Pyrazolopyrimidine Sigma Ligands Selectivity
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Solution Overview
Problem
There is a need for compounds with pharmacological activity towards sigma receptors that are both effective and selective, and possess good pharmaceutical properties such as administration, distribution, metabolism, and excretion, which are currently lacking in existing sigma receptor ligands.
Innovation Solution
Development of novel pyrazolo[3,4-d]pyrimidine compounds with specific structural formulas that exhibit high affinity for sigma receptors, including sigma-1 and sigma-2 receptors, and their use in pharmaceutical compositions for various therapeutic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing sigma receptor ligands are used, then pharmacological activity towards sigma receptors is achieved, but pharmaceutical properties such as administration, distribution, metabolism, and excretion are insufficient
Solution Approach 1:
The patent applies parameter changes by systematically modifying the chemical structure of pyrazolo[3,4-d]pyrimidine compounds through varying substituents at different positions (R1-R6 groups). These structural parameter changes optimize both the pharmacological activity towards sigma receptors and the pharmaceutical properties including administration, distribution, metabolism, and excretion characteristics.
Solution Approach 2:
The invention creates composite molecular structures by combining the pyrazolo[3,4-d]pyrimidine core with various functional groups and substituents. This composite approach allows the molecule to simultaneously achieve high affinity for sigma receptors while incorporating pharmacophores that improve pharmaceutical properties such as solubility, metabolic stability, and tissue distribution.
2Reliability
If known sigma receptor ligands like rimcazole are used, then treatment of psychosis is achieved, but selectivity and effectiveness are limited
Solution Approach 1:
The patent applies local quality by introducing specific substituents at particular positions on the pyrazolo[3,4-d]pyrimidine ring system. Each substituent position (R1-R6) can be independently optimized to enhance selectivity for sigma-1 versus sigma-2 receptors, allowing precise control over which receptor subtype is primarily activated or blocked.
Solution Approach 2:
The molecular structure is segmented into distinct functional regions: the pyrazolo[3,4-d]pyrimidine core provides the basic sigma receptor binding capability, while separate substituent groups (R1-R6) can be independently optimized for selectivity, pharmacokinetic properties, and specific receptor subtype preference, allowing modular optimization of the ligand.
Data Source
AI summary
The present invention relates to new pyrazolo[3,4-d]pyrimidine compounds having a great affinity for sigma receptors, especially sigma-1 receptors as well as to the process for the preparation thereof, to composition comprising them and to their use as medicaments.