UA74813C2 - Azapolycyclic compounds condensated with aryl - Google Patents

Azapolycyclic compounds condensated with aryl Download PDF

Info

Publication number: UA74813C2
Authority: UA; Ukraine
Prior art keywords: dodeca; diazatetracyclo; triene; azatricyclo; tetraene
Prior art date: 2000-02-25

Application number

UA2002075792A

Other languages

English (en)

Ukrainian (uk)

Inventor

Paige Roanne Palmer Brooks

Original Assignee

Pfizer Prod Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-02-25

Filing date

2001-08-02

Publication date

2006-02-15

2001-08-02 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2006-02-15 Publication of UA74813C2 publication Critical patent/UA74813C2/uk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 288
125000003118 aryl group Chemical group 0.000 title description 15
238000000034 method Methods 0.000 claims abstract description 125
150000003839 salts Chemical class 0.000 claims abstract description 36
238000011282 treatment Methods 0.000 claims abstract description 15
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
239000000203 mixture Substances 0.000 claims description 123
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 58
230000009467 reduction Effects 0.000 claims description 22
208000024827 Alzheimer disease Diseases 0.000 claims description 14
239000000126 substance Substances 0.000 claims description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 12
206010015037 epilepsy Diseases 0.000 claims description 12
229960002715 nicotine Drugs 0.000 claims description 12
208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 11
208000002193 Pain Diseases 0.000 claims description 11
ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 11
208000035475 disorder Diseases 0.000 claims description 11
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 10
241000208125 Nicotiana Species 0.000 claims description 10
235000002637 Nicotiana tabacum Nutrition 0.000 claims description 10
208000030886 Traumatic Brain injury Diseases 0.000 claims description 10
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 10
230000009529 traumatic brain injury Effects 0.000 claims description 10
206010010904 Convulsion Diseases 0.000 claims description 9
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 8
208000023105 Huntington disease Diseases 0.000 claims description 8
206010057852 Nicotine dependence Diseases 0.000 claims description 8
208000018737 Parkinson disease Diseases 0.000 claims description 8
208000025569 Tobacco Use disease Diseases 0.000 claims description 8
208000010877 cognitive disease Diseases 0.000 claims description 8
208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 7
230000007000 age related cognitive decline Effects 0.000 claims description 7
208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 7
208000032841 Bulimia Diseases 0.000 claims description 6
206010006550 Bulimia nervosa Diseases 0.000 claims description 6
206010009900 Colitis ulcerative Diseases 0.000 claims description 6
208000011231 Crohn disease Diseases 0.000 claims description 6
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 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
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
208000019695 Migraine disease Diseases 0.000 claims description 6
208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 6
208000028017 Psychotic disease Diseases 0.000 claims description 6
206010039966 Senile dementia Diseases 0.000 claims description 6
208000000323 Tourette Syndrome Diseases 0.000 claims description 6
208000016620 Tourette disease Diseases 0.000 claims description 6
208000025865 Ulcer Diseases 0.000 claims description 6
201000006704 Ulcerative Colitis Diseases 0.000 claims description 6
201000004810 Vascular dementia Diseases 0.000 claims description 6
208000022531 anorexia Diseases 0.000 claims description 6
206010003119 arrhythmia Diseases 0.000 claims description 6
229940125717 barbiturate Drugs 0.000 claims description 6
229940049706 benzodiazepine Drugs 0.000 claims description 6
229960003920 cocaine Drugs 0.000 claims description 6
206010061428 decreased appetite Diseases 0.000 claims description 6
206010013932 dyslexia Diseases 0.000 claims description 6
210000004211 gastric acid Anatomy 0.000 claims description 6
231100000869 headache Toxicity 0.000 claims description 6
208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
206010027599 migraine Diseases 0.000 claims description 6
229940005483 opioid analgesics Drugs 0.000 claims description 6
208000028591 pheochromocytoma Diseases 0.000 claims description 6
201000002212 progressive supranuclear palsy Diseases 0.000 claims description 6
201000000980 schizophrenia Diseases 0.000 claims description 6
229940124530 sulfonamide Drugs 0.000 claims description 6
235000019505 tobacco product Nutrition 0.000 claims description 6
231100000397 ulcer Toxicity 0.000 claims description 6
208000019901 Anxiety disease Diseases 0.000 claims description 5
206010003805 Autism Diseases 0.000 claims description 5
208000020706 Autistic disease Diseases 0.000 claims description 5
208000020925 Bipolar disease Diseases 0.000 claims description 5
208000000094 Chronic Pain Diseases 0.000 claims description 5
206010020772 Hypertension Diseases 0.000 claims description 5
206010025476 Malabsorption Diseases 0.000 claims description 5
208000004155 Malabsorption Syndromes Diseases 0.000 claims description 5
206010043118 Tardive Dyskinesia Diseases 0.000 claims description 5
206010047139 Vasoconstriction Diseases 0.000 claims description 5
230000003187 abdominal effect Effects 0.000 claims description 5
208000005298 acute pain Diseases 0.000 claims description 5
230000036506 anxiety Effects 0.000 claims description 5
208000019906 panic disease Diseases 0.000 claims description 5
230000001603 reducing effect Effects 0.000 claims description 5
208000019116 sleep disease Diseases 0.000 claims description 5
230000025033 vasoconstriction Effects 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 4
201000002849 spasmodic dystonia Diseases 0.000 claims description 4
230000009931 harmful effect Effects 0.000 claims description 3
201000010099 disease Diseases 0.000 claims description 2
208000008589 Obesity Diseases 0.000 claims 2
150000001557 benzodiazepines Chemical class 0.000 claims 2
208000009326 ileitis Diseases 0.000 claims 2
235000020824 obesity Nutrition 0.000 claims 2
208000009954 pyoderma gangrenosum Diseases 0.000 claims 2
IFPMZBBHBZQTOV-UHFFFAOYSA-N 1,3,5-trinitro-2-(2,4,6-trinitrophenyl)-4-[2,4,6-trinitro-3-(2,4,6-trinitrophenyl)phenyl]benzene Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C(C=2C(=C(C=3C(=CC(=CC=3[N+]([O-])=O)[N+]([O-])=O)[N+]([O-])=O)C(=CC=2[N+]([O-])=O)[N+]([O-])=O)[N+]([O-])=O)=C1[N+]([O-])=O IFPMZBBHBZQTOV-UHFFFAOYSA-N 0.000 claims 1
208000014094 Dystonic disease Diseases 0.000 claims 1
208000010118 dystonia Diseases 0.000 claims 1
230000001052 transient effect Effects 0.000 claims 1
229960001124 trientine Drugs 0.000 claims 1
230000015572 biosynthetic process Effects 0.000 abstract description 14
238000003786 synthesis reaction Methods 0.000 abstract description 11
239000000543 intermediate Substances 0.000 abstract description 4
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 354
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 352
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 145
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 90
239000000243 solution Substances 0.000 description 83
229910001868 water Inorganic materials 0.000 description 80
239000003921 oil Substances 0.000 description 79
235000019198 oils Nutrition 0.000 description 79
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
125000000217 alkyl group Chemical group 0.000 description 72
238000006243 chemical reaction Methods 0.000 description 72
