SK15952000A3 - Aryl-anelovaná azapolycyklická zlúčenina, jej použitie a farmaceutické kompozície na jej báze - Google Patents

Info

Publication number

SK15952000A3

SK15952000A3 SK1595-2000A SK15952000A SK15952000A3 SK 15952000 A3 SK15952000 A3 SK 15952000A3 SK 15952000 A SK15952000 A SK 15952000A SK 15952000 A3 SK15952000 A3 SK 15952000A3

Authority

SK

Slovakia

Prior art keywords

trideca

triene

tetraene

alkyl

formula

Prior art date

1998-04-29

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 300
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 8
• 125000003118 aryl group Chemical group 0.000 title claims description 14
• 150000003839 salts Chemical class 0.000 claims abstract description 23
• 239000000460 chlorine Substances 0.000 claims description 59
• 229910052739 hydrogen Inorganic materials 0.000 claims description 48
• 239000001257 hydrogen Substances 0.000 claims description 47
• 125000000217 alkyl group Chemical group 0.000 claims description 42
• 229920006395 saturated elastomer Polymers 0.000 claims description 40
• -1 hydroxy, nitro, amino Chemical group 0.000 claims description 39
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 38
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 24
• 229910052757 nitrogen Inorganic materials 0.000 claims description 22
• 125000004432 carbon atom Chemical group C* 0.000 claims description 20
• 125000001424 substituent group Chemical group 0.000 claims description 20
• 230000009467 reduction Effects 0.000 claims description 18
• 125000001153 fluoro group Chemical group F* 0.000 claims description 15
• 206010012335 Dependence Diseases 0.000 claims description 14
• 208000018737 Parkinson disease Diseases 0.000 claims description 14
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 14
• 229910052736 halogen Inorganic materials 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
• 241000124008 Mammalia Species 0.000 claims description 13
• 208000002193 Pain Diseases 0.000 claims description 13
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 229910052760 oxygen Inorganic materials 0.000 claims description 12
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 11
• 206010015037 epilepsy Diseases 0.000 claims description 11
• 150000002367 halogens Chemical class 0.000 claims description 11
• 125000001072 heteroaryl group Chemical group 0.000 claims description 11
• 239000001301 oxygen Substances 0.000 claims description 11
• 208000019901 Anxiety disease Diseases 0.000 claims description 10
• 241000208125 Nicotiana Species 0.000 claims description 10
• 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 10
• 208000006011 Stroke Diseases 0.000 claims description 10
• 230000036506 anxiety Effects 0.000 claims description 10
• 208000010877 cognitive disease Diseases 0.000 claims description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 9
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
• 208000023105 Huntington disease Diseases 0.000 claims description 9
• 125000002619 bicyclic group Chemical group 0.000 claims description 9
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
• 229910052794 bromium Inorganic materials 0.000 claims description 9
• 230000006735 deficit Effects 0.000 claims description 9
• 201000010099 disease Diseases 0.000 claims description 9
• 229910052731 fluorine Inorganic materials 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 150000002431 hydrogen Chemical class 0.000 claims description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 7
• 208000020925 Bipolar disease Diseases 0.000 claims description 7
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
• 208000025865 Ulcer Diseases 0.000 claims description 7
• 208000005298 acute pain Diseases 0.000 claims description 7
• 208000022531 anorexia Diseases 0.000 claims description 7
• 206010061428 decreased appetite Diseases 0.000 claims description 7
• 239000011737 fluorine Substances 0.000 claims description 7
• 125000005842 heteroatom Chemical group 0.000 claims description 7
• 125000002950 monocyclic group Chemical group 0.000 claims description 7
• 208000032841 Bulimia Diseases 0.000 claims description 6
• 206010006550 Bulimia nervosa Diseases 0.000 claims description 6
• 208000000094 Chronic Pain Diseases 0.000 claims description 6
• 208000015943 Coeliac disease Diseases 0.000 claims description 6
• 206010019233 Headaches Diseases 0.000 claims description 6
