OA10576A - 3-(5-Tetrazolyl-benzyl) amino-piperidine derivatives and antagonists of tachykinins - Google Patents

3-(5-Tetrazolyl-benzyl) amino-piperidine derivatives and antagonists of tachykinins Download PDF

Info

Publication number: OA10576A
Authority: OA; OAPI
Prior art keywords: tetrazol; piperidin; methoxy; phenyl; formula
Prior art date: 1993-09-22

Application number

OA60801A

Other languages

English (en)

Inventor

Brian Evans

Middlemiss David

Naylor Alan

Neil Anthony Pegg

Maria Victoria Vinader

Gerard Martin Paul Giblin

Tania Hubbard

Michael Menteith Hann

Xiao-Qing Lewell

Stephen Paul Watson

Duncan Robert Armour

Original Assignee

Glaxo Group Ltd

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.)

1993-09-22

Filing date

1996-03-21

Publication date

2002-06-03

1993-09-22 Priority claimed from GB939319606A external-priority patent/GB9319606D0/en

1993-12-31 Priority claimed from GB9326583A external-priority patent/GB9326583D0/en

1996-03-21 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

2002-06-03 Publication of OA10576A publication Critical patent/OA10576A/en

Links

102000003141 Tachykinin Human genes 0.000 title claims abstract description 9
108060008037 tachykinin Proteins 0.000 title claims abstract description 9
239000005557 antagonist Substances 0.000 title description 3
DNPSSGUSLPNJNX-UHFFFAOYSA-N 3-[[3-(2H-tetrazol-5-yl)phenyl]methyl]piperidin-1-amine Chemical class N1N=NN=C1C=1C=CC=C(CC2CN(CCC2)N)C1 DNPSSGUSLPNJNX-UHFFFAOYSA-N 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 26
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 22
239000001257 hydrogen Substances 0.000 claims abstract description 19
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 18
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
125000005843 halogen group Chemical group 0.000 claims abstract description 8
230000001404 mediated effect Effects 0.000 claims abstract description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 302
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 32
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 12
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 claims description 7
102100024304 Protachykinin-1 Human genes 0.000 claims description 7
101800003906 Substance P Proteins 0.000 claims description 7
235000019270 ammonium chloride Nutrition 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
150000002431 hydrogen Chemical group 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
238000002560 therapeutic procedure Methods 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 2
241000124008 Mammalia Species 0.000 claims 1
150000003839 salts Chemical class 0.000 abstract description 17
230000008569 process Effects 0.000 abstract description 11
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
125000002252 acyl group Chemical group 0.000 abstract 1
150000003053 piperidines Chemical class 0.000 abstract 1
239000012453 solvate Substances 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 320
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 177
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 124
239000000203 mixture Substances 0.000 description 114
239000007787 solid Substances 0.000 description 113
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
239000000543 intermediate Substances 0.000 description 102
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 99
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 90
239000000243 solution Substances 0.000 description 89
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 67
229940093499 ethyl acetate Drugs 0.000 description 59
235000019439 ethyl acetate Nutrition 0.000 description 59
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
229910021529 ammonia Inorganic materials 0.000 description 47
235000019441 ethanol Nutrition 0.000 description 46
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
229910052757 nitrogen Inorganic materials 0.000 description 33
239000002904 solvent Substances 0.000 description 32
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 30
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
229910052938 sodium sulfate Inorganic materials 0.000 description 28
235000011152 sodium sulphate Nutrition 0.000 description 28
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 26
239000007832 Na2SO4 Substances 0.000 description 25
-1 oxalic Chemical class 0.000 description 25
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
235000011167 hydrochloric acid Nutrition 0.000 description 22
229960000443 hydrochloric acid Drugs 0.000 description 22
239000003921 oil Substances 0.000 description 20
235000019198 oils Nutrition 0.000 description 20
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
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
239000012458 free base Substances 0.000 description 18
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 15
229960000583 acetic acid Drugs 0.000 description 15
239000000725 suspension Substances 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
206010047700 Vomiting Diseases 0.000 description 14
239000002253 acid Substances 0.000 description 14
239000000460 chlorine Substances 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
239000012267 brine Substances 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 13
239000010410 layer Substances 0.000 description 13
235000017550 sodium carbonate Nutrition 0.000 description 13
229910000029 sodium carbonate Inorganic materials 0.000 description 13
229940001593 sodium carbonate Drugs 0.000 description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
239000000843 powder Substances 0.000 description 12
239000000284 extract Substances 0.000 description 11
229910052943 magnesium sulfate Inorganic materials 0.000 description 11
235000019341 magnesium sulphate Nutrition 0.000 description 11
239000012044 organic layer Substances 0.000 description 11
238000010992 reflux Methods 0.000 description 11
238000003756 stirring Methods 0.000 description 11
238000009472 formulation Methods 0.000 description 10
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 10
LGWHVLLTRCDFDK-UHFFFAOYSA-N 2-methoxy-5-(5-methyltetrazol-1-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1N1C(C)=NN=N1 LGWHVLLTRCDFDK-UHFFFAOYSA-N 0.000 description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 9
208000002193 Pain Diseases 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
235000011054 acetic acid Nutrition 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
239000002775 capsule Substances 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
238000004949 mass spectrometry Methods 0.000 description 8
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
PITHNUWDJUJELK-UHFFFAOYSA-N 2-methoxy-5-(tetrazol-1-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1N1N=NN=C1 PITHNUWDJUJELK-UHFFFAOYSA-N 0.000 description 7
PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 7
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
238000010511 deprotection reaction Methods 0.000 description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
229910000041 hydrogen chloride Inorganic materials 0.000 description 7
238000004452 microanalysis Methods 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
239000006071 cream Substances 0.000 description 6
239000003814 drug Substances 0.000 description 6
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 6
239000011737 fluorine Substances 0.000 description 6
229910052731 fluorine Inorganic materials 0.000 description 6
239000012362 glacial acetic acid Substances 0.000 description 6
VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 6
235000011181 potassium carbonates Nutrition 0.000 description 6
239000000047 product Substances 0.000 description 6
230000005855 radiation Effects 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
235000011121 sodium hydroxide Nutrition 0.000 description 6
229940083608 sodium hydroxide Drugs 0.000 description 6
239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
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 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
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 5
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
235000011114 ammonium hydroxide Nutrition 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
238000001816 cooling Methods 0.000 description 5
UBSPKGKFFQKZJB-UHFFFAOYSA-N methyl 4-nitrobutanoate Chemical compound COC(=O)CCC[N+]([O-])=O UBSPKGKFFQKZJB-UHFFFAOYSA-N 0.000 description 5
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 5
239000011734 sodium Substances 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 5
CMIBUZBMZCBCAT-HZPDHXFCSA-N (2r,3r)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(=O)C1=CC=C(C)C=C1 CMIBUZBMZCBCAT-HZPDHXFCSA-N 0.000 description 4
RDLGAKSDKYJGDS-UHFFFAOYSA-N 2-hydroxy-5-(tetrazol-1-yl)benzaldehyde Chemical compound C1=C(C=O)C(O)=CC=C1N1N=NN=C1 RDLGAKSDKYJGDS-UHFFFAOYSA-N 0.000 description 4
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
125000000217 alkyl group Chemical group 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
239000012043 crude product Substances 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
229940079593 drug Drugs 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
150000004678 hydrides Chemical class 0.000 description 4
239000005457 ice water Substances 0.000 description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
239000007788 liquid Substances 0.000 description 4
