BG105859A - Тетрахидропиранови производни и тяхното използване като терапевтични вещества - Google Patents

Тетрахидропиранови производни и тяхното използване като терапевтични вещества Download PDF

Info

Publication number: BG105859A
Authority: BG; Bulgaria
Prior art keywords: alkyl; alkoxy; formula; phenyl; hydrogen
Prior art date: 1999-03-19

Application number

BG105859A

Other languages

Bulgarian (bg)

English (en)

Inventor

Simon OWEN

Eileen SEWARD

Christopher Swain

Brian WILLLIAMS

Original Assignee

Merck Sharp & Dohme Limited

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.)

1999-03-19

Filing date

2001-08-30

Publication date

2002-04-30

1999-03-19 Priority claimed from GBGB9906480.0A external-priority patent/GB9906480D0/en

1999-10-18 Priority claimed from GBGB9924616.7A external-priority patent/GB9924616D0/en

2001-08-30 Application filed by Merck Sharp & Dohme Limited filed Critical Merck Sharp & Dohme Limited

2002-04-30 Publication of BG105859A publication Critical patent/BG105859A/bg

Links

150000003527 tetrahydropyrans Chemical class 0.000 title description 2
230000001225 therapeutic effect Effects 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 112
125000000217 alkyl group Chemical group 0.000 claims abstract description 81
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 51
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 50
239000001257 hydrogen Substances 0.000 claims abstract description 47
-1 fluoroC1-4alkyl Chemical group 0.000 claims abstract description 43
150000003839 salts Chemical class 0.000 claims abstract description 26
229910052736 halogen Inorganic materials 0.000 claims abstract description 25
150000002367 halogens Chemical class 0.000 claims abstract description 24
208000002193 Pain Diseases 0.000 claims abstract description 18
230000036407 pain Effects 0.000 claims abstract description 18
125000001424 substituent group Chemical group 0.000 claims abstract description 18
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
206010047700 Vomiting Diseases 0.000 claims abstract description 10
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 10
125000005842 heteroatom Chemical group 0.000 claims abstract description 8
208000019695 Migraine disease Diseases 0.000 claims abstract description 6
206010027599 migraine Diseases 0.000 claims abstract description 6
206010036376 Postherpetic Neuralgia Diseases 0.000 claims abstract description 4
230000002265 prevention Effects 0.000 claims abstract description 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 2
125000003545 alkoxy group Chemical group 0.000 claims description 56
239000000203 mixture Substances 0.000 claims description 38
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
229910052731 fluorine Inorganic materials 0.000 claims description 24
239000011737 fluorine Substances 0.000 claims description 24
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 19
238000006243 chemical reaction Methods 0.000 claims description 19
229910052757 nitrogen Inorganic materials 0.000 claims description 18
238000000034 method Methods 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
125000006413 ring segment Chemical group 0.000 claims description 13
125000001153 fluoro group Chemical group F* 0.000 claims description 12
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 11
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 8
102000003141 Tachykinin Human genes 0.000 claims description 8
125000003342 alkenyl group Chemical group 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
108060008037 tachykinin Proteins 0.000 claims description 8
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 7
125000000304 alkynyl group Chemical group 0.000 claims description 7
125000004122 cyclic group Chemical group 0.000 claims description 7
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
125000006239 protecting group Chemical group 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
229920002554 vinyl polymer Polymers 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 3
150000001412 amines Chemical class 0.000 claims description 3
150000001540 azides Chemical class 0.000 claims description 3
239000003054 catalyst Substances 0.000 claims description 3
239000003153 chemical reaction reagent Substances 0.000 claims description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
150000002390 heteroarenes Chemical class 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
239000002243 precursor Substances 0.000 claims description 3
239000011347 resin Substances 0.000 claims description 3
229920005989 resin Polymers 0.000 claims description 3
125000004434 sulfur atom Chemical group 0.000 claims description 3
238000002560 therapeutic procedure Methods 0.000 claims description 3
230000008673 vomiting Effects 0.000 claims 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 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
125000002993 cycloalkylene group Chemical group 0.000 claims description 2
125000003709 fluoroalkyl group Chemical group 0.000 claims description 2
238000005304 joining Methods 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
230000007794 irritation Effects 0.000 claims 2
CYXMOAZSOPXQOD-UHFFFAOYSA-N 1-methyl-2-(2-methylphenoxy)benzene Chemical compound CC1=CC=CC=C1OC1=CC=CC=C1C CYXMOAZSOPXQOD-UHFFFAOYSA-N 0.000 claims 1
125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
230000003993 interaction Effects 0.000 claims 1
125000000686 lactone group Chemical group 0.000 claims 1
208000019901 Anxiety disease Diseases 0.000 abstract description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 3
