SA91120058B1 - مركبات علاجية حلقية غير متجانسة - Google Patents

Info

Publication number

SA91120058B1

SA91120058B1 SA91120058A SA91120058A SA91120058B1 SA 91120058 B1 SA91120058 B1 SA 91120058B1 SA 91120058 A SA91120058 A SA 91120058A SA 91120058 A SA91120058 A SA 91120058A SA 91120058 B1 SA91120058 B1 SA 91120058B1

Authority

SA

Saudi Arabia

Prior art keywords

compound

formula

mixture

physiologically

functional derivative

Prior art date

1990-06-07

Links

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• Global Dossier
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• 150000002391 heterocyclic compounds Chemical class 0.000 title 1
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims abstract description 27
• 238000000034 method Methods 0.000 claims abstract description 15
• 238000002360 preparation method Methods 0.000 claims abstract description 15
• 239000003814 drug Substances 0.000 claims abstract description 12
• 229940079593 drug Drugs 0.000 claims abstract description 8
• 238000011321 prophylaxis Methods 0.000 claims abstract 3
• 150000001875 compounds Chemical class 0.000 claims description 107
• 239000000203 mixture Substances 0.000 claims description 74
• 150000003839 salts Chemical class 0.000 claims description 23
• 238000011282 treatment Methods 0.000 claims description 16
• 239000013543 active substance Substances 0.000 claims description 14
• 238000006243 chemical reaction Methods 0.000 claims description 14
• 208000019695 Migraine disease Diseases 0.000 claims description 13
• 206010027599 migraine Diseases 0.000 claims description 13
• 239000000556 agonist Substances 0.000 claims description 4
• 239000002775 capsule Substances 0.000 claims description 4
• 238000011065 in-situ storage Methods 0.000 claims description 4
• 238000002156 mixing Methods 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 3
• 229940124597 therapeutic agent Drugs 0.000 claims description 3
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
• 239000012453 solvate Substances 0.000 claims 6
• 238000004519 manufacturing process Methods 0.000 claims 2
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical group ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 1
• 239000003795 chemical substances by application Substances 0.000 claims 1
• AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 claims 1
• 230000003449 preventive effect Effects 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 8
• 150000002475 indoles Chemical class 0.000 abstract description 5
• 229940054051 antipsychotic indole derivative Drugs 0.000 abstract description 3
• 239000000018 receptor agonist Substances 0.000 abstract description 2
• 229940044601 receptor agonist Drugs 0.000 abstract description 2
• 231100001231 less toxic Toxicity 0.000 abstract 1
• 239000003440 toxic substance Substances 0.000 abstract 1
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 83
• 239000000243 solution Substances 0.000 description 64
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 56
• 239000000047 product Substances 0.000 description 50
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
• 239000007787 solid Substances 0.000 description 28
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
• 239000002585 base Substances 0.000 description 14
• 239000002904 solvent Substances 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
• 238000002844 melting Methods 0.000 description 12
• 230000008018 melting Effects 0.000 description 12
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
• 239000004480 active ingredient Substances 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 239000000706 filtrate Substances 0.000 description 9
• 239000006260 foam Substances 0.000 description 9
• 238000009472 formulation Methods 0.000 description 9
• 239000012458 free base Substances 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• -1 2-sulfonylaminoethyl Chemical group 0.000 description 8
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
• 229960000583 acetic acid Drugs 0.000 description 8
• 239000012141 concentrate Substances 0.000 description 8
• 235000008504 concentrate Nutrition 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 239000000284 extract Substances 0.000 description 7
• 238000010438 heat treatment Methods 0.000 description 7
• 239000001257 hydrogen Substances 0.000 description 7
• 229910052739 hydrogen Inorganic materials 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 235000019198 oils Nutrition 0.000 description 7
• 239000000377 silicon dioxide Substances 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 239000003826 tablet Substances 0.000 description 7
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
• 235000011054 acetic acid Nutrition 0.000 description 6
• 238000007792 addition Methods 0.000 description 6
• 235000019359 magnesium stearate Nutrition 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• 230000002265 prevention Effects 0.000 description 6
• 239000012279 sodium borohydride Substances 0.000 description 6
• 229910000033 sodium borohydride Inorganic materials 0.000 description 6
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
• 238000007083 alkoxycarbonylation reaction Methods 0.000 description 5
• 230000032050 esterification Effects 0.000 description 5
• 238000005886 esterification reaction Methods 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 238000006396 nitration reaction Methods 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 239000000829 suppository Substances 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• 230000002792 vascular Effects 0.000 description 5
• DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 4
• 208000002177 Cataract Diseases 0.000 description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• 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 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• 239000012190 activator Substances 0.000 description 4
