IL106445A - History of 1,2,4-Trans-Triazole 4-Transform, Preparation and Pharmaceutical Preparations Containing Them - Google Patents

History of 1,2,4-Trans-Triazole 4-Transform, Preparation and Pharmaceutical Preparations Containing Them

Info

Publication number: IL106445A
Authority: IL; Israel
Prior art keywords: formula; compound; triazol; indol; methyl
Prior art date: 1992-07-30

Application number

IL106445A

Other languages

English (en)

Hebrew (he)

Other versions

IL106445A0 (en

Original Assignee

Merck Sharp & Dohme

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.)

1992-07-30

Filing date

1993-07-22

Publication date

1998-01-04

1992-07-30 Priority claimed from GB929216192A external-priority patent/GB9216192D0/en

1992-07-30 Priority claimed from GB929216264A external-priority patent/GB9216264D0/en

1992-10-23 Priority claimed from GB929222261A external-priority patent/GB9222261D0/en

1993-07-22 Application filed by Merck Sharp & Dohme filed Critical Merck Sharp & Dohme

1993-11-15 Publication of IL106445A0 publication Critical patent/IL106445A0/xx

1998-01-04 Publication of IL106445A publication Critical patent/IL106445A/en

Links

-1 4-substituted 1, 2, 4-triazole Chemical class 0.000 title claims abstract description 35
238000002360 preparation method Methods 0.000 title claims description 13
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
229940042055 systemic antimycotics triazole derivative Drugs 0.000 title abstract description 5
150000003839 salts Chemical class 0.000 claims abstract description 24
239000000651 prodrug Substances 0.000 claims abstract description 17
229940002612 prodrug Drugs 0.000 claims abstract description 17
239000000556 agonist Substances 0.000 claims abstract description 10
150000001875 compounds Chemical class 0.000 claims description 87
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 36
238000000034 method Methods 0.000 claims description 22
238000006243 chemical reaction Methods 0.000 claims description 15
229910052799 carbon Inorganic materials 0.000 claims description 14
125000004432 carbon atom Chemical group C* 0.000 claims description 14
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 8
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 7
230000008569 process Effects 0.000 claims description 7
238000010511 deprotection reaction Methods 0.000 claims description 6
238000007069 methylation reaction Methods 0.000 claims description 6
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
SGNYSBAWYXBXPR-UHFFFAOYSA-N 3-(1-methylpyrrolidin-3-yl)-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C1N(C)CCC1C1=CNC2=CC=C(N3C=NN=C3)C=C12 SGNYSBAWYXBXPR-UHFFFAOYSA-N 0.000 claims description 5
230000011987 methylation Effects 0.000 claims description 5
150000001558 benzoic acid derivatives Chemical class 0.000 claims description 4
125000001401 1,2,4-triazol-4-yl group Chemical group N=1N=C([H])N([*])C=1[H] 0.000 claims description 3
SGNYSBAWYXBXPR-NSHDSACASA-N C1N(C)CC[C@@H]1C1=CNC2=CC=C(N3C=NN=C3)C=C12 Chemical compound C1N(C)CC[C@@H]1C1=CNC2=CC=C(N3C=NN=C3)C=C12 SGNYSBAWYXBXPR-NSHDSACASA-N 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
IGNXHSPBUUSUHB-UHFFFAOYSA-N n,n-dimethyl-2-[5-(1,2,4-triazol-4-yl)-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1N1C=NN=C1 IGNXHSPBUUSUHB-UHFFFAOYSA-N 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 1
230000002265 prevention Effects 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
208000019695 Migraine disease Diseases 0.000 abstract description 7
206010027599 migraine Diseases 0.000 abstract description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
208000035475 disorder Diseases 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
239000000243 solution Substances 0.000 description 43
239000000203 mixture Chemical class 0.000 description 37
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 34
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
239000002904 solvent Substances 0.000 description 16
229910001868 water Inorganic materials 0.000 description 14
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
235000019439 ethyl acetate Nutrition 0.000 description 12
239000002253 acid Substances 0.000 description 11
239000000284 extract Substances 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 10
239000000741 silica gel Substances 0.000 description 10
229910002027 silica gel Inorganic materials 0.000 description 10
229960001866 silicon dioxide Drugs 0.000 description 10
101150041968 CDC13 gene Proteins 0.000 description 9
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
239000003826 tablet Substances 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 description 8
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
229920006395 saturated elastomer Polymers 0.000 description 8
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 7
239000000047 product Substances 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
229920002261 Corn starch Polymers 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000008120 corn starch Substances 0.000 description 6
239000012043 crude product Substances 0.000 description 6