125000005843 halogen group Chemical group 0.000 abstract description 3
230000036506 anxiety Effects 0.000 abstract description 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 3
241000689227 Cora <basidiomycete fungus> Species 0.000 abstract 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
125000004399 C1-C4 alkenyl group Chemical group 0.000 abstract 1
206010061218 Inflammation Diseases 0.000 abstract 1
230000004054 inflammatory process Effects 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
239000000243 solution Substances 0.000 description 30
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 25
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
208000035475 disorder Diseases 0.000 description 18
150000002431 hydrogen Chemical group 0.000 description 17
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
239000002904 solvent Substances 0.000 description 14
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
239000000460 chlorine Chemical group 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 10
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
229910052801 chlorine Inorganic materials 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
239000012267 brine Substances 0.000 description 7
201000010099 disease Diseases 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000003826 tablet Substances 0.000 description 6
230000001154 acute effect Effects 0.000 description 5
201000006549 dyspepsia Diseases 0.000 description 5
239000000284 extract Substances 0.000 description 5
238000009472 formulation Methods 0.000 description 5
238000007429 general method Methods 0.000 description 5
239000006187 pill Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
206010012218 Delirium Diseases 0.000 description 4
206010028980 Neoplasm Diseases 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
208000028017 Psychotic disease Diseases 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
230000006378 damage Effects 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000012458 free base Substances 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
239000007787 solid Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
206010012289 Dementia Diseases 0.000 description 3
201000004624 Dermatitis Diseases 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
102100037346 Substance-P receptor Human genes 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000002249 anxiolytic agent Substances 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
239000002585 base Substances 0.000 description 3
238000002512 chemotherapy Methods 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
150000008282 halocarbons Chemical class 0.000 description 3
208000024798 heartburn Diseases 0.000 description 3
208000027866 inflammatory disease Diseases 0.000 description 3
239000011630 iodine Substances 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
150000002596 lactones Chemical group 0.000 description 3
239000000463 material Substances 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000006199 nebulizer Substances 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
208000033808 peripheral neuropathy Diseases 0.000 description 3
239000000843 powder Substances 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
238000010898 silica gel chromatography Methods 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
208000011580 syndromic disease Diseases 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
TYIXRLWPLCQBNQ-UHFFFAOYSA-N 2-ethyl-3-phenyloxane Chemical compound CCC1OCCCC1c1ccccc1 TYIXRLWPLCQBNQ-UHFFFAOYSA-N 0.000 description 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
MFZASGSSOQORSM-UHFFFAOYSA-N 4-o-benzyl 1-o-butyl piperidine-1,4-dicarboxylate Chemical compound C1CN(C(=O)OCCCC)CCC1C(=O)OCC1=CC=CC=C1 MFZASGSSOQORSM-UHFFFAOYSA-N 0.000 description 2
208000008811 Agoraphobia Diseases 0.000 description 2
208000024827 Alzheimer disease Diseases 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
208000008035 Back Pain Diseases 0.000 description 2
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
206010058019 Cancer Pain Diseases 0.000 description 2
206010010741 Conjunctivitis Diseases 0.000 description 2
208000020401 Depressive disease Diseases 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
208000005171 Dysmenorrhea Diseases 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
101000600903 Homo sapiens Substance-P receptor Proteins 0.000 description 2
206010020751 Hypersensitivity Diseases 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
208000008930 Low Back Pain Diseases 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
208000019022 Mood disease Diseases 0.000 description 2
208000000112 Myalgia Diseases 0.000 description 2
208000018737 Parkinson disease Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
208000013200 Stress disease Diseases 0.000 description 2
208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
230000003187 abdominal effect Effects 0.000 description 2
239000013543 active substance Substances 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
229910052796 boron Inorganic materials 0.000 description 2
210000000133 brain stem Anatomy 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
230000003111 delayed effect Effects 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000010828 elution Methods 0.000 description 2
239000012055 enteric layer Substances 0.000 description 2
230000001667 episodic effect Effects 0.000 description 2
230000002496 gastric effect Effects 0.000 description 2
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
208000014674 injury Diseases 0.000 description 2
230000003601 intercostal effect Effects 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