• 239000002671 adjuvant Substances 0.000 description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 238000011049 filling Methods 0.000 description 4
• 239000007903 gelatin capsule Substances 0.000 description 4
• 239000011521 glass Substances 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
• 150000002828 nitro derivatives Chemical class 0.000 description 4
• 239000002798 polar solvent Substances 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• BSLCGNWSUGHJMV-FVGYRXGTSA-N (4s)-4-[(4-aminophenyl)methyl]-1,3-oxazolidin-2-one;hydrochloride Chemical compound Cl.C1=CC(N)=CC=C1C[C@@H]1NC(=O)OC1 BSLCGNWSUGHJMV-FVGYRXGTSA-N 0.000 description 3
• ANOPNEVQPPHZLO-FVGYRXGTSA-N (4s)-4-[(4-hydrazinylphenyl)methyl]-1,3-oxazolidin-2-one;hydrochloride Chemical compound Cl.C1=CC(NN)=CC=C1C[C@@H]1NC(=O)OC1 ANOPNEVQPPHZLO-FVGYRXGTSA-N 0.000 description 3
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
• 239000005695 Ammonium acetate Substances 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
• 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 3
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
• 240000007472 Leucaena leucocephala Species 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 239000007868 Raney catalyst Substances 0.000 description 3
• 229910000564 Raney nickel Inorganic materials 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• 238000010521 absorption reaction Methods 0.000 description 3
• 235000001014 amino acid Nutrition 0.000 description 3
• 150000001413 amino acids Chemical class 0.000 description 3
• 235000019257 ammonium acetate Nutrition 0.000 description 3
• 229940043376 ammonium acetate Drugs 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 230000003197 catalytic effect Effects 0.000 description 3
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
• 230000002496 gastric effect Effects 0.000 description 3
• 235000011187 glycerol Nutrition 0.000 description 3
• 239000008240 homogeneous mixture Substances 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 239000011976 maleic acid Substances 0.000 description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 229940069328 povidone Drugs 0.000 description 3
• 238000003825 pressing Methods 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• GTVVZTAFGPQSPC-QMMMGPOBSA-N (2s)-2-azaniumyl-3-(4-nitrophenyl)propanoate Chemical compound OC(=O)[C@@H](N)CC1=CC=C([N+]([O-])=O)C=C1 GTVVZTAFGPQSPC-QMMMGPOBSA-N 0.000 description 2
• 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 2
• LTLKJYMNUSSFAH-UHFFFAOYSA-N 4-chloro-1,1-dimethoxybutane Chemical compound COC(OC)CCCCl LTLKJYMNUSSFAH-UHFFFAOYSA-N 0.000 description 2
• CGFGIKNLZTZJDE-UHFFFAOYSA-N 4-oxobutanenitrile Chemical compound O=CCCC#N CGFGIKNLZTZJDE-UHFFFAOYSA-N 0.000 description 2
• KWSLGOVYXMQPPX-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenyl]-2h-tetrazole Chemical compound FC(F)(F)C1=CC=CC(C2=NNN=N2)=C1 KWSLGOVYXMQPPX-UHFFFAOYSA-N 0.000 description 2
• 241001093575 Alma Species 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• 208000006561 Cluster Headache Diseases 0.000 description 2
• 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 2
• 239000001856 Ethyl cellulose Substances 0.000 description 2
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
• 229930040373 Paraformaldehyde Natural products 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
• 150000001241 acetals Chemical class 0.000 description 2
• 150000001412 amines Chemical class 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
• 239000007864 aqueous solution Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• AYJRCSIUFZENHW-UHFFFAOYSA-L barium carbonate Chemical compound [Ba+2].[O-]C([O-])=O AYJRCSIUFZENHW-UHFFFAOYSA-L 0.000 description 2
• 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 2
• 239000008366 buffered solution Substances 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 239000002270 dispersing agent Substances 0.000 description 2
• 238000006073 displacement reaction Methods 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
• 235000019325 ethyl cellulose Nutrition 0.000 description 2
• 229920001249 ethyl cellulose Polymers 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 150000002429 hydrazines Chemical class 0.000 description 2
• 238000005984 hydrogenation reaction Methods 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
• 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 2
• 125000001041 indolyl group Chemical group 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 2
• 239000000787 lecithin Substances 0.000 description 2
• 235000010445 lecithin Nutrition 0.000 description 2
• 229940067606 lecithin Drugs 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• 150000002688 maleic acid derivatives Chemical class 0.000 description 2
• 238000004452 microanalysis Methods 0.000 description 2
• TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 229920002866 paraformaldehyde Polymers 0.000 description 2
• 239000008194 pharmaceutical composition Substances 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
• 239000004299 sodium benzoate Substances 0.000 description 2
• 235000010234 sodium benzoate Nutrition 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• 229910001379 sodium hypophosphite Inorganic materials 0.000 description 2
• 235000010288 sodium nitrite Nutrition 0.000 description 2
• 229940080313 sodium starch Drugs 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 125000000565 sulfonamide group Chemical group 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 210000005166 vasculature Anatomy 0.000 description 2
• 239000005526 vasoconstrictor agent Substances 0.000 description 2
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