CA2008911C - Methode de preparation du chlorhydrate de 6-bromo-5-hydroxy-4-dimethylaminomethyl-1-methyl-2-phenylthiomethylindole -3-c rboxylate d'ethyle, avec une molecule d'eau; preparation pharmaceutique a base de ce compose, possedant des proprietes - Google Patents

Methode de preparation du chlorhydrate de 6-bromo-5-hydroxy-4-dimethylaminomethyl-1-methyl-2-phenylthiomethylindole -3-c rboxylate d'ethyle, avec une molecule d'eau; preparation pharmaceutique a base de ce compose, possedant des proprietes

Info

Publication number: CA2008911C
Authority: CA; Canada
Prior art keywords: ethyl; bromo; carboxylate; preparation; hydroxy
Prior art date: 1990-01-30
Legal status (The legal status 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 status listed.): Expired - Fee Related

Application number

CA002008911A

Other languages

English (en)

Other versions

CA2008911A1 (fr

Inventor

Fedor A. Trofimov

Nina G. Tsyshkova

Nadezhda S. Bogdanova

Irina S. Nikolaeva

Svetlana A. Zotova

Ljudmila A. Savinova

Alexei Nikolaevich Grinev

Grigory Nikolaevich Pershin

Zinaida M. Sakhaschik

Evgenia A. Svirina

Alla N. Fomina

Elena N. Padeiskaya

Dmitry M. Zlydnikov

Olga I. Kubar

Evgenia G. Shvetsova

Elena A. Bryantseva

Valentina V. Peters

Svetlana N. Kutchak

Anatoly G. Konoplyannikov

Boris P. Surinov

Vera A. Yadrovskaya

Elena P. Savina

Nina A. Karpova

Ljudmila S. Safonova

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

LENINGRADSKY NAUCHNO-ISSLEDOVATELSKY INSTITUT EPIDEMIOLOGII I MIKROBIOLOGII IMENI PASTERA

NAUCHNO-ISSLEDOVATELSKY INSTITUT MEDITSINSKOI RADIOLOGII AKADEMII MEDITSINSKIKH NAUK SSSR

Vsesojuzny Nauchno-Issledovatelsky Khimiko-Farmatsevtichesky Institut Imeni Sordzhonikidze (vnikhfi)

Original Assignee

LENINGRADSKY NAUCHNO-ISSLEDOVATELSKY INSTITUT EPIDEMIOLOGII I MIKROBIOLOGII IMENI PASTERA

NAUCHNO-ISSLEDOVATELSKY INSTITUT MEDITSINSKOI RADIOLOGII AKADEMII MEDITSINSKIKH NAUK SSSR

Vsesojuzny Nauchno-Issledovatelsky Khimiko-Farmatsevtichesky Institut Imeni Sordzhonikidze (vnikhfi)

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.)

1990-01-30

Filing date

1990-01-30

Publication date

1996-12-10

1990-01-30 Application filed by LENINGRADSKY NAUCHNO-ISSLEDOVATELSKY INSTITUT EPIDEMIOLOGII I MIKROBIOLOGII IMENI PASTERA, NAUCHNO-ISSLEDOVATELSKY INSTITUT MEDITSINSKOI RADIOLOGII AKADEMII MEDITSINSKIKH NAUK SSSR, Vsesojuzny Nauchno-Issledovatelsky Khimiko-Farmatsevtichesky Institut Imeni Sordzhonikidze (vnikhfi) filed Critical LENINGRADSKY NAUCHNO-ISSLEDOVATELSKY INSTITUT EPIDEMIOLOGII I MIKROBIOLOGII IMENI PASTERA