238000000746 purification Methods 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)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 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 4
239000000375 suspending agent Substances 0.000 description 4
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 4
238000001665 trituration Methods 0.000 description 4
239000008215 water for injection Substances 0.000 description 4
NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 3
YQNRPEFJKQVSNX-UHFFFAOYSA-N 2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1N1C(C(F)(F)F)=NN=N1 YQNRPEFJKQVSNX-UHFFFAOYSA-N 0.000 description 3
GFMAFYNUQDLPBP-UHFFFAOYSA-N 2-phenylpiperidin-3-amine Chemical compound NC1CCCNC1C1=CC=CC=C1 GFMAFYNUQDLPBP-UHFFFAOYSA-N 0.000 description 3
IJIBRSFAXRFPPN-UHFFFAOYSA-N 5-bromo-2-methoxybenzaldehyde Chemical compound COC1=CC=C(Br)C=C1C=O IJIBRSFAXRFPPN-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
229920003084 Avicel® PH-102 Polymers 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
206010020751 Hypersensitivity Diseases 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
241000282341 Mustela putorius furo Species 0.000 description 3
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
230000007815 allergy Effects 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
229910000085 borane Inorganic materials 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
238000004296 chiral HPLC 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
238000007796 conventional method Methods 0.000 description 3
201000010099 disease Diseases 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
230000008570 general process Effects 0.000 description 3
239000004312 hexamethylene tetramine Substances 0.000 description 3
235000010299 hexamethylene tetramine Nutrition 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
208000027866 inflammatory disease Diseases 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000012528 membrane Substances 0.000 description 3
201000001119 neuropathy Diseases 0.000 description 3
230000007823 neuropathy Effects 0.000 description 3
239000002674 ointment Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000003381 stabilizer Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000001117 sulphuric acid Substances 0.000 description 3
235000011149 sulphuric acid Nutrition 0.000 description 3
238000012360 testing method Methods 0.000 description 3
150000003536 tetrazoles Chemical class 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
DZYPLFAASKBQBS-ICSRJNTNSA-N (2s,3s)-n-[[2-methoxy-5-(tetrazol-1-yl)phenyl]methyl]-2-phenylpiperidin-3-amine Chemical compound C1([C@@H]2NCCC[C@@H]2NCC2=CC(=CC=C2OC)N2N=NN=C2)=CC=CC=C1 DZYPLFAASKBQBS-ICSRJNTNSA-N 0.000 description 2
KQBDLOVXZHOAJI-UHFFFAOYSA-N (4-phenylmethoxyphenyl)azanium;chloride Chemical compound Cl.C1=CC(N)=CC=C1OCC1=CC=CC=C1 KQBDLOVXZHOAJI-UHFFFAOYSA-N 0.000 description 2
XTYXKLZQDSOFES-PWSUYJOCSA-N (5r,6s)-6-(4-methoxyphenyl)-5-nitropiperidin-2-one Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@H]([N+]([O-])=O)CCC(=O)N1 XTYXKLZQDSOFES-PWSUYJOCSA-N 0.000 description 2
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
ZGEOYRPBZDERPR-UHFFFAOYSA-N 1-[3-(1,3-dioxolan-2-yl)-4-methoxyphenyl]tetrazole Chemical compound COC1=CC=C(N2N=NN=C2)C=C1C1OCCO1 ZGEOYRPBZDERPR-UHFFFAOYSA-N 0.000 description 2
WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 2
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 2
PXHJVNQZUHJEPS-UHFFFAOYSA-N 2-(3-fluorophenyl)-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1C1=CC=CC(F)=C1 PXHJVNQZUHJEPS-UHFFFAOYSA-N 0.000 description 2
RQQJAMKQXWKJMY-UHFFFAOYSA-N 2-(4-methylphenyl)-3-nitropyridine Chemical compound C1=CC(C)=CC=C1C1=NC=CC=C1[N+]([O-])=O RQQJAMKQXWKJMY-UHFFFAOYSA-N 0.000 description 2
NJLAQWFIXLFBKW-UHFFFAOYSA-N 2-(4-nitrophenyl)tetrazole Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1N=NC=N1 NJLAQWFIXLFBKW-UHFFFAOYSA-N 0.000 description 2
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
QPFZIKLBJMQIOE-UHFFFAOYSA-N 2-fluoro-4-(5-methyltetrazol-1-yl)phenol Chemical compound CC1=NN=NN1C1=CC=C(O)C(F)=C1 QPFZIKLBJMQIOE-UHFFFAOYSA-N 0.000 description 2
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
ALAWBLGYKHSCEU-UHFFFAOYSA-N 4-(5-ethyltetrazol-1-yl)phenol Chemical compound CCC1=NN=NN1C1=CC=C(O)C=C1 ALAWBLGYKHSCEU-UHFFFAOYSA-N 0.000 description 2
VENLNRWSCKIJFP-UHFFFAOYSA-N 4-(5-methylsulfanyltetrazol-1-yl)phenol Chemical compound CSC1=NN=NN1C1=CC=C(O)C=C1 VENLNRWSCKIJFP-UHFFFAOYSA-N 0.000 description 2
PQGLYPKJONLLFZ-UHFFFAOYSA-N 4-(5-phenyltetrazol-1-yl)phenol Chemical compound C1=CC(O)=CC=C1N1C(C=2C=CC=CC=2)=NN=N1 PQGLYPKJONLLFZ-UHFFFAOYSA-N 0.000 description 2
DSSMRGRPMUPZRP-UHFFFAOYSA-N 4-(5-propyltetrazol-1-yl)phenol Chemical compound CCCC1=NN=NN1C1=CC=C(O)C=C1 DSSMRGRPMUPZRP-UHFFFAOYSA-N 0.000 description 2
AXJKWXIVFCNRCQ-UHFFFAOYSA-N 4-(tetrazol-1-yl)phenol Chemical compound C1=CC(O)=CC=C1N1N=NN=C1 AXJKWXIVFCNRCQ-UHFFFAOYSA-N 0.000 description 2
HELCKJWIYMGRIB-UHFFFAOYSA-N 4-(tetrazol-2-yl)aniline Chemical compound C1=CC(N)=CC=C1N1N=NC=N1 HELCKJWIYMGRIB-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
UOYXRXIWIBKGOM-UHFFFAOYSA-N 4-[5-(trifluoromethyl)tetrazol-1-yl]phenol Chemical compound C1=CC(O)=CC=C1N1C(C(F)(F)F)=NN=N1 UOYXRXIWIBKGOM-UHFFFAOYSA-N 0.000 description 2
ZJRZRSRWOWMNHE-UHFFFAOYSA-N 5-cyclopropyl-1-(4-phenylmethoxyphenyl)tetrazole Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1N1N=NN=C1C1CC1 ZJRZRSRWOWMNHE-UHFFFAOYSA-N 0.000 description 2
QONQTHCHUWXHBZ-UHFFFAOYSA-N 6-(3-bromo-4-methylphenyl)piperidine-2,5-dione Chemical compound C1=C(Br)C(C)=CC=C1C1C(=O)CCC(=O)N1 QONQTHCHUWXHBZ-UHFFFAOYSA-N 0.000 description 2
YNRWWYKVAHHVGF-UHFFFAOYSA-N 6-(3-bromophenyl)-5-hydroxyiminopiperidin-2-one Chemical compound ON=C1CCC(=O)NC1C1=CC=CC(Br)=C1 YNRWWYKVAHHVGF-UHFFFAOYSA-N 0.000 description 2
UGNQIOIMMKKDEC-UHFFFAOYSA-N 6-(3-bromophenyl)piperidine-2,5-dione Chemical compound BrC1=CC=CC(C2C(CCC(=O)N2)=O)=C1 UGNQIOIMMKKDEC-UHFFFAOYSA-N 0.000 description 2
YVEKLBOLDXKKSU-UHFFFAOYSA-N 6-(3-chlorophenyl)-5-hydroxyiminopiperidin-2-one Chemical compound ON=C1CCC(=O)NC1C1=CC=CC(Cl)=C1 YVEKLBOLDXKKSU-UHFFFAOYSA-N 0.000 description 2
KUSDAAUSAZOEDD-UHFFFAOYSA-N 6-(3-chlorophenyl)-5-nitropiperidin-2-one Chemical compound [O-][N+](=O)C1CCC(=O)NC1C1=CC=CC(Cl)=C1 KUSDAAUSAZOEDD-UHFFFAOYSA-N 0.000 description 2
XUWAPPWBVIKXJS-UHFFFAOYSA-N 6-(3-chlorophenyl)piperidine-2,5-dione Chemical compound ClC1=CC=CC(C2C(CCC(=O)N2)=O)=C1 XUWAPPWBVIKXJS-UHFFFAOYSA-N 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
239000005695 Ammonium acetate Substances 0.000 description 2
206010002383 Angina Pectoris Diseases 0.000 description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
208000032131 Diabetic Neuropathies Diseases 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
239000004150 EU approved colour Substances 0.000 description 2
208000001640 Fibromyalgia Diseases 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
206010061218 Inflammation Diseases 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 2
208000019695 Migraine disease Diseases 0.000 description 2
NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
208000003251 Pruritus Diseases 0.000 description 2
206010038776 Retching Diseases 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
239000004133 Sodium thiosulphate Substances 0.000 description 2
NNWLFMQCSCIQEA-UHFFFAOYSA-N [2-methoxy-5-(tetrazol-1-yl)phenyl]methanol Chemical compound C1=C(CO)C(OC)=CC=C1N1N=NN=C1 NNWLFMQCSCIQEA-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
229960004050 aminobenzoic acid Drugs 0.000 description 2
235000019257 ammonium acetate Nutrition 0.000 description 2
229940043376 ammonium acetate Drugs 0.000 description 2
230000003474 anti-emetic effect Effects 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000003637 basic solution Substances 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
230000027455 binding Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
210000000170 cell membrane Anatomy 0.000 description 2
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000006482 condensation reaction Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 2
KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 2
238000007907 direct compression Methods 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
201000006549 dyspepsia Diseases 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
229940093476 ethylene glycol Drugs 0.000 description 2
239000012530 fluid Substances 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
239000000499 gel Substances 0.000 description 2
238000007429 general method Methods 0.000 description 2
239000008187 granular material Substances 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
150000002466 imines Chemical class 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
230000004054 inflammatory process Effects 0.000 description 2
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
239000006210 lotion Substances 0.000 description 2
206010025482 malaise Diseases 0.000 description 2
239000000463 material Substances 0.000 description 2
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
206010027599 migraine Diseases 0.000 description 2
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
WYWIFABBXFUGLM-UHFFFAOYSA-N oxymetazoline Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C)=C1CC1=NCCN1 WYWIFABBXFUGLM-UHFFFAOYSA-N 0.000 description 2
ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
208000033808 peripheral neuropathy Diseases 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000008363 phosphate buffer Substances 0.000 description 2
