Chiral heterocyclic compound with hedgehog pathway antagonist activity, method and use thereof
AssigneeSuzhou Kintor Pharmaceuticals, Inc.
InventorXiaohu ZHANG
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Abstract
A chiral heterocyclic compound with hedgehog pathway antagonist activity, method and use thereof are provided. The chiral heterocyclic compound with hedgehog pathway antagonist activity has the structure represented by formula I. A pharmaceutical composition and combined application composition are also provided. Novel molecules of formula II that inhibit hedgehog pathway signaling and therapeutic applications for the treatment of malignancies, prevention of tumor regrowth, sensitization of radio-chemo therapies, and other diseases related to hedgehog signaling are also provided.
Claims21
1-31. (canceled)
A method for preparing a chiral heterocyclic compound with Hedgehog pathway antagonist activity according to formula I,
- comprising steps:
- i) mixing (1S, 2S)-(+)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine, dichloro (p-methyl cumene) ruthenium (II) dimer, amine and formic acid-acetonitrile solution to give a mixed solution;
- mixing compound
- in acetonitrile solution with the mixed solution to react;
- adjusting the pH of the system to about 8.0 by sodium bicarbonate;
- performing extraction and purification to prepare
- ii) coupling reaction of the compound
- and compound
- to prepare compound
- and
- iii) oxidizing the methylthio of the compound
- and reacting with 4-hydroxypiperazine to obtain the chiral heterocyclic compound
A compound of Formula III:
- or a pharmaceutically acceptable salt, stereoisomer, or solvate thereof, wherein
- R2 and R′2 are independently H, C1-3 alkyl, CD3, or CF3, with the proviso that at least one of R2 and R′2 is not H and when only one of R2 and R′2 is H, the compound is not racemic;
- R1 is —NRxRy, wherein Rx and Ry are independently H, alkyl, cycloalkyl, alkylcycloalkyl, C(O)R″, or —NRxRy together to form a 4-7 membered heterocycle, wherein the 4-7 membered heterocycle is substituted or unsubstituted;
- R″ is C1-5 alkyl;
- W1, W2, W3, W4, W5, W6, W7, W8 and W9 are independently H or D;
- and
- A is N or CH.
Dependencies are inferred from the claim text.