239000000047 product Substances 0.000 description 67
229920006395 saturated elastomer Polymers 0.000 description 67
239000011541 reaction mixture Substances 0.000 description 57
239000007864 aqueous solution Substances 0.000 description 55
239000010410 layer Substances 0.000 description 55
239000007787 solid Substances 0.000 description 54
102100033891 Arylsulfatase I Human genes 0.000 description 51
101000925544 Homo sapiens Arylsulfatase I Proteins 0.000 description 51
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 48
239000012044 organic layer Substances 0.000 description 47
238000002844 melting Methods 0.000 description 45
230000008018 melting Effects 0.000 description 45
229910052757 nitrogen Inorganic materials 0.000 description 44
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 40
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
125000006239 protecting group Chemical group 0.000 description 33
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
-1 no -trogroup Chemical group 0.000 description 30
238000010992 reflux Methods 0.000 description 30
125000004435 hydrogen atom Chemical group [H]* 0.000 description 29
229920000742 Cotton Polymers 0.000 description 27
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
239000000741 silica gel Substances 0.000 description 26
229910002027 silica gel Inorganic materials 0.000 description 26
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
238000001914 filtration Methods 0.000 description 23
125000004433 nitrogen atom Chemical group N* 0.000 description 23
239000002904 solvent Substances 0.000 description 23
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 22
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 20
238000006722 reduction reaction Methods 0.000 description 20
238000002290 gas chromatography-mass spectrometry Methods 0.000 description 19
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
229910052739 hydrogen Inorganic materials 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
239000002253 acid Substances 0.000 description 17
239000001257 hydrogen Substances 0.000 description 17
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 17
206010012335 Dependence Diseases 0.000 description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 16
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
238000004458 analytical method Methods 0.000 description 15
238000004587 chromatography analysis Methods 0.000 description 15
125000001153 fluoro group Chemical group F* 0.000 description 15
238000003756 stirring Methods 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical group OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
125000003277 amino group Chemical group 0.000 description 14
238000009835 boiling Methods 0.000 description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
125000001424 substituent group Chemical group 0.000 description 14
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 14
239000002585 base Substances 0.000 description 13
239000003054 catalyst Substances 0.000 description 13
125000005843 halogen group Chemical group 0.000 description 13
ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 12
238000010511 deprotection reaction Methods 0.000 description 12
229910052731 fluorine Inorganic materials 0.000 description 12
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
229910052770 Uranium Inorganic materials 0.000 description 11
229910052799 carbon Inorganic materials 0.000 description 11
238000005984 hydrogenation reaction Methods 0.000 description 11
239000011780 sodium chloride Substances 0.000 description 11
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 10
125000004093 cyano group Chemical group *C#N 0.000 description 10
229910052763 palladium Inorganic materials 0.000 description 10
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
125000003342 alkenyl group Chemical group 0.000 description 9
239000011737 fluorine Substances 0.000 description 9
238000010438 heat treatment Methods 0.000 description 9
229910052740 iodine Inorganic materials 0.000 description 9
239000000463 material Substances 0.000 description 9
239000012528 membrane Substances 0.000 description 9
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 9
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
241000124008 Mammalia Species 0.000 description 8
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
125000004432 carbon atom Chemical group C* 0.000 description 8
239000003153 chemical reaction reagent Substances 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
229910052760 oxygen Inorganic materials 0.000 description 8
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 8
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 7
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
229910052783 alkali metal Inorganic materials 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
230000027455 binding Effects 0.000 description 7
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 7
239000012458 free base Substances 0.000 description 7
125000001072 heteroaryl group Chemical group 0.000 description 7
239000011630 iodine Substances 0.000 description 7
229910052697 platinum Inorganic materials 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
239000000377 silicon dioxide Substances 0.000 description 7
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
VQMXWPLTZBKNEH-UHFFFAOYSA-N 1,3-difluoro-2-iodobenzene Chemical compound FC1=CC=CC(F)=C1I VQMXWPLTZBKNEH-UHFFFAOYSA-N 0.000 description 6
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
239000003377 acid catalyst Substances 0.000 description 6
150000001340 alkali metals Chemical class 0.000 description 6
125000003282 alkyl amino group Chemical group 0.000 description 6
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
239000000872 buffer Substances 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000001816 cooling Methods 0.000 description 6
238000000354 decomposition reaction Methods 0.000 description 6
235000019253 formic acid Nutrition 0.000 description 6
229910052736 halogen Inorganic materials 0.000 description 6
229940098779 methanesulfonic acid Drugs 0.000 description 6
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
239000001301 oxygen Substances 0.000 description 6
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
239000000843 powder Substances 0.000 description 6
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 6
239000007858 starting material Substances 0.000 description 6
238000012360 testing method Methods 0.000 description 6
UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 6
229910015900 BF3 Inorganic materials 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 5
241000700159 Rattus Species 0.000 description 5
229920002472 Starch Polymers 0.000 description 5
229910052784 alkaline earth metal Inorganic materials 0.000 description 5
125000000304 alkynyl group Chemical group 0.000 description 5
239000012298 atmosphere Substances 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
125000002619 bicyclic group Chemical group 0.000 description 5
210000004556 brain Anatomy 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
125000001309 chloro group Chemical group Cl* 0.000 description 5
239000013078 crystal Substances 0.000 description 5
239000008240 homogeneous mixture Substances 0.000 description 5
XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 5
239000002798 polar solvent Substances 0.000 description 5
239000012047 saturated solution Substances 0.000 description 5
239000012279 sodium borohydride Substances 0.000 description 5
229910000033 sodium borohydride Inorganic materials 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
239000008107 starch Substances 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