PEUGKEHLRUVPAN-UHFFFAOYSA-N piperidin-3-amine Chemical compound NC1CCCNC1 PEUGKEHLRUVPAN-UHFFFAOYSA-N 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
229920000728 polyester Polymers 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
229920001296 polysiloxane Polymers 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
230000002335 preservative effect Effects 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
239000008213 purified water Substances 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
235000010288 sodium nitrite Nutrition 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
239000003053 toxin Substances 0.000 description 2
231100000765 toxin Toxicity 0.000 description 2
108700012359 toxins Proteins 0.000 description 2
230000000472 traumatic effect Effects 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
230000008673 vomiting Effects 0.000 description 2
238000005406 washing Methods 0.000 description 2
DUNKXUFBGCUVQW-UHFFFAOYSA-J zirconium tetrachloride Chemical compound Cl[Zr](Cl)(Cl)Cl DUNKXUFBGCUVQW-UHFFFAOYSA-J 0.000 description 2
WYQSQYKQFQLDJV-UNMCSNQZSA-N (2s,3s)-n-[[5-(5-cyclopropyltetrazol-1-yl)-2-methoxyphenyl]methyl]-2-phenylpiperidin-3-amine Chemical compound C1([C@@H]2NCCC[C@@H]2NCC2=CC(=CC=C2OC)N2C(=NN=N2)C2CC2)=CC=CC=C1 WYQSQYKQFQLDJV-UNMCSNQZSA-N 0.000 description 1
RMGYQBHKEWWTOY-UHFFFAOYSA-N (3,4-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(F)=C1 RMGYQBHKEWWTOY-UHFFFAOYSA-N 0.000 description 1
WPVBHUUZDFUIJA-UHFFFAOYSA-N (3-fluoro-4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1F WPVBHUUZDFUIJA-UHFFFAOYSA-N 0.000 description 1
KNXQDJCZSVHEIW-UHFFFAOYSA-N (3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(F)=C1 KNXQDJCZSVHEIW-UHFFFAOYSA-N 0.000 description 1
YJQDBKGGRPJSOI-UHFFFAOYSA-N (3-formyl-4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1C=O YJQDBKGGRPJSOI-UHFFFAOYSA-N 0.000 description 1
PWMVXBCPDVMGTP-UHFFFAOYSA-N (3-formyl-4-methoxyphenyl)cyanamide Chemical compound COC1=CC=C(NC#N)C=C1C=O PWMVXBCPDVMGTP-UHFFFAOYSA-N 0.000 description 1
FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 1
NKTAIXUWRAJQFA-UHFFFAOYSA-N (4-anilinophenyl) acetate Chemical compound C1=CC(OC(=O)C)=CC=C1NC1=CC=CC=C1 NKTAIXUWRAJQFA-UHFFFAOYSA-N 0.000 description 1
BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 1
YPLUMYCVGMWPHW-PWSUYJOCSA-N (5r,6s)-6-(3-bromo-4-methylphenyl)-5-nitropiperidin-2-one Chemical compound C1=C(Br)C(C)=CC=C1[C@H]1[C@H]([N+]([O-])=O)CCC(=O)N1 YPLUMYCVGMWPHW-PWSUYJOCSA-N 0.000 description 1
FZHWJJRTEIUGMD-KOLCDFICSA-N (5r,6s)-6-(3-bromophenyl)-5-nitropiperidin-2-one Chemical compound [O-][N+](=O)[C@@H]1CCC(=O)N[C@H]1C1=CC=CC(Br)=C1 FZHWJJRTEIUGMD-KOLCDFICSA-N 0.000 description 1
FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
FGWYWKIOMUZSQF-UHFFFAOYSA-N 1,1,1-triethoxypropane Chemical compound CCOC(CC)(OCC)OCC FGWYWKIOMUZSQF-UHFFFAOYSA-N 0.000 description 1
JAFMOTJMRSZOJE-UHFFFAOYSA-N 1,1,1-trimethoxybutane Chemical compound CCCC(OC)(OC)OC JAFMOTJMRSZOJE-UHFFFAOYSA-N 0.000 description 1
KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 description 1
OKFQMBUOPVEZKI-UHFFFAOYSA-N 1-(3-fluoro-4-phenylmethoxyphenyl)-5-methyltetrazole Chemical compound CC1=NN=NN1C(C=C1F)=CC=C1OCC1=CC=CC=C1 OKFQMBUOPVEZKI-UHFFFAOYSA-N 0.000 description 1
MOXZSKYLLSPATM-UHFFFAOYSA-N 1-(4-hydroxyphenyl)-2h-tetrazole-5-thione Chemical compound C1=CC(O)=CC=C1N1C(=S)N=NN1 MOXZSKYLLSPATM-UHFFFAOYSA-N 0.000 description 1
PHMJZCMURONFOQ-UHFFFAOYSA-N 1-(4-phenylmethoxyphenyl)-5-(trifluoromethyl)tetrazole Chemical compound FC(F)(F)C1=NN=NN1C(C=C1)=CC=C1OCC1=CC=CC=C1 PHMJZCMURONFOQ-UHFFFAOYSA-N 0.000 description 1
ZOENJPQKPLXOGE-UHFFFAOYSA-N 1-(cyclopropylmethyl)tetrazole Chemical compound C1=NN=NN1CC1CC1 ZOENJPQKPLXOGE-UHFFFAOYSA-N 0.000 description 1
WATHQDUMPVLRMV-UHFFFAOYSA-N 1-[3-(1,3-dioxolan-2-yl)-4-methoxyphenyl]-5-methylsulfonyltetrazole Chemical compound COC1=CC=C(N2C(=NN=N2)S(C)(=O)=O)C=C1C1OCCO1 WATHQDUMPVLRMV-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
SINBGNJPYWNUQI-UHFFFAOYSA-N 2,2,2-trifluoro-1-imidazol-1-ylethanone Chemical compound FC(F)(F)C(=O)N1C=CN=C1 SINBGNJPYWNUQI-UHFFFAOYSA-N 0.000 description 1
UUUDBNXLHYOQJA-UHFFFAOYSA-N 2,2,2-trifluoro-n-(4-phenylmethoxyphenyl)acetamide Chemical compound C1=CC(NC(=O)C(F)(F)F)=CC=C1OCC1=CC=CC=C1 UUUDBNXLHYOQJA-UHFFFAOYSA-N 0.000 description 1
PBOFYVXABUFIMT-UHFFFAOYSA-N 2,2,2-trifluoro-n-(4-phenylmethoxyphenyl)ethanimidoyl chloride Chemical compound C1=CC(N=C(Cl)C(F)(F)F)=CC=C1OCC1=CC=CC=C1 PBOFYVXABUFIMT-UHFFFAOYSA-N 0.000 description 1
RNUVPMNFUREPOF-UHFFFAOYSA-N 2,6-dideoxy-3-O-methyl-beta-D-arabino-hexopyranosyl-(1->4)-2,6-dideoxy-3-O-methyl-beta-D-arabino-hexopyranosyl-(1->4)-2,6-dideoxy-3-O-methyl-D-lyxo-hexopyranose Natural products O1C(C)C(O)C(OC)CC1OC1C(OC)CC(OC2C(CC(O)OC2C)OC)OC1C RNUVPMNFUREPOF-UHFFFAOYSA-N 0.000 description 1
NATSYHRCJNDGIA-UHFFFAOYSA-N 2-(3,4-difluorophenyl)-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1C1=CC=C(F)C(F)=C1 NATSYHRCJNDGIA-UHFFFAOYSA-N 0.000 description 1
FVSSIWUXRRPEPW-UHFFFAOYSA-N 2-(3-fluoro-4-methylphenyl)-3-nitropyridine Chemical compound C1=C(F)C(C)=CC=C1C1=NC=CC=C1[N+]([O-])=O FVSSIWUXRRPEPW-UHFFFAOYSA-N 0.000 description 1
WOFJRVBRBNYZFI-UHFFFAOYSA-N 2-(4-fluorophenyl)-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1C1=CC=C(F)C=C1 WOFJRVBRBNYZFI-UHFFFAOYSA-N 0.000 description 1
RFWYLXGEHPBJHF-UHFFFAOYSA-N 2-(4-fluorophenyl)piperidin-3-amine Chemical compound NC1CCCNC1C1=CC=C(F)C=C1 RFWYLXGEHPBJHF-UHFFFAOYSA-N 0.000 description 1
ZUSDSFAYTSYKET-UHFFFAOYSA-N 2-(5-methyltetrazol-1-yl)benzaldehyde Chemical compound CC1=NN=NN1C1=CC=CC=C1C=O ZUSDSFAYTSYKET-UHFFFAOYSA-N 0.000 description 1
DPERHGGMHVLAJA-UHFFFAOYSA-N 2-[1-(3-formyl-4-methoxyphenyl)tetrazol-5-yl]acetamide Chemical compound C1=C(C=O)C(OC)=CC=C1N1C(CC(N)=O)=NN=N1 DPERHGGMHVLAJA-UHFFFAOYSA-N 0.000 description 1
VNKLAQDBLDONTM-UHFFFAOYSA-N 2-hydroxy-5-(5-methylsulfanyltetrazol-1-yl)benzaldehyde Chemical compound CSC1=NN=NN1C1=CC=C(O)C(C=O)=C1 VNKLAQDBLDONTM-UHFFFAOYSA-N 0.000 description 1
PMKUXKYBORWOLE-UHFFFAOYSA-N 2-hydroxy-5-(5-phenyltetrazol-1-yl)benzaldehyde Chemical compound C1=C(C=O)C(O)=CC=C1N1C(C=2C=CC=CC=2)=NN=N1 PMKUXKYBORWOLE-UHFFFAOYSA-N 0.000 description 1
MNMFUOLBSGIHHW-UHFFFAOYSA-N 2-hydroxy-5-(5-propyltetrazol-1-yl)benzaldehyde Chemical compound CCCC1=NN=NN1C1=CC=C(O)C(C=O)=C1 MNMFUOLBSGIHHW-UHFFFAOYSA-N 0.000 description 1
HUZDUGOQWSFXGK-UHFFFAOYSA-N 2-hydroxy-5-[5-(trifluoromethyl)tetrazol-1-yl]benzaldehyde Chemical compound C1=C(C=O)C(O)=CC=C1N1C(C(F)(F)F)=NN=N1 HUZDUGOQWSFXGK-UHFFFAOYSA-N 0.000 description 1
RRRANKAAMRHRNT-UHFFFAOYSA-N 2-methoxy-5-(1-methyltetrazol-5-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1C1=NN=NN1C RRRANKAAMRHRNT-UHFFFAOYSA-N 0.000 description 1
VJYKDNKGQKIUSE-UHFFFAOYSA-N 2-methoxy-5-(2-methyltetrazol-5-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1C1=NN(C)N=N1 VJYKDNKGQKIUSE-UHFFFAOYSA-N 0.000 description 1
VBEHKYGAZVEBIA-UHFFFAOYSA-N 2-methoxy-5-(2h-tetrazol-5-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1C1=NN=NN1 VBEHKYGAZVEBIA-UHFFFAOYSA-N 0.000 description 1
YEZGKPPNYNFRNK-UHFFFAOYSA-N 2-methoxy-5-(5-methylsulfanyltetrazol-1-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1N1C(SC)=NN=N1 YEZGKPPNYNFRNK-UHFFFAOYSA-N 0.000 description 1
CLCRZYKTNHZYKS-UHFFFAOYSA-N 2-methoxy-5-(5-methylsulfonyltetrazol-1-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1N1C(S(C)(=O)=O)=NN=N1 CLCRZYKTNHZYKS-UHFFFAOYSA-N 0.000 description 1
SFIFGMJFJJWWSY-UHFFFAOYSA-N 2-methoxy-5-(5-phenyltetrazol-1-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1N1C(C=2C=CC=CC=2)=NN=N1 SFIFGMJFJJWWSY-UHFFFAOYSA-N 0.000 description 1
ADAQJXCXQIWYLW-UHFFFAOYSA-N 2-methoxy-5-(5-propyltetrazol-1-yl)benzaldehyde Chemical compound CCCC1=NN=NN1C1=CC=C(OC)C(C=O)=C1 ADAQJXCXQIWYLW-UHFFFAOYSA-N 0.000 description 1
UQMAWQAAKUZBHQ-UHFFFAOYSA-N 2-methoxy-5-(tetrazol-1-yl)benzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1N1N=NN=C1 UQMAWQAAKUZBHQ-UHFFFAOYSA-N 0.000 description 1
BYYVHDGSSPZEAN-UHFFFAOYSA-N 2-methoxy-5-(tetrazol-1-ylmethyl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1CN1N=NN=C1 BYYVHDGSSPZEAN-UHFFFAOYSA-N 0.000 description 1
BQLVODDCLKODKL-UHFFFAOYSA-N 2-methoxy-5-(tetrazol-2-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1N1N=NC=N1 BQLVODDCLKODKL-UHFFFAOYSA-N 0.000 description 1
YGQZWFYEBCZSAI-UHFFFAOYSA-N 2-methoxy-5-(tetrazol-2-ylmethyl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1CN1N=NC=N1 YGQZWFYEBCZSAI-UHFFFAOYSA-N 0.000 description 1
CDXWVKFXOLZNPJ-UHFFFAOYSA-N 2-propan-2-yl-5-(tetrazol-1-yl)benzaldehyde Chemical compound C1=C(C=O)C(C(C)C)=CC=C1N1N=NN=C1 CDXWVKFXOLZNPJ-UHFFFAOYSA-N 0.000 description 1
WTXXUAHMTVAQHW-UHFFFAOYSA-N 3-bromo-4-methylbenzaldehyde Chemical compound CC1=CC=C(C=O)C=C1Br WTXXUAHMTVAQHW-UHFFFAOYSA-N 0.000 description 1
SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 description 1
SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 1
ABONMZLRXQTGAL-UHFFFAOYSA-N 3-fluoro-2-hydroxy-5-(5-methyltetrazol-1-yl)benzaldehyde Chemical compound CC1=NN=NN1C1=CC(F)=C(O)C(C=O)=C1 ABONMZLRXQTGAL-UHFFFAOYSA-N 0.000 description 1
DLLRQHPHTKZQLZ-UHFFFAOYSA-N 3-fluoro-2-methoxy-5-(5-methyltetrazol-1-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=C(F)C=C1N1C(C)=NN=N1 DLLRQHPHTKZQLZ-UHFFFAOYSA-N 0.000 description 1
XLEYXHRMSUPJST-UHFFFAOYSA-N 3-fluoro-4-phenylmethoxyaniline Chemical compound FC1=CC(N)=CC=C1OCC1=CC=CC=C1 XLEYXHRMSUPJST-UHFFFAOYSA-N 0.000 description 1
LXKJBKXZXYCLSP-UHFFFAOYSA-N 4-(5-cyclopropyltetrazol-1-yl)phenol Chemical compound C1=CC(O)=CC=C1N1C(C2CC2)=NN=N1 LXKJBKXZXYCLSP-UHFFFAOYSA-N 0.000 description 1