238000001914 filtration Methods 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 5
230000009467 reduction Effects 0.000 description 5
238000010992 reflux Methods 0.000 description 5
235000011149 sulphuric acid Nutrition 0.000 description 5
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
229960001413 acetanilide Drugs 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
239000006187 pill Substances 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
238000006783 Fischer indole synthesis reaction Methods 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
229920000388 Polyphosphate Polymers 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
238000009903 catalytic hydrogenation reaction 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
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
230000000694 effects Effects 0.000 description 3
235000019441 ethanol Nutrition 0.000 description 3
150000002429 hydrazines Chemical class 0.000 description 3
239000000852 hydrogen donor Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
239000000463 material Substances 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
239000001205 polyphosphate Substances 0.000 description 3
235000011176 polyphosphates Nutrition 0.000 description 3
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical class [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000001117 sulphuric acid Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000009901 transfer hydrogenation reaction Methods 0.000 description 3
150000003852 triazoles Chemical class 0.000 description 3
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
125000003047 N-acetyl group Chemical group 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
238000006859 Swern oxidation reaction Methods 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
235000011054 acetic acid Nutrition 0.000 description 2
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
150000001448 anilines Chemical class 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
230000027455 binding Effects 0.000 description 2
239000002775 capsule Substances 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
239000012055 enteric layer Substances 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
235000013305 food Nutrition 0.000 description 2
239000012458 free base Substances 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
230000003179 granulation Effects 0.000 description 2
238000005469 granulation Methods 0.000 description 2
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
239000007788 liquid Substances 0.000 description 2
125000004492 methyl ester group Chemical group 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
150000002828 nitro derivatives Chemical class 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
239000012071 phase Substances 0.000 description 2
HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 2
229940067157 phenylhydrazine Drugs 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
238000010791 quenching Methods 0.000 description 2
230000000171 quenching effect Effects 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
239000000018 receptor agonist Substances 0.000 description 2
229940044601 receptor agonist Drugs 0.000 description 2
238000000926 separation method Methods 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
235000010265 sodium sulphite Nutrition 0.000 description 2
235000011150 stannous chloride Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
238000012360 testing method Methods 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical class CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical class C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
MCMYIRWUHUCLGR-UHFFFAOYSA-N 1,1-dimethoxy-n-methylbutan-2-amine Chemical compound CCC(NC)C(OC)OC MCMYIRWUHUCLGR-UHFFFAOYSA-N 0.000 description 1
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical class COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
DHGMDHQNUNRMIN-UHFFFAOYSA-N 1-benzylpyrrolidin-3-one Chemical compound C1C(=O)CCN1CC1=CC=CC=C1 DHGMDHQNUNRMIN-UHFFFAOYSA-N 0.000 description 1
CWEGCQIIDCZZED-UHFFFAOYSA-N 1-benzylpyrrolidine Chemical compound C=1C=CC=CC=1CN1CCCC1 CWEGCQIIDCZZED-UHFFFAOYSA-N 0.000 description 1
HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 1
FLBZZWJMNUTZIP-UHFFFAOYSA-N 2-(1-benzylpyrrolidin-3-yl)acetaldehyde Chemical compound C1C(CC=O)CCN1CC1=CC=CC=C1 FLBZZWJMNUTZIP-UHFFFAOYSA-N 0.000 description 1
RLBGFQHGJXQUKY-UHFFFAOYSA-N 2-(1-methylpiperidin-4-yl)acetaldehyde Chemical compound CN1CCC(CC=O)CC1 RLBGFQHGJXQUKY-UHFFFAOYSA-N 0.000 description 1
CEBFTHCDPATJQH-UHFFFAOYSA-N 2-(1-methylpiperidin-4-yl)acetaldehyde methylsulfinylmethane Chemical compound CS(=O)C.CN1CCC(CC1)CC=O CEBFTHCDPATJQH-UHFFFAOYSA-N 0.000 description 1
CILPHQCEVYJUDN-UHFFFAOYSA-N 2-(5-methyl-2-propan-2-ylcyclohexyl)oxyacetic acid Chemical compound CC(C)C1CCC(C)CC1OCC(O)=O CILPHQCEVYJUDN-UHFFFAOYSA-N 0.000 description 1
DFCLRLMPUDXMII-UHFFFAOYSA-N 2-(hydroxymethylidene)-4,7,7-trimethylbicyclo[2.2.1]heptan-3-one Chemical compound C1CC2(C)C(=O)C(=CO)C1C2(C)C DFCLRLMPUDXMII-UHFFFAOYSA-N 0.000 description 1
QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 description 1
SGNYSBAWYXBXPR-LLVKDONJSA-N 3-[(3s)-1-methylpyrrolidin-3-yl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C1N(C)CC[C@H]1C1=CNC2=CC=C(N3C=NN=C3)C=C12 SGNYSBAWYXBXPR-LLVKDONJSA-N 0.000 description 1
QXIUMMLTJVHILT-UHFFFAOYSA-N 4-[3-(tert-butylamino)-2-hydroxypropoxy]-1H-indole-2-carbonitrile Chemical compound CC(C)(C)NCC(O)COC1=CC=CC2=C1C=C(C#N)N2 QXIUMMLTJVHILT-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 1
LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
206010009094 Chronic paroxysmal hemicrania Diseases 0.000 description 1
208000006561 Cluster Headache Diseases 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 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
108010010803 Gelatin Proteins 0.000 description 1
206010019233 Headaches Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
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 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
JLVHTNZNKOSCNB-YSVLISHTSA-N Mesulergine Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NS(=O)(=O)N(C)C)=C3C2=CN(C)C3=C1 JLVHTNZNKOSCNB-YSVLISHTSA-N 0.000 description 1
FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
101150029512 SCG2 gene Proteins 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
206010043269 Tension headache Diseases 0.000 description 1
208000008548 Tension-Type Headache Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
229940081735 acetylcellulose Drugs 0.000 description 1
230000009471 action Effects 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229940024606 amino acid Drugs 0.000 description 1
150000003862 amino acid derivatives Chemical class 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229940090047 auto-injector Drugs 0.000 description 1
230000008901 benefit Effects 0.000 description 1
LELJGPOJCNNZQE-UHFFFAOYSA-N benzoic acid 3-(1-methylpiperidin-4-yl)-5-(1,2,4-triazol-4-yl)-1H-indole Chemical compound CN1CCC(CC1)C1=CNC2=CC=C(C=C12)N1C=NN=C1.C(C1=CC=CC=C1)(=O)O LELJGPOJCNNZQE-UHFFFAOYSA-N 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000012267 brine Substances 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
208000018912 cluster headache syndrome Diseases 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
230000008602 contraction Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
229940109239 creatinine Drugs 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
229960001760 dimethyl sulfoxide Drugs 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
210000001198 duodenum Anatomy 0.000 description 1
239000008157 edible vegetable oil Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
235000020375 flavoured syrup Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
231100000869 headache Toxicity 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000010410 layer Substances 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229950008693 mesulergine Drugs 0.000 description 1
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
BMFMUHLTSDBYKC-UHFFFAOYSA-N methyl 2-(1-methylpiperidin-4-yl)acetate Chemical compound COC(=O)CC1CCN(C)CC1 BMFMUHLTSDBYKC-UHFFFAOYSA-N 0.000 description 1
CTSAXXHOGZNKJR-UHFFFAOYSA-N methyl 2-diethoxyphosphorylacetate Chemical compound CCOP(=O)(OCC)CC(=O)OC CTSAXXHOGZNKJR-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
229920001206 natural gum Polymers 0.000 description 1
238000011587 new zealand white rabbit Methods 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
NQRLPDFELNCFHW-UHFFFAOYSA-N nitroacetanilide Chemical compound CC(=O)NC1=CC=C([N+]([O-])=O)C=C1 NQRLPDFELNCFHW-UHFFFAOYSA-N 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
239000012454 non-polar solvent Substances 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000012053 oil suspension Substances 0.000 description 1
150000003891 oxalate salts Chemical class 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
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 1
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
239000003182 parenteral nutrition solution Substances 0.000 description 1
208000007777 paroxysmal Hemicrania Diseases 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
230000036515 potency Effects 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
230000004044 response Effects 0.000 description 1
210000003752 saphenous vein Anatomy 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000004208 shellac Substances 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000004289 sodium hydrogen sulphite Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
DGQOCLATAPFASR-UHFFFAOYSA-N tetrahydroxy-1,4-benzoquinone Chemical compound OC1=C(O)C(=O)C(O)=C(O)C1=O DGQOCLATAPFASR-UHFFFAOYSA-N 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
230000009466 transformation Effects 0.000 description 1
PTMFUWGXPRYYMC-UHFFFAOYSA-N triethylazanium;formate Chemical compound OC=O.CCN(CC)CC PTMFUWGXPRYYMC-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical group C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)

