| 摘要 |
Provided are immediate or prolonged administration of certain salts of KATP channel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving KATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals. |
| 主权项 |
1. A method for the preparation of a salt of a compound of Formula I comprising:
reacting one equivalent of a cation source selected from the group consisting of an alkali metal hydroxide or an organic cation source comprising an ammonium or at least one tertiary amine group with a compound of Formula I,wherein:
R1 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, cycloalkyl, and substituted cycloalkyl provided however that when R1 is a substituted lower alkyl or a substituted cycloalkyl, then the substituent does not include an amino group; R2a is hydrogen; X is a 1, 2 or 3 carbon atom chain, wherein each atom is optionally substituted with halogen, hydroxyl, lower alkyl, substituted lower alkyl, lower alkoxy, cycloalkyl, substituted cycloalkyl, or substituted lower alkoxy, provided however that when an atom of the chain is substituted with substituted lower alkyl, substituted lower alkoxy or substituted cycloalkyl, then the substituent does not include an amino group; and ring B is polyunsaturated or aromatic; said compound of Formula I is dissolved in a solvent selected from the group consisting of acetonitrile, low molecular weight ketones, tetrahydrofuran, 2-methyltetrahydrofuran, dimethylformamide and n-methyl pyrrolidinone, and removing the solvent. |