XWEZECGCHUPQKW-UHFFFAOYSA-N 4-(tetrazol-2-yl)phenol Chemical compound C1=CC(O)=CC=C1N1N=NC=N1 XWEZECGCHUPQKW-UHFFFAOYSA-N 0.000 description 1
YMQPKONILWWJQG-UHFFFAOYSA-N 4-bromo-1,2-difluorobenzene Chemical compound FC1=CC=C(Br)C=C1F YMQPKONILWWJQG-UHFFFAOYSA-N 0.000 description 1
CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-UHFFFAOYSA-N 0.000 description 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
SUFKNMKUIYHURJ-UHFFFAOYSA-N 4-nitrobutanoic acid Chemical compound OC(=O)CCC[N+]([O-])=O SUFKNMKUIYHURJ-UHFFFAOYSA-N 0.000 description 1
XSJYQLAPUDCMNM-UHFFFAOYSA-N 5-(1-ethyltetrazol-5-yl)-2-methoxybenzaldehyde Chemical compound CCN1N=NN=C1C1=CC=C(OC)C(C=O)=C1 XSJYQLAPUDCMNM-UHFFFAOYSA-N 0.000 description 1
OZEVSTJDURDJOF-UHFFFAOYSA-N 5-(5-cyclopropyltetrazol-1-yl)-2-hydroxybenzaldehyde Chemical compound C1=C(C=O)C(O)=CC=C1N1C(C2CC2)=NN=N1 OZEVSTJDURDJOF-UHFFFAOYSA-N 0.000 description 1
YQFVRTPCYXZCII-UHFFFAOYSA-N 5-(5-cyclopropyltetrazol-1-yl)-2-methoxybenzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1N1C(C2CC2)=NN=N1 YQFVRTPCYXZCII-UHFFFAOYSA-N 0.000 description 1
PVRMGKBHWRHNIU-UHFFFAOYSA-N 5-(5-ethyltetrazol-1-yl)-2-hydroxybenzaldehyde Chemical compound CCC1=NN=NN1C1=CC=C(O)C(C=O)=C1 PVRMGKBHWRHNIU-UHFFFAOYSA-N 0.000 description 1
BESKRBMEPBFSIT-UHFFFAOYSA-N 5-(5-ethyltetrazol-1-yl)-2-methoxybenzaldehyde Chemical compound CCC1=NN=NN1C1=CC=C(OC)C(C=O)=C1 BESKRBMEPBFSIT-UHFFFAOYSA-N 0.000 description 1
SFDHVKDDZIMQON-UHFFFAOYSA-N 5-(bromomethyl)-2-methoxybenzaldehyde Chemical compound COC1=CC=C(CBr)C=C1C=O SFDHVKDDZIMQON-UHFFFAOYSA-N 0.000 description 1
JQPZRQLUCZVWEO-UHFFFAOYSA-N 5-(chloromethyl)-2-methoxybenzaldehyde Chemical compound COC1=CC=C(CCl)C=C1C=O JQPZRQLUCZVWEO-UHFFFAOYSA-N 0.000 description 1
VLRPYFOEJAVUFG-UHFFFAOYSA-N 5-[1-(cyclopropylmethyl)tetrazol-5-yl]-2-methoxybenzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1C1=NN=NN1CC1CC1 VLRPYFOEJAVUFG-UHFFFAOYSA-N 0.000 description 1
FFSSSYQCLNKPPT-UHFFFAOYSA-N 5-[5-(diethylamino)tetrazol-1-yl]-2-methoxybenzaldehyde Chemical compound CCN(CC)C1=NN=NN1C1=CC=C(OC)C(C=O)=C1 FFSSSYQCLNKPPT-UHFFFAOYSA-N 0.000 description 1
MBOQPWSBMDNBDD-UHFFFAOYSA-N 5-bromo-1-(cyclopropylmethyl)tetrazole Chemical compound BrC1=NN=NN1CC1CC1 MBOQPWSBMDNBDD-UHFFFAOYSA-N 0.000 description 1
SQTWGTRJXOVEMT-UHFFFAOYSA-N 5-bromo-1-ethyltetrazole Chemical compound CCN1N=NN=C1Br SQTWGTRJXOVEMT-UHFFFAOYSA-N 0.000 description 1
RTXTWVRCMVPXMT-UHFFFAOYSA-N 5-bromo-2-cyclopropyltetrazole Chemical compound N1=C(Br)N=NN1C1CC1 RTXTWVRCMVPXMT-UHFFFAOYSA-N 0.000 description 1
NEAOORGDJCBWDL-UHFFFAOYSA-N 5-hydroxyimino-6-(4-methoxyphenyl)piperidin-2-one Chemical compound C1=CC(OC)=CC=C1C1C(=NO)CCC(=O)N1 NEAOORGDJCBWDL-UHFFFAOYSA-N 0.000 description 1
ZMPDDLKERLVLHI-UHFFFAOYSA-N 6-(3-bromo-4-methylphenyl)-5-hydroxyiminopiperidin-2-one Chemical compound C1=C(Br)C(C)=CC=C1C1C(=NO)CCC(=O)N1 ZMPDDLKERLVLHI-UHFFFAOYSA-N 0.000 description 1
RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
QSIXZRWGOIPIGR-UHFFFAOYSA-N 6-(4-methoxyphenyl)piperidine-2,5-dione Chemical compound C1=CC(OC)=CC=C1C1C(=O)CCC(=O)N1 QSIXZRWGOIPIGR-UHFFFAOYSA-N 0.000 description 1
ZZAAXHUOCIAQCI-UHFFFAOYSA-N 6-[4-(trifluoromethyl)phenyl]piperidine-2,5-dione Chemical compound C1=CC(C(F)(F)F)=CC=C1C1C(=O)CCC(=O)N1 ZZAAXHUOCIAQCI-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 1
208000030507 AIDS Diseases 0.000 description 1
206010065040 AIDS dementia complex Diseases 0.000 description 1
235000019489 Almond oil Nutrition 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
206010003571 Astrocytoma Diseases 0.000 description 1
208000025978 Athletic injury Diseases 0.000 description 1
AXXLAOYVJJFFKW-UHFFFAOYSA-N B1CCCCCCCC1C1CCCCCCCC1 Chemical compound B1CCCCCCCC1C1CCCCCCCC1 AXXLAOYVJJFFKW-UHFFFAOYSA-N 0.000 description 1
208000008035 Back Pain Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
108010006654 Bleomycin Proteins 0.000 description 1
206010006458 Bronchitis chronic Diseases 0.000 description 1
206010058019 Cancer Pain Diseases 0.000 description 1
244000284152 Carapichea ipecacuanha Species 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
208000001387 Causalgia Diseases 0.000 description 1
206010064012 Central pain syndrome Diseases 0.000 description 1
208000000094 Chronic Pain Diseases 0.000 description 1
208000006561 Cluster Headache Diseases 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
208000027932 Collagen disease Diseases 0.000 description 1
208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 1
208000013586 Complex regional pain syndrome type 1 Diseases 0.000 description 1
239000004821 Contact adhesive Substances 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
206010011224 Cough Diseases 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
108010092160 Dactinomycin Proteins 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
201000004624 Dermatitis Diseases 0.000 description 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
208000005171 Dysmenorrhea Diseases 0.000 description 1
241000792859 Enema Species 0.000 description 1
244000166102 Eucalyptus leucoxylon Species 0.000 description 1
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
208000007882 Gastritis Diseases 0.000 description 1
208000018522 Gastrointestinal disease Diseases 0.000 description 1
206010017964 Gastrointestinal infection Diseases 0.000 description 1
206010061974 Gastrointestinal obstruction Diseases 0.000 description 1
206010017999 Gastrointestinal pain Diseases 0.000 description 1
208000021965 Glossopharyngeal Nerve disease Diseases 0.000 description 1
206010019233 Headaches Diseases 0.000 description 1
208000032843 Hemorrhage Diseases 0.000 description 1
206010063491 Herpes zoster oticus Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010053317 Hydrophobia Diseases 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
206010020601 Hyperchlorhydria Diseases 0.000 description 1
XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
206010021639 Incontinence Diseases 0.000 description 1
208000027601 Inner ear disease Diseases 0.000 description 1
206010049949 Intercostal neuralgia Diseases 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
239000012448 Lithium borohydride Substances 0.000 description 1
GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
208000008930 Low Back Pain Diseases 0.000 description 1
235000019759 Maize starch Nutrition 0.000 description 1
206010026749 Mania Diseases 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
208000027530 Meniere disease Diseases 0.000 description 1
201000009906 Meningitis Diseases 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
206010028391 Musculoskeletal Pain Diseases 0.000 description 1
CKRZKMFTZCFYGB-UHFFFAOYSA-N N-phenylhydroxylamine Chemical compound ONC1=CC=CC=C1 CKRZKMFTZCFYGB-UHFFFAOYSA-N 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
108010040718 Neurokinin-1 Receptors Proteins 0.000 description 1
102000002002 Neurokinin-1 Receptors Human genes 0.000 description 1
108010040722 Neurokinin-2 Receptors Proteins 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
206010068106 Occipital neuralgia Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
208000004983 Phantom Limb Diseases 0.000 description 1
206010056238 Phantom pain Diseases 0.000 description 1
240000006711 Pistacia vera Species 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
208000004550 Postoperative Pain Diseases 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
201000001263 Psoriatic Arthritis Diseases 0.000 description 1
208000036824 Psoriatic arthropathy Diseases 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 1
206010067171 Regurgitation Diseases 0.000 description 1
208000025747 Rheumatic disease Diseases 0.000 description 1
206010049002 Scar pain Diseases 0.000 description 1
208000008765 Sciatica Diseases 0.000 description 1
206010040744 Sinus headache Diseases 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
239000004141 Sodium laurylsulphate Substances 0.000 description 1
206010041738 Sports injury Diseases 0.000 description 1
102100037342 Substance-K receptor Human genes 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
239000000150 Sympathomimetic Substances 0.000 description 1
206010043269 Tension headache Diseases 0.000 description 1
208000008548 Tension-Type Headache Diseases 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
208000024780 Urticaria Diseases 0.000 description 1
206010047163 Vasospasm Diseases 0.000 description 1
208000012886 Vertigo Diseases 0.000 description 1
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
229940122803 Vinca alkaloid Drugs 0.000 description 1
PQNWGZHIYGTORX-UHFFFAOYSA-N [2-(1,3-dioxolan-2-yl)-4-methoxyphenyl]cyanamide Chemical compound COC1=CC=C(NC#N)C(C2OCCO2)=C1 PQNWGZHIYGTORX-UHFFFAOYSA-N 0.000 description 1
YTBXWZCLISYAQW-UHFFFAOYSA-N [N].[Li]CCCC Chemical compound [N].[Li]CCCC YTBXWZCLISYAQW-UHFFFAOYSA-N 0.000 description 1
210000001015 abdomen Anatomy 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
239000008351 acetate buffer Substances 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
230000009471 action Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000002411 adverse Effects 0.000 description 1
229910000086 alane Inorganic materials 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
239000008168 almond oil Substances 0.000 description 1
208000008445 altitude sickness Diseases 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000000454 anti-cipatory effect Effects 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