230000035987 intoxication Effects 0.000 description 2
231100000566 intoxication Toxicity 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
201000003152 motion sickness Diseases 0.000 description 2
210000003205 muscle Anatomy 0.000 description 2
208000013465 muscle pain Diseases 0.000 description 2
210000005036 nerve Anatomy 0.000 description 2
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
201000008482 osteoarthritis Diseases 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
235000015424 sodium Nutrition 0.000 description 2
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
239000007909 solid dosage form Substances 0.000 description 2
210000002784 stomach Anatomy 0.000 description 2
230000035882 stress Effects 0.000 description 2
208000011117 substance-related disease Diseases 0.000 description 2
239000004094 surface-active agent Substances 0.000 description 2
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 2
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
208000004371 toothache Diseases 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
230000008733 trauma Effects 0.000 description 2
206010044652 trigeminal neuralgia Diseases 0.000 description 2
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
MMSCIQKQJVBPIR-RXMQYKEDSA-N (1r)-1-[3,5-bis(trifluoromethyl)phenyl]ethanol Chemical compound C[C@@H](O)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 MMSCIQKQJVBPIR-RXMQYKEDSA-N 0.000 description 1
QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
GZZGBHWWPCEWAL-ZYHUDNBSSA-N (3R,4S)-4-ethenyl-3-phenyloxan-2-one Chemical compound C=C[C@@H]1CCOC(=O)[C@H]1C1=CC=CC=C1 GZZGBHWWPCEWAL-ZYHUDNBSSA-N 0.000 description 1
JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
LNAANGYWIDUDRG-UHFFFAOYSA-N 1-butoxycarbonylpiperidine-4-carboxylic acid Chemical compound CCCCOC(=O)N1CCC(C(O)=O)CC1 LNAANGYWIDUDRG-UHFFFAOYSA-N 0.000 description 1
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
TZOIYNLRZQUAQF-UHFFFAOYSA-N 2-phenyloxane Chemical compound O1CCCCC1C1=CC=CC=C1 TZOIYNLRZQUAQF-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
AVVPWXPJNPXAFS-UHFFFAOYSA-N 3-phenyloxane Chemical compound C1CCOCC1C1=CC=CC=C1 AVVPWXPJNPXAFS-UHFFFAOYSA-N 0.000 description 1
TVUAPEXVBKMDAI-UHFFFAOYSA-N 4-ethenyl-3-phenyloxan-2-ol Chemical compound OC1OCCC(C=C)C1C1=CC=CC=C1 TVUAPEXVBKMDAI-UHFFFAOYSA-N 0.000 description 1
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
CXBOBBRQOWTQNB-UHFFFAOYSA-N 5-phenyl-2,3-dihydropyran-6-one Chemical compound O=C1OCCC=C1C1=CC=CC=C1 CXBOBBRQOWTQNB-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
208000000187 Abnormal Reflex Diseases 0.000 description 1
206010001540 Akathisia Diseases 0.000 description 1
208000000044 Amnesia Diseases 0.000 description 1
208000031091 Amnestic disease Diseases 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
206010003645 Atopy Diseases 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
208000020925 Bipolar disease Diseases 0.000 description 1
206010048962 Brain oedema Diseases 0.000 description 1
208000009079 Bronchial Spasm Diseases 0.000 description 1
208000014181 Bronchial disease Diseases 0.000 description 1
206010006458 Bronchitis chronic Diseases 0.000 description 1
201000004813 Bronchopneumonia Diseases 0.000 description 1
206010006482 Bronchospasm Diseases 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
206010008469 Chest discomfort Diseases 0.000 description 1
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
208000027932 Collagen disease Diseases 0.000 description 1
208000013586 Complex regional pain syndrome type 1 Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
201000003883 Cystic fibrosis Diseases 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
206010012239 Delusion Diseases 0.000 description 1
208000024254 Delusional disease Diseases 0.000 description 1
208000016192 Demyelinating disease Diseases 0.000 description 1
206010012335 Dependence Diseases 0.000 description 1
206010012442 Dermatitis contact Diseases 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
201000010374 Down Syndrome Diseases 0.000 description 1
206010013935 Dysmenorrhoea Diseases 0.000 description 1
206010015137 Eructation Diseases 0.000 description 1
206010015866 Extravasation Diseases 0.000 description 1
206010015958 Eye pain Diseases 0.000 description 1
208000001640 Fibromyalgia Diseases 0.000 description 1
208000010235 Food Addiction Diseases 0.000 description 1
201000011240 Frontotemporal dementia Diseases 0.000 description 1
208000007882 Gastritis Diseases 0.000 description 1
208000018522 Gastrointestinal disease Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
208000011688 Generalised anxiety disease Diseases 0.000 description 1
201000005569 Gout Diseases 0.000 description 1
239000007818 Grignard reagent Substances 0.000 description 1
208000031886 HIV Infections Diseases 0.000 description 1
208000004547 Hallucinations Diseases 0.000 description 1
206010019196 Head injury Diseases 0.000 description 1
206010019233 Headaches Diseases 0.000 description 1
208000023105 Huntington disease Diseases 0.000 description 1
206010020710 Hyperphagia Diseases 0.000 description 1
206010021639 Incontinence Diseases 0.000 description 1
208000022559 Inflammatory bowel disease Diseases 0.000 description 1
208000027601 Inner ear disease Diseases 0.000 description 1
LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
208000007914 Labor Pain Diseases 0.000 description 1
208000035945 Labour pain Diseases 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
208000027530 Meniere disease Diseases 0.000 description 1
