CA2511888A1 - Deuterated cyclosporin analogs and their use as immunomodulating agents - Google Patents
Deuterated cyclosporin analogs and their use as immunomodulating agents Download PDFInfo
- Publication number
- CA2511888A1 CA2511888A1 CA002511888A CA2511888A CA2511888A1 CA 2511888 A1 CA2511888 A1 CA 2511888A1 CA 002511888 A CA002511888 A CA 002511888A CA 2511888 A CA2511888 A CA 2511888A CA 2511888 A1 CA2511888 A1 CA 2511888A1
- Authority
- CA
- Canada
- Prior art keywords
- cyclosporine
- derivatives
- substitution
- chemical
- disclosed
- Prior art date
- 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.)
- Granted
Links
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical class 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 title abstract 9
- 239000002955 immunomodulating agent Substances 0.000 title 1
- 238000006467 substitution reaction Methods 0.000 abstract 5
- 229930105110 Cyclosporin A Natural products 0.000 abstract 3
- 108010036949 Cyclosporine Proteins 0.000 abstract 3
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 abstract 3
- 229910052805 deuterium Inorganic materials 0.000 abstract 3
- 239000000126 substance Substances 0.000 abstract 3
- 238000000034 method Methods 0.000 abstract 2
- 230000001988 toxicity Effects 0.000 abstract 2
- 231100000419 toxicity Toxicity 0.000 abstract 2
- 108010036941 Cyclosporins Proteins 0.000 abstract 1
- 206010062016 Immunosuppression Diseases 0.000 abstract 1
- 125000003275 alpha amino acid group Chemical class 0.000 abstract 1
- 150000001413 amino acids Chemical class 0.000 abstract 1
- 229930182912 cyclosporin Natural products 0.000 abstract 1
- 230000001506 immunosuppresive effect Effects 0.000 abstract 1
- 230000000155 isotopic effect Effects 0.000 abstract 1
- 230000004060 metabolic process Effects 0.000 abstract 1
Landscapes
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently-known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) chemical substitution and optionally deuterium substitution of amino acid 1, and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. The most active derivatives of the invention were those possessing both chemical and deuterium substitution. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6136097P | 1997-10-08 | 1997-10-08 | |
| US60/061,360 | 1997-10-08 | ||
| CA002372639A CA2372639C (en) | 1997-10-08 | 1998-10-08 | Deuterated cyclosporine analogs and their use as immunomodulating agents |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002372639A Division CA2372639C (en) | 1997-10-08 | 1998-10-08 | Deuterated cyclosporine analogs and their use as immunomodulating agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2511888A1 true CA2511888A1 (en) | 1999-04-15 |
| CA2511888C CA2511888C (en) | 2009-04-14 |
Family
ID=35311262
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002511888A Expired - Lifetime CA2511888C (en) | 1997-10-08 | 1998-10-08 | Deuterated cyclosporin analogs and their use as immunomodulating agents |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2511888C (en) |
-
1998
- 1998-10-08 CA CA002511888A patent/CA2511888C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA2511888C (en) | 2009-04-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20181009 |
|
| MKEX | Expiry |
Effective date: 20181009 |