230000002921 anti-spasmodic effect Effects 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
239000003972 antineoplastic antibiotic Substances 0.000 description 1
229940124575 antispasmodic agent Drugs 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
206010003074 arachnoiditis Diseases 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
230000002917 arthritic effect Effects 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
PXWLUICTRPHECG-UHFFFAOYSA-N azane;trihydrochloride Chemical compound N.Cl.Cl.Cl PXWLUICTRPHECG-UHFFFAOYSA-N 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
229960004365 benzoic acid Drugs 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
229960001561 bleomycin Drugs 0.000 description 1
OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
230000037396 body weight Effects 0.000 description 1
MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
210000003461 brachial plexus Anatomy 0.000 description 1
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
239000000337 buffer salt Substances 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
229950005499 carbon tetrachloride Drugs 0.000 description 1
229960005243 carmustine Drugs 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
210000000038 chest Anatomy 0.000 description 1
229960004630 chlorambucil Drugs 0.000 description 1
JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
208000007451 chronic bronchitis Diseases 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
229960004316 cisplatin Drugs 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
208000018912 cluster headache syndrome Diseases 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
208000010877 cognitive disease Diseases 0.000 description 1
238000004040 coloring Methods 0.000 description 1
208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
239000003246 corticosteroid Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
201000003146 cystitis Diseases 0.000 description 1
229960000684 cytarabine Drugs 0.000 description 1
229960003901 dacarbazine Drugs 0.000 description 1
229960000640 dactinomycin Drugs 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
XUWHAWMETYGRKB-UHFFFAOYSA-N delta-valerolactam Natural products O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
235000019700 dicalcium phosphate Nutrition 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
208000019836 digestive system infectious disease Diseases 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
SURBAJYBTYLRMQ-UHFFFAOYSA-N dioxido(propan-2-yloxy)borane Chemical compound CC(C)OB([O-])[O-] SURBAJYBTYLRMQ-UHFFFAOYSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
208000002173 dizziness Diseases 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
229960004679 doxorubicin Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
229940047652 ear drops Drugs 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
229960002179 ephedrine Drugs 0.000 description 1
230000001667 episodic effect Effects 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
239000002038 ethyl acetate fraction Substances 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
SHTHWCQBJTUESB-UHFFFAOYSA-N ethyl hypofluorite Chemical compound CCOF SHTHWCQBJTUESB-UHFFFAOYSA-N 0.000 description 1
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
229960005420 etoposide Drugs 0.000 description 1
238000000605 extraction Methods 0.000 description 1
229940012356 eye drops Drugs 0.000 description 1
208000006275 fascioliasis Diseases 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
229960002949 fluorouracil Drugs 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
230000005176 gastrointestinal motility Effects 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
201000011349 geniculate herpes zoster Diseases 0.000 description 1
239000011521 glass Substances 0.000 description 1
201000005442 glossopharyngeal neuralgia Diseases 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 description 1
229960003727 granisetron Drugs 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
229940116364 hard fat Drugs 0.000 description 1
231100000869 headache Toxicity 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
229960001330 hydroxycarbamide Drugs 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
238000002513 implantation Methods 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
206010022000 influenza Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
229960005208 ipecacuanha Drugs 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
229960004592 isopropanol Drugs 0.000 description 1
FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
229960002247 lomustine Drugs 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
210000004086 maxillary sinus Anatomy 0.000 description 1
235000012054 meals Nutrition 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
OEPZEFLBTTVFTK-UHFFFAOYSA-N methyl 5-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]furan-2-carboxylate Chemical compound O1C(C(=O)OC)=CC=C1CN1C(C)=CC(C(F)(F)F)=N1 OEPZEFLBTTVFTK-UHFFFAOYSA-N 0.000 description 1
PSCXCIPPRCFAAO-UHFFFAOYSA-N methyl 5-amino-2-methoxybenzoate Chemical compound COC(=O)C1=CC(N)=CC=C1OC PSCXCIPPRCFAAO-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
229960004584 methylprednisolone Drugs 0.000 description 1
TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 1
229960004503 metoclopramide Drugs 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229960004857 mitomycin Drugs 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
229960005181 morphine Drugs 0.000 description 1
201000003152 motion sickness Diseases 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
239000003158 myorelaxant agent Substances 0.000 description 1
230000001670 myorelaxant effect Effects 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
APHSYPVEGXYNKI-UHFFFAOYSA-N n-(4-phenylmethoxyphenyl)cyclopropanecarboxamide Chemical compound C1CC1C(=O)NC(C=C1)=CC=C1OCC1=CC=CC=C1 APHSYPVEGXYNKI-UHFFFAOYSA-N 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
229940100662 nasal drops Drugs 0.000 description 1
230000008693 nausea Effects 0.000 description 1
208000019382 nerve compression syndrome Diseases 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
239000002687 nonaqueous vehicle Substances 0.000 description 1
229960005343 ondansetron Drugs 0.000 description 1
229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
229960001528 oxymetazoline Drugs 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
150000004686 pentahydrates Chemical class 0.000 description 1
206010034674 peritonitis Diseases 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
239000002574 poison Substances 0.000 description 1
229920000058 polyacrylate Polymers 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920000098 polyolefin Polymers 0.000 description 1
229920002689 polyvinyl acetate Polymers 0.000 description 1
239000011118 polyvinyl acetate Substances 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
230000002980 postoperative effect Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
229960000624 procarbazine Drugs 0.000 description 1
XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
229960003908 pseudoephedrine Drugs 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
238000007789 sealing Methods 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
239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229920005573 silicon-containing polymer Polymers 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000004296 sodium metabisulphite Substances 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
229940080313 sodium starch Drugs 0.000 description 1
229960003010 sodium sulfate Drugs 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
208000005198 spinal stenosis Diseases 0.000 description 1
230000003019 stabilising effect Effects 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000003890 substance P antagonist Substances 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000001975 sympathomimetic effect Effects 0.000 description 1
229940064707 sympathomimetics Drugs 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000009897 systematic 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
150000003892 tartrate salts Chemical class 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
230000000542 thalamic effect Effects 0.000 description 1
230000008719 thickening Effects 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
208000004371 toothache Diseases 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
229940100640 transdermal system Drugs 0.000 description 1
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Substances CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 1
QXTIBZLKQPJVII-UHFFFAOYSA-N triethylsilicon Chemical compound CC[Si](CC)CC QXTIBZLKQPJVII-UHFFFAOYSA-N 0.000 description 1
206010044652 trigeminal neuralgia Diseases 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
230000002485 urinary effect Effects 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000002455 vasospastic effect Effects 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
231100000889 vertigo Toxicity 0.000 description 1
208000027491 vestibular disease Diseases 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- A61P1/08—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
- 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
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Rheumatology (AREA)
Hospice & Palliative Care (AREA)
Otolaryngology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)