IL106445A 1992-07-30 1993-07-22 History of 1,2,4-Trans-Triazole 4-Transform, Preparation and Pharmaceutical Preparations Containing Them IL106445A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB929216192A GB9216192D0 (en)	1992-07-30	1992-07-30	Therapeutic agents
GB929216264A GB9216264D0 (en)	1992-07-30	1992-07-30	Therapeutic agents
GB929222261A GB9222261D0 (en)	1992-10-23	1992-10-23	Therapeutic agents

Publications (2)

Publication Number	Publication Date
IL106445A0 IL106445A0 (en)	1993-11-15
IL106445A true IL106445A (en)	1998-01-04

Family

ID=27266308

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL106445A IL106445A (en)	1992-07-30	1993-07-22	History of 1,2,4-Trans-Triazole 4-Transform, Preparation and Pharmaceutical Preparations Containing Them

Country Status (12)

Country	Link
US (1)	US5554629A (es)
EP (1)	EP0581538B1 (es)
JP (1)	JP2599557B2 (es)
CN (1)	CN1037101C (es)
AT (1)	ATE177096T1 (es)
AU (1)	AU664102B2 (es)
CA (1)	CA2101219A1 (es)
DE (1)	DE69323667T2 (es)
ES (1)	ES2127789T3 (es)
IL (1)	IL106445A (es)
MX (1)	MX9304595A (es)
WO (1)	WO1994003446A1 (es)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9402016D0 (en) *	1994-02-02	1994-03-30	Merck Sharp & Dohme	Therapeutic agents
GB9402011D0 (en) *	1994-02-02	1994-03-30	Merck Sharp & Dohme	Therapeutic agents
GB9410031D0 (en) *	1994-05-19	1994-07-06	Merck Sharp & Dohme	Therapeutic agents
US5552402A (en) *	1994-05-19	1996-09-03	Merck, Sharp & Dohme Ltd.	Five-membered heteroaromatic compounds as 5-HT receptor agonists
JPH10503768A (ja) *	1994-08-02	1998-04-07	メルクシヤープエンドドームリミテツド	アゼチジン、ピロリジンおよびピペリジン誘導体
US5521196A (en) *	1994-10-05	1996-05-28	Eli Lilly And Company	5-HT1F agonists for the treatment of migraine
GB9423460D0 (en) *	1994-11-21	1995-01-11	Merck Sharp & Dohme	Therapeutic agents
US5521197A (en) *	1994-12-01	1996-05-28	Eli Lilly And Company	3-<1-alkylenearyl>-4-<1,2,3,6-tetrahydropyridinyl>-and 3-<1-alkylenearyl>-4-piperidinyl-1h-indoles: new 5-HT1F agonists
NZ305166A (en) *	1995-03-20	1998-12-23	Lilly Co Eli	5-substituted-3-(1,2,3,6-tetrahydropyridin-4-yl)- and 3-(piperidin-4-yl)-1h-indoles; preparation and medicaments
JPH11513666A (ja) *	1995-10-10	1999-11-24	イーライ・リリー・アンド・カンパニー	Ｎ−［２−置換−３−（２−アミノエチル）−１ｈ−インドール−５−イル］−アミド：新規５−ｈｔ▲下１ｆ▼作動剤
US5998438A (en) *	1996-11-26	1999-12-07	Allelix Biopharmaceuticals, Inc.	5-cyclo indole compounds
US6391891B1 (en)	1997-08-09	2002-05-21	Smithkline Beecham Plc	Bicyclic compounds as ligands for 5-HT1 receptors
FR2767827A1 (fr) *	1997-09-03	1999-02-26	Adir	Nouveaux derives de l'indole et de l'indazole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US7189753B1 (en)	1997-11-06	2007-03-13	Cady Roger K	Preemptive prophylaxis of migraine
DE69908330T2 (de) *	1998-03-09	2004-02-12	H. Lundbeck A/S	5-heteroaryl-substituierte indole
TWI466879B (zh)	2005-04-13	2015-01-01	Neuraxon Inc	具有一氧化氮合成酶抑制活性之取代的吲哚化合物
TW200808780A (en)	2006-04-13	2008-02-16	Neuraxon Inc	1,5 and 3,6- substituted indole compounds having NOS inhibitory activity
NZ586082A (en)	2007-11-16	2013-03-28	Neuraxon Inc	Indole compounds and methods for treating visceral pain
WO2010084507A2 (en) *	2008-07-15	2010-07-29	Sun Pharmaceutical Industries Ltd.	Process for the preparation of n-methyl-2-[3-(1-methyl-4-piperidyl)-1h-indol-5-yl]-ethanesulfonamide and its acid addition salts