• 206010020651 Hyperkinesia Diseases 0.000 claims description 6
• 208000000269 Hyperkinesis Diseases 0.000 claims description 6
• 206010020772 Hypertension Diseases 0.000 claims description 6
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
• 208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 6
• 208000008589 Obesity Diseases 0.000 claims description 6
• 208000002389 Pouchitis Diseases 0.000 claims description 6
• 208000028017 Psychotic disease Diseases 0.000 claims description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
• 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 6
• 201000004810 Vascular dementia Diseases 0.000 claims description 6
• 206010003119 arrhythmia Diseases 0.000 claims description 6
• 206010013932 dyslexia Diseases 0.000 claims description 6
• 125000005843 halogen group Chemical group 0.000 claims description 6
• 231100000869 headache Toxicity 0.000 claims description 6
• 229910052740 iodine Inorganic materials 0.000 claims description 6
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
• 206010027175 memory impairment Diseases 0.000 claims description 6
• 235000020824 obesity Nutrition 0.000 claims description 6
• 201000000980 schizophrenia Diseases 0.000 claims description 6
• 208000019116 sleep disease Diseases 0.000 claims description 6
• 230000001148 spastic effect Effects 0.000 claims description 6
• 125000004434 sulfur atom Chemical group 0.000 claims description 6
• 208000011580 syndromic disease Diseases 0.000 claims description 6
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 5
• 206010003805 Autism Diseases 0.000 claims description 5
• 208000020706 Autistic disease Diseases 0.000 claims description 5
• 206010057852 Nicotine dependence Diseases 0.000 claims description 5
• 208000025569 Tobacco Use disease Diseases 0.000 claims description 5
• 208000000323 Tourette Syndrome Diseases 0.000 claims description 5
• 208000016620 Tourette disease Diseases 0.000 claims description 5
• 125000003545 alkoxy group Chemical group 0.000 claims description 5
• 229910052801 chlorine Inorganic materials 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 208000013403 hyperactivity Diseases 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 208000019906 panic disease Diseases 0.000 claims description 5
• 239000000126 substance Substances 0.000 claims description 5
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
• 208000024827 Alzheimer disease Diseases 0.000 claims description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
• 208000014094 Dystonic disease Diseases 0.000 claims description 4
• 208000034308 Grand mal convulsion Diseases 0.000 claims description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
• 206010039966 Senile dementia Diseases 0.000 claims description 4
• 206010047139 Vasoconstriction Diseases 0.000 claims description 4
• 208000010118 dystonia Diseases 0.000 claims description 4
• 239000011630 iodine Substances 0.000 claims description 4
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 4
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 4
• 231100000397 ulcer Toxicity 0.000 claims description 4
• 230000025033 vasoconstriction Effects 0.000 claims description 4
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
• MNOULQLXILYKNV-UHFFFAOYSA-N 5-[4-(trifluoromethyl)phenyl]-1h-pyrazole Chemical group C1=CC(C(F)(F)F)=CC=C1C1=CC=NN1 MNOULQLXILYKNV-UHFFFAOYSA-N 0.000 claims description 3
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
• 125000004429 atom Chemical group 0.000 claims description 3
• 210000004211 gastric acid Anatomy 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• 230000003287 optical effect Effects 0.000 claims description 3
• 125000004043 oxo group Chemical group O=* 0.000 claims description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
• 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 2
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 2
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 2
• 125000003342 alkenyl group Chemical group 0.000 claims description 2
• 125000003282 alkyl amino group Chemical group 0.000 claims description 2
• 125000002947 alkylene group Chemical group 0.000 claims description 2
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000002837 carbocyclic group Chemical group 0.000 claims description 2
• 125000004122 cyclic group Chemical group 0.000 claims description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