239000012258 stirred mixture Substances 0.000 description 5
125000004434 sulfur atom Chemical group 0.000 description 5
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 4
108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 4
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
150000001342 alkaline earth metals Chemical class 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
150000001721 carbon Chemical group 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
LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
239000011777 magnesium Substances 0.000 description 4
229910052749 magnesium Inorganic materials 0.000 description 4
150000004702 methyl esters Chemical class 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
125000002950 monocyclic group Chemical group 0.000 description 4
229910017604 nitric acid Inorganic materials 0.000 description 4
WURFKUQACINBSI-UHFFFAOYSA-M ozonide Chemical compound [O]O[O-] WURFKUQACINBSI-UHFFFAOYSA-M 0.000 description 4
238000005949 ozonolysis reaction Methods 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
238000011160 research Methods 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
238000000859 sublimation Methods 0.000 description 4
230000008022 sublimation Effects 0.000 description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 4
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 4
239000008096 xylene Substances 0.000 description 4
150000003738 xylenes Chemical class 0.000 description 4
OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 description 3
HXLJFMRZKCSTQD-UHFFFAOYSA-N 3-oxoindane-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)CC(=O)C2=C1 HXLJFMRZKCSTQD-UHFFFAOYSA-N 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
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
206010008748 Chorea Diseases 0.000 description 3
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 3
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
229910004373 HOAc Inorganic materials 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
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
150000008065 acid anhydrides Chemical class 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
239000000969 carrier Substances 0.000 description 3
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 3
208000012601 choreatic disease Diseases 0.000 description 3
208000035127 classic pyoderma gangrenosum Diseases 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
ANJTVLIZGCUXLD-DTWKUNHWSA-N cytisine Chemical compound C1NC[C@H]2CN3C(=O)C=CC=C3[C@@H]1C2 ANJTVLIZGCUXLD-DTWKUNHWSA-N 0.000 description 3
238000001035 drying Methods 0.000 description 3
239000000284 extract Substances 0.000 description 3
150000002367 halogens Chemical class 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
235000012907 honey Nutrition 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
230000000977 initiatory effect Effects 0.000 description 3
238000002955 isolation Methods 0.000 description 3
150000007517 lewis acids Chemical class 0.000 description 3
230000001537 neural effect Effects 0.000 description 3
238000006396 nitration reaction Methods 0.000 description 3
235000006408 oxalic acid Nutrition 0.000 description 3
235000011056 potassium acetate Nutrition 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
239000011734 sodium Substances 0.000 description 3
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
230000009870 specific binding Effects 0.000 description 3
229910052717 sulfur Inorganic materials 0.000 description 3
238000010626 work up procedure Methods 0.000 description 3
DIVNUTGTTIRPQA-UHFFFAOYSA-N (3,4-dimethoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1OC DIVNUTGTTIRPQA-UHFFFAOYSA-N 0.000 description 2
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 2
UEMGWPRHOOEKTA-UHFFFAOYSA-N 1,3-difluorobenzene Chemical compound FC1=CC=CC(F)=C1 UEMGWPRHOOEKTA-UHFFFAOYSA-N 0.000 description 2
IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 2
IPWBFGUBXWMIPR-UHFFFAOYSA-N 1-bromo-2-fluorobenzene Chemical compound FC1=CC=CC=C1Br IPWBFGUBXWMIPR-UHFFFAOYSA-N 0.000 description 2
DSPXASHHKFVPCL-UHFFFAOYSA-N 1-isocyanocyclohexene Chemical compound [C-]#[N+]C1=CCCCC1 DSPXASHHKFVPCL-UHFFFAOYSA-N 0.000 description 2
UJODSSUMBIFQRE-UHFFFAOYSA-N 10-azatricyclo[6.3.1.02,7]dodeca-2,4,6-triene 4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.C12=CC=CC=C2C2CC1CNC2 UJODSSUMBIFQRE-UHFFFAOYSA-N 0.000 description 2
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 2
XDIAMRVROCPPBK-UHFFFAOYSA-N 2,2-dimethylpropan-1-amine Chemical compound CC(C)(C)CN XDIAMRVROCPPBK-UHFFFAOYSA-N 0.000 description 2
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
XCRCSPKQEDMVBO-UHFFFAOYSA-N 2-bromo-1,4-difluorobenzene Chemical compound FC1=CC=C(F)C(Br)=C1 XCRCSPKQEDMVBO-UHFFFAOYSA-N 0.000 description 2
KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
KUSCNUBEMOJEPO-UHFFFAOYSA-N 3-cyano-3-trimethylsilyloxy-1,2-dihydroindene-1-carboxylic acid Chemical compound C1=CC=C2C(O[Si](C)(C)C)(C#N)CC(C(O)=O)C2=C1 KUSCNUBEMOJEPO-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
STNJBCKSHOAVAJ-UHFFFAOYSA-N Methacrolein Chemical compound CC(=C)C=O STNJBCKSHOAVAJ-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
229910004298 SiO 2 Inorganic materials 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
230000001430 anti-depressive effect Effects 0.000 description 2
239000000935 antidepressant agent Substances 0.000 description 2
229940005513 antidepressants Drugs 0.000 description 2
239000012736 aqueous medium Substances 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
125000005002 aryl methyl group Chemical group 0.000 description 2
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 2
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
239000012267 brine Substances 0.000 description 2
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
235000014121 butter Nutrition 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
239000003245 coal Substances 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
239000013058 crude material Substances 0.000 description 2
NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
150000002168 ethanoic acid esters Chemical class 0.000 description 2
239000000945 filler Substances 0.000 description 2
239000007789 gas Substances 0.000 description 2
239000000499 gel Substances 0.000 description 2
ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
150000002431 hydrogen Chemical class 0.000 description 2
125000002883 imidazolyl group Chemical group 0.000 description 2
239000012535 impurity Substances 0.000 description 2
208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 2
238000011534 incubation Methods 0.000 description 2
150000004694 iodide salts Chemical class 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
229940011051 isopropyl acetate Drugs 0.000 description 2
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
235000015110 jellies Nutrition 0.000 description 2
150000003951 lactams Chemical group 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
229910003002 lithium salt Inorganic materials 0.000 description 2
159000000002 lithium salts Chemical class 0.000 description 2
239000007937 lozenge 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
238000004519 manufacturing process Methods 0.000 description 2
KUMXXUZXCQZORN-UHFFFAOYSA-N methyl 3-cyano-3-trimethylsilyloxy-1,2-dihydroindene-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)CC(O[Si](C)(C)C)(C#N)C2=C1 KUMXXUZXCQZORN-UHFFFAOYSA-N 0.000 description 2
UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
238000002156 mixing Methods 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
239000002674 ointment Substances 0.000 description 2
239000012285 osmium tetroxide Substances 0.000 description 2
