XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 239000011425 bamboo Substances 0.000 description 2
• 239000011324 bead Substances 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 229940065144 cannabinoids Drugs 0.000 description 2
• 239000004202 carbamide Substances 0.000 description 2
• 235000013877 carbamide Nutrition 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• DRVWBEJJZZTIGJ-UHFFFAOYSA-N cerium(3+);oxygen(2-) Chemical class [O-2].[O-2].[O-2].[Ce+3].[Ce+3] DRVWBEJJZZTIGJ-UHFFFAOYSA-N 0.000 description 2
• 239000012320 chlorinating reagent Substances 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 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 description 2
• 230000001149 cognitive effect Effects 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 229940125782 compound 2 Drugs 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 150000004141 diterpene derivatives Chemical class 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 239000007920 enema Substances 0.000 description 2
• 229940095399 enema Drugs 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 239000002532 enzyme inhibitor Substances 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000003925 fat Substances 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 230000030135 gastric motility Effects 0.000 description 2
• 235000011187 glycerol Nutrition 0.000 description 2
• IZKZIDXHCDIZKY-UHFFFAOYSA-N heptane-1,1-diamine Chemical compound CCCCCCC(N)N IZKZIDXHCDIZKY-UHFFFAOYSA-N 0.000 description 2
• 125000004404 heteroalkyl group Chemical group 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• 125000000623 heterocyclic group Chemical group 0.000 description 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
• 239000005414 inactive ingredient Substances 0.000 description 2
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 230000000155 isotopic effect Effects 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 235000013372 meat Nutrition 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 239000002207 metabolite Substances 0.000 description 2
• 229910021645 metal ion Inorganic materials 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound 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
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 230000000926 neurological effect Effects 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 239000003208 petroleum Substances 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 230000000087 stabilizing effect Effects 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 2
• 239000010455 vermiculite Substances 0.000 description 2
• 229910052902 vermiculite Inorganic materials 0.000 description 2
• 235000019354 vermiculite Nutrition 0.000 description 2
• 238000003260 vortexing Methods 0.000 description 2
• 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical group C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• FDHOKMCJHQRFPP-UHFFFAOYSA-N 1-(2-chlorophenyl)-4-cyano-5-(4-methoxyphenyl)-n-phenylpyrazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=C(C#N)C(C(=O)NC=2C=CC=CC=2)=NN1C1=CC=CC=C1Cl FDHOKMCJHQRFPP-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
• YLUSMKAJIQOXPV-UHFFFAOYSA-N 2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-9-amine Chemical compound C1CCCC2=C1N=C1CCCC1=C2N YLUSMKAJIQOXPV-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
• VQNDBXJTIJKJPV-UHFFFAOYSA-N 2h-triazolo[4,5-b]pyridine Chemical compound C1=CC=NC2=NNN=C21 VQNDBXJTIJKJPV-UHFFFAOYSA-N 0.000 description 1
• FBSWPFFKBBRXJB-UHFFFAOYSA-N 3-(4-chlorophenyl)-1h-indole Chemical compound C1=CC(Cl)=CC=C1C1=CNC2=CC=CC=C12 FBSWPFFKBBRXJB-UHFFFAOYSA-N 0.000 description 1
• WSNKEJIFARPOSQ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(1-benzothiophen-2-ylmethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC2=CC3=C(S2)C=CC=C3)C=CC=1 WSNKEJIFARPOSQ-UHFFFAOYSA-N 0.000 description 1
• 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
• CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
• 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 241000254032 Acrididae Species 0.000 description 1
• 240000000530 Alcea rosea Species 0.000 description 1
• 235000017334 Alcea rosea Nutrition 0.000 description 1
• 235000017303 Althaea rosea Nutrition 0.000 description 1
• 208000023584 Alzheimer disease 10 Diseases 0.000 description 1
• 229920000945 Amylopectin Polymers 0.000 description 1
• 241001494510 Arundo Species 0.000 description 1
• YXSLJKQTIDHPOT-UHFFFAOYSA-N Atracurium Dibesylate Chemical compound C1=C(OC)C(OC)=CC=C1CC1[N+](CCC(=O)OCCCCCOC(=O)CC[N+]2(C)C(C3=CC(OC)=C(OC)C=C3CC2)CC=2C=C(OC)C(OC)=CC=2)(C)CCC2=CC(OC)=C(OC)C=C21 YXSLJKQTIDHPOT-UHFFFAOYSA-N 0.000 description 1
• 206010003694 Atrophy Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 229940124802 CB1 antagonist Drugs 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 1
• 102000003858 Chymases Human genes 0.000 description 1
• 108090000227 Chymases Proteins 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• WUFQLZTXIWKION-UHFFFAOYSA-N Deoxypeganine Chemical compound C1C2=CC=CC=C2N=C2N1CCC2 WUFQLZTXIWKION-UHFFFAOYSA-N 0.000 description 1
• 208000020401 Depressive disease Diseases 0.000 description 1
• 206010013647 Drowning Diseases 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• WJYIASZWHGOTOU-UHFFFAOYSA-N Heptylamine Chemical compound CCCCCCCN WJYIASZWHGOTOU-UHFFFAOYSA-N 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