1990-01-30 Priority to CA002008911A priority Critical patent/CA2008911C/fr

1991-07-30 Publication of CA2008911A1 publication Critical patent/CA2008911A1/fr

1996-12-10 Application granted granted Critical

1996-12-10 Publication of CA2008911C publication Critical patent/CA2008911C/fr

2010-01-30 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

230000000840 anti-viral effect Effects 0.000 title claims abstract description 11
230000001939 inductive effect Effects 0.000 title claims abstract description 11
230000002519 immonomodulatory effect Effects 0.000 title claims abstract description 6
238000004519 manufacturing process Methods 0.000 title claims abstract description 5
239000000825 pharmaceutical preparation Substances 0.000 title claims abstract 5
102000014150 Interferons Human genes 0.000 title claims description 32
108010050904 Interferons Proteins 0.000 title claims description 32
229940079322 interferon Drugs 0.000 title claims description 32
PLWQHPWNKPKQJT-UHFFFAOYSA-N ethyl 6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-(phenylsulfanylmethyl)indole-3-carboxylate;hydron;chloride;hydrate Chemical compound O.Cl.CN1C2=CC(Br)=C(O)C(CN(C)C)=C2C(C(=O)OCC)=C1CSC1=CC=CC=C1 PLWQHPWNKPKQJT-UHFFFAOYSA-N 0.000 title claims 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 25
239000003960 organic solvent Substances 0.000 claims abstract description 23
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims abstract description 20
239000007795 chemical reaction product Substances 0.000 claims abstract description 16
239000003795 chemical substances by application Substances 0.000 claims abstract description 16
150000001875 compounds Chemical class 0.000 claims abstract description 13
238000010992 reflux Methods 0.000 claims abstract description 13
239000011541 reaction mixture Substances 0.000 claims abstract description 11
150000008044 alkali metal hydroxides Chemical class 0.000 claims abstract description 5
MESMQGKAVXOGHJ-UHFFFAOYSA-N ethyl 5-acetyloxy-6-bromo-2-(bromomethyl)-1-methylindole-3-carboxylate Chemical compound BrC1=C(OC(C)=O)C=C2C(C(=O)OCC)=C(CBr)N(C)C2=C1 MESMQGKAVXOGHJ-UHFFFAOYSA-N 0.000 claims abstract description 4
DAFNNZWQTJQQAP-UHFFFAOYSA-N ethyl 6-bromo-5-hydroxy-1-methyl-2-(phenylsulfanylmethyl)indole-3-carboxylate Chemical compound CN1C2=CC(Br)=C(O)C=C2C(C(=O)OCC)=C1CSC1=CC=CC=C1 DAFNNZWQTJQQAP-UHFFFAOYSA-N 0.000 claims abstract description 4
230000000694 effects Effects 0.000 claims description 28
238000000034 method Methods 0.000 claims description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
230000008569 process Effects 0.000 claims description 15
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
238000005902 aminomethylation reaction Methods 0.000 claims description 7
239000000203 mixture Substances 0.000 claims description 7
VGIVLIHKENZQHQ-UHFFFAOYSA-N n,n,n',n'-tetramethylmethanediamine Chemical compound CN(C)CN(C)C VGIVLIHKENZQHQ-UHFFFAOYSA-N 0.000 claims description 7
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 6
229920002472 Starch Polymers 0.000 claims description 6
229950005499 carbon tetrachloride Drugs 0.000 claims description 6
AEWNSBCPMQKSLN-UHFFFAOYSA-N ethyl 5-acetyloxy-1,2-dimethylindole-3-carboxylate Chemical compound C1=C(OC(C)=O)C=C2C(C(=O)OCC)=C(C)N(C)C2=C1 AEWNSBCPMQKSLN-UHFFFAOYSA-N 0.000 claims description 6
235000019698 starch Nutrition 0.000 claims description 6
239000008107 starch Substances 0.000 claims description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
238000002955 isolation Methods 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 3
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
235000004443 Ricinus communis Nutrition 0.000 claims 1
125000001246 bromo group Chemical group Br* 0.000 claims 1
125000000532 dioxanyl group Chemical group 0.000 claims 1
239000012022 methylating agents‎ Substances 0.000 claims 1
238000002360 preparation method Methods 0.000 description 126
229960001614 levamisole Drugs 0.000 description 25
HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical group C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 24
241001465754 Metazoa Species 0.000 description 23
241000699670 Mus sp. Species 0.000 description 20
210000002966 serum Anatomy 0.000 description 19
241000700605 Viruses Species 0.000 description 17
206010028980 Neoplasm Diseases 0.000 description 16
238000004113 cell culture Methods 0.000 description 16
239000000243 solution Substances 0.000 description 16
241000282414 Homo sapiens Species 0.000 description 14
241000699666 Mus <mouse, genus> Species 0.000 description 12
210000004027 cell Anatomy 0.000 description 12
230000006698 induction Effects 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 10
210000004698 lymphocyte Anatomy 0.000 description 9
241000712461 unidentified influenza virus Species 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
230000002354 daily effect Effects 0.000 description 8
238000011161 development Methods 0.000 description 8
230000018109 developmental process Effects 0.000 description 8
239000000047 product Substances 0.000 description 8
238000012360 testing method Methods 0.000 description 8
