http://rdf.ncbi.nlm.nih.gov/pubchem/patent/CA-2180445-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_f8c0982b0f02b1ed6d20a315370a3a3a |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D405-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D407-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D305-14 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D409-12 |
| filingDate | 1995-01-10-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_c572bb4f4fbefd55dfd25daba933b388 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_61834c241fdcff00fd967a9cd8d42cf9 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_e6a58eb426fdc37c28d9c5786669c1d2 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_3a6fc409097163e59715e9123e428a3e |
| publicationDate | 1995-07-13-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | CA-2180445-A1 |
| titleOfInvention | Chemical switching of taxo-diterpenoids between low solubility active forms and high solubility inactive forms |
| abstract | Cyclic chemical switching method is employed for solubilizing and desolubilizing taxo-diterpenoids with respect to aqueous solvents. 2-Halogenated onium salts of aza-arenes (I and II) (see figure I and II) wherein: R0 is a halogen selected from the group consisting of Cl, Br, F, and I; Z1 and Z2 are each selected from the group consisting of C and N; Z3 is selected from the group consisting of S and O; R1 is selected from the group consisting of C1-C6 alkyl, allyl, arenxyl, propargyl, and fused aryl; R2 and R6 are each selected from the group consisting of H, C1-C6 alkyl, allyl, arenxyl, propargyl, and fused aryl; if Z1 is C, then R3 is selected from the group consisting of H, C1-C6 alkyl, allyl, arenxyl, propargyl, C1-C6 O-alkyl, OH, halogen, and fused aryl; if Z1 is N, then R3 is absent; R4 and R8 are each selected from the group consisting of H, C1-C6 alkyl, allyl, arenxyl, propargyl, C1-C6 O-alkyl, OH, halogen, and fused aryl; if Z2 is C, then R5 is selected from the group consisting of H, C1-C6 alkyl, allyl, arenxyl, propargyl, C1-C6 O-alkyl, OH, halogen, and fused aryl; if Z2 is N, then R5 is absent, and S- is a counter ion; are employed to derivatize taxo-diterpenoids so as to alter their solubility in aqueous solvents. The onium salt of aza-arene includes a delocalized charge which imparts polarity and aqueous solubility to taxo-diterpenoid derivatives. Solubilization is achieved in a one step derivatization with the onium salt of 2-halogenated aza-arenes. Desolubilization is achieved by contacting onium salts of taxo-diterpenoid-C n,2-O-aza-arenes with serum protein to displace the 2-O-aza-arene and form a soluble protein:taxo-diterpenoid intermediate. This protein:taxo-diterpenoid intermediate then dissociates over time to provide a bioactive taxo-diterpenoid. Preferred taxo-diterpenoids include taxol, C-2 substituted taxol, and Taxotere .TM.. These same onium salts of taxo-diterpenoid-C n, 2-O-aza-arenes are employed as water soluble prodrugs. For example, taxol-2'-methylpyridinium tosylate (MPT) is characterized by an elevated aqueous solubility, rapid activation by serum protein, good stability in most other aqueous solutions, formation of a protein:taxol intermediate and good retention within the circulatory system. The toxicity of the activated form is comparable or greater than underivatized taxol. Furthermore, taxol-2'-MPT can be synthesized by a simple one step reaction between taxol and 2-fluoro-1-MPT. The invention is applicable to taxol and taxol mimetics having hydroxyls that are reactive with onium salts of 2-halogenated-aza-arenes. For example, taxol and Taxotere each have reactive hydroxyls at the 2' and 7 positions. The invention is also applicable to a wide array of 2-halogenated-aza-arenes. |
| priorityDate | 1994-01-11-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
Total number of triples: 27.