• 150000003457 sulfones Chemical class 0.000 claims description 2
• 150000003462 sulfoxides Chemical class 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• 230000001629 suppression Effects 0.000 claims 2
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims 1
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims 1
• 206010010904 Convulsion Diseases 0.000 claims 1
• NDJKXXJCMXVBJW-UHFFFAOYSA-N Heptadecane Natural products CCCCCCCCCCCCCCCCC NDJKXXJCMXVBJW-UHFFFAOYSA-N 0.000 claims 1
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims 1
• 239000013256 coordination polymer Substances 0.000 claims 1
• 206010013663 drug dependence Diseases 0.000 claims 1
• NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 claims 1
• 230000002496 gastric effect Effects 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims 1
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims 1
• 208000011117 substance-related disease Diseases 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 86
• 239000000543 intermediate Substances 0.000 abstract description 10
• 238000003786 synthesis reaction Methods 0.000 abstract description 10
• 230000015572 biosynthetic process Effects 0.000 abstract description 8
• 208000012902 Nervous system disease Diseases 0.000 abstract 1
• 208000025966 Neurological disease Diseases 0.000 abstract 1
• 230000000926 neurological effect Effects 0.000 abstract 1
• 208000020016 psychiatric disease Diseases 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 157
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 116
• 238000006243 chemical reaction Methods 0.000 description 109
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
• 235000019439 ethyl acetate Nutrition 0.000 description 77
• 239000000203 mixture Substances 0.000 description 68
• 238000004809 thin layer chromatography Methods 0.000 description 55
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
• 239000003921 oil Substances 0.000 description 52
• 235000019198 oils Nutrition 0.000 description 52
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
• 239000000243 solution Substances 0.000 description 45
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
• 239000000047 product Substances 0.000 description 31
• 239000002904 solvent Substances 0.000 description 31
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
• 239000012044 organic layer Substances 0.000 description 29
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
• 239000012267 brine Substances 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
• 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 26
• 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 26
• 239000007787 solid Substances 0.000 description 26
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
• 238000010992 reflux Methods 0.000 description 24
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
• 239000010410 layer Substances 0.000 description 22
• 238000002360 preparation method Methods 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 239000002585 base Substances 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
• 239000000741 silica gel Substances 0.000 description 17
• 229910002027 silica gel Inorganic materials 0.000 description 17
• 239000011734 sodium Substances 0.000 description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
• 239000002253 acid Substances 0.000 description 16
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
• 229920000742 Cotton Polymers 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 14
• 238000006722 reduction reaction Methods 0.000 description 14
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 13
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
• 125000006239 protecting group Chemical group 0.000 description 12
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 11
• 230000035484 reaction time Effects 0.000 description 11
• FAMLQSCGIQGDPV-UHFFFAOYSA-N 3,4-dihydroxy-6-[4-hydroxy-5-(hydroxymethyl)-2-(sulfooxymethyl)oxolan-3-yl]oxy-5-sulfooxyoxane-2-carboxylic acid Chemical compound OC1C(CO)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(O)C(C(O)=O)O1 FAMLQSCGIQGDPV-UHFFFAOYSA-N 0.000 description 10
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 10
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 10
• 230000027455 binding Effects 0.000 description 10
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 10
• 238000010511 deprotection reaction Methods 0.000 description 10