208000016285 Movement disease Diseases 0.000 description 1
206010028391 Musculoskeletal Pain Diseases 0.000 description 1
208000028389 Nerve injury Diseases 0.000 description 1
108010040718 Neurokinin-1 Receptors Proteins 0.000 description 1
201000005625 Neuroleptic malignant syndrome Diseases 0.000 description 1
206010029333 Neurosis Diseases 0.000 description 1
208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
208000027089 Parkinsonian disease Diseases 0.000 description 1
206010034010 Parkinsonism Diseases 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
206010034912 Phobia Diseases 0.000 description 1
208000000609 Pick Disease of the Brain Diseases 0.000 description 1
208000005374 Poisoning Diseases 0.000 description 1
208000031649 Postoperative Nausea and Vomiting Diseases 0.000 description 1
208000004550 Postoperative Pain Diseases 0.000 description 1
206010073211 Postural tremor Diseases 0.000 description 1
208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
102100024304 Protachykinin-1 Human genes 0.000 description 1
208000003251 Pruritus Diseases 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
208000001431 Psychomotor Agitation Diseases 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 1
206010038687 Respiratory distress Diseases 0.000 description 1
206010038934 Retinopathy proliferative Diseases 0.000 description 1
208000020114 Schizophrenia and other psychotic disease Diseases 0.000 description 1
208000008765 Sciatica Diseases 0.000 description 1
206010039710 Scleroderma Diseases 0.000 description 1
206010039966 Senile dementia Diseases 0.000 description 1
208000019568 Shared Paranoid disease Diseases 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
206010041250 Social phobia Diseases 0.000 description 1
208000029033 Spinal Cord disease Diseases 0.000 description 1
206010072005 Spinal pain Diseases 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
208000007107 Stomach Ulcer Diseases 0.000 description 1
208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
101800003906 Substance P Proteins 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
206010042496 Sunburn Diseases 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
208000024780 Urticaria Diseases 0.000 description 1
208000001407 Vascular Headaches Diseases 0.000 description 1
201000004810 Vascular dementia Diseases 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
238000005299 abrasion Methods 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
229940081735 acetylcellulose Drugs 0.000 description 1
230000009471 action Effects 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
230000007815 allergy Effects 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
230000006986 amnesia Effects 0.000 description 1
238000002266 amputation Methods 0.000 description 1
201000002426 animal phobia Diseases 0.000 description 1
230000000949 anxiolytic effect Effects 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
210000000576 arachnoid Anatomy 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
208000027687 belching Diseases 0.000 description 1
230000008901 benefit Effects 0.000 description 1
NIUOXPFOKFTCJG-UHFFFAOYSA-N benzyl 4-methylpiperidine-4-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)C1(C)CCNCC1 NIUOXPFOKFTCJG-UHFFFAOYSA-N 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
208000028683 bipolar I disease Diseases 0.000 description 1
208000006752 brain edema Diseases 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
235000014121 butter Nutrition 0.000 description 1
229960001948 caffeine Drugs 0.000 description 1
VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
SQKWGPOIVHMUNF-UHFFFAOYSA-K cerium(3+);trichloride;hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Cl-].[Ce+3] SQKWGPOIVHMUNF-UHFFFAOYSA-K 0.000 description 1
YKBPPCMNICNBEU-UHFFFAOYSA-M cesium;chloride;hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cs+] YKBPPCMNICNBEU-UHFFFAOYSA-M 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
229920001429 chelating resin Polymers 0.000 description 1
208000007451 chronic bronchitis Diseases 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
210000000589 cicatrix Anatomy 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229960003920 cocaine Drugs 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
208000010247 contact dermatitis Diseases 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 description 1
201000003146 cystitis Diseases 0.000 description 1
231100000868 delusion Toxicity 0.000 description 1
229960002086 dextran Drugs 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
235000019700 dicalcium phosphate Nutrition 0.000 description 1
230000001079 digestive effect Effects 0.000 description 1
235000014632 disordered eating Nutrition 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000035622 drinking Effects 0.000 description 1
208000000718 duodenal ulcer Diseases 0.000 description 1
210000001198 duodenum Anatomy 0.000 description 1
208000024732 dysthymic disease Diseases 0.000 description 1
235000005686 eating Nutrition 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
230000002327 eosinophilic effect Effects 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000036251 extravasation Effects 0.000 description 1
210000001097 facial muscle Anatomy 0.000 description 1
208000006275 fascioliasis Diseases 0.000 description 1
230000003176 fibrotic effect Effects 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012054 flavored emulsion Substances 0.000 description 1
235000020375 flavoured syrup Nutrition 0.000 description 1
125000004428 fluoroalkoxy group Chemical group 0.000 description 1
235000013305 food Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