229910000489 osmium tetroxide Inorganic materials 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
125000004430 oxygen atom Chemical group O* 0.000 description 2
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 2
239000006072 paste Substances 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
229910052698 phosphorus Inorganic materials 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
230000008569 process Effects 0.000 description 2
238000012545 processing Methods 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
230000001681 protective effect Effects 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000006268 reductive amination 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
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
235000012239 silicon dioxide Nutrition 0.000 description 2
235000010288 sodium nitrite Nutrition 0.000 description 2
239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 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
150000003512 tertiary amines Chemical class 0.000 description 2
125000003831 tetrazolyl group Chemical group 0.000 description 2
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
239000011135 tin Substances 0.000 description 2
230000009466 transformation Effects 0.000 description 2
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 2
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
238000001665 trituration Methods 0.000 description 2
238000005406 washing Methods 0.000 description 2
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-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
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
125000006530 (C4-C6) alkyl 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
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
125000000355 1,3-benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
IEGYXSAHRKJELM-UHFFFAOYSA-N 1,4-dihydro-1,4-methanonaphthalene Chemical compound C12=CC=CC=C2C2CC1C=C2 IEGYXSAHRKJELM-UHFFFAOYSA-N 0.000 description 1
JVTSHOJDBRTPHD-UHFFFAOYSA-N 2,2,2-trifluoroacetaldehyde Chemical compound FC(F)(F)C=O JVTSHOJDBRTPHD-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
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
RZJOIMPUMMQKFR-UHFFFAOYSA-N 2-bromo-1-fluoro-4-(trifluoromethyl)benzene Chemical compound FC1=CC=C(C(F)(F)F)C=C1Br RZJOIMPUMMQKFR-UHFFFAOYSA-N 0.000 description 1
QLRKALMVPCQTMU-UHFFFAOYSA-N 2-bromo-1-fluoro-4-methylbenzene Chemical compound CC1=CC=C(F)C(Br)=C1 QLRKALMVPCQTMU-UHFFFAOYSA-N 0.000 description 1
OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 1
RAAGZOYMEQDCTD-UHFFFAOYSA-N 2-fluorobenzoyl chloride Chemical compound FC1=CC=CC=C1C(Cl)=O RAAGZOYMEQDCTD-UHFFFAOYSA-N 0.000 description 1
LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 1
GMLDCZYTIPCVMO-UHFFFAOYSA-N 2-methylidenebutanal Chemical compound CCC(=C)C=O GMLDCZYTIPCVMO-UHFFFAOYSA-N 0.000 description 1
DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
KKBAQAHAWLUGNK-UHFFFAOYSA-N 230615-47-1 Chemical compound C12=CC=CC=C2C2C(O)C(O)C1C2 KKBAQAHAWLUGNK-UHFFFAOYSA-N 0.000 description 1
TYMBNRMIBWOQGH-UHFFFAOYSA-N 3,3-dimethoxypropanoic acid Chemical compound COC(OC)CC(O)=O TYMBNRMIBWOQGH-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
ZXVONLUNISGICL-UHFFFAOYSA-N 4,6-dinitro-o-cresol Chemical group CC1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1O ZXVONLUNISGICL-UHFFFAOYSA-N 0.000 description 1
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
YPMOAQISONSSNL-UHFFFAOYSA-N 8-hydroxyoctyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCCCCCCO YPMOAQISONSSNL-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
235000006491 Acacia senegal Nutrition 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
102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
235000017060 Arachis glabrata Nutrition 0.000 description 1
244000105624 Arachis hypogaea Species 0.000 description 1
235000010777 Arachis hypogaea Nutrition 0.000 description 1
235000018262 Arachis monticola Nutrition 0.000 description 1
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
241000675108 Citrus tangerina Species 0.000 description 1
DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
241000632511 Daviesia arborea Species 0.000 description 1
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 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
229920000084 Gum arabic Polymers 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
206010021033 Hypomenorrhoea Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
241001465754 Metazoa Species 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 1
LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
241001274216 Naso Species 0.000 description 1
101100263222 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) rbg-5 gene Proteins 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
208000006311 Pyoderma Diseases 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
YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 1
244000000231 Sesamum indicum Species 0.000 description 1
235000003434 Sesamum indicum Nutrition 0.000 description 1
229910020163 SiOCl Inorganic materials 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Chemical class 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
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
238000006069 Suzuki reaction reaction Methods 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
229940123445 Tricyclic antidepressant Drugs 0.000 description 1
239000007983 Tris buffer Substances 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
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
229960004373 acetylcholine Drugs 0.000 description 1
150000007513 acids Chemical class 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
230000001476 alcoholic 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
239000003513 alkali Substances 0.000 description 1
229910001854 alkali hydroxide 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
150000003973 alkyl amines Chemical class 0.000 description 1
238000005804 alkylation reaction Methods 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
238000010640 amide synthesis reaction Methods 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
235000012501 ammonium carbonate Nutrition 0.000 description 1
230000006933 amyloid-beta aggregation Effects 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
IINTYPGTDUHETB-UHFFFAOYSA-N azane 1-(3-chloropentan-3-yl)-2-ethylbenzene Chemical compound N.CCC1=CC=CC=C1C(Cl)(CC)CC IINTYPGTDUHETB-UHFFFAOYSA-N 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
229910052788 barium Inorganic materials 0.000 description 1
150000007514 bases Chemical class 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
150000008316 benzisoxazoles Chemical class 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
150000003939 benzylamines Chemical class 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000037396 body weight Effects 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
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical class O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 1
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
229910000024 caesium carbonate Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
JUNWLZAGQLJVLR-UHFFFAOYSA-J calcium diphosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O JUNWLZAGQLJVLR-UHFFFAOYSA-J 0.000 description 1
239000002775 capsule Substances 0.000 description 1
230000006315 carbonylation Effects 0.000 description 1
238000005810 carbonylation reaction Methods 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
150000001768 cations 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
239000003638 chemical reducing agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000001713 cholinergic effect Effects 0.000 description 1