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3475437A (en) *	1964-06-05	1969-10-28	Boehringer Sohn Ingelheim	3-tertiary amino lower alkylpseudoindoles
GB1237008A (en) *	1968-12-18	1971-06-30	Pfizer Ltd	Novel indoline derivatives
US3686213A (en) *	1970-08-28	1972-08-22	American Cyanamid Co	Substituted aminoethyl indoles
DE2520816C3 (de) *	1975-05-09	1979-02-15	Bayer Ag, 5090 Leverkusen	Methinfarbstoffe
BE889931A (fr) *	1980-08-12	1982-02-11	Glaxo Group Ltd	Derives indoliques, leur preparation et leurs applications en tant que medicaments
CH652394A5 (fr) *	1980-08-12	1985-11-15	Glaxo Group Ltd	Derives indoliques, leur preparation et medicaments les renfermant.
ZW19381A1 (en) *	1980-08-12	1983-03-09	Glaxo Group Ltd	Heterocyclic compounds
US4453001A (en) *	1982-02-22	1984-06-05	Sandoz, Inc.	Isoxazolyl indolamines as intermediates
JPS58150576A (ja) *	1982-03-03	1983-09-07	Sumitomo Chem Co Ltd	新規な１，２，４−オキサジアゾ−ル誘導体
US4692531A (en) *	1984-06-22	1987-09-08	Bristol-Myers Company	Substituted 3,4-diamino-1,2,5-thiadiazoles having histamine H2 -receptor antagonist activity
GB8419575D0 (en) *	1984-08-01	1984-09-05	Glaxo Group Ltd	Chemical compounds
DE3430284A1 (de) *	1984-08-17	1986-02-27	Troponwerke GmbH & Co KG, 5000 Köln	Neue tryptamin-derivate, ein verfahren zu ihrer herstellung und ihre verwendung
IE58370B1 (en) *	1985-04-10	1993-09-08	Lundbeck & Co As H	Indole derivatives
DE3531658A1 (de) *	1985-09-05	1987-03-12	Boehringer Mannheim Gmbh	Heterocyclisch substituierte indole, zwischenprodukte, verfahren zu ihrer herstellung und arzneimittel
GB8724912D0 (en) *	1987-10-23	1987-11-25	Wellcome Found	Indole derivatives
US5225431A (en) *	1987-10-23	1993-07-06	Burroughs Wellcome Co.	Therapeutic substituted indole compounds and compositions thereof
NZ227841A (en) *	1988-02-12	1991-08-27	Merck Sharp & Dohme	Heterocyclic compounds with at least two non-condensed five membered rings and pharmaceutical compositions
SI21560B (sl) *	1990-06-07	2005-04-30	Astrazeneca Ab	3,5-disubstituirani indolni derivati kot "5-HT1-podobni" receptorski agonisti
SK278998B6 (sk) *	1991-02-01	1998-05-06	Merck Sharp & Dohme Limited	Deriváty imidazolu, triazolu a tetrazolu, spôsob i

