1291075-79-0

Upstream product

• 1450-75-5 5-Bromo-2-hydroxyacetophenone 
• 1291077-31-0 (±)-(E)-3-[1'-benzoyl-4-oxospiro(chromane-2,4’-azepane)-6-yl]acrylic acid 
• 1291077-30-9 (±)-(E)-3-[1'-benzoyl-4-oxospiro(chromane-2,4’-azepane)-6-yl]acrylic acid methyl ester 
• 1291076-30-6 (±)-(E)-3-[4-oxospiro(chromane-2,4’-azepane)-6-yl]acrylic acid methyl ester hydrochloride 
• 1291076-34-0 (±)-(E)-3-[1'-tert-butoxycarbonyl-4-oxospiro(chromane-2,4’-azepane)-6-yl]acrylic acid methyl ester 
• 188975-88-4 tert-butyl 4-oxoazepane-1-carboxylate 
• 1291076-33-9 (±)-6-bromo-4-oxospiro[chromane-2,4'-azepane-6-yl]-1'-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

Synthesis, biological characterization and molecular modeling insights of spirochromanes as potent HDAC inhibitors

In the last decades, inhibitors of histone deacetylases (HDAC) have become an important class of anti-cancer agents. In a previous study we described the synthesis of spiro[chromane-2,4′-piperidine]hydroxamic acid derivatives able to inhibit histone deacetylase enzymes. Herein, we present our exploration for new derivatives by replacing the piperidine moiety with various cycloamines. The goal was to obtain highly potent compounds with a good in vitro ADME profile. In addition, molecular modeling studies unravelled the binding mode of these inhibitors.

Spirocyclic derivatives as histone deacetylase inhibitors

This invention is related to new histone deacetylase inhibitors according to the general formula (I), wherein: is a single or a double bond; m and n are independently zero or an integer from 1 to 4; p is zero or an integer from 1 to 3, with the proviso that when p is zero, n and m cannot be both 1; R is hydrogen; C1-C6 alkyl, optionally substituted by cycloalkyl, aryl or by heteroaryl; (CO)R2; (SO2)R3; cycloalkyl; aryl; or heteroaryl; R1 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; X is CH2, oxygen or NR4; Y is CHR5 or NR6; Z is CR7R8 or C=R9; and R2, R3, R4, R5, R6, R7, R9, and R9 are as further defined in the specification; and pharmaceutical acceptable salts thereof.

SPIROCYCLIC DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS

This invention is related to new histone deacetylase inhibitors according to the general formula (I), wherein: m and n are independently zero or an integer from 1 to 4; p is zero or an integer from 1 to 3, with the proviso that when p is zero, n and m cannot be both 1; R is hydrogen; C1-C6 alkyl, optionally substituted by C3-C8 cycloalkyl, C6-C10 aryl or hetero(C2-C9)aryl; (CO)R2; (SO2)R3; C3-C8 cycloalkyl; C6-C10 aryl; or hetero(C2-C9)aryl; R1 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; Y is CH2 or NR4; Z is C=R5; and R2, R3, R4, and R5 are as further defined in the specification; and pharmaceutical acceptable salts thereof.