230000006949 cholinergic function Effects 0.000 description 1
229910052681 coesite Inorganic materials 0.000 description 1
230000003930 cognitive ability Effects 0.000 description 1
230000006999 cognitive decline Effects 0.000 description 1
239000002475 cognitive enhancer Substances 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
229940125890 compound Ia Drugs 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
239000000498 cooling water Substances 0.000 description 1
239000013256 coordination polymer Substances 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 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
229910052906 cristobalite Inorganic materials 0.000 description 1
MLUCVPSAIODCQM-NSCUHMNNSA-N crotonaldehyde Chemical compound C\C=C\C=O MLUCVPSAIODCQM-NSCUHMNNSA-N 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
BWDQQALBJCTLRJ-UHFFFAOYSA-N ctk1a6251 Chemical class C12=CC=CC=C2C2=CC=C1C2 BWDQQALBJCTLRJ-UHFFFAOYSA-N 0.000 description 1
DQRLCTAGMVGVFH-UHFFFAOYSA-N cyanide;hydrochloride Chemical compound Cl.N#[C-] DQRLCTAGMVGVFH-UHFFFAOYSA-N 0.000 description 1
UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
230000007423 decrease Effects 0.000 description 1
239000008367 deionised water Substances 0.000 description 1
229910021641 deionized water Inorganic materials 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
235000019821 dicalcium diphosphate Nutrition 0.000 description 1
229910000393 dicalcium diphosphate Inorganic materials 0.000 description 1
HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
230000001076 estrogenic effect Effects 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
AINBZKYUNWUTRE-UHFFFAOYSA-N ethanol;propan-2-ol Chemical compound CCO.CC(C)O AINBZKYUNWUTRE-UHFFFAOYSA-N 0.000 description 1
239000012530 fluid Substances 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
235000011389 fruit/vegetable juice Nutrition 0.000 description 1
239000001530 fumaric acid Chemical class 0.000 description 1
125000000524 functional group Chemical group 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
229940050410 gluconate Drugs 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
229940015043 glyoxal Drugs 0.000 description 1
238000000227 grinding Methods 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons 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
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
208000014674 injury Diseases 0.000 description 1
229910052500 inorganic mineral Inorganic materials 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
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
229940043355 kinase inhibitor Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
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 1
ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 1
239000011968 lewis acid catalyst Substances 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate 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
230000001404 mediated effect Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
FBBDOOHMGLLEGJ-UHFFFAOYSA-N methane;hydrochloride Chemical compound C.Cl FBBDOOHMGLLEGJ-UHFFFAOYSA-N 0.000 description 1
OVJJVYHDJVQFSF-UHFFFAOYSA-N methyl 2-hydroxy-2-methoxyacetate Chemical compound COC(O)C(=O)OC OVJJVYHDJVQFSF-UHFFFAOYSA-N 0.000 description 1
SMCVPMKCDDNUCQ-UHFFFAOYSA-N methyl 3,3-dimethoxypropanoate Chemical compound COC(OC)CC(=O)OC SMCVPMKCDDNUCQ-UHFFFAOYSA-N 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 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
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
239000000472 muscarinic agonist Substances 0.000 description 1
230000003551 muscarinic effect Effects 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
239000003076 neurotropic agent Substances 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000008203 oral pharmaceutical composition Substances 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
230000036407 pain Effects 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
230000036961 partial effect Effects 0.000 description 1
235000020232 peanut Nutrition 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000003757 phosphotransferase inhibitor Substances 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
NFOHLBHARAZXFQ-UHFFFAOYSA-L platinum(2+);dihydroxide Chemical compound O[Pt]O NFOHLBHARAZXFQ-UHFFFAOYSA-L 0.000 description 1
239000002574 poison Substances 0.000 description 1
231100000614 poison Toxicity 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
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
239000012286 potassium permanganate Substances 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000002243 precursor Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
238000003672 processing method Methods 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
229940080818 propionamide Drugs 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
150000003217 pyrazoles Chemical class 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000003235 pyrrolidines Chemical class 0.000 description 1
ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
238000011002 quantification Methods 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
239000011435 rock Substances 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
230000035939 shock Effects 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
239000002002 slurry Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 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
235000011083 sodium citrates Nutrition 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-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
239000007921 spray Substances 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
238000011272 standard treatment Methods 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
229910052682 stishovite Inorganic materials 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
125000001174 sulfone group Chemical group 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000001629 suppression Effects 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
208000011580 syndromic disease 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
235000002906 tartaric acid Nutrition 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
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
229910052718 tin Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
238000000844 transformation Methods 0.000 description 1
230000008736 traumatic injury Effects 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
239000003029 tricyclic antidepressant agent Substances 0.000 description 1
229910052905 tridymite Inorganic materials 0.000 description 1
AVBGNFCMKJOFIN-UHFFFAOYSA-N triethylammonium acetate Chemical compound CC(O)=O.CCN(CC)CC AVBGNFCMKJOFIN-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
238000003828 vacuum filtration Methods 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
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
CITILBVTAYEWKR-UHFFFAOYSA-L zinc trifluoromethanesulfonate Chemical compound [Zn+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F CITILBVTAYEWKR-UHFFFAOYSA-L 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/08—Bridged systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
- C07D221/24—Camphidines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Addiction (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Psychology (AREA)
Rheumatology (AREA)
Obesity (AREA)
Anesthesiology (AREA)
Orthopedic Medicine & Surgery (AREA)
Child & Adolescent Psychology (AREA)
Diabetes (AREA)
Hematology (AREA)
Hospice & Palliative Care (AREA)
Toxicology (AREA)
Nutrition Science (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