230000009471 action Effects 0.000 description 7
230000007423 decrease Effects 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
239000002955 immunomodulating agent Substances 0.000 description 6
229940121354 immunomodulator Drugs 0.000 description 6
208000015181 infectious disease Diseases 0.000 description 6
210000000952 spleen Anatomy 0.000 description 6
230000009385 viral infection Effects 0.000 description 6
206010035664 Pneumonia Diseases 0.000 description 5
OZBDFBJXRJWNAV-UHFFFAOYSA-N Rimantadine hydrochloride Chemical compound Cl.C1C(C2)CC3CC2CC1(C(N)C)C3 OZBDFBJXRJWNAV-UHFFFAOYSA-N 0.000 description 5
210000002950 fibroblast Anatomy 0.000 description 5
210000001161 mammalian embryo Anatomy 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 4
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
241000700159 Rattus Species 0.000 description 4
239000002585 base Substances 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
238000000921 elemental analysis Methods 0.000 description 4
230000002434 immunopotentiative effect Effects 0.000 description 4
230000001965 increasing effect Effects 0.000 description 4
206010022000 influenza Diseases 0.000 description 4
231100000225 lethality Toxicity 0.000 description 4
210000002540 macrophage Anatomy 0.000 description 4
210000004379 membrane Anatomy 0.000 description 4
239000012528 membrane Substances 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
230000009467 reduction Effects 0.000 description 4
238000003756 stirring Methods 0.000 description 4
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
241000700198 Cavia Species 0.000 description 3
241000712431 Influenza A virus Species 0.000 description 3
206010039491 Sarcoma Diseases 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
230000000052 comparative effect Effects 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000003814 drug Substances 0.000 description 3
230000005713 exacerbation Effects 0.000 description 3
230000006870 function Effects 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
230000002584 immunomodulator Effects 0.000 description 3
230000000091 immunopotentiator Effects 0.000 description 3
239000002799 interferon inducing agent Substances 0.000 description 3
239000000843 powder Substances 0.000 description 3
230000033458 reproduction Effects 0.000 description 3
206010040882 skin lesion Diseases 0.000 description 3
231100000444 skin lesion Toxicity 0.000 description 3
231100000331 toxic Toxicity 0.000 description 3
230000002588 toxic effect Effects 0.000 description 3
238000011282 treatment Methods 0.000 description 3
208000017667 Chronic Disease Diseases 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
206010054979 Secondary immunodeficiency Diseases 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
230000002009 allergenic effect Effects 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
210000000628 antibody-producing cell Anatomy 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000000969 carrier Substances 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
238000001816 cooling Methods 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
229940093499 ethyl acetate Drugs 0.000 description 2
235000019439 ethyl acetate Nutrition 0.000 description 2
229960000443 hydrochloric acid Drugs 0.000 description 2
235000011167 hydrochloric acid Nutrition 0.000 description 2
230000001900 immune effect Effects 0.000 description 2
230000028993 immune response Effects 0.000 description 2
230000003053 immunization Effects 0.000 description 2
238000002649 immunization Methods 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
208000037797 influenza A Diseases 0.000 description 2
208000037798 influenza B Diseases 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
210000003024 peritoneal macrophage Anatomy 0.000 description 2
230000003449 preventive effect Effects 0.000 description 2
230000009257 reactivity Effects 0.000 description 2
238000004904 shortening Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
238000004448 titration Methods 0.000 description 2
230000003253 viricidal effect Effects 0.000 description 2
OZCXZQSCHLRTPE-UHFFFAOYSA-N 2-(phenylsulfanylmethyl)-1h-indole Chemical compound C=1C2=CC=CC=C2NC=1CSC1=CC=CC=C1 OZCXZQSCHLRTPE-UHFFFAOYSA-N 0.000 description 1
MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
206010059866 Drug resistance Diseases 0.000 description 1
206010016275 Fear Diseases 0.000 description 1
206010019233 Headaches Diseases 0.000 description 1
208000029433 Herpesviridae infectious disease Diseases 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
206010020751 Hypersensitivity 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
206010061598 Immunodeficiency Diseases 0.000 description 1
208000029462 Immunodeficiency disease Diseases 0.000 description 1
241000713196 Influenza B virus Species 0.000 description 1
206010022004 Influenza like illness Diseases 0.000 description 1
OKIBNKKYNPBDRS-UHFFFAOYSA-N Mefluidide Chemical compound CC(=O)NC1=CC(NS(=O)(=O)C(F)(F)F)=C(C)C=C1C OKIBNKKYNPBDRS-UHFFFAOYSA-N 0.000 description 1