OA60801A 1993-09-22 1996-03-21 3-(5-Tetrazolyl-benzyl) amino-piperidine derivatives and antagonists of tachykinins OA10576A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB939319606A GB9319606D0 (en)	1993-09-22	1993-09-22	Chemical compounds
GB9326583A GB9326583D0 (en)	1993-12-31	1993-12-31	Chemical compounds

Publications (1)

Publication Number	Publication Date
OA10576A true OA10576A (en)	2002-06-03

Family

ID=26303560

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA60801A OA10576A (en)	1993-09-22	1996-03-21	3-(5-Tetrazolyl-benzyl) amino-piperidine derivatives and antagonists of tachykinins

Country Status (29)

Country	Link
US (2)	US5703240A (is)
EP (1)	EP0720609B1 (is)
JP (2)	JP2865872B2 (is)
CN (1)	CN1061041C (is)
AP (1)	AP495A (is)
AT (1)	ATE173255T1 (is)
AU (1)	AU681190B2 (is)
BG (1)	BG62169B1 (is)
CA (1)	CA2172529A1 (is)
CO (1)	CO4290298A1 (is)
CZ (1)	CZ285479B6 (is)
DE (1)	DE69414590T2 (is)
DK (1)	DK0720609T3 (is)
ES (1)	ES2123829T3 (is)
FI (1)	FI961270A7 (is)
GR (1)	GR3029354T3 (is)
HR (1)	HRP940575B1 (is)
HU (1)	HU217428B (is)
IL (1)	IL111002A (is)
IS (1)	IS4208A (is)
NO (1)	NO307830B1 (is)
NZ (1)	NZ273614A (is)
OA (1)	OA10576A (is)
PE (1)	PE18295A1 (is)
PL (1)	PL179585B1 (is)
SI (1)	SI0720609T1 (is)
SK (1)	SK280901B6 (is)
UA (1)	UA44711C2 (is)
WO (1)	WO1995008549A1 (is)