UA2002075792A 2000-02-25 2001-08-02 Azapolycyclic compounds condensated with aryl UA74813C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US09/514,002 US6605610B1 (en)	1997-12-31	2000-02-25	Aryl fused azapolycyclic compounds
PCT/IB2001/000153 WO2001062736A1 (en)	2000-02-25	2001-02-08	Aryl fused azapolycyclic compounds

Publications (1)

Publication Number	Publication Date
UA74813C2 true UA74813C2 (en)	2006-02-15

Family

ID=24045406

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2002075792A UA74813C2 (en)	2000-02-25	2001-08-02	Azapolycyclic compounds condensated with aryl

Country Status (39)

Country	Link
US (3)	US6605610B1 (et)
EP (2)	EP1619192B1 (et)
JP (1)	JP2003524002A (et)
KR (1)	KR100537976B1 (et)
CN (1)	CN1263745C (et)
AP (1)	AP1860A (et)
AT (2)	ATE453643T1 (et)
AU (2)	AU784081B2 (et)
BG (1)	BG65891B1 (et)
BR (1)	BR0108610A (et)
CA (1)	CA2401229C (et)
CR (1)	CR6726A (et)
CU (1)	CU23148A3 (et)
CY (1)	CY1105301T1 (et)
CZ (1)	CZ303203B6 (et)
DE (2)	DE60120366T2 (et)
DK (2)	DK1619192T3 (et)
DZ (1)	DZ3328A1 (et)
EA (1)	EA005316B1 (et)
EE (1)	EE200200475A (et)
ES (2)	ES2336800T3 (et)
GE (1)	GEP20053454B (et)
HR (1)	HRP20020700A2 (et)
HU (1)	HU229482B1 (et)
IL (2)	IL150639A0 (et)
IS (1)	IS2293B (et)
MA (1)	MA26875A1 (et)
MX (1)	MXPA02008311A (et)
NO (1)	NO323608B1 (et)
NZ (1)	NZ519973A (et)
OA (1)	OA12181A (et)
PL (1)	PL365163A1 (et)
PT (1)	PT1259489E (et)
RS (1)	RS51123B (et)
SI (1)	SI1259489T1 (et)
SK (1)	SK12042002A3 (et)
UA (1)	UA74813C2 (et)
WO (1)	WO2001062736A1 (et)
ZA (1)	ZA200206768B (et)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RS50069B (sr) *	1997-12-31	2009-01-22	Pfizer Products Inc.,	Aril kondenzovana azapoliciklična jedinjenja
WO2002085843A2 (en) *	2001-04-20	2002-10-31	Pfizer Products Inc.	Process for the preparation of 1,3-substituted indenes and aryl-fused azapolycyclic compounds
CA2460118A1 (en) *	2001-10-31	2003-05-08	Pfizer Products Inc.	Nicotinic acetylcholine receptor agonists in the treatment of restless legs syndrome
WO2003045437A1 (en) *	2001-11-30	2003-06-05	Pfizer Products Inc.	Pharmaceutical compositions of 5,7,14-triazatetracyclo[10.3.1.0(2,11).0(4,9)]-hexadeca-2(11)3,5,7,9-pentaene
CN1596263A (zh) *	2001-11-30	2005-03-16	辉瑞产品公司	芳基－稠合的氮杂多环化合物
CA2487849A1 (en)	2002-07-18	2004-01-29	Cytos Biotechnology Ag	Hapten-carrier conjugates comprising virus like particles and uses thereof
WO2004037850A2 (en) *	2002-10-22	2004-05-06	Millipore Corporation	Multi-sided immersion formation of composite structures and method
WO2004048318A1 (en) *	2002-11-25	2004-06-10	Pfizer Products Inc.	Improved process for the preparation of 1,3-substituted indenes
BRPI0406670A (pt) *	2003-01-15	2005-12-20	Pfizer Prod Inc	Processo para a preparação de lactamas policìclicas fundidos com arila
WO2004103372A1 (en) *	2003-05-20	2004-12-02	Pfizer Products Inc.	Pharmaceutical compositions of varenicline
WO2004108725A1 (en) *	2003-06-04	2004-12-16	Pfizer Products Inc.	Preparation of substituted quinoxalines from the dianline with 2,3-dihydroxy-1,4-dioxane
CA2533100A1 (en) *	2003-07-21	2005-01-27	Pfizer Products Inc.	Aryl fused azapolycyclic compounds
US8580842B2 (en)	2003-09-30	2013-11-12	Abbott Gmbh & Co. Kg	Heteroaryl-substituted 1,3-dihydroindol-2-one derivatives and medicaments containing them
SG147437A1 (en)	2003-10-14	2008-11-28	Xenoport Inc	Crystalline form of gamma-aminobutyric acid analog
WO2005063296A2 (en) *	2003-12-23	2005-07-14	Pfizer Products Inc.	Therapeutic combination for cognition enhancement and psychotic disorders
WO2006006071A1 (en) *	2004-07-07	2006-01-19	Pfizer Products Inc.	Resolution of an aryl-fused azapolycyclic compound
MX2007010375A (es) *	2005-02-24	2007-09-25	Pfizer Prod Inc	Preparacion de quinoxalina sustituida de elevada pureza.
CN101420939A (zh) *	2006-04-24	2009-04-29	辉瑞产品公司	用于药物递送装置的不对称膜
EP2086977A2 (en) *	2006-11-09	2009-08-12	Pfizer Products Inc.	Polymorphs of nicotinic intermediates
US8486979B2 (en) *	2006-12-12	2013-07-16	Abbvie Inc.	1,2,4 oxadiazole compounds and methods of use thereof
US20080167286A1 (en)	2006-12-12	2008-07-10	Abbott Laboratories	Pharmaceutical compositions and their methods of use
UY30846A1 (es) *	2006-12-30	2008-07-31	Abbott Gmbh & Amp	Derivados de oxindol sustituidos, medicamentos que los comprenden y uso de los mismos
US20090062257A1 (en) *	2007-08-29	2009-03-05	Protia, Llc	Deuterium-enriched varenicline
WO2009034431A2 (en)	2007-09-10	2009-03-19	Pfizer Inc.	Controlled-release dosage forms for varenicline
WO2009065872A2 (en) *	2007-11-20	2009-05-28	Medichem, S.A.	Improved processes for the synthesis of varenicline l-tartrate
US8703775B2 (en) *	2007-12-07	2014-04-22	AbbVie Deutschland GmbH & Co. KG	Amidomethyl-substituted oxindole derivatives and the use thereof for the treatment of vasopressin-dependent illnesses
CA2707671C (en)	2007-12-07	2016-02-02	Abbott Gmbh & Co. Kg	5,6-disubstituted oxindole-derivatives and use thereof for treating vasopressine-dependent diseases
US8703774B2 (en) *	2007-12-07	2014-04-22	AbbVie Deutschland GmbH & Co. KG	Carbamate-substituted oxindole derivatives and use thereof for the treatment of vasopressin-dependent diseases
CA2707669C (en) *	2007-12-07	2016-07-05	Wilfried Braje	5-halogen-substituted oxindole derivatives and use thereof for treating vasopressine-dependent diseases
US8383657B2 (en)	2007-12-21	2013-02-26	Abbott Laboratories	Thiazolylidine urea and amide derivatives and methods of use thereof
WO2009146031A1 (en)	2008-03-31	2009-12-03	University Of South Florida	Methods of treating disease-induced ataxia and non-ataxic imbalance
US8039620B2 (en) *	2008-05-22	2011-10-18	Teva Pharmaceutical Industries Ltd.	Varenicline tosylate, an intermediate in the preparation process of varenicline L-tartrate
US20090318695A1 (en) *	2008-06-19	2009-12-24	Vinod Kumar Kansal	Processes for the preparation of varenicline and intermediates thereof
WO2010005643A1 (en) *	2008-07-10	2010-01-14	Teva Pharmaceutical Industries Ltd.	Processes for purifying varenicline l-tartrate salt and preparing crystalline forms of varenicline l-tartrate salt
US8314235B2 (en) *	2008-09-01	2012-11-20	Actavis Group Ptc Ehf	Process for preparing varenicline, varenicline intermediates, pharmaceutically acceptable salts thereof
BRPI1008020A2 (pt)	2009-02-11	2016-03-15	Sunovion Pharmaceuticals Inc	antagonistas e agonistas inversos h3 da histamina e métodos de uso dos mesmos
EP2435080A2 (en)	2009-05-29	2012-04-04	Abbott Laboratories	Pharmaceutical compositions for the treatment of pain
EP2438054A1 (en) *	2009-06-22	2012-04-11	Teva Pharmaceutical Industries Ltd.	Solid states forms of varenicline salts and processes for preparation thereof
EP3590498A4 (en)	2017-03-03	2020-12-16	CTC Bio, Inc.	PREPARATION, INCLUDING AN INCLUSION COMPLEX OF VARENICLINE OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREFOR, FOR ORAL ADMINISTRATION
AU2020416203A1 (en) *	2020-01-03	2022-06-16	Blue Oak Pharmaceuticals, Inc.	Compounds and compositions for treating CNS disorders
CN115322105A (zh) *	2021-05-11	2022-11-11	江苏润安制药有限公司	一种合成艾拉莫德关键中间体的方法