208000008457 Neurologic Manifestations Diseases 0.000 description 1
206010060860 Neurological symptom Diseases 0.000 description 1
102000010410 Nogo Proteins Human genes 0.000 description 1
108010077641 Nogo Proteins Proteins 0.000 description 1
241001494479 Pecora Species 0.000 description 1
CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical compound ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 1
241000700584 Simplexvirus Species 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
241000375392 Tana Species 0.000 description 1
241000711975 Vesicular stomatitis virus Species 0.000 description 1
230000005856 abnormality Effects 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
230000004075 alteration Effects 0.000 description 1
WOLHOYHSEKDWQH-UHFFFAOYSA-N amantadine hydrochloride Chemical compound [Cl-].C1C(C2)CC3CC2CC1([NH3+])C3 WOLHOYHSEKDWQH-UHFFFAOYSA-N 0.000 description 1
QXAITBQSYVNQDR-UHFFFAOYSA-N amitraz Chemical compound C=1C=C(C)C=C(C)C=1N=CN(C)C=NC1=CC=C(C)C=C1C QXAITBQSYVNQDR-UHFFFAOYSA-N 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
230000002155 anti-virotic effect Effects 0.000 description 1
230000000890 antigenic effect Effects 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
238000009227 behaviour therapy Methods 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
238000011088 calibration curve Methods 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
230000008859 change Effects 0.000 description 1
230000000973 chemotherapeutic effect Effects 0.000 description 1
210000003837 chick embryo Anatomy 0.000 description 1
230000000875 corresponding effect Effects 0.000 description 1
239000013078 crystal Substances 0.000 description 1
239000012531 culture fluid Substances 0.000 description 1
230000034994 death Effects 0.000 description 1
230000003412 degenerative effect Effects 0.000 description 1
230000000994 depressogenic effect Effects 0.000 description 1
230000003544 deproteinization Effects 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
230000013020 embryo development Effects 0.000 description 1
210000002257 embryonic structure Anatomy 0.000 description 1
206010014599 encephalitis Diseases 0.000 description 1
210000003743 erythrocyte Anatomy 0.000 description 1
ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 1
230000003203 everyday effect Effects 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
208000024908 graft versus host disease Diseases 0.000 description 1
230000012010 growth Effects 0.000 description 1
231100000869 headache Toxicity 0.000 description 1
230000002489 hematologic effect Effects 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
230000009610 hypersensitivity Effects 0.000 description 1
230000008105 immune reaction Effects 0.000 description 1
230000036039 immunity Effects 0.000 description 1
230000007813 immunodeficiency Effects 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 1
239000000411 inducer Substances 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
230000035987 intoxication Effects 0.000 description 1
231100000566 intoxication Toxicity 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
230000007774 longterm Effects 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
231100000243 mutagenic effect Toxicity 0.000 description 1
230000003505 mutagenic effect Effects 0.000 description 1
VMWJCFLUSKZZDX-UHFFFAOYSA-N n,n-dimethylmethanamine Chemical compound [CH2]N(C)C VMWJCFLUSKZZDX-UHFFFAOYSA-N 0.000 description 1
PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
231100000957 no side effect Toxicity 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000003950 pathogenic mechanism Effects 0.000 description 1
231100000915 pathological change Toxicity 0.000 description 1
230000036285 pathological change Effects 0.000 description 1
230000035515 penetration Effects 0.000 description 1
210000003200 peritoneal cavity Anatomy 0.000 description 1
210000001539 phagocyte Anatomy 0.000 description 1
239000000902 placebo Substances 0.000 description 1
229940068196 placebo Drugs 0.000 description 1
230000007542 postnatal development Effects 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
230000005855 radiation Effects 0.000 description 1
230000036647 reaction Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
229920002477 rna polymer Polymers 0.000 description 1
238000009589 serological test Methods 0.000 description 1
239000002356 single layer Substances 0.000 description 1
208000019116 sleep disease Diseases 0.000 description 1
208000022925 sleep disturbance Diseases 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
210000000130 stem cell Anatomy 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
238000002636 symptomatic treatment Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000003390 teratogenic effect Effects 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000002024 thermoprotective effect Effects 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000005748 tumor development Effects 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
238000002255 vaccination Methods 0.000 description 1
229960005486 vaccine Drugs 0.000 description 1

