Pro-drugs of NSAIAs with very high skin and membranes penetration rates and their new medicinal uses
US10233198B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | May 26, 2016 |
| Grant date | Mar 19, 2019 |
| Priority date | — |
| Expiry date | May 26, 2036 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07D491/052
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
The novel positively charged pro-drugs of NSAIAs in the general formulas (1, 2a, 2b, 2c, or 2d) “Structure 1, 2a, 2b, 2c, or 2d” were designed and synthesized. The compounds of the general formulas (1, 2a, 2b, 2c, or 2d) “Structure 1, 2a, 2b, 2c, or 2d” indicated above can be prepared from metal salts, organic base salts, or immobilized base salts of NSAIAs with suitable halide compounds. The positively charged amino groups in the pro-drugs in this invention largely increase the solubility of the drugs in water and will bond to the negative charge on the phosphate head group of membrane. Thus, the local concentration of the outside of the membrane or skin will be very high and will facilitate the passage of these pro-drugs from a region of high concentration to a region of low concentration. This bonding will disturb the membrane a little bit and may make some room for the lipophilic portion of the pro-drug. When the molecules of membrane move, the membrane may “crack” a little bit due to the bonding of the pro-drug. This will let the pro-drug insert into the membrane. At pH 7.4, only about 99% of the amino group is protonated. When the amino group is not protonated, the bonding be…
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.