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3471503A (en)	1967-05-05	1969-10-07	Mcneilab Inc	1,2,3,5,6,7-hexahydro-4-phenethyl-2,6-methano-4h-4- benzazonin-12-ols
RS50069B (sr) *	1997-12-31	2009-01-22	Pfizer Products Inc.,	Aril kondenzovana azapoliciklična jedinjenja
EP0955301A3 (en)	1998-04-27	2001-04-18	Pfizer Products Inc.	7-aza-bicyclo[2.2.1]-heptane derivatives, their preparation and use according to their affinity for neuronal nicotinic acetylcholine receptors
WO1999055680A1 (en)	1998-04-29	1999-11-04	Pfizer Products Inc.	Aryl fused azapolycyclic compounds
ES2305373T3 (es) *	1999-01-29	2008-11-01	Abbott Laboratories	Derivados diazabiciclicos como ligandos del receptor nicotinico de la acetilcolina.
FR2788982B1 (fr) *	1999-02-02	2002-08-02	Synthelabo	Compositions pharmaceutiques contenant de la nicotine et leur application dans le sevrage tabagique
IL137937A0 (en) *	1999-08-27	2001-10-31	Pfizer Prod Inc	A pharmaceutical composition for the prevention and treatment of nicotine addiction in a mammal
JP2004532826A (ja) *	2001-03-19	2004-10-28	スローン−ケッタリングインスティトゥートフォーカンサーリサーチ	（ｓ，ｒ，ｒ）−（−）−アクチノニンおよびそのアナログの不斉合成、ならびにそれらの使用
CA2533100A1 (en) *	2003-07-21	2005-01-27	Pfizer Products Inc.	Aryl fused azapolycyclic compounds
US8123947B2 (en)	2007-10-22	2012-02-28	Baxter International Inc.	Priming and air removal systems and methods for dialysis