Families Citing this family (105)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9317987D0 (en) *	1993-08-26	1993-10-13	Glaxo Group Ltd	Chemical compounds
IL111002A (en) *	1993-09-22	1998-09-24	Glaxo Group Ltd	Piperidine derivatives their preparation and pharmaceutical compositions containing them
ES2229259T3 (es) *	1995-01-12	2005-04-16	Glaxo Group Limited	Derivados de piperidina con actividad antagonista de taquiquinina.
GB9505692D0 (en) *	1995-03-21	1995-05-10	Glaxo Group Ltd	Chemical compounds
GB9513117D0 (en) *	1995-06-28	1995-08-30	Merck Sharp & Dohme	Therapeutic agents
TW458774B (en)	1995-10-20	2001-10-11	Pfizer	Antiemetic pharmaceutical compositions
US6211199B1 (en)	1995-11-17	2001-04-03	Aventis Pharmaceuticals Inc.	Substituted 4-(1H-benzimidazol-2-yl-amino)piperidines useful for the treatment of allergic diseases
GB9525296D0 (en) *	1995-12-11	1996-02-07	Merck Sharp & Dohme	Therapeutic agents
US5932571A (en) *	1996-02-21	1999-08-03	Hoechst Marion Roussel, Inc.	Substituted N-methyl-N-(4-(4-(1H-benzimidazol-2-yl) {1,4}diazepan-1-yl)-2-(aryl) butyl) benzamides useful for the treatment of allergic diseases
US5998439A (en)	1996-02-21	1999-12-07	Hoescht Marion Roussel, Inc.	Substituted N-methyl-N-(4-(piperidin-1-yl)-2-(aryl)butyl)benzamides useful for the treatment of allergic diseases
US5922737A (en) *	1996-02-21	1999-07-13	Hoechst Marion Roussel, Inc.	Substituted N-methyl-N-(4-(4-(1H-Benzimidazol-2-YL-amino) piperidin-1-YL)-2-(arlyl) butyl) benzamides useful for the treatment of allergic diseases
EP0912173A1 (en) *	1996-06-26	1999-05-06	Warner-Lambert Company	Use of a tachykinin antagonist for the manufacture of a medicament for the treatment of emesis
MX9706196A (es) *	1996-08-14	1998-02-28	Pfizer	Compuestos triciclicos de piperidinilamino como antagonistas de la sustancia p.
MX9706944A (es) *	1996-09-12	1998-08-30	Pfizer	Quinuclidinas sustituidas con tetrazolilo como antagonistas de la sustancia p.
US6117855A (en)	1996-10-07	2000-09-12	Merck Sharp & Dohme Ltd.	Use of a NK-1 receptor antagonist and an antidepressant and/or an anti-anxiety agent
ATE288756T1 (de) *	1996-12-02	2005-02-15	Merck Sharp & Dohme	Verwendung von nk-1 rezeptorantagonisten zur behandlung von schweren depressionen, die von angstzuständen begleitet werden
US5977104A (en) *	1996-12-02	1999-11-02	Merck Sharp & Dohme Ltd.	Use of NK-1 receptor antagonists for treating bipolar disorders
JP2001504849A (ja) *	1996-12-02	2001-04-10	メルクシヤープエンドドームリミテツド	ストレス障害の治療のためのｎｋ−１受容体拮抗薬の使用
US6100256A (en) *	1996-12-02	2000-08-08	Merck Sharp & Dohme Ltd.	Use of NK-1 receptors antagonists for treating schizophrenic disorders
CA2273853A1 (en) *	1996-12-02	1998-06-11	Merck Sharp & Dohme Limited	Use of nk-1 receptor antagonists for treating cognitive disorders
DE69732133T2 (de) *	1996-12-02	2005-12-22	Merck Sharp & Dohme Ltd., Hoddesdon	Verwendung von NK-1 Rezeptorantagonisten zur Behandlung von schweren Depressionen
CA2273856A1 (en) *	1996-12-02	1998-06-11	Merck Sharp & Dohme Limited	Use of nk-1 receptor antagonists for treating bipolar disorders
US6613765B1 (en)	1996-12-02	2003-09-02	Merck Sharp & Dohme Limited	Use of NK-1 receptor antagonists for treating major depressive disorders
US6114315A (en) *	1996-12-02	2000-09-05	Merck Sharp & Dohme Ltd.	Use of NK-1 receptor antagonists for treating major depressive disorders with anxiety
AU729708B2 (en) *	1996-12-02	2001-02-08	Merck Sharp & Dohme Limited	Use of NK-1 receptor antagonists for treating severe anxiety disorders
AU731674B2 (en) *	1996-12-02	2001-04-05	Merck Sharp & Dohme Limited	Use of NK-1 receptor antagonists for treating substance use disorders
AU734872B2 (en) *	1996-12-02	2001-06-21	Merck Sharp & Dohme Limited	Use of NK-1 receptor antagonists for treating movement disorders
CA2273351A1 (en) *	1996-12-02	1998-06-11	Merck Sharp & Dohme Limited	Use of nk-1 receptor antagonists for treating sexual dysfunction
WO1998024445A1 (en) *	1996-12-02	1998-06-11	Merck Sharp & Dohme Limited	Use of nk-1 receptor antagonists for treating schizophrenic disorders
US5861417A (en) *	1996-12-19	1999-01-19	Hoechst Marion Roussel, Inc.	Heterocyclic substituted pyrrolidine amide derivatives
CA2287487A1 (en) *	1997-04-24	1998-10-29	Merck Sharp & Dohme Limited	Use of nk-1 receptor antagonists for treating eating disorders
EP0991622A1 (en)	1997-06-27	2000-04-12	MERCK SHARP & DOHME LTD.	Substituted 3-(benzylamino)piperidine derivatives and their use as therapeutic agents
WO1999007375A1 (en) *	1997-08-04	1999-02-18	Merck Sharp & Dohme Limited	Use of nk-1 receptor antagonists for treating aggressive behaviour disorders
CA2298777A1 (en) *	1997-08-04	1999-02-18	Merck Sharp & Dohme Limited	Use of nk-1 receptor antagonists for treating mania
GB9716463D0 (en) *	1997-08-04	1997-10-08	Merck Sharp & Dohme	Therapeutic agents
GB9716457D0 (en) *	1997-08-04	1997-10-08	Merck Sharp & Dohme	Therapeutic agents
GB9723544D0 (en) *	1997-11-07	1998-01-07	Merck Sharp & Dohme	Therapeutic agents
US6156749A (en) *	1997-12-01	2000-12-05	Merck Sharp & Dohme Limited	Use of NK-1 receptor antagonists for treating movement disorders
US6087348A (en) *	1997-12-01	2000-07-11	Merck Sharp & Dohme Ltd.	Use of NK-1 receptor antagonists for treating stress disorders
US6271230B1 (en)	1997-12-01	2001-08-07	Merck Sharp & Dohme Limited	Use of NK-1 receptor antagonists for treating cognitive disorders
GB9816897D0 (en) *	1998-08-04	1998-09-30	Merck Sharp & Dohme	Therapeutic use
ATE434437T1 (de) *	1999-02-18	2009-07-15	Novasearch Ag	Verwendung von antagonisten der 5-ht3-rezeptoren zur behandlung von muskuloeskeletalen erkrankungen
JP2001039954A (ja) *	1999-05-24	2001-02-13	Tomono Agrica Co Ltd	ヘテロ環誘導体
US7163949B1 (en)	1999-11-03	2007-01-16	Amr Technology, Inc.	4-phenyl substituted tetrahydroisoquinolines and use thereof
MXPA02004330A (es)	1999-11-03	2004-07-30	Albany Molecular Res Inc	Tetrahidroisoquinolinas aril-y heteroaril-sustituidas y uso de las mismas para bloquear la recaptacion de norepinefrina, dopamina y serotonina..
AU7334901A (en)	2000-07-11	2002-01-21	Du Pont Pharm Co	Novel 4-phenyl substituted tetrahydroisoquinolines and therapeutic use thereof
AU2001292320A1 (en) *	2000-10-02	2002-04-15	Tanabe Seiyaku Co., Ltd.	Benzylamine compound, process for producing the same, and intermediate therefor
US7498332B2 (en)	2001-02-14	2009-03-03	Duke University	Therapy for cerebral vasospasm
US20040142929A1 (en) *	2001-07-06	2004-07-22	Ramon Merce-Vidal	Derivatives of aryl (or heteroaryl) azolylcarbinoles for the treatment of urinary incontinence
US20030083345A1 (en) *	2001-07-10	2003-05-01	Torsten Hoffmann	Method of treatment and/or prevention of brain, spinal or nerve injury
JP2006508948A (ja) *	2002-10-30	2006-03-16	メルク　エンド　カムパニー　インコーポレーテッド	ケモカイン受容体活性のヘテロアリールピペリジンモジュレーター
GB0308968D0 (en) *	2003-04-17	2003-05-28	Glaxo Group Ltd	Medicaments
KR100785395B1 (ko)	2003-08-01	2007-12-13	도요 가세이 고교 가부시키가이샤	알콕시-테트라졸-1-일-벤즈알데히드 화합물 및 그의제조방법
CN1580283A (zh) *	2003-08-13	2005-02-16	清华大学	一种检测核酸分子的方法
JP4864719B2 (ja) *	2003-11-26	2012-02-01	ファイザー・プロダクツ・インク	Ｇｓｋ−３インヒビターとしてのアミノピラゾール誘導体
GB0409098D0 (en) *	2004-04-23	2004-05-26	Glaxo Group Ltd	Medicament
BRPI0513359A (pt)	2004-07-15	2008-05-06	Amr Technology Inc	tetraidroisoquinolinas substituìdas por arila e heteroarila e uso destes para bloquear a recaptação de norepinefrina, dopamina, e serotonina
JP2006137691A (ja) *	2004-11-11	2006-06-01	Toyo Kasei Kogyo Co Ltd	２−アルコキシ−５−テトラゾリル−ベンズアルデヒド化合物の製造方法
EP1888050B1 (en)	2005-05-17	2012-03-21	Merck Sharp & Dohme Ltd.	cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexanepropanoic acid for the treatment of cancer
UA95454C2 (uk)	2005-07-15	2011-08-10	Амр Текнолоджи, Інк.	Арил- і гетероарилзаміщені тетрагідробензазепіни і їх застосування для блокування зворотного захоплення норепінефрину, допаміну і серотоніну
KR20080048502A (ko)	2005-09-29	2008-06-02	머크 앤드 캄파니 인코포레이티드	멜라노코르틴-4 수용체 조절제로서의 아실화스피로피페리딘 유도체
GB0603041D0 (en)	2006-02-15	2006-03-29	Angeletti P Ist Richerche Bio	Therapeutic compounds
EP2083831B1 (en)	2006-09-22	2013-12-25	Merck Sharp & Dohme Corp.	Method of treatment using fatty acid synthesis inhibitors
US20110218176A1 (en)	2006-11-01	2011-09-08	Barbara Brooke Jennings-Spring	Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development
AR064777A1 (es)	2007-01-10	2009-04-22	Inst Di Reserche D Biolog Mole	Indazoles sustituidos con amida como inhibidores de poli (adp- ribosa) polimerasa (parp)
US20100105688A1 (en)	2007-01-24	2010-04-29	Glaxo Group Limited	Pharmaceutical compositions comprising 3,5-diamino-6-(2,3-dichlophenyl)-1,2,4-triazine or r(-)-2,4-diamino-5-(2,3-dichlorophenyl)-6-fluoromethyl pyrimidine and an nk1
US8106086B2 (en)	2007-04-02	2012-01-31	Msd K.K.	Indoledione derivative
EP2532643A1 (en)	2007-06-08	2012-12-12	MannKind Corporation	IRE-1A Inhibitors
AU2008269154B2 (en)	2007-06-27	2014-06-12	Merck Sharp & Dohme Llc	4-carboxybenzylamino derivatives as histone deacetylase inhibitors
CN102014631A (zh)	2008-03-03	2011-04-13	泰格尔医药科技公司	酪氨酸激酶抑制剂
US9156812B2 (en)	2008-06-04	2015-10-13	Bristol-Myers Squibb Company	Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine
JP2011525538A (ja) *	2008-06-24	2011-09-22	バレアントプハルマセウトイカルスインターナショナル	カリウムチャネルモジュレーターとして有用なベンジルオキシアニリド誘導体
US8691825B2 (en)	2009-04-01	2014-04-08	Merck Sharp & Dohme Corp.	Inhibitors of AKT activity
EP2429296B1 (en)	2009-05-12	2017-12-27	Albany Molecular Research, Inc.	7-([1,2,4,]triazolo[1,5,-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4- tetrahydroisoquinoline and use thereof
MX2011011901A (es)	2009-05-12	2012-01-20	Albany Molecular Res Inc	Tetrahidroisoquinolinas aril, heteroaril, y heterociclo sustituidas y uso de las mismas.
CN102638982B (zh)	2009-05-12	2015-07-08	百时美施贵宝公司	(S)-7-([1,2,4]三唑并[1,5-a]吡啶-6-基)-4-(3,4-二氯苯基)-1,2,3,4-四氢异喹啉的晶型及其用途
AU2010307198B9 (en)	2009-10-14	2014-02-13	Merck Sharp & Dohme Corp.	Substituted piperidines that increase p53 activity and the uses thereof
EP2584903B1 (en)	2010-06-24	2018-10-24	Merck Sharp & Dohme Corp.	Novel heterocyclic compounds as erk inhibitors
JP6043285B2 (ja)	2010-08-02	2016-12-14	サーナ・セラピューティクス・インコーポレイテッドＳｉｒｎａＴｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ．	低分子干渉核酸（ｓｉＮＡ）を用いたカテニン（カドヘリン結合型タンパク質）β１（ＣＴＮＮＢ１）遺伝子発現のＲＮＡ干渉媒介性阻害
LT2606134T (lt)	2010-08-17	2019-07-25	Sirna Therapeutics, Inc.	Hepatito b viruso (hbv) geno raiškos slopinimas, tarpininkaujant rnr interferencijai naudojant mažą interferuojančią nukleorūgštį (sina)
EP2608669B1 (en)	2010-08-23	2016-06-22	Merck Sharp & Dohme Corp.	NOVEL PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS
US8946216B2 (en)	2010-09-01	2015-02-03	Merck Sharp & Dohme Corp.	Indazole derivatives useful as ERK inhibitors
EP2615916B1 (en)	2010-09-16	2017-01-04	Merck Sharp & Dohme Corp.	Fused pyrazole derivatives as novel erk inhibitors
WO2012058210A1 (en)	2010-10-29	2012-05-03	Merck Sharp & Dohme Corp.	RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACIDS (siNA)
EP2654748B1 (en)	2010-12-21	2016-07-27	Merck Sharp & Dohme Corp.	Indazole derivatives useful as erk inhibitors
EP2699568A1 (en)	2011-04-21	2014-02-26	Piramal Enterprises Limited	A crystalline form of a salt of a morpholino sulfonyl indole derivative and a process for its preparation
NO2729147T3 (is)	2011-07-04	2018-02-03
EP2770987B1 (en)	2011-10-27	2018-04-04	Merck Sharp & Dohme Corp.	Novel compounds that are erk inhibitors
EP3453762B1 (en)	2012-05-02	2021-04-21	Sirna Therapeutics, Inc.	Short interfering nucleic acid (sina) compositions
EP2900241B1 (en)	2012-09-28	2018-08-08	Merck Sharp & Dohme Corp.	Novel compounds that are erk inhibitors
AU2013352568B2 (en)	2012-11-28	2019-09-19	Merck Sharp & Dohme Llc	Compositions and methods for treating cancer
ES2707305T3 (es)	2012-12-20	2019-04-03	Merck Sharp & Dohme	Imidazopiridinas sustituidas como inhibidores de HDM2
US9540377B2 (en)	2013-01-30	2017-01-10	Merck Sharp & Dohme Corp.	2,6,7,8 substituted purines as HDM2 inhibitors
EP3041938A1 (en)	2013-09-03	2016-07-13	Moderna Therapeutics, Inc.	Circular polynucleotides
WO2018071283A1 (en)	2016-10-12	2018-04-19	Merck Sharp & Dohme Corp.	Kdm5 inhibitors
JP7158425B2 (ja)	2017-06-30	2022-10-21	チェイスセラピューティクスコーポレイション	Ｎｋ－１アンタゴニスト組成物およびうつ病の処置における使用法
US11098059B2 (en)	2017-11-08	2021-08-24	Merck Sharp & Dohme Corp.	PRMT5 inhibitors
WO2019094311A1 (en)	2017-11-08	2019-05-16	Merck Sharp & Dohme Corp.	Prmt5 inhibitors
ES2980110T3 (es)	2018-02-26	2024-09-30	Ospedale San Raffaele Srl	Antagonistas de NK-1 para uso en el tratamiento del dolor ocular
US11993602B2 (en)	2018-08-07	2024-05-28	Merck Sharp & Dohme Llc	PRMT5 inhibitors
US12173026B2 (en)	2018-08-07	2024-12-24	Merck Sharp & Dohme Llc	PRMT5 inhibitors
WO2020033284A1 (en)	2018-08-07	2020-02-13	Merck Sharp & Dohme Corp.	Prmt5 inhibitors
EP4117673A1 (en)	2020-03-11	2023-01-18	Ospedale San Raffaele S.r.l.	Treatment of stem cell deficiency
CN117623228B (zh) *	2023-12-07	2025-12-02	江西赣锋锂业集团股份有限公司	一种四氢铝锂的制备方法
CN120441539A (zh) *	2024-02-08	2025-08-08	上海数因信科智能科技有限公司	四唑类化合物、其药物组合物及其应用

