WO1992007566A3 - Antifungal activity of and prevention of drug induced nephrotoxicity by methylxanthine analogues - Google Patents
Antifungal activity of and prevention of drug induced nephrotoxicity by methylxanthine analogues Download PDFInfo
- Publication number
- WO1992007566A3 WO1992007566A3 PCT/US1991/008086 US9108086W WO9207566A3 WO 1992007566 A3 WO1992007566 A3 WO 1992007566A3 US 9108086 W US9108086 W US 9108086W WO 9207566 A3 WO9207566 A3 WO 9207566A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- analogs
- methylxanthine
- 4coh
- analogues
- prevention
- Prior art date
Links
- RTAPDZBZLSXHQQ-UHFFFAOYSA-N 8-methyl-3,7-dihydropurine-2,6-dione Chemical class N1C(=O)NC(=O)C2=C1N=C(C)N2 RTAPDZBZLSXHQQ-UHFFFAOYSA-N 0.000 title abstract 3
- 229940079593 drug Drugs 0.000 title abstract 2
- 239000003814 drug Substances 0.000 title abstract 2
- 230000000843 anti-fungal effect Effects 0.000 title 1
- 231100000268 induced nephrotoxicity Toxicity 0.000 title 1
- 230000002265 prevention Effects 0.000 title 1
- 206010017533 Fungal infection Diseases 0.000 abstract 2
- 208000031888 Mycoses Diseases 0.000 abstract 2
- 230000009885 systemic effect Effects 0.000 abstract 2
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 abstract 1
- 241000222122 Candida albicans Species 0.000 abstract 1
- 206010007134 Candida infections Diseases 0.000 abstract 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 abstract 1
- 108010036949 Cyclosporine Proteins 0.000 abstract 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 abstract 1
- 229960003942 amphotericin b Drugs 0.000 abstract 1
- 201000003984 candidiasis Diseases 0.000 abstract 1
- 229960001265 ciclosporin Drugs 0.000 abstract 1
- 229930182912 cyclosporin Natural products 0.000 abstract 1
- 230000004064 dysfunction Effects 0.000 abstract 1
- 230000024924 glomerular filtration Effects 0.000 abstract 1
- 230000009467 reduction Effects 0.000 abstract 1
- 230000008327 renal blood flow Effects 0.000 abstract 1
- 230000008085 renal dysfunction Effects 0.000 abstract 1
- 230000001988 toxicity Effects 0.000 abstract 1
- 231100000419 toxicity Toxicity 0.000 abstract 1
- 230000002792 vascular Effects 0.000 abstract 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
- A61K38/13—Cyclosporins
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention involves the usage of certain hemorheological methylxanthine analogs having structure (I) where R1 is -(CH2)4COCH3, or -(CH2)4COH(CH3)2 and R2 is -CH3, -H or CH2OCH2CH3. These methylxanthine analogs may be used for treating a systemic fungal infection, for example candidiasis. Administration of the analogs, preferably by parenteral means, at least once and possibly on a multiple dosage schedule may be used to effectively ameliorate systemic fungal infections. The preferred therapeutically effective dosage for such treatment is between 1 mg and 100 mg per kg animal weight. A preferred analog for this treatment is when R1 is -(CH2)4COH(CH3)2 and R2 is -H. The above analogs may generally be used to treat an animal to inhibit developement of or to alleviate renal dysfunction manifested by reductions in renal blood flow and glomerular filtration rates with increased vascular resistance. This dysfunction may be independent or relate to the toxicity of other drugs such as cyclosporine or amphotericin B.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US60815890A | 1990-11-01 | 1990-11-01 | |
| US608,158 | 1990-11-01 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1992007566A2 WO1992007566A2 (en) | 1992-05-14 |
| WO1992007566A3 true WO1992007566A3 (en) | 1992-10-15 |
Family
ID=24435308
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1991/008086 WO1992007566A2 (en) | 1990-11-01 | 1991-11-01 | Antifungal activity of and prevention of drug induced nephrotoxicity by methylxanthine analogues |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU9084991A (en) |
| WO (1) | WO1992007566A2 (en) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4430127A1 (en) * | 1994-08-25 | 1996-03-14 | Hoechst Ag | Combination preparation containing cyclosporin A or FK506 and a xanthine derivative |
| US5981536A (en) * | 1996-07-31 | 1999-11-09 | Hoechst Aktiengesellschaft | Use of xanthine derivatives for the modulation of apoptosis |
| US5856330A (en) * | 1996-07-31 | 1999-01-05 | Hoechst Aktiengesellschaft | Use of xanthine derivatives for the inhibition of dephosphorylation of cofilin |
| US6294350B1 (en) * | 1997-06-05 | 2001-09-25 | Dalhousie University | Methods for treating fibroproliferative diseases |