Classifications

- E—FIXED CONSTRUCTIONS
- E04—BUILDING
- E04B—GENERAL BUILDING CONSTRUCTIONS; WALLS, e.g. PARTITIONS; ROOFS; FLOORS; CEILINGS; INSULATION OR OTHER PROTECTION OF BUILDINGS
- E04B1/00—Constructions in general; Structures which are not restricted either to walls, e.g. partitions, or floors or ceilings or roofs
- E04B1/32—Arched structures; Vaulted structures; Folded structures
- E04B1/3211—Structures with a vertical rotation axis or the like, e.g. semi-spherical structures
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- E—FIXED CONSTRUCTIONS
- E04—BUILDING
- E04B—GENERAL BUILDING CONSTRUCTIONS; WALLS, e.g. PARTITIONS; ROOFS; FLOORS; CEILINGS; INSULATION OR OTHER PROTECTION OF BUILDINGS
- E04B1/00—Constructions in general; Structures which are not restricted either to walls, e.g. partitions, or floors or ceilings or roofs
- E04B1/32—Arched structures; Vaulted structures; Folded structures
- E04B2001/327—Arched structures; Vaulted structures; Folded structures comprised of a number of panels or blocs connected together forming a self-supporting structure

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Architecture (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Health & Medical Sciences (AREA)
Oncology (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Physics & Mathematics (AREA)
Communicable Diseases (AREA)
Virology (AREA)
Electromagnetism (AREA)
Civil Engineering (AREA)
Structural Engineering (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA002008911A 1990-01-30 1990-01-30 Methode de preparation du chlorhydrate de 6-bromo-5-hydroxy-4-dimethylaminomethyl-1-methyl-2-phenylthiomethylindole -3-c rboxylate d'ethyle, avec une molecule d'eau; preparation pharmaceutique a base de ce compose, possedant des proprietes Expired - Fee Related CA2008911C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA002008911A CA2008911C (fr)	1990-01-30	1990-01-30	Methode de preparation du chlorhydrate de 6-bromo-5-hydroxy-4-dimethylaminomethyl-1-methyl-2-phenylthiomethylindole -3-c rboxylate d'ethyle, avec une molecule d'eau; preparation pharmaceutique a base de ce compose, possedant des proprietes

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA002008911A CA2008911C (fr)	1990-01-30	1990-01-30	Methode de preparation du chlorhydrate de 6-bromo-5-hydroxy-4-dimethylaminomethyl-1-methyl-2-phenylthiomethylindole -3-c rboxylate d'ethyle, avec une molecule d'eau; preparation pharmaceutique a base de ce compose, possedant des proprietes