• 206010062717 Increased upper airway secretion Diseases 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• LHXOCOHMBFOVJS-OAHLLOKOSA-N Ladostigil Chemical compound CCN(C)C(=O)OC1=CC=C2CC[C@@H](NCC#C)C2=C1 LHXOCOHMBFOVJS-OAHLLOKOSA-N 0.000 description 1
• 239000005949 Malathion Substances 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 241000751119 Mila <angiosperm> Species 0.000 description 1
• 102000014171 Milk Proteins Human genes 0.000 description 1
• 108010011756 Milk Proteins Proteins 0.000 description 1
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
• 150000001200 N-acyl ethanolamides Chemical class 0.000 description 1
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000007443 Neurasthenia Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• 102000016979 Other receptors Human genes 0.000 description 1
• 241000282320 Panthera leo Species 0.000 description 1
• 206010033799 Paralysis Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
• 102000029797 Prion Human genes 0.000 description 1
• 108091000054 Prion Proteins 0.000 description 1
• 238000001237 Raman spectrum Methods 0.000 description 1
• 208000033464 Reiter syndrome Diseases 0.000 description 1
• IYAVYMAGJPJCNJ-UHFFFAOYSA-N S=[SH2] Chemical compound S=[SH2] IYAVYMAGJPJCNJ-UHFFFAOYSA-N 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 241000862969 Stella Species 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 239000012317 TBTU Substances 0.000 description 1
• 239000004098 Tetracycline Substances 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 102000005488 Thioesterase Human genes 0.000 description 1
• 229910052770 Uranium Inorganic materials 0.000 description 1
• 240000006365 Vitis vinifera Species 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• ROZSPJBPUVWBHW-UHFFFAOYSA-N [Ru]=O Chemical class [Ru]=O ROZSPJBPUVWBHW-UHFFFAOYSA-N 0.000 description 1
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 230000001270 agonistic effect Effects 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 125000000539 amino acid group Chemical group 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 229940039856 aricept Drugs 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000005129 aryl carbonyl group Chemical group 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• 206010003549 asthenia Diseases 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 229960001862 atracurium Drugs 0.000 description 1
• 230000037444 atrophy Effects 0.000 description 1
• CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 239000012964 benzotriazole Substances 0.000 description 1
• 239000012867 bioactive agent Substances 0.000 description 1
• 238000007664 blowing Methods 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000001273 butane Substances 0.000 description 1
• ULEAQRIQMIQDPJ-UHFFFAOYSA-N butane-1,2-diamine Chemical compound CCC(N)CN ULEAQRIQMIQDPJ-UHFFFAOYSA-N 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 210000003710 cerebral cortex Anatomy 0.000 description 1
• 239000003610 charcoal Substances 0.000 description 1
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• DRWMGJONTCWKES-UHFFFAOYSA-N chloroform;hydrochloride Chemical compound Cl.ClC(Cl)Cl DRWMGJONTCWKES-UHFFFAOYSA-N 0.000 description 1
• 125000000068 chlorophenyl group Chemical group 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 238000005352 clarification Methods 0.000 description 1
• 229960003920 cocaine Drugs 0.000 description 1
• 235000012716 cod liver oil Nutrition 0.000 description 1
• 239000003026 cod liver oil Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 238000010668 complexation reaction Methods 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 235000008504 concentrate Nutrition 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 230000001054 cortical effect Effects 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 238000012258 culturing Methods 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
• DCZFGQYXRKMVFG-UHFFFAOYSA-N cyclohexane-1,4-dione Chemical compound O=C1CCC(=O)CC1 DCZFGQYXRKMVFG-UHFFFAOYSA-N 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• YMWUJEATGCHHMB-DICFDUPASA-N deuterated dichloromethane Substances [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• JXSJBGJIGXNWCI-UHFFFAOYSA-N diethyl 2-[(dimethoxyphosphorothioyl)thio]succinate Chemical compound CCOC(=O)CC(SP(=S)(OC)OC)C(=O)OCC JXSJBGJIGXNWCI-UHFFFAOYSA-N 0.000 description 1
• CKQQMPJQZXIYMJ-UHFFFAOYSA-N dihydrate;dihydrochloride Chemical compound O.O.Cl.Cl CKQQMPJQZXIYMJ-UHFFFAOYSA-N 0.000 description 1
• KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
• MUCZHBLJLSDCSD-UHFFFAOYSA-N diisopropyl fluorophosphate Chemical compound CC(C)OP(F)(=O)OC(C)C MUCZHBLJLSDCSD-UHFFFAOYSA-N 0.000 description 1
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
• 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 238000004043 dyeing Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 150000002081 enamines Chemical class 0.000 description 1
• 239000002621 endocannabinoid Substances 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 229940125532 enzyme inhibitor Drugs 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
• 229940108366 exelon Drugs 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 210000001320 hippocampus Anatomy 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 208000013403 hyperactivity Diseases 0.000 description 1
• UVNXNSUKKOLFBM-UHFFFAOYSA-N imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=CSC2=NC=CN21 UVNXNSUKKOLFBM-UHFFFAOYSA-N 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 238000002329 infrared spectrum Methods 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229960005490 ipidacrine Drugs 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 229950008812 ladostigil Drugs 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• 210000004558 lewy body Anatomy 0.000 description 1
