CA1336073C - Traitement des tumeurs malignes a l'aide de 8-aminoadenosine - 3', 5' - phosphate cyclique et son mode de preparation - Google Patents
Traitement des tumeurs malignes a l'aide de 8-aminoadenosine - 3', 5' - phosphate cyclique et son mode de preparationInfo
- Publication number
- CA1336073C CA1336073C CA000616661A CA616661A CA1336073C CA 1336073 C CA1336073 C CA 1336073C CA 000616661 A CA000616661 A CA 000616661A CA 616661 A CA616661 A CA 616661A CA 1336073 C CA1336073 C CA 1336073C
- Authority
- CA
- Canada
- Prior art keywords
- cyclic phosphate
- day
- tumor
- aminoadenosine
- chloroadenosine
- 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.)
- Expired - Fee Related
Links
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- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 208000025421 tumor of uterus Diseases 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000616661A CA1336073C (fr) | 1987-12-21 | 1993-06-16 | Traitement des tumeurs malignes a l'aide de 8-aminoadenosine - 3', 5' - phosphate cyclique et son mode de preparation |
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US136,407 | 1987-12-21 | ||
| US07/136,407 US4861873A (en) | 1987-12-21 | 1987-12-21 | 8-Chloroadenosine 3', 5'-cyclic monophosphate preparations |
| US18007088A | 1988-04-11 | 1988-04-11 | |
| US180,070 | 1988-04-11 | ||
| CA000564584A CA1326849C (fr) | 1987-12-21 | 1988-04-20 | Traitement de tumeurs malignes a l'aide de 8-chloroadenosine-3', 5'-cyclophosphate, et sa preparation |
| CA000616661A CA1336073C (fr) | 1987-12-21 | 1993-06-16 | Traitement des tumeurs malignes a l'aide de 8-aminoadenosine - 3', 5' - phosphate cyclique et son mode de preparation |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000564584A Division CA1326849C (fr) | 1987-12-21 | 1988-04-20 | Traitement de tumeurs malignes a l'aide de 8-chloroadenosine-3', 5'-cyclophosphate, et sa preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1336073C true CA1336073C (fr) | 1995-06-27 |
Family
ID=27167930
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000616661A Expired - Fee Related CA1336073C (fr) | 1987-12-21 | 1993-06-16 | Traitement des tumeurs malignes a l'aide de 8-aminoadenosine - 3', 5' - phosphate cyclique et son mode de preparation |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1336073C (fr) |
-
1993
- 1993-06-16 CA CA000616661A patent/CA1336073C/fr not_active Expired - Fee Related
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