Akt Inhibitor Salt Formulation for pH Stability
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Solution Overview
Problem
Current Akt inhibitors lack potency, selectivity, and bioavailability, and pharmaceutical compositions containing these inhibitors often precipitate at certain pH ranges, making them unsuitable for delivery to patients.
Innovation Solution
Development of novel Akt inhibitors, such as 4-[5-(2-amino-ethanesulfonyl)-isoquinolin-7-yl]-phenol and its pharmaceutically acceptable salts, which exhibit increased potency, selectivity, and bioavailability, and are formulated to remain stable across specific pH ranges to prevent precipitation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current Akt inhibitors are used, then they can be delivered to patients, but they lack potency, selectivity, and bioavailability
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of Akt inhibitors to optimize their pharmacological properties. Specifically, the compound 4-[5-(2-amino-ethanesulfonyl)-isoquinolin-7-yl]-phenol and its salts are designed with specific molecular parameters (functional groups, stereochemistry, pKa values) to achieve enhanced potency, selectivity, and bioavailability simultaneously, resolving the contradiction between reliability and ease of manufacture.
Solution Approach 2:
The patent employs composite materials by creating pharmaceutically acceptable salts of the Akt inhibitor (e.g., hydrochloride salts, sulfate salts) to improve bioavailability. These salt forms combine the active pharmaceutical ingredient with suitable counterions to enhance solubility, stability, and absorption characteristics, thereby improving bioavailability while maintaining the core inhibitory activity.
2Ease of operation
If pharmaceutical compositions containing Akt inhibitors are formulated, then they can be delivered to patients, but they precipitate at certain pH ranges
Solution Approach 1:
The patent applies parameter changes by formulating the Akt inhibitor as specific salt forms (hydrochloride, sulfate, etc.) with controlled pKa values and solubility characteristics. These parameter modifications enable the composition to remain stable and soluble across the physiological pH range (pH 1-7.4), preventing precipitation while maintaining deliverability through various administration routes.
Solution Approach 2:
The patent uses pharmaceutically acceptable salts as intermediary compounds to bridge the gap between the active Akt inhibitor and the delivery system. These salt forms act as mediators that improve solubility and stability in aqueous environments without compromising the pharmacological activity of the parent compound, enabling safe and effective patient delivery.
3Reliability
If Akt inhibitors are developed with increased potency and selectivity, then they can effectively treat disorders, but their bioavailability may be compromised
Solution Approach 1:
The patent applies parameter changes by optimizing the molecular structure of the Akt inhibitor (compound 4-[5-(2-amino-ethanesulfonyl)-isoquinolin-7-yl]-phenol) to achieve a balance between potency/selectivity and bioavailability. Specific structural parameters (molecular weight, logP, hydrogen bonding capacity, pKa) are tuned to ensure the compound maintains high therapeutic efficacy while achieving sufficient absorption and distribution in the body.
Solution Approach 2:
The patent employs composite materials by formulating the potent Akt inhibitor as pharmaceutically acceptable salts (e.g., hydrochloride, sulfate) that enhance bioavailability. These salt forms improve solubility and absorption characteristics, ensuring that sufficient quantities of the active compound reach the target tissues to exert the desired therapeutic effect.
Data Source
AI summary
4-[5-(2-Amino-ethanesulfonyl)-isoquinolin-7-yl]-phenol or a pharmaceutically acceptable salt thereof or a hydrate of the compound or the salt thereof as Akt inhibitors that are antineoplastic and/or antiviral agents as well as compositions comprising these compounds and methods of using these compounds.