• 229910052763 palladium Inorganic materials 0.000 description 10
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 9
• 239000012528 membrane Substances 0.000 description 9
• 229960002715 nicotine Drugs 0.000 description 9
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 9
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 8
• 239000003446 ligand Substances 0.000 description 8
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 7
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 7
• 235000011056 potassium acetate Nutrition 0.000 description 7
• 230000008569 process Effects 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-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
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 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 6
• 239000000706 filtrate Substances 0.000 description 6
• AAZBSOLTQSSLMB-UHFFFAOYSA-N n-(methoxymethyl)cyclopent-3-ene-1-carboxamide Chemical compound COCNC(=O)C1CC=CC1 AAZBSOLTQSSLMB-UHFFFAOYSA-N 0.000 description 6
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 6
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 6
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
• 150000001408 amides Chemical class 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 150000001450 anions Chemical class 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 125000001309 chloro group Chemical group Cl* 0.000 description 5
• RMCWOSMNBMMDPL-UHFFFAOYSA-N cyclopent-3-ene-1-carbaldehyde Chemical compound O=CC1CC=CC1 RMCWOSMNBMMDPL-UHFFFAOYSA-N 0.000 description 5
• 239000012458 free base Substances 0.000 description 5
• 239000012442 inert solvent Substances 0.000 description 5
• CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 5
• 238000001465 metallisation Methods 0.000 description 5
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 5
• 239000012285 osmium tetroxide Substances 0.000 description 5
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 5
• 239000002798 polar solvent Substances 0.000 description 5
• 238000001953 recrystallisation Methods 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
• 238000010561 standard procedure Methods 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 5
• FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 5
• 101150041968 CDC13 gene Proteins 0.000 description 4
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 4
• 210000004556 brain Anatomy 0.000 description 4
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
• 239000012954 diazonium Substances 0.000 description 4
• 150000001989 diazonium salts Chemical class 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• 239000003480 eluent Substances 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 229910052759 nickel Inorganic materials 0.000 description 4
• 150000002828 nitro derivatives Chemical class 0.000 description 4
• 238000006268 reductive amination reaction Methods 0.000 description 4
• 239000012265 solid product Substances 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 150000003512 tertiary amines Chemical class 0.000 description 4
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
• 239000003981 vehicle Substances 0.000 description 4
• 150000003970 1-benzazocines Chemical class 0.000 description 3
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
• 206010009900 Colitis ulcerative Diseases 0.000 description 3
• 208000011231 Crohn disease Diseases 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-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
• 239000002841 Lewis acid Substances 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 208000006311 Pyoderma Diseases 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 description 3
• 150000008065 acid anhydrides Chemical class 0.000 description 3
• 239000003513 alkali Substances 0.000 description 3
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 3
• 229910021529 ammonia Inorganic materials 0.000 description 3
• 239000012736 aqueous medium Substances 0.000 description 3
• 239000012131 assay buffer Substances 0.000 description 3
• 229940125717 barbiturate Drugs 0.000 description 3
• 229940049706 benzodiazepine Drugs 0.000 description 3
• 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 3
• 230000003197 catalytic effect Effects 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 239000003638 chemical reducing agent Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 229960003920 cocaine Drugs 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• 125000006165 cyclic alkyl group Chemical group 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
