CBP/p300 Bromodomain Inhibitor Crystal Forms for Solubility
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Solution Overview
Problem
Existing methods for inhibiting CBP/p300, which are pivotal in gene activation and heightened in advanced human cancers, are challenging due to the difficulty in blocking transcription factors with small molecules, necessitating novel and potent compounds for therapeutic intervention.
Innovation Solution
Development of non-amorphous solid forms and pharmaceutically acceptable salts of compounds that modulate CBP/p300 bromodomains, including specific crystalline forms and acid addition salts, to inhibit CBP/p300 activity effectively.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecules are used to block transcription factors, then CBP/p300 activity can be inhibited, but the development of such inhibitors has proven extremely challenging
Solution Approach 1:
The patent uses bromodomain inhibitors as intermediary compounds that indirectly inhibit CBP/p300 activity by binding to the bromodomain region, rather than directly blocking the transcription factor activity. This intermediary approach facilitates easier drug development while achieving the desired inhibition effect.
Solution Approach 2:
The patent modifies the chemical structure parameters of the inhibitors by providing multiple crystal forms and salt forms (e.g., hydrochloride, sulfate, phosphate salts) of the bromodomain inhibitors. These parameter changes in crystal structure and salt association improve the pharmacological properties and bioavailability of the inhibitors, making them more effective for therapeutic use.
2Reliability
If novel compounds are developed to inhibit CBP/p300, then therapeutic efficacy can be improved, but solubility and bioavailability issues may arise
Solution Approach 1:
The patent changes the physical and chemical parameters of the inhibitor compounds by providing multiple crystal forms and salt forms. These parameter changes in crystalline structure and salt association significantly improve the solubility, dissolution rates, and bioavailability of the inhibitors, thereby enhancing their therapeutic efficacy.
Solution Approach 2:
The patent creates composite formulations by combining the bromodomain inhibitor with various salt forms and crystal structures. These composite material approaches optimize the pharmacological properties of the inhibitors, improving their solubility and bioavailability while maintaining therapeutic efficacy.
3Reliability
If solid forms and salts are developed to enhance solubility and bioavailability, then therapeutic effectiveness is improved, but the complexity of formulation increases
Solution Approach 1:
The patent simplifies the formulation process by providing specific crystal forms and salt forms of the inhibitors with predetermined physical and chemical properties. These parameter changes in crystalline structure and salt association directly improve solubility and bioavailability without requiring complex formulation development.
Data Source
AI summary
The present disclosure is directed to solid and salt forms of inhibitors of the CBP/p300 family of bromodomains made up of salts and crystalline forms of Formula (I). The compounds can be useful in the treatment of disease or disorders associated with the inhibition of the CBP/p300 family of bromodomains. For instance, the disclosure is concerned with compounds and compositions for inhibition of the CBP/p300 family of bromodomains, methods of treating diseases or disorders associated with the inhibition of CBP/p300 family of bromodomains (e.g., certain forms of cancer), and methods of synthesis of these compounds.