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5232929A (en) *	1990-11-28	1993-08-03	Pfizer Inc.	3-aminopiperidine derivatives and related nitrogen containing heterocycles and pharmaceutical compositions and use
US5332817A (en) *	1990-01-04	1994-07-26	Pfizer Inc.	3-aminopiperidine derivatives and related nitrogen containing heterocycles
UA41251C2 (uk) *	1990-01-04	2001-09-17	Пфайзер, Інк.	Гідровані азотвмісні гетероциклічні сполуки, похідні піперидину, фармацевтична композиція та спосіб пригнічення активності речовини р в організмі
BR9206161A (pt) *	1991-06-20	1995-10-31	Pfizer	Derivados fluoroalcoxibenzilamino de heterociclos contendo nitrogénio
ES2147759T3 (es) *	1992-12-10	2000-10-01	Pfizer	Heterociclos no aromaticos sustituidos con aminometileno y uso como antagonistas de la sustancia p.
IL111002A (en) *	1993-09-22	1998-09-24	Glaxo Group Ltd	Piperidine derivatives their preparation and pharmaceutical compositions containing them

1994
- 1994-09-19 IL IL11100294A patent/IL111002A/en not_active IP Right Cessation
- 1994-09-19 IS IS4208A patent/IS4208A/is unknown
- 1994-09-20 CZ CZ96830A patent/CZ285479B6/cs not_active IP Right Cessation
- 1994-09-20 WO PCT/EP1994/003129 patent/WO1995008549A1/en not_active Ceased
- 1994-09-20 AU AU76974/94A patent/AU681190B2/en not_active Ceased
- 1994-09-20 EP EP94927627A patent/EP0720609B1/en not_active Expired - Lifetime
- 1994-09-20 JP JP7509554A patent/JP2865872B2/ja not_active Expired - Lifetime
- 1994-09-20 PL PL94313619A patent/PL179585B1/pl unknown
- 1994-09-20 HU HU9600722A patent/HU217428B/hu not_active IP Right Cessation
- 1994-09-20 UA UA96031099A patent/UA44711C2/uk unknown
- 1994-09-20 AT AT94927627T patent/ATE173255T1/de not_active IP Right Cessation
- 1994-09-20 NZ NZ273614A patent/NZ273614A/en unknown
- 1994-09-20 CA CA002172529A patent/CA2172529A1/en not_active Abandoned
- 1994-09-20 DK DK94927627T patent/DK0720609T3/da active
- 1994-09-20 ES ES94927627T patent/ES2123829T3/es not_active Expired - Lifetime
- 1994-09-20 PE PE1994251007A patent/PE18295A1/es not_active Application Discontinuation
- 1994-09-20 CN CN94194145A patent/CN1061041C/zh not_active Expired - Fee Related
- 1994-09-20 DE DE69414590T patent/DE69414590T2/de not_active Expired - Lifetime
- 1994-09-20 HR HR940575A patent/HRP940575B1/xx not_active IP Right Cessation
- 1994-09-20 SI SI9430208T patent/SI0720609T1/xx unknown
- 1994-09-20 SK SK383-96A patent/SK280901B6/sk unknown
- 1994-09-20 US US08/612,843 patent/US5703240A/en not_active Expired - Lifetime
- 1994-09-20 CO CO94042544A patent/CO4290298A1/es unknown
- 1994-09-21 AP APAP/P/1994/000671A patent/AP495A/en active
1996
- 1996-03-19 FI FI961270A patent/FI961270A7/fi unknown
- 1996-03-21 NO NO961156A patent/NO307830B1/no not_active IP Right Cessation
- 1996-03-21 OA OA60801A patent/OA10576A/en unknown
- 1996-04-09 BG BG100487A patent/BG62169B1/bg unknown
1997
- 1997-07-23 US US08/899,190 patent/US5843966A/en not_active Expired - Lifetime
1998
- 1998-08-07 JP JP10224991A patent/JPH11106341A/ja active Pending
1999
- 1999-02-10 GR GR990400441T patent/GR3029354T3/el unknown

Also Published As

Publication number	Publication date
CN1135218A (zh)	1996-11-06
AP495A (en)	1996-05-28
FI961270A0 (fi)	1996-03-19
CZ285479B6 (cs)	1999-08-11
CZ83096A3 (en)	1996-09-11
HU217428B (hu)	2000-01-28
IL111002A0 (en)	1994-11-28
DE69414590D1 (de)	1998-12-17
AP9400671A0 (en)	1994-10-31
HUT75648A (en)	1997-05-28
JPH09505275A (ja)	1997-05-27
PL313619A1 (en)	1996-07-08
US5703240A (en)	1997-12-30
NO961156L (no)	1996-05-21
NZ273614A (en)	1997-09-22
DE69414590T2 (de)	1999-04-15
DK0720609T3 (da)	1999-07-26
HU9600722D0 (en)	1996-05-28
ES2123829T3 (es)	1999-01-16
ATE173255T1 (de)	1998-11-15
HK1004219A1 (en)	1998-11-20
CN1061041C (zh)	2001-01-24
BG62169B1 (bg)	1999-04-30
GR3029354T3 (en)	1999-05-28
SK280901B6 (sk)	2000-09-12
JPH11106341A (ja)	1999-04-20
IS4208A (is)	1995-03-23
FI961270A7 (fi)	1996-05-03
JP2865872B2 (ja)	1999-03-08
NO307830B1 (no)	2000-06-05
NO961156D0 (no)	1996-03-21
EP0720609A1 (en)	1996-07-10
EP0720609B1 (en)	1998-11-11
SK38396A3 (en)	1997-02-05
WO1995008549A1 (en)	1995-03-30
HRP940575B1 (en)	2000-06-30
PE18295A1 (es)	1995-07-27
US5843966A (en)	1998-12-01
BG100487A (bg)	1996-12-31
HRP940575A2 (en)	1997-02-28
CO4290298A1 (es)	1996-04-17
UA44711C2 (uk)	2002-03-15
AU7697494A (en)	1995-04-10
SI0720609T1 (en)	1999-02-28
AU681190B2 (en)	1997-08-21
CA2172529A1 (en)	1995-03-30
IL111002A (en)	1998-09-24
PL179585B1 (pl)	2000-09-29

Publication	Publication Date	Title
AP495A (en)	1996-05-28	Piperidine derivatives
EP0802912B1 (en)	2004-10-13	Piperidine derivatives having tachykinin antagonist activity
US5830892A (en)	1998-11-03	Piperidine and morphonline derivatives and their use as therapeutic agents
EP0799231B1 (en)	1999-03-17	Spiroketal derivatives, compositions containing them and their use as therapeutic agents
US5985896A (en)	1999-11-16	Piperidine and morpholine derivatives and their use as therapeutic agents
AU715558B2 (en)	2000-02-03	Spiro-piperidine derivatives and their use as tachykinin antagonists
AU710873B2 (en)	1999-09-30	Morpholine derivatives and their use as therapeutic agents
US5962485A (en)	1999-10-05	N-(2-benzyloxy-1-phenethyl)-N-(2'-methoxyethyl)amino-methane compounds are useful as tachykinin antagonists
JPH09507484A (ja)	1997-07-29	置換モルホリン誘導体およびその治療剤としての使用
JPH11502810A (ja)	1999-03-09	ニューロキニンアンタゴニストとしての３−ベンジルアミノ−２−フェニルピペリジン
JP3026945B2 (ja)	2000-03-27	３−アザ及び３−オキサピペリドンタキキニン拮抗薬
JP3752130B2 (ja)	2006-03-08	掻痒治療用新規４−アリールピペリジン誘導体
RU2136675C1 (ru)	1999-09-10	Производные 3-(5-тетразолилбензил)аминопиперидина, способы их получения и фармацевтическая композиция на их основе
HK1004219B (en)	2000-03-17	3-(5-tetrazolyl-benzyl)amino-piperidine derivatives and antagonists of tachykinins
FR2873373A1 (fr)	2006-01-27	Derives de 4-arylmorpholin-3-one, leur preparation et leur application en therapeutique