2000
- 2000-02-25 US US09/514,002 patent/US6605610B1/en not_active Expired - Fee Related
2001
- 2001-02-08 CZ CZ20022778A patent/CZ303203B6/cs not_active IP Right Cessation
- 2001-02-08 EA EA200200716A patent/EA005316B1/ru not_active IP Right Cessation
- 2001-02-08 CA CA002401229A patent/CA2401229C/en not_active Expired - Fee Related
- 2001-02-08 DZ DZ013328A patent/DZ3328A1/fr active
- 2001-02-08 DE DE60120366T patent/DE60120366T2/de not_active Expired - Lifetime
- 2001-02-08 DK DK05106835.1T patent/DK1619192T3/da active
- 2001-02-08 ES ES05106835T patent/ES2336800T3/es not_active Expired - Lifetime
- 2001-02-08 JP JP2001562518A patent/JP2003524002A/ja active Pending
- 2001-02-08 MX MXPA02008311A patent/MXPA02008311A/es active IP Right Grant
- 2001-02-08 HR HRP20020700 patent/HRP20020700A2/hr not_active Application Discontinuation
- 2001-02-08 AU AU28748/01A patent/AU784081B2/en not_active Ceased
- 2001-02-08 RS YUP-596/02A patent/RS51123B/sr unknown
- 2001-02-08 DK DK01953630T patent/DK1259489T3/da active
- 2001-02-08 KR KR10-2002-7011140A patent/KR100537976B1/ko not_active Expired - Fee Related
- 2001-02-08 GE GE4911A patent/GEP20053454B/en unknown
- 2001-02-08 NZ NZ519973A patent/NZ519973A/en not_active IP Right Cessation
- 2001-02-08 BR BR0108610-3A patent/BR0108610A/pt not_active Application Discontinuation
- 2001-02-08 EP EP05106835A patent/EP1619192B1/en not_active Expired - Lifetime
- 2001-02-08 DE DE60140965T patent/DE60140965D1/de not_active Expired - Lifetime
- 2001-02-08 WO PCT/IB2001/000153 patent/WO2001062736A1/en not_active Ceased
- 2001-02-08 IL IL15063901A patent/IL150639A0/xx active IP Right Grant
- 2001-02-08 AT AT05106835T patent/ATE453643T1/de not_active IP Right Cessation
- 2001-02-08 CN CNB018055737A patent/CN1263745C/zh not_active Expired - Fee Related
- 2001-02-08 EP EP01953630A patent/EP1259489B1/en not_active Expired - Lifetime
- 2001-02-08 PL PL01365163A patent/PL365163A1/xx not_active Application Discontinuation
- 2001-02-08 SK SK1204-2002A patent/SK12042002A3/sk not_active Application Discontinuation
- 2001-02-08 HU HU0204580A patent/HU229482B1/hu not_active IP Right Cessation
- 2001-02-08 ES ES01953630T patent/ES2263640T3/es not_active Expired - Lifetime
- 2001-02-08 AP APAP/P/2002/002604A patent/AP1860A/en active
- 2001-02-08 OA OA1200200256A patent/OA12181A/en unknown
- 2001-02-08 AT AT01953630T patent/ATE328872T1/de active
- 2001-02-08 SI SI200130584T patent/SI1259489T1/sl unknown
- 2001-02-08 PT PT01953630T patent/PT1259489E/pt unknown
- 2001-02-08 EE EEP200200475A patent/EE200200475A/et unknown
- 2001-08-02 UA UA2002075792A patent/UA74813C2/uk unknown
2002
- 2002-07-05 BG BG106908A patent/BG65891B1/bg unknown
- 2002-07-05 IS IS6459A patent/IS2293B/is unknown
- 2002-07-08 IL IL150639A patent/IL150639A/en not_active IP Right Cessation
- 2002-08-09 CR CR6726A patent/CR6726A/es unknown
- 2002-08-13 MA MA26775A patent/MA26875A1/fr unknown
- 2002-08-21 CU CU177A patent/CU23148A3/es not_active IP Right Cessation
- 2002-08-22 ZA ZA200206768A patent/ZA200206768B/xx unknown
- 2002-08-23 NO NO20024042A patent/NO323608B1/no not_active IP Right Cessation
2003
- 2003-01-03 US US10/336,532 patent/US7144882B2/en not_active Expired - Fee Related
- 2003-01-03 US US10/336,508 patent/US7205300B2/en not_active Expired - Fee Related
2005
- 2005-11-18 AU AU2005234671A patent/AU2005234671B2/en not_active Ceased
2006
- 2006-07-21 CY CY20061101011T patent/CY1105301T1/el unknown

Also Published As

Publication number	Publication date
BR0108610A (pt)	2002-11-19
MXPA02008311A (es)	2002-12-09
KR100537976B1 (ko)	2005-12-21
AU2874801A (en)	2001-09-03
NO323608B1 (no)	2007-06-18
HU229482B1 (en)	2014-01-28
EP1619192A3 (en)	2006-03-22
EA005316B1 (ru)	2004-12-30
YU59602A (sh)	2005-06-10
US7144882B2 (en)	2006-12-05
EP1259489A1 (en)	2002-11-27
ATE328872T1 (de)	2006-06-15
RS51123B (sr)	2010-10-31
ZA200206768B (en)	2003-09-23
CZ20022778A3 (cs)	2003-09-17
JP2003524002A (ja)	2003-08-12
BG106908A (bg)	2003-04-30
DE60120366T2 (de)	2007-07-05
US20030130260A1 (en)	2003-07-10
IL150639A (en)	2011-10-31
MA26875A1 (fr)	2004-12-20
EA200200716A1 (ru)	2003-02-27
HUP0204580A3 (en)	2005-04-28
HRP20020700A2 (en)	2004-12-31
CY1105301T1 (el)	2010-03-03
DK1619192T3 (da)	2010-03-29
DK1259489T3 (da)	2006-10-09
KR20030005209A (ko)	2003-01-17
CR6726A (es)	2003-10-28
AP1860A (en)	2008-07-02
EP1619192A2 (en)	2006-01-25
SK12042002A3 (sk)	2004-02-03
PT1259489E (pt)	2006-08-31
IL150639A0 (en)	2003-02-12
DE60140965D1 (de)	2010-02-11
DE60120366D1 (de)	2006-07-20
NO20024042L (no)	2002-10-17
NZ519973A (en)	2004-04-30
CN1406227A (zh)	2003-03-26
US6605610B1 (en)	2003-08-12
CN1263745C (zh)	2006-07-12
PL365163A1 (en)	2004-12-27
WO2001062736A1 (en)	2001-08-30
EE200200475A (et)	2003-12-15
SI1259489T1 (sl)	2006-10-31
DZ3328A1 (et)	2001-08-30
IS2293B (is)	2007-10-15
GEP20053454B (en)	2005-02-25
EP1259489B1 (en)	2006-06-07
ATE453643T1 (de)	2010-01-15
HK1050894A1 (en)	2003-07-11
AU2005234671B2 (en)	2008-04-17
ES2263640T3 (es)	2006-12-16
CU23148A3 (es)	2006-06-29
HUP0204580A2 (hu)	2003-04-28
OA12181A (en)	2006-05-09
CA2401229A1 (en)	2001-08-30
CA2401229C (en)	2007-10-02
NO20024042D0 (no)	2002-08-23
IS6459A (is)	2002-07-05
ES2336800T3 (es)	2010-04-16
US20030130261A1 (en)	2003-07-10
BG65891B1 (bg)	2010-04-30
AU784081B2 (en)	2006-02-02
AP2002002604A0 (en)	2002-09-30
US7205300B2 (en)	2007-04-17
AU2005234671A1 (en)	2005-12-15
EP1619192B1 (en)	2009-12-30
CZ303203B6 (cs)	2012-05-23

Publication	Publication Date	Title
UA74813C2 (en)	2006-02-15	Azapolycyclic compounds condensated with aryl
EP1044189B1 (en)	2008-02-13	Aryl fused azapolycyclic compounds
EP1383733B1 (en)	2008-03-05	Process for the preparation of 1,3-substituted indenes and aryl-fused azapolycyclic compounds
AU2002234836A1 (en)	2003-04-17	Process for the preparation of 1,3-substituted indenes and aryl-fused azapolycyclic compounds