WO1990014086A1 - Utilisation de derives de l'acridine dans le traitement d'infections retrovirales chez l'homme - Google Patents
Utilisation de derives de l'acridine dans le traitement d'infections retrovirales chez l'homme Download PDFInfo
- Publication number
- WO1990014086A1 WO1990014086A1 PCT/CH1990/000132 CH9000132W WO9014086A1 WO 1990014086 A1 WO1990014086 A1 WO 1990014086A1 CH 9000132 W CH9000132 W CH 9000132W WO 9014086 A1 WO9014086 A1 WO 9014086A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- treatment
- acridine
- diamino
- prophylaxis
- intended
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 11
- 206010038997 Retroviral infections Diseases 0.000 title description 2
- 229940027998 antiseptic and disinfectant acridine derivative Drugs 0.000 title description 2
- 125000000641 acridinyl group Chemical class C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 title 1
- WDVSHHCDHLJJJR-UHFFFAOYSA-N Proflavine Chemical compound C1=CC(N)=CC2=NC3=CC(N)=CC=C3C=C21 WDVSHHCDHLJJJR-UHFFFAOYSA-N 0.000 claims abstract description 13
- KKAJSJJFBSOMGS-UHFFFAOYSA-N 3,6-diamino-10-methylacridinium chloride Chemical compound [Cl-].C1=C(N)C=C2[N+](C)=C(C=C(N)C=C3)C3=CC2=C1 KKAJSJJFBSOMGS-UHFFFAOYSA-N 0.000 claims abstract description 12
- 208000005074 Retroviridae Infections Diseases 0.000 claims abstract description 6
- 241000700605 Viruses Species 0.000 claims abstract description 6
- -1 heterocyclic nitrogenous compound Chemical class 0.000 claims abstract description 5
- XJGFWWJLMVZSIG-UHFFFAOYSA-N 9-aminoacridine Chemical compound C1=CC=C2C(N)=C(C=CC=C3)C3=NC2=C1 XJGFWWJLMVZSIG-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229960001441 aminoacridine Drugs 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- 238000011321 prophylaxis Methods 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 229910017464 nitrogen compound Inorganic materials 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 208000029483 Acquired immunodeficiency Diseases 0.000 claims 1
- 208000008771 Lymphadenopathy Diseases 0.000 claims 1
- 210000001744 T-lymphocyte Anatomy 0.000 claims 1
- 238000007912 intraperitoneal administration Methods 0.000 claims 1
- 208000018555 lymphatic system disease Diseases 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 239000002831 pharmacologic agent Substances 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 230000009385 viral infection Effects 0.000 claims 1
- 208000030507 AIDS Diseases 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 3
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 13
- 229940023020 acriflavine Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 9
- 229960000286 proflavine Drugs 0.000 description 9
- 241000725303 Human immunodeficiency virus Species 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 230000000798 anti-retroviral effect Effects 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 241001430294 unidentified retrovirus Species 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical class C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 241000598436 Human T-cell lymphotropic virus Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000713880 Spleen focus-forming virus Species 0.000 description 1
- BGLGAKMTYHWWKW-UHFFFAOYSA-N acridine yellow Chemical compound [H+].[Cl-].CC1=C(N)C=C2N=C(C=C(C(C)=C3)N)C3=CC2=C1 BGLGAKMTYHWWKW-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 239000003085 diluting agent Substances 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
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 238000005956 quaternization reaction Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
Definitions
- the subject of the invention is a pharmaceutical composition intended for the treatment or prophylaxis of human retrovirus infections, in particular those with a virus which generates the acquired immunodeficiency syndrome (SIDA / AIDS). It also relates to, as medicaments for the treatment or prophylaxis of such infections, the heterocyclic compounds used in these compositions.
- SIDA / AIDS acquired immunodeficiency syndrome
- HIV retrovirus (LAV / HTLV III) seems to be one of the most worrying for civilization today: it is responsible for the acquired immunodeficiency syndrome (SIDA / Engl.: AIDS). It is mainly transmitted by sexual or blood pathway, it affects a growing number of people and its spread is today described as endemic.
- AZT has the disadvantage of being unstable when heated (it is generally stored at -20 ° C), of producing side effects that are poorly tolerated by individuals weakened by the disease and of being very expensive. AZT is also insoluble in water, which limits the forms of application.
- the present invention makes it possible to advantageously fill this gap by proposing, as a medicament intended for the treatment or prophylaxis of human retrovirus infections, at least one nitrogen-heterocyclic compound chosen from 3,6-diamino-10-methyl chloride. -acridinium, 3,6-diamino-acridine and 9-amino-acridine.
- ACD-y Acridine Yellow
- the compounds used in the context of the present invention all comprise at least one amino group attached to the nitrogen heterocycle; they can be represented as follows: Acriflavine (ACF)
- the anti-retroviral activity of the compounds mentioned in the context of the present invention has been demonstrated, inter alia, on the leukemigenic virus of Friends (spleen focus forming virus / SFFV-F) during in vivo experiments described below. .
- acriflavine (ACF) was found to be significantly more effective than AZT at a dose of comparable toxicity, the proflavin (PF) with activity similar to that of AZT.
- AIDS AIDS
- the nitrogen heterocyclic compounds proposed by the invention as medicaments have the great advantage of being readily available on the market and of being remarkably stable at room temperature.
- their toxicity has been the subject of numerous investigations: it is perfectly known and the same goes for possible side effects.
- Said compounds also have the advantage of being water-soluble, which facilitates their application all the more, by the oral or intravenous route for example.