230000006870 function Effects 0.000 description 1
206010017758 gastric cancer Diseases 0.000 description 1
208000010749 gastric carcinoma Diseases 0.000 description 1
201000011587 gastric lymphoma Diseases 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
208000029364 generalized anxiety disease Diseases 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000000380 hallucinogen Substances 0.000 description 1
231100000869 headache Toxicity 0.000 description 1
208000031169 hemorrhagic disease Diseases 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
230000035859 hyperreflexia Effects 0.000 description 1
206010020745 hyperreflexia Diseases 0.000 description 1
230000009610 hypersensitivity Effects 0.000 description 1
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
230000001900 immune effect Effects 0.000 description 1
230000036039 immunity Effects 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
230000007803 itching Effects 0.000 description 1
239000010410 layer Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
230000033001 locomotion Effects 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
240000004308 marijuana Species 0.000 description 1
235000012054 meals Nutrition 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
229960002900 methylcellulose Drugs 0.000 description 1
238000002156 mixing Methods 0.000 description 1
210000003097 mucus Anatomy 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000000025 natural resin Substances 0.000 description 1
208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 1
230000008764 nerve damage Effects 0.000 description 1
208000004296 neuralgia Diseases 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
230000002981 neuropathic effect Effects 0.000 description 1
201000001119 neuropathy Diseases 0.000 description 1
230000007823 neuropathy Effects 0.000 description 1
208000015238 neurotic disease Diseases 0.000 description 1
229960002715 nicotine Drugs 0.000 description 1
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
230000000422 nocturnal effect Effects 0.000 description 1
239000007764 o/w emulsion Substances 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
229940127240 opiate Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
125000000962 organic group Chemical group 0.000 description 1
235000020830 overeating Nutrition 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
230000008058 pain sensation Effects 0.000 description 1
208000002851 paranoid schizophrenia Diseases 0.000 description 1
235000021400 peanut butter Nutrition 0.000 description 1
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
210000000578 peripheral nerve Anatomy 0.000 description 1
208000027232 peripheral nervous system disease Diseases 0.000 description 1
208000030062 persistent idiopathic facial pain Diseases 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
231100000572 poisoning Toxicity 0.000 description 1
230000000607 poisoning effect Effects 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
208000028173 post-traumatic stress disease Diseases 0.000 description 1
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
230000006785 proliferative vitreoretinopathy Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
239000003380 propellant Substances 0.000 description 1
208000020016 psychiatric disease Diseases 0.000 description 1
238000000746 purification Methods 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
230000005855 radiation Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000011514 reflex Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
230000000698 schizophrenic effect Effects 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000028327 secretion Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
230000036299 sexual function Effects 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
208000019116 sleep disease Diseases 0.000 description 1
208000000649 small cell carcinoma Diseases 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
230000000392 somatic effect Effects 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
201000001716 specific phobia Diseases 0.000 description 1
210000000278 spinal cord Anatomy 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
201000000498 stomach carcinoma Diseases 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000005062 synaptic transmission Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000057 synthetic resin Substances 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
201000000596 systemic lupus erythematosus Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000010998 test method Methods 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
108700012359 toxins Proteins 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
150000003852 triazoles Chemical group 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
230000002455 vasospastic effect Effects 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
208000027491 vestibular disease Diseases 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
210000001835 viscera Anatomy 0.000 description 1
208000009935 visceral pain Diseases 0.000 description 1
239000007762 w/o emulsion Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- 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
- A61P25/06—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
- A61P25/22—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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Pain & Pain Management (AREA)
Otolaryngology (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicinal Preparation (AREA)
Pyrane Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