• 150000007517 lewis acids Chemical class 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• 230000001537 neural effect Effects 0.000 description 3
• 229910017604 nitric acid Inorganic materials 0.000 description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
• 150000002923 oximes Chemical class 0.000 description 3
• 150000002989 phenols Chemical class 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• 230000000750 progressive effect Effects 0.000 description 3
• ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 238000007363 ring formation reaction Methods 0.000 description 3
• 239000001632 sodium acetate Substances 0.000 description 3
• 235000017281 sodium acetate Nutrition 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 235000017550 sodium carbonate Nutrition 0.000 description 3
• 239000011593 sulfur Chemical group 0.000 description 3
• 238000012360 testing method 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
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
• DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 2
• 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 2
• DOKIZZLGXWADTH-UHFFFAOYSA-N 3-(cyclopent-3-en-1-ylmethyl)-1,2-difluoro-4-methoxybenzene Chemical compound COC1=CC=C(F)C(F)=C1CC1CC=CC1 DOKIZZLGXWADTH-UHFFFAOYSA-N 0.000 description 2
• ASHGTJPOSUFTGB-UHFFFAOYSA-N 3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1 ASHGTJPOSUFTGB-UHFFFAOYSA-N 0.000 description 2
• ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
• VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 208000028698 Cognitive impairment Diseases 0.000 description 2
• ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 2
• 238000005618 Fries rearrangement reaction Methods 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
• 108010025020 Nerve Growth Factor Proteins 0.000 description 2
• 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 2
• 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 2
• 206010033799 Paralysis Diseases 0.000 description 2
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 208000030886 Traumatic Brain injury Diseases 0.000 description 2
• ZVXBDWFXGJUTFZ-UHFFFAOYSA-N [2-(cyclopent-3-en-1-ylmethyl)-3,4-difluorophenyl] trifluoromethanesulfonate Chemical compound FC1=CC=C(OS(=O)(=O)C(F)(F)F)C(CC2CC=CC2)=C1F ZVXBDWFXGJUTFZ-UHFFFAOYSA-N 0.000 description 2
• BFEWVVDVMGINNF-UHFFFAOYSA-N [2-(cyclopent-3-ene-1-carbonyl)-3-methoxyphenyl] trifluoromethanesulfonate Chemical compound COC1=CC=CC(OS(=O)(=O)C(F)(F)F)=C1C(=O)C1CC=CC1 BFEWVVDVMGINNF-UHFFFAOYSA-N 0.000 description 2
• HBVXGDQQAHMWNB-UHFFFAOYSA-N [2-(cyclopent-3-ene-1-carbonyl)-4-methoxyphenyl] trifluoromethanesulfonate Chemical compound COC1=CC=C(OS(=O)(=O)C(F)(F)F)C(C(=O)C2CC=CC2)=C1 HBVXGDQQAHMWNB-UHFFFAOYSA-N 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
• 150000008041 alkali metal carbonates Chemical class 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• 150000003939 benzylamines Chemical class 0.000 description 2
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
• 150000001642 boronic acid derivatives Chemical class 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 230000006315 carbonylation Effects 0.000 description 2
• 238000005810 carbonylation reaction Methods 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• XHNVQRLSWKLQMW-UHFFFAOYSA-N cyclopent-3-en-1-yl-(2,3-difluoro-6-methoxyphenyl)methanol Chemical compound COC1=CC=C(F)C(F)=C1C(O)C1CC=CC1 XHNVQRLSWKLQMW-UHFFFAOYSA-N 0.000 description 2
• JVGLWFQWWWOGMP-UHFFFAOYSA-N cyclopent-3-en-1-yl-(2,5-dimethoxyphenyl)methanone Chemical compound COC1=CC=C(OC)C(C(=O)C2CC=CC2)=C1 JVGLWFQWWWOGMP-UHFFFAOYSA-N 0.000 description 2
• XIQKURBYPSNQHJ-UHFFFAOYSA-N cyclopent-3-en-1-yl-(2,6-dimethoxyphenyl)methanone Chemical compound COC1=CC=CC(OC)=C1C(=O)C1CC=CC1 XIQKURBYPSNQHJ-UHFFFAOYSA-N 0.000 description 2
• WPFKBLXPAXCNAA-UHFFFAOYSA-N cyclopent-3-en-1-yl-(2-hydroxy-5-methoxyphenyl)methanone Chemical compound COC1=CC=C(O)C(C(=O)C2CC=CC2)=C1 WPFKBLXPAXCNAA-UHFFFAOYSA-N 0.000 description 2
• MEPVEXYHDOILDX-UHFFFAOYSA-N cyclopent-3-en-1-yl-(2-hydroxy-6-methoxyphenyl)methanone Chemical compound COC1=CC=CC(O)=C1C(=O)C1CC=CC1 MEPVEXYHDOILDX-UHFFFAOYSA-N 0.000 description 2