| JP4486167B2 (en) * | 1998-02-27 | 2010-06-23 | アスビオファーマ株式会社 | Preventive or therapeutic agent for drug-induced renal injury |
| SE0000234D0 (en) * | 2000-01-26 | 2000-01-26 | Kjell Grankvist | Antifungal drug composition and drug delivery system |
| US20090239886A1 (en) | 2008-02-29 | 2009-09-24 | Concert Pharmaceuticals, Inc. | Substituted xanthine derivatives |
| US20110053961A1 (en) | 2009-02-27 | 2011-03-03 | Concert Pharmaceuticals, Inc. | Substituted xanthine derivatives |
| MX2012002704A (en) | 2009-09-02 | 2012-03-21 | Concert Pharmaceuticals Inc | Substituted xanthine derivatives. |
| WO2012031138A2 (en) | 2010-09-01 | 2012-03-08 | Concert Pharmaceuticals, Inc. | Polymorphs of (s)-1-(4,4,6,6,6-pentadeutero-5-hydroxyhexyl)-3-7-dimethyl-1h-purine-2,6(3h,7h)dione |
| US20140296263A1 (en) | 2011-07-19 | 2014-10-02 | Concert Pharmaceuticals, Inc. | Substituted xanthine derivatives |
| WO2013155465A1 (en) | 2012-04-13 | 2013-10-17 | Concert Pharmaceuticals, Inc. | Substituted xanthine derivatives |
| WO2013159006A1 (en) | 2012-04-20 | 2013-10-24 | Concert Pharmaceuticals, Inc. | Polymorphs of (s)-1-(4,4,6,6,6-pentadeutero-5-hydroxyhexyl)-3,7-dimethyl-1h-purine-2,6(3h,7h)-dione |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0344586A2 (en) * | 1988-05-27 | 1989-12-06 | Taiho Pharmaceutical Co., Ltd. | Medicine containing a TNF inhibitor |
| EP0414175A2 (en) * | 1989-08-22 | 1991-02-27 | Hoechst Aktiengesellschaft | Use of xanthine derivatives to reduce nephrotoxicity |
-
1991
- 1991-11-01 WO PCT/US1991/008086 patent/WO1992007566A2/en active Application Filing
- 1991-11-01 AU AU90849/91A patent/AU9084991A/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0344586A2 (en) * | 1988-05-27 | 1989-12-06 | Taiho Pharmaceutical Co., Ltd. | Medicine containing a TNF inhibitor |
| EP0414175A2 (en) * | 1989-08-22 | 1991-02-27 | Hoechst Aktiengesellschaft | Use of xanthine derivatives to reduce nephrotoxicity |
Non-Patent Citations (9)
| Title |
|---|
| Antimicrobial Agents and Chemotherapy, vol. 34, no. 2, February 1990, American Society for Microbiology, K.M. WASAN et al.: "Pentoxifylline in amphotericin B toxicity rat model", pages 241-244, see the whole article * |
| Chemical Abstracts, vol. 92, no. 19, 12 May 1980, (Columbus, Ohio, US), A.J. KOSTAKIS et al.: "The effect of pentoxifylline on rejection of rat cardiac allografts", see page 46, abstract no. 157772a, & IRCS MED. SCI.: LIBR. COMPEND. 1980, 81(1), 15, see the entire document * |
| Chemical Abstracts, vol. 96, no. 13, 29 March 1982, (Columbus, Ohio, US), V.L. KIRPATOVSKII et al.: "Pharmacological protection of the kidneys from ischemic injury. Mechanism for the realization of antiischemic protection of donor kidneys with preparations from various pharmacological groups", see page 91, abstract no. 97660h, & VESTN. AKAD. MED. NAUK. SSSR 1982, (1), 73-8, see the entire document * |
| Chemical Abstracts, vol. 96, no. 17, 26 April 1982, (Columbus, Ohio, US), A.J. KOSTAKIS et al.: "Prolongation of cardiac and renal allograft survival by pentoxifylline in rats", see page 55, abstract no. 135560k, & IRCS MED. SCI.: LIBR. COMPEND. 1982, 10(1), 77-8, see the entire document * |
| Chemical Abstracts, vol. 98, no. 1, 3 January 1983, (Columbus, Ohio, US), V.L. KIRPATOVSKII et al.: "Pharmacological protection of the kidneys from ischemic damage. Efficacy of antiischemic protection of the kidneys in simulated terminal state of the donors", see page 32, abstract no. 304a, & VESTN. AKAD. MED. NAUK. SSSR 1982, (9), 89-92, see the entire document * |
| Clinical Pharmcology & Therapeutics, vol. 47, no. 2, February 1990, K.L. BERENS et al.: "Effect of pentoxifylline (PTX) on dose-dependent cisplatin (C) nephrotoxicity", page 201, see the whole article * |
| Comprehensive Therapy, vol. 15, no. 5, 1989, G.P. STELLIN et al.: "Current and potential therapeutic effects of pentoxifylline", pages 11-13, see page 13 * |
| J. Infect. Dis., vol. 162, no. 1, July 1990, The University of Chicago, D.R. LUKE et al.: "Enhancement of the treatment of experimental candidiasis with vascular decongestants", pages 211-214, see the whole article * |
| Renal Failure, vol. 11, nos. 2,3, 1989, Marcel Dekker, Inc., L.J. BRUNNER et al.: "Prevention of cyclosporine-induced nephrotoxicity with pentoxitylline", pages 97-104, see the whole article * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU9084991A (en) | 1992-05-26 |
| WO1992007566A2 (en) | 1992-05-14 |
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