1993
- 1993-07-22 IL IL106445A patent/IL106445A/en not_active IP Right Cessation
- 1993-07-23 AU AU42155/93A patent/AU664102B2/en not_active Ceased
- 1993-07-23 WO PCT/GB1993/001570 patent/WO1994003446A1/en active Search and Examination
- 1993-07-23 CA CA002101219A patent/CA2101219A1/en not_active Abandoned
- 1993-07-23 JP JP5202571A patent/JP2599557B2/ja not_active Expired - Lifetime
- 1993-07-23 AT AT93305829T patent/ATE177096T1/de not_active IP Right Cessation
- 1993-07-23 DE DE69323667T patent/DE69323667T2/de not_active Expired - Fee Related
- 1993-07-23 ES ES93305829T patent/ES2127789T3/es not_active Expired - Lifetime
- 1993-07-23 EP EP93305829A patent/EP0581538B1/en not_active Expired - Lifetime
- 1993-07-29 MX MX9304595A patent/MX9304595A/es not_active IP Right Cessation
- 1993-07-30 CN CN93109405A patent/CN1037101C/zh not_active Expired - Fee Related
1995
- 1995-06-29 US US08/496,839 patent/US5554629A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
JP2599557B2 (ja)	1997-04-09
AU4215593A (en)	1994-02-03
AU664102B2 (en)	1995-11-02
JPH06184139A (ja)	1994-07-05
WO1994003446A1 (en)	1994-02-17
CA2101219A1 (en)	1994-01-31
CN1089262A (zh)	1994-07-13
EP0581538B1 (en)	1999-03-03
CN1037101C (zh)	1998-01-21
DE69323667D1 (de)	1999-04-08
ES2127789T3 (es)	1999-05-01
IL106445A0 (en)	1993-11-15
MX9304595A (es)	1994-02-28
US5554629A (en)	1996-09-10
EP0581538A1 (en)	1994-02-02
DE69323667T2 (de)	1999-09-30
ATE177096T1 (de)	1999-03-15

Legal Events

Date	Code	Title
1998-06-15	FF	Patent granted
1998-11-26	KB	Patent renewed
1999-12-31	KB	Patent renewed
2004-03-28	RH1	Patent not in force

Publication	Publication Date	Title
US5567726A (en)	1996-10-22	Imidazole, Triazole and tetrazole derivatives
EP0581538B1 (en)	1999-03-03	4-Substituted 1,2,4-triazole derivatives
US5510362A (en)	1996-04-23	Imidazole, triazole and tetrazole derivatives
US5602162A (en)	1997-02-11	Imidazole, triazole and tetrazole derivatives
US5514682A (en)	1996-05-07	Fused imidazole and triazole derivatives as 5-HT1 receptor agonists
EP0619805B1 (en)	2000-03-15	5-(hetero- or carbocyclylamino)-indole derivatives, their preparation and their use as 5-ht1 agonists
AU740064B2 (en)	2001-10-25	Heterocyclic substituted piperidines and uses thereof
NO178572B (no)	1996-01-15	Nye N-alkylenpiperidinoforbindelser og deres enantiomere og farmasöytiske blandinger inneholdende dem
NO178573B (no)	1996-01-15	Polycykliske aminforbindelser og deres enantiomere, mellomprodukter for fremstilling av dem og farmasöytiske blandinger inneholdende dem
EP2268640B1 (en)	2016-10-12	Process for preparing enantiomerically pure indolopyridines
US5607957A (en)	1997-03-04	Imidazole, triazole and tetrazole derivatives
ES2228884T3 (es)	2005-04-16	Nuevos derivados de imidazol.
US5902819A (en)	1999-05-11	Triazole derivatives
WO2005040130A1 (en)	2005-05-06	1h-imidazole derivatives as cannabinoid receptor modulators
WO1995021167A1 (en)	1995-08-10	Triazole derivatives
EP0906318A1 (en)	1999-04-07	Piperazine, piperidine and tetrahydropyridine derivatives as 5-ht receptor agonists