BG105859A 1999-03-19 2001-08-30 Тетрахидропиранови производни и тяхното използване като терапевтични вещества BG105859A (bg)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GBGB9906480.0A GB9906480D0 (en)	1999-03-19	1999-03-19	Therapeutic agents
GBGB9924616.7A GB9924616D0 (en)	1999-10-18	1999-10-18	Therapeutic agents
PCT/GB2000/000977 WO2000056728A1 (en)	1999-03-19	2000-03-16	Tetrahydropyran derivatives and their use as therapeutic agents

Publications (1)

Publication Number	Publication Date
BG105859A true BG105859A (bg)	2002-04-30

Family

ID=26315315

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG105859A BG105859A (bg)	1999-03-19	2001-08-30	Тетрахидропиранови производни и тяхното използване като терапевтични вещества

Country Status (23)

Country	Link
US (1)	US6458830B1 (de)
EP (1)	EP1165540B1 (de)
JP (1)	JP2002540107A (de)
KR (1)	KR20010113773A (de)
CN (1)	CN1344264A (de)
AT (1)	ATE247096T1 (de)
AU (2)	AU746251B2 (de)
BG (1)	BG105859A (de)
BR (1)	BR0009127A (de)
CA (1)	CA2367985A1 (de)
CO (1)	CO5150225A1 (de)
CZ (1)	CZ20013377A3 (de)
DE (1)	DE60004504T2 (de)
EA (1)	EA200100902A1 (de)
EE (1)	EE200100491A (de)
ES (1)	ES2203434T3 (de)
HU (1)	HUP0200441A3 (de)
IL (1)	IL144236A0 (de)
NO (1)	NO20014529L (de)
PE (1)	PE20001556A1 (de)
PL (1)	PL350123A1 (de)
SK (1)	SK13322001A3 (de)
WO (2)	WO2000056728A1 (de)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE10001785A1 (de) *	2000-01-18	2001-07-19	Boehringer Ingelheim Pharma	NK¶1¶-Rezeptor-Antagonisten zur Behandlung des Restless Legs Syndroms
GB0017256D0 (en)	2000-07-13	2000-08-30	Merck Sharp & Dohme	Therapeutic agents
GB0020721D0 (en)	2000-08-22	2000-10-11	Merck Sharp & Dohme	Therapeutic agents
PE20020444A1 (es)	2000-09-22	2002-06-14	Merck & Co Inc	Antagonistas de receptores de taquiquinina zwitterionica
JP2004518671A (ja)	2001-01-17	2004-06-24	メルクシャープエンドドームリミテッド	ニューロキニン受容体アンタゴニストとしてのテトラヒドロピラン誘導体
GB0121874D0 (en)	2001-09-10	2001-10-31	Merck Sharp & Dohme	Therapeutic agents
GB0217068D0 (en) *	2002-07-23	2002-08-28	Merck Sharp & Dohme	Therapeutic agents