• XVSYDLITVYBCBD-UHFFFAOYSA-N cyclopent-3-ene-1-carboxylic acid Chemical compound OC(=O)C1CC=CC1 XVSYDLITVYBCBD-UHFFFAOYSA-N 0.000 description 2
• NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
• 238000004821 distillation Methods 0.000 description 2
• 150000002170 ethers Chemical class 0.000 description 2
• 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 150000004795 grignard reagents Chemical class 0.000 description 2
• 150000004820 halides Chemical class 0.000 description 2
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 229910052500 inorganic mineral Inorganic materials 0.000 description 2
• 235000015110 jellies Nutrition 0.000 description 2
• 150000002576 ketones Chemical class 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 229910052744 lithium Inorganic materials 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
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• 235000010755 mineral Nutrition 0.000 description 2
• 239000011707 mineral Substances 0.000 description 2
• 230000009871 nonspecific binding Effects 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 229940127240 opiate Drugs 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 238000007248 oxidative elimination reaction Methods 0.000 description 2
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 238000006798 ring closing metathesis reaction Methods 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 2
• 239000003772 serotonin uptake inhibitor Substances 0.000 description 2
• 238000007086 side reaction Methods 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 239000002002 slurry Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
• 125000003831 tetrazolyl group Chemical group 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• 229920002554 vinyl polymer Polymers 0.000 description 2
• 238000010792 warming Methods 0.000 description 2
• 239000008096 xylene Substances 0.000 description 2
• 150000003738 xylenes Chemical class 0.000 description 2
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
• 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
• VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
• 125000003161 (C1-C6) alkylene group Chemical group 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
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
• YBBLOADPFWKNGS-UHFFFAOYSA-N 1,1-dimethylurea Chemical compound CN(C)C(N)=O YBBLOADPFWKNGS-UHFFFAOYSA-N 0.000 description 1
• KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
• KFUSEUYYWQURPO-UHFFFAOYSA-N 1,2-dichloroethene Chemical compound ClC=CCl KFUSEUYYWQURPO-UHFFFAOYSA-N 0.000 description 1
• 125000000355 1,3-benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
• NTOIKDYVJIWVSU-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methylbenzoyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C1=CC=C(C)C=C1 NTOIKDYVJIWVSU-UHFFFAOYSA-N 0.000 description 1
• HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 description 1
• TXLHNFOLHRXMAU-UHFFFAOYSA-N 2-(4-benzylphenoxy)-n,n-diethylethanamine;hydron;chloride Chemical compound Cl.C1=CC(OCCN(CC)CC)=CC=C1CC1=CC=CC=C1 TXLHNFOLHRXMAU-UHFFFAOYSA-N 0.000 description 1
• UTXKFUOTSBIFCO-UHFFFAOYSA-N 2-(cyclopent-3-en-1-ylmethyl)-3,4-difluorophenol Chemical compound OC1=CC=C(F)C(F)=C1CC1CC=CC1 UTXKFUOTSBIFCO-UHFFFAOYSA-N 0.000 description 1
• WMWSRFWQGCHVHE-UHFFFAOYSA-N 2-(cyclopent-3-en-1-ylmethyl)-5-methoxyphenol Chemical compound OC1=CC(OC)=CC=C1CC1CC=CC1 WMWSRFWQGCHVHE-UHFFFAOYSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• HTFXWAOSQODIBI-UHFFFAOYSA-N 2-benzyl-1,3-dihydropyrrolo[3,4-c]pyridine Chemical compound C1C2=CC=NC=C2CN1CC1=CC=CC=C1 HTFXWAOSQODIBI-UHFFFAOYSA-N 0.000 description 1
• DWCGNRKFLRLWCJ-UHFFFAOYSA-N 2-bromo-1,4-dimethoxybenzene Chemical compound COC1=CC=C(OC)C(Br)=C1 DWCGNRKFLRLWCJ-UHFFFAOYSA-N 0.000 description 1
• JIQXVIJARQLCOY-UHFFFAOYSA-N 2-bromo-4-fluoro-1-methoxybenzene Chemical compound COC1=CC=C(F)C=C1Br JIQXVIJARQLCOY-UHFFFAOYSA-N 0.000 description 1
• BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 1
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
• OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
• NYSXBFLEQUHZNB-UHFFFAOYSA-N 5-bromo-6-methoxy-1,3-benzodioxole Chemical compound C1=C(Br)C(OC)=CC2=C1OCO2 NYSXBFLEQUHZNB-UHFFFAOYSA-N 0.000 description 1
• IAFXUBMJZVEXDZ-UHFFFAOYSA-N 6-methoxytricyclo[7.2.1.02,7]dodeca-2(7),3,5-triene-10,11-diol Chemical compound OC1C(O)C2CC1CC1=C2C=CC=C1OC IAFXUBMJZVEXDZ-UHFFFAOYSA-N 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 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 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
