3-aminoalkyl-indol-2-one derivatives for selective vasopressin receptor targeting
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Solution Overview
Problem
Current compounds described in previous patent applications lack selectivity for human V1a and V1b receptors of arginine vasopressin (AVP), which are crucial for therapeutic and diagnostic applications, particularly in regulating blood pressure and detecting small cell lung cancer.
Innovation Solution
Development of new 3-aminoalkyl-1,3-dihydro-2 derivatives of H-indol-2-one compounds with specific structural modifications that exhibit strong affinity and high selectivity for human V1a and V1b receptors, allowing for targeted therapeutic and diagnostic approaches.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current compounds from previous patent applications are used, then they can interact with vasopressin receptors, but they lack selectivity for human V1a and V1b receptors
Solution Approach 1:
The patent applies local quality by introducing specific substituent patterns at defined positions on the indol-2-one core structure. Different substituents (R1-R7) are placed at specific locations to create distinct interaction profiles with V1a versus V1b receptors, thereby achieving selectivity while maintaining overall receptor affinity
Solution Approach 2:
The patent employs parameter changes by systematically varying chemical parameters such as substituent types, chain lengths, and functional groups on the indol-2-one scaffold. These parameter modifications tune the compounds' affinity and selectivity characteristics for different vasopressin receptor subtypes
2Reliability
If new 3-aminoalkyl-1,3-dihydro-2H-indol-2-one derivatives are developed, then high selectivity for V1a and V1b receptors is achieved, but the complexity of compound synthesis increases
Solution Approach 1:
The patent applies segmentation by dividing the molecular structure into modular components (core indol-2-one structure plus variable substituent groups). This modular approach allows systematic synthesis where different R1-R7 groups can be independently selected and attached, managing synthesis complexity while achieving selectivity
Solution Approach 2:
The patent employs universality by designing a core indol-2-one scaffold that serves multiple functions: maintaining receptor affinity, providing structural stability, and enabling selective substitution. This universal core structure simplifies synthesis by allowing the same backbone to be used across multiple selective analogs
Data Source
AI summary
The subject matter of the present invention is compounds corresponding to formula (I) in which: X is an unsubstituted or substituted (C1-C5)alkylene divalent radical; R1 is: an -NR8R9 group; or a piperidin-4-yl radical or a piperidin-3-yl radical which is unsubstituted or substituted; R2 is a halogen atom, an Alk group, or an OAlk group; R3 is a methoxy; R4 is a hydrogen atom, a halogen atom, an Alk group, a hydroxyl or an OAlk group; R5 is a hydrogen atom, a halogen atom, an Alk group, a hydroxyl, an OAlk group, a -CO2Alk group or a -CH2OH radical; R6 is a hydrogen atom, an Alk group, a hydroxyl, an OAlk group, a (C3-C5)cycloalkoxy or an -NR10CONR11R12 group; R7 is a hydrogen atom, a halogen atom, an Alk group, a hydroxyl or an OAlk group; or else R7 is in the -3- position with respect to the phenyl and together with R6 they are a trimethylene radical; R8 and R9 are each independently a hydrogen atom or a (C1- C4)alkyl; or else R8 and R9, together with the nitrogen atom to which they are attached, constitute an unsubstituted or substituted heterocyclic radical; R10 is a hydrogen atom or a (C1-C4)alkyl; R11 and R12 are each independently a hydrogen atom or a (C1-C4)alkyl; Alk is a (C1-C4)alkyl which is unsubstituted or substituted one or more times with a fluorine atom. Method for the preparation thereof and therapeutic use thereof.