Publications (2)

Publication Number	Publication Date
CA2008911A1 CA2008911A1 (fr)	1991-07-30
CA2008911C true CA2008911C (fr)	1996-12-10

Family

ID=76956514

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002008911A Expired - Fee Related CA2008911C (fr)	1990-01-30	1990-01-30	Methode de preparation du chlorhydrate de 6-bromo-5-hydroxy-4-dimethylaminomethyl-1-methyl-2-phenylthiomethylindole -3-c rboxylate d'ethyle, avec une molecule d'eau; preparation pharmaceutique a base de ce compose, possedant des proprietes

Country Status (1)

Country	Link
CA (1)	CA2008911C (fr)

1990
- 1990-01-30 CA CA002008911A patent/CA2008911C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2008911A1 (fr)	1991-07-30

Legal Events

Date	Code	Title	Description
1992-01-28	EEER	Examination request
2000-01-31	MKLA	Lapsed

Publication	Publication Date	Title
US5198552A (en)	1993-03-30	Indole derivative having antiviral, interferon-inducing and immunomodulatory effects
US4659603A (en)	1987-04-21	Immunostimulating agents
RU2033157C1 (ru)	1995-04-20	Средство, обладающее интерферониндуцирующей и иммуномодулирующей (иммуностимулирующей) активностью
US3991190A (en)	1976-11-09	Treatment of viral infections
US4871540A (en)	1989-10-03	Process for producing a biologically active substance and compositions containing the same
AU2004272001A1 (en)	2005-03-24	Methods and compositions for treating herpes infections
CA2008911C (fr)	1996-12-10	Methode de preparation du chlorhydrate de 6-bromo-5-hydroxy-4-dimethylaminomethyl-1-methyl-2-phenylthiomethylindole -3-c rboxylate d'ethyle, avec une molecule d'eau; preparation pharmaceutique a base de ce compose, possedant des proprietes
JPS60202822A (ja)	1985-10-14	抗ウイルス薬
CN114588161A (zh)	2022-06-07	具有防治肺炎作用的次黄碱衍生物
CN114450278A (zh)	2022-05-06	一个烟醇醚衍生物的马来酸盐及其晶型和应用
JP4580479B2 (ja)	2010-11-10	抗ｈｉｖ感染症剤
US4737521A (en)	1988-04-12	Suramin sodium for use as an immunostimulant
JPS60115574A (ja)	1985-06-22	１，２−ジチオラン誘導体、その製法、医薬および用途
US4892876A (en)	1990-01-09	Method for inhibiting HIV and an pharmaceutical composition therefor
JPH0572903B2 (fr)	1993-10-13
WO2021195185A1 (fr)	2021-09-30	Procédé de traitement d'une infection à coronavirus par administration d'éthyl-mercure ou d'un dérivé thiol de celui-ci
JPH02172920A (ja)	1990-07-04	抗潰瘍剤
US5503830A (en)	1996-04-02	Compounds having immunostimulating activity and methods of use thereof
JP2535633B2 (ja)	1996-09-18	エチル６―ブロモ―５―オキシ―４―ジメチルアミノメチル―１―メチル―２―フェニルチオメチルインド―ル―３―カルボキシレ―トハイドロクロライドモノハイドレ―ト，その調製方法、それを含む抗ウイルス性，インタ―フェロン―誘導及び免疫変調効果を持つ薬剤の調製
US4857529A (en)	1989-08-15	Interferon inducing, anti-vaccinia, and/or anti-influenza compositions
JP2799368B2 (ja)	1998-09-17	抗原虫剤
US4230725A (en)	1980-10-28	Antiviral agent
TW536400B (en)	2003-06-11	Pharmaceutical composition for the treatment of immunodeficiency disease which cause by HIV infection
JPH0193526A (ja)	1989-04-12	白血球減少の回復剤
JP2024543668A (ja)	2024-11-21	自然免疫活性化薬物およびその用途