• 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
• DJHGAFSJWGLOIV-UHFFFAOYSA-K Arsenate3- Chemical compound [O-][As]([O-])([O-])=O DJHGAFSJWGLOIV-UHFFFAOYSA-K 0.000 description 1
• 238000006220 Baeyer-Villiger oxidation reaction Methods 0.000 description 1
• KLYCPFXDDDMZNQ-UHFFFAOYSA-N Benzyne Chemical compound C1=CC#CC=C1 KLYCPFXDDDMZNQ-UHFFFAOYSA-N 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
• 108010009685 Cholinergic Receptors Proteins 0.000 description 1
• SCEUMVXKTWKOCD-UHFFFAOYSA-N Cl.C1NCC2CC3=C(F)C(F)=CC=C3C1C2 Chemical compound Cl.C1NCC2CC3=C(F)C(F)=CC=C3C1C2 SCEUMVXKTWKOCD-UHFFFAOYSA-N 0.000 description 1
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 239000007818 Grignard reagent Substances 0.000 description 1
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 1
• 239000003810 Jones reagent Substances 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 102000018697 Membrane Proteins Human genes 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 241000872931 Myoporum sandwicense Species 0.000 description 1
• UGJBHEZMOKVTIM-UHFFFAOYSA-N N-formylglycine Chemical compound OC(=O)CNC=O UGJBHEZMOKVTIM-UHFFFAOYSA-N 0.000 description 1
• 102000007072 Nerve Growth Factors Human genes 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 241000218657 Picea Species 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
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 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 1
• 238000006069 Suzuki reaction reaction Methods 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
• 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
• 238000005644 Wolff-Kishner reduction reaction Methods 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• CATITEQSSYWKFN-UHFFFAOYSA-N [2-(cyclopent-3-en-1-ylmethyl)-5-methoxyphenyl] trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC(OC)=CC=C1CC1CC=CC1 CATITEQSSYWKFN-UHFFFAOYSA-N 0.000 description 1
• 159000000021 acetate salts Chemical class 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 102000034337 acetylcholine receptors Human genes 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
• 150000008046 alkali metal hydrides Chemical class 0.000 description 1
• 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
• 125000005262 alkoxyamine group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 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
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 229940035676 analgesics Drugs 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 239000000730 antalgic agent Substances 0.000 description 1
• 230000001430 anti-depressive effect Effects 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 239000000935 antidepressant agent Substances 0.000 description 1
• 229940005513 antidepressants Drugs 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000012223 aqueous fraction Substances 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 229940000489 arsenate Drugs 0.000 description 1
• 150000001543 aryl boronic acids Chemical class 0.000 description 1
• 238000006254 arylation reaction Methods 0.000 description 1
• 238000000429 assembly Methods 0.000 description 1
• 230000000712 assembly Effects 0.000 description 1
• 150000001541 aziridines Chemical class 0.000 description 1
• 230000003542 behavioural effect Effects 0.000 description 1
• 150000008316 benzisoxazoles Chemical class 0.000 description 1
• 125000001743 benzylic group Chemical group 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 229910000085 borane Inorganic materials 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• 239000005388 borosilicate glass Substances 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 150000001649 bromium compounds Chemical class 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• 239000001273 butane Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 229960003563 calcium carbonate Drugs 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 150000005323 carbonate salts Chemical class 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
• 230000001713 cholinergic effect Effects 0.000 description 1
• 230000006949 cholinergic function Effects 0.000 description 1
• KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
• 230000001149 cognitive effect Effects 0.000 description 1