US20060247216A1 (en) *	2002-10-25	2006-11-02	Haj-Yehia Abdullah I	Steroid compounds comprising superoxide dismutase mimic groups and nitric oxide donor groups, and their use in the preparation of medicaments
US20060166894A1 (en) *	2002-11-29	2006-07-27	Yissum Research Development Company Of The Hebrew University Of Jerusalem	Ace-inhibitors having antioxidant and no-donor activity
AU2004218228A1 (en) *	2003-03-07	2004-09-16	Merck Sharp & Dohme Limited	Tetrahydropyran compounds as tachykinin antagonists
CA2579000C (en) *	2004-09-08	2013-02-05	Altana Pharma Ag	Novel 3-thia-10-aza-phenanthrene derivatives
JP2008521804A (ja) *	2004-11-30	2008-06-26	マリンクロッド・インコーポレイテッド	ベンズフェタミンの結晶化方法
CN101203512A (zh) *	2005-04-22	2008-06-18	第一三共株式会社	杂环化合物
CN100395242C (zh) *	2006-06-08	2008-06-18	华东理工大学	烷氧基萘和萘醌类吡喃碳糖苷化合物及其制备方法
DE102007010077B4 (de) *	2007-02-28	2010-04-08	RUHR-UNIVERSITäT BOCHUM	[1,3]-Dioxane zur Modulation von GABAa-Rezeptoren
WO2013004766A1 (en)	2011-07-04	2013-01-10	Ferrari Giulio	Nk-1 receptor antagonists for treating corneal neovascularisation
WO2014039504A1 (en) *	2012-09-04	2014-03-13	Lauren Sciences Llc	Bolaamphiphilic compounds, compositions and uses thereof
CN106535884A (zh)	2014-06-06	2017-03-22	弗雷克萨斯生物科学公司	免疫调节剂
UY36390A (es)	2014-11-05	2016-06-01	Flexus Biosciences Inc	Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido), sus métodos de síntesis y composiciones farmacéuticas que los contienen
MX2017005462A (es) *	2014-11-05	2017-07-28	Flexus Biosciences Inc	Agentes inmunorreguladores.
UY36391A (es)	2014-11-05	2016-06-01	Flexus Biosciences Inc	Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido1), sus métodos de síntesis y composiciones farmacèuticas que las contienen
HU231150B1 (hu)	2017-03-13	2021-03-29	Richter Gedeon Nyrt	Eljárás racém 3-alkilpiperidin-3-karbonsav-etil-észterek optikai izomerjeinek elválasztására
JP7183196B2 (ja) *	2018-02-06	2022-12-05	第一三共株式会社	アミノアルキル化合物
CN111918647A (zh)	2018-02-26	2020-11-10	圣拉斐尔医院有限公司	用于治疗眼痛的nk-1拮抗剂
WO2021180885A1 (en)	2020-03-11	2021-09-16	Ospedale San Raffaele S.R.L.	Treatment of stem cell deficiency

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9301920D0 (en) *	1993-02-01	1993-03-17	Foundation For Ethnobiology Th	Polycetylenes