• 239000012669 liquid formulation Substances 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 238000005567 liquid scintillation counting Methods 0.000 description 1
• 244000144972 livestock Species 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 238000003819 low-pressure liquid chromatography Methods 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229960000453 malathion Drugs 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 230000008774 maternal effect Effects 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• BAXLBXFAUKGCDY-UHFFFAOYSA-N mebendazole Chemical compound [CH]1C2=NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CC=C1 BAXLBXFAUKGCDY-UHFFFAOYSA-N 0.000 description 1
• 229960003439 mebendazole Drugs 0.000 description 1
• LDDHMLJTFXJGPI-UHFFFAOYSA-N memantine hydrochloride Chemical compound Cl.C1C(C2)CC3(C)CC1(C)CC2(N)C3 LDDHMLJTFXJGPI-UHFFFAOYSA-N 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 235000021239 milk protein Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 229960005181 morphine Drugs 0.000 description 1
• 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 1
• 230000036473 myasthenia Effects 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 230000000324 neuroprotective effect Effects 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 239000002547 new drug Substances 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 229910052762 osmium Inorganic materials 0.000 description 1
• SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-O oxonium Chemical compound [OH3+] XLYOFNOQVPJJNP-UHFFFAOYSA-O 0.000 description 1
• 125000005429 oxyalkyl group Chemical group 0.000 description 1
• 238000012856 packing Methods 0.000 description 1
• 239000003182 parenteral nutrition solution Substances 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 208000026435 phlegm Diseases 0.000 description 1
• DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
• 238000005375 photometry Methods 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 239000000049 pigment Substances 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229960000502 poloxamer Drugs 0.000 description 1
• 229920001983 poloxamer Polymers 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 238000002600 positron emission tomography Methods 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 229940124606 potential therapeutic agent Drugs 0.000 description 1
• 238000000634 powder X-ray diffraction Methods 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 238000002203 pretreatment Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 239000001294 propane Substances 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 239000002287 radioligand Substances 0.000 description 1
• 239000002994 raw material Substances 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 208000002574 reactive arthritis Diseases 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000008929 regeneration Effects 0.000 description 1
• 238000011069 regeneration method Methods 0.000 description 1
• 238000000611 regression analysis Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 239000013037 reversible inhibitor Substances 0.000 description 1
• 229960004136 rivastigmine Drugs 0.000 description 1
• 229910001925 ruthenium oxide Inorganic materials 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 239000004576 sand Substances 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• 238000007632 sclerotherapy Methods 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
• 238000005204 segregation Methods 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 230000001568 sexual effect Effects 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 239000002689 soil Substances 0.000 description 1
• 238000000279 solid-state nuclear magnetic resonance spectrum Methods 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 150000003413 spiro compounds Chemical class 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 239000004575 stone Substances 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 229960002317 succinimide Drugs 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 125000004354 sulfur functional group Chemical group 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 150000003505 terpenes Chemical class 0.000 description 1
• 235000007586 terpenes Nutrition 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 229960002180 tetracycline Drugs 0.000 description 1
• 229930101283 tetracycline Natural products 0.000 description 1
• 235000019364 tetracycline Nutrition 0.000 description 1
• 150000003522 tetracyclines Chemical class 0.000 description 1
• IPOBMWQSKXACEW-UHFFFAOYSA-N tetradecylurea Chemical compound CCCCCCCCCCCCCCNC(N)=O IPOBMWQSKXACEW-UHFFFAOYSA-N 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 108020002982 thioesterase Proteins 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 150000008648 triflates Chemical class 0.000 description 1
• 230000010415 tropism Effects 0.000 description 1
• 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• DNYWZCXLKNTFFI-UHFFFAOYSA-N uranium Chemical compound [U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U] DNYWZCXLKNTFFI-UHFFFAOYSA-N 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 235000019871 vegetable fat Nutrition 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000001993 wax Substances 0.000 description 1