• 239000002475 cognitive enhancer Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000006482 condensation reaction Methods 0.000 description 1
• 235000009508 confectionery Nutrition 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 229940045803 cuprous chloride Drugs 0.000 description 1
• 238000007872 degassing Methods 0.000 description 1
• 239000008367 deionised water Substances 0.000 description 1
• 229910021641 deionized water Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
• OJKBCQOJVMAHDX-UHFFFAOYSA-N diethyl(pyridin-3-yl)borane Chemical compound CCB(CC)C1=CC=CN=C1 OJKBCQOJVMAHDX-UHFFFAOYSA-N 0.000 description 1
• SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• 150000002009 diols Chemical class 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• HAXUFHXMBCWDPM-UHFFFAOYSA-N fluoromethoxybenzene Chemical compound FCOC1=CC=CC=C1 HAXUFHXMBCWDPM-UHFFFAOYSA-N 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• IYWCBYFJFZCCGV-UHFFFAOYSA-N formamide;hydrate Chemical compound O.NC=O IYWCBYFJFZCCGV-UHFFFAOYSA-N 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 238000003306 harvesting Methods 0.000 description 1
• ZYCMDWDFIQDPLP-UHFFFAOYSA-N hbr bromine Chemical compound Br.Br ZYCMDWDFIQDPLP-UHFFFAOYSA-N 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• LFKYBJLFJOOKAE-UHFFFAOYSA-N imidazol-2-ylidenemethanone Chemical compound O=C=C1N=CC=N1 LFKYBJLFJOOKAE-UHFFFAOYSA-N 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 150000004694 iodide salts Chemical class 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• CBEQRNSPHCCXSH-UHFFFAOYSA-N iodine monobromide Chemical compound IBr CBEQRNSPHCCXSH-UHFFFAOYSA-N 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 229910000103 lithium hydride Inorganic materials 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 150000005217 methyl ethers Chemical class 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 239000000472 muscarinic agonist Substances 0.000 description 1
• 230000003551 muscarinic effect Effects 0.000 description 1
• KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
• IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical group CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
• DYFFAVRFJWYYQO-UHFFFAOYSA-N n-methyl-n-phenylaniline Chemical compound C=1C=CC=CC=1N(C)C1=CC=CC=C1 DYFFAVRFJWYYQO-UHFFFAOYSA-N 0.000 description 1
• OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
• 239000003900 neurotrophic factor Substances 0.000 description 1
• 238000006396 nitration reaction Methods 0.000 description 1
• 229910017464 nitrogen compound Inorganic materials 0.000 description 1
• 150000002830 nitrogen compounds Chemical class 0.000 description 1
• 229940073020 nitrol Drugs 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 230000000269 nucleophilic effect Effects 0.000 description 1
• 229940005483 opioid analgesics Drugs 0.000 description 1
• 238000007122 ortho-metalation reaction Methods 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229920001223 polyethylene glycol Polymers 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
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 235000011181 potassium carbonates Nutrition 0.000 description 1
• 239000000276 potassium ferrocyanide Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 239000001294 propane Substances 0.000 description 1
• 125000004076 pyridyl 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
• 150000003254 radicals Chemical class 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 238000005204 segregation Methods 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 229960001790 sodium citrate Drugs 0.000 description 1
• 235000011083 sodium citrates Nutrition 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000012289 standard assay Methods 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000006188 syrup Substances 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
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid 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
• 150000003509 tertiary alcohols Chemical class 0.000 description 1
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
• XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 235000019505 tobacco product Nutrition 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
• COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
• PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1