- mice from the DBA 2 strain 0.2 ml of a 1% solution of a spleen extract contaminated with the leukemigenic retrovirus from Friends was inoculated into mice from the DBA 2 strain divided into groups of eight. . About 1 hour after this injection, each infected mouse was administered, intraperitoneally, an aqueous solution of the heterocyclic compound chosen, at the doses shown in the table below. A group of 8 infected mice was kept as such as a control sample.
- a blood plasma sample was taken from the treated and untreated infected mice, and 0.1 ml of this plasma, as is, injected, respectively, after 10% and 1% dilution, into uncontaminated mice from of the DBA2 strain. This injection was done intravenously.
- the number of viruses received by the latter was determined eight days after this injection, by counting the foci of unit formation in the spleen.
- the effect of the drug substances used in this experiment was expressed by means of the report between the number of outbreaks counted following injection of plasma from infected infected mice and the number of outbreaks counted following injection of plasma from "control" mice. The values obtained are expressed logarithmically and are reported in the attached figure.
- PF proflavin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH196589A CH678275A5 (enrdf_load_html_response) | 1989-05-25 | 1989-05-25 | |
| CH1965/89-5 | 1989-05-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1990014086A1 true WO1990014086A1 (fr) | 1990-11-29 |
Family
ID=4222755
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CH1990/000132 WO1990014086A1 (fr) | 1989-05-25 | 1990-05-22 | Utilisation de derives de l'acridine dans le traitement d'infections retrovirales chez l'homme |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU5630990A (enrdf_load_html_response) |
| CH (1) | CH678275A5 (enrdf_load_html_response) |
| WO (1) | WO1990014086A1 (enrdf_load_html_response) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0375471A3 (fr) * | 1988-12-19 | 1992-07-08 | Ste Civile De Recherche Newpharm | Utilisation de 1,2,3,4-tétrahydro-acridines pour le traitement du SIDA, et composés |
| EP0649656A1 (fr) * | 1993-10-22 | 1995-04-26 | Laboratoire M. Richard | Compositions pharmaceutiques à base d'acriflavine utiles pour le traitement de l'herpès et du zona |
| FR2711527A1 (fr) * | 1993-10-22 | 1995-05-05 | Richard Laboratoire M | Utilisation de l'acriflavine comme agent anti HIV. |
| WO1996007423A1 (fr) * | 1995-03-23 | 1996-03-14 | Oleg Viktorovich Travkin | Substance pharmaceutique immunomodulatrice |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3489837A (en) * | 1968-07-11 | 1970-01-13 | Leroy J Hyman | Synergistic antiseptic composition consisting of 9-aminoacridine hydrochloride and benzethonium chloride |
| EP0196515A1 (en) * | 1985-03-14 | 1986-10-08 | Baxter Travenol Laboratories, Inc. | Photodynamic inactivation of virus in therapeutic protein compositions |
-
1989
- 1989-05-25 CH CH196589A patent/CH678275A5/fr not_active IP Right Cessation
-
1990
- 1990-05-22 AU AU56309/90A patent/AU5630990A/en not_active Abandoned
- 1990-05-22 WO PCT/CH1990/000132 patent/WO1990014086A1/fr unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3489837A (en) * | 1968-07-11 | 1970-01-13 | Leroy J Hyman | Synergistic antiseptic composition consisting of 9-aminoacridine hydrochloride and benzethonium chloride |
| EP0196515A1 (en) * | 1985-03-14 | 1986-10-08 | Baxter Travenol Laboratories, Inc. | Photodynamic inactivation of virus in therapeutic protein compositions |
Non-Patent Citations (4)
| Title |
|---|
| Biomed. & Pharmacother., Vol. 43, No. 4, 1989, Elsevier, (Paris, FR), G. MATHE et al.: "Amino Acridines Action on Friend's Retrovirus in Relation to their Molecular Ionization", pages 235-236 * |
| Chem.-Biol. Interactions, Vol. 8, No. 2, 1988, Elsevier Scientific Publishing Co., (Amsterdam, NL), R. MENEGHINI: "Repair Replication of Opossum Lymphocyte DNA: Effect of Compounds that Bind to DNA", pages 113-126 * |
| Life Sciences, Vol. 15, No. 1974, Pergamon Press, (US), R. GRAHAM SMITH et al.: "Agents which Inhibit Reverse Transcriptases", pages 1711-1730 * |
| Mutation Research, Vol. 68, No. 3, 1979, Elsevier/North-Holland Biomedical Press, (Amsterdam, NL), P.E. CROSSEN: "The Effect of Acridine Compounds on Siter-Chromatid Exchange Formation in Cultured Human Lymphocytes", pages 295-299 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0375471A3 (fr) * | 1988-12-19 | 1992-07-08 | Ste Civile De Recherche Newpharm | Utilisation de 1,2,3,4-tétrahydro-acridines pour le traitement du SIDA, et composés |
| EP0649656A1 (fr) * | 1993-10-22 | 1995-04-26 | Laboratoire M. Richard | Compositions pharmaceutiques à base d'acriflavine utiles pour le traitement de l'herpès et du zona |
| FR2711527A1 (fr) * | 1993-10-22 | 1995-05-05 | Richard Laboratoire M | Utilisation de l'acriflavine comme agent anti HIV. |
| FR2711526A1 (fr) * | 1993-10-22 | 1995-05-05 | Richard Laboratoire M | Utilisation de l'Acriflavine comme agent anti herpès et anti zona. |
| WO1996007423A1 (fr) * | 1995-03-23 | 1996-03-14 | Oleg Viktorovich Travkin | Substance pharmaceutique immunomodulatrice |
Also Published As
| Publication number | Publication date |
|---|---|
| AU5630990A (en) | 1990-12-18 |
| CH678275A5 (enrdf_load_html_response) | 1991-08-30 |
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