2000
- 2000-03-10 CO CO00017612A patent/CO5150225A1/es unknown
- 2000-03-13 PE PE2000000218A patent/PE20001556A1/es not_active Application Discontinuation
- 2000-03-16 IL IL14423600A patent/IL144236A0/xx unknown
- 2000-03-16 CZ CZ20013377A patent/CZ20013377A3/cs unknown
- 2000-03-16 HU HU0200441A patent/HUP0200441A3/hu unknown
- 2000-03-16 WO PCT/GB2000/000977 patent/WO2000056728A1/en not_active Ceased
- 2000-03-16 EP EP00911045A patent/EP1165540B1/de not_active Expired - Lifetime
- 2000-03-16 AU AU33042/00A patent/AU746251B2/en not_active Ceased
- 2000-03-16 EA EA200100902A patent/EA200100902A1/ru unknown
- 2000-03-16 PL PL00350123A patent/PL350123A1/xx not_active Application Discontinuation
- 2000-03-16 BR BR0009127-8A patent/BR0009127A/pt not_active Application Discontinuation
- 2000-03-16 DE DE60004504T patent/DE60004504T2/de not_active Expired - Fee Related
- 2000-03-16 CN CN00805114A patent/CN1344264A/zh active Pending
- 2000-03-16 WO PCT/GB2000/000974 patent/WO2000056727A1/en not_active Ceased
- 2000-03-16 KR KR1020017011885A patent/KR20010113773A/ko not_active Withdrawn
- 2000-03-16 SK SK1332-2001A patent/SK13322001A3/sk unknown
- 2000-03-16 EE EEP200100491A patent/EE200100491A/xx unknown
- 2000-03-16 JP JP2000606588A patent/JP2002540107A/ja not_active Withdrawn
- 2000-03-16 CA CA002367985A patent/CA2367985A1/en not_active Abandoned
- 2000-03-16 US US09/936,343 patent/US6458830B1/en not_active Expired - Fee Related
- 2000-03-16 AU AU33044/00A patent/AU3304400A/en not_active Abandoned
- 2000-03-16 AT AT00911045T patent/ATE247096T1/de not_active IP Right Cessation
- 2000-03-16 ES ES00911045T patent/ES2203434T3/es not_active Expired - Lifetime
2001
- 2001-08-30 BG BG105859A patent/BG105859A/bg unknown
- 2001-09-18 NO NO20014529A patent/NO20014529L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CA2367985A1 (en)	2000-09-28
ATE247096T1 (de)	2003-08-15
DE60004504D1 (de)	2003-09-18
KR20010113773A (ko)	2001-12-28
DE60004504T2 (de)	2004-06-24
HUP0200441A2 (hu)	2002-07-29
NO20014529L (no)	2001-11-13
AU3304400A (en)	2000-10-09
WO2000056728A1 (en)	2000-09-28
CN1344264A (zh)	2002-04-10
SK13322001A3 (sk)	2002-02-05
US6458830B1 (en)	2002-10-01
EP1165540B1 (de)	2003-08-13
JP2002540107A (ja)	2002-11-26
EA200100902A1 (ru)	2002-02-28
CZ20013377A3 (cs)	2002-02-13
AU746251B2 (en)	2002-04-18
WO2000056727A1 (en)	2000-09-28
EE200100491A (et)	2002-12-16
CO5150225A1 (es)	2002-04-29
IL144236A0 (en)	2002-05-23
EP1165540A1 (de)	2002-01-02
NO20014529D0 (no)	2001-09-18
BR0009127A (pt)	2001-12-26
PL350123A1 (en)	2002-11-04
PE20001556A1 (es)	2001-01-13
HUP0200441A3 (en)	2002-09-30
ES2203434T3 (es)	2004-04-16
AU3304200A (en)	2000-10-09

Publication	Publication Date	Title
BG105859A (bg)	2002-04-30	Тетрахидропиранови производни и тяхното използване като терапевтични вещества
DE69521208T2 (de)	2001-11-08	Morpholinderivate und ihre verwendung als therapeutische mittel
US5728695A (en)	1998-03-17	Spiroketal derivatives, compositions containing them and their use as therapeutic agents
AU715558B2 (en)	2000-02-03	Spiro-piperidine derivatives and their use as tachykinin antagonists
AU713095B2 (en)	1999-11-25	3-benzylaminopyrrolidines and -piperidines as tachykinin receptor antagonists
US5985896A (en)	1999-11-16	Piperidine and morpholine derivatives and their use as therapeutic agents
JP3071467B2 (ja)	2000-07-31	置換モルホリン誘導体およびその治療剤としての使用
HU217428B (hu)	2000-01-28	3-(5-Tetrazolil-benzil)-amino-piperidin-származékok, eljárás előállításukra és ezeket a vegyületeket tartalmazó gyógyászati készítmények
WO1997001553A1 (en)	1997-01-16	Piperidine and morpholine derivatives and their use as therapeutic agents
JP2000500154A (ja)	2000-01-11	モルホリン誘導体及び治療薬としてのそれらの使用
EA032559B1 (ru)	2019-06-28	Бициклические аннелированные гетероарильные или арильные соединения и их применение в качестве ингибиторов irak4
JP2014524886A (ja)	2014-09-25	カリウムチャネル遮断剤としてのアミン誘導体
JP2026503035A (ja)	2026-01-27	新規な可逆性ｄｐｐ１阻害剤及びその用途
WO2002016344A1 (en)	2002-02-28	Tetrahydropyran derivatives as nk-1 receptor antagonists
MXPA01009408A (en)	2002-06-05	Tetrahydropyran derivatives and their use as therapeutic agents
CA2237638A1 (en)	1997-05-29	Spiro-piperidine derivatives and their use as tachykinin antagonists