MCL1 Inhibitor Synthesis via Segmented Intermediates
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Solution Overview
Problem
There is a need for synthetic methods and intermediates to prepare compounds that inhibit MCL1, which are useful in treating cancers, on a manufacturing scale.
Innovation Solution
The disclosure provides methods for preparing compounds by reacting specific corresponding compounds to form intermediate compounds, which can then be converted into the final compound or its salt, using various reagents, catalysts, and solvents under specific conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional synthetic methods are used to prepare MCL1 inhibitor compounds, then the compounds can be prepared in the laboratory, but the methods are not suitable for manufacturing scale production
Solution Approach 1:
The patent divides the synthesis of MCL1 inhibitor compounds into multiple discrete steps with specific intermediates (compounds of formulae I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI, XXXVII, XXXVIII, XXXIX, XL, XLI, XLII, XLIII, XLIV, XLV, XLVI, XLVII, XLVIII, XLIX, L, LI, LII, LIII, LIV, LV, LVI, LVII, LVIII, LIX, LX, LXI, LXII, LXIII, LXIV, LXV, LXVI, LXVII, LXVIII, LXIX, LXX, LXXI, LXXII, LXXIII, LXXIV, LXXV, LXXVI, LXXVII, LXXVIII, LXXIX, LXXX, LXXXI, LXXXII, LXXXIII, LXXXIV, LXXXV, LXXXVI, LXXXVII, LXXXVIII, LXXXIX, XC, XCI, XCII, XCIII, XCIV, XCV, XCVI, XCVII, XCVIII, XCIX, C). Each step is optimized for manufacturing scalability while maintaining synthetic feasibility through detailed procedural specifications.
2Reliability
If MCL1 inhibitors are developed for cancer treatment, then therapeutic efficacy is achieved, but scalable manufacturing methods are needed to meet production demands
Solution Approach 1:
The patent optimizes reaction parameters including temperature ranges, solvent types, catalyst selections, and stoichiometric ratios for each synthesis step to simultaneously ensure high purity MCL1 inhibitor production (maintaining therapeutic efficacy) and scalable manufacturing capability. Specific parameters are tuned for each intermediate transformation to balance quality and quantity production requirements.
Data Source
AI summary
The present disclosure relates to methods and intermediates for the synthesis of certain compounds that inhibit MCL1, for use in the treatment of cancers.