Crystalline C5a Receptor Salt Forms for Oral Bioavailability
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Solution Overview
Problem
The efficient delivery of biologically relevant amounts of Compound 1, (2R,3S)-2-(4-(cyclopentylamino)phenyl)-1-(2-fluoro-6-methylbenzoyl)-N-(4-methyl-3-(trifluoromethyl)phenyl)piperidine-3-carboxamide, is challenging, and no salt forms of this compound have been reported, which hinders improvements in solubility and bioavailability.
Innovation Solution
Development of crystalline salt forms of Compound 1, including besylate, tosylate, napadisylate, napsylate, camsylate, and edisylate salts, each characterized by specific X-ray powder diffraction patterns and other physical properties, enhancing solubility and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the free form of complement component c5a receptor is used, then it can bind to C5a with high affinity, but it has low oral bioavailability and short plasma half-life
Solution Approach 1:
The patent changes the physical-chemical parameters of the c5a receptor by converting it into different salt forms (sulfate, hydrochloride, phosphate, acetate, formate, nitrate, perchlorate, bromide, iodide, fluoride, oxalate, maleate, tartrate, lactate, and citrate salts). This parameter change improves the pharmacokinetic properties including oral bioavailability and plasma half-life while maintaining the ability to bind C5a with high affinity.
2Reliability
If the free form of complement component c5a receptor is used, then it can bind to C5a with high affinity, but it exhibits poor pharmacokinetic properties
Solution Approach 1:
The patent improves pharmacokinetic properties by changing the chemical form of the c5a receptor from free base to various salt forms. These salt forms exhibit improved solubility, stability, and bioavailability, making the drug easier to manufacture and administer while maintaining high binding affinity to C5a.
3Object-affected harmful factors
If conventional anti-inflammatory drugs are used, then inflammation can be treated, but they cause gastrointestinal side effects and have limited efficacy in severe cases
Solution Approach 1:
The patent introduces a new intermediary substance - the c5a receptor antagonist - that blocks the C5a receptor to prevent inflammation. This alternative pathway avoids the gastrointestinal side effects associated with conventional anti-inflammatory drugs like NSAIDs and aspirin, providing effective treatment without harmful gastrointestinal effects.
Data Source
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AI summary
Provided herein are salt forms of a complement component 5a receptor having the formula of Compound 1. Also provided herein are pharmaceutical compositions and methods of treatment using the salt forms of Compound 1, described herein.