Long-acting low-addiction HNK derivative and preparation method therefor
The present application relates to a compound having the effects of being an antidepressant, anesthetizing, alleviating pain, improving cognitive functions, protecting lungs, preventing or treating amyotrophic lateral sclerosis or preventing or treating complex regional pain syndrome. Compared with existing known HNK compounds, the compound provided in the present application has a longer drug efficacy period. Moreover the compound provided in the present application basically does not produce addiction.
1 . A compound represented by Formula I, or a salt, stereoisomer or tautomer thereof:
wherein,
m is an integer from 0 to 3, and n is an integer from 0 to 4;
R 1 and R 2 are each independently one or more selected from a group consisting of H, halogen, hydroxyl, amino, cyano, substituted or unsubstituted C 1 -C 6 alkyl group, substituted or unsubstituted C 2 -C 6 alkenyl group, substituted or unsubstituted C 2 -C 6 alkynyl group, substituted or unsubstituted C 3 -C 10 cycloalkyl group, substituted or unsubstituted C 2 -C 10 heterocyclic group, substituted or unsubstituted C 1 -C 6 alkoxy group, substituted or unsubstituted mono- and di-C 1 -C 6 alkylamino group, substituted or unsubstituted aryl group, and substituted or unsubstituted heteroaryl group;
R 3 is halogen;
R 4 is selected from a group consisting of H, substituted or unsubstituted C 1 -C 6 alkyl group, substituted or unsubstituted C 1 -C 8 acyl group, substituted or unsubstituted arylacyl group, and substituted or unsubstituted heteroarylacyl group;
R 5 is selected from a group consisting of substituted or unsubstituted C 3 -C 10 cycloalkylene group, substituted or unsubstituted C 2 -C 10 heterocyclylene group, substituted or unsubstituted arylene group, and substituted or unsubstituted heteroarylene group;
R 6 and R 7 are independently selected from a group consisting of H, substituted or unsubstituted C 1 -C 6 alkyl group, substituted or unsubstituted C 2 -C 6 alkenyl group, substituted or unsubstituted C 2 -C 6 alkynyl group, substituted or unsubstituted C 3 -C 10 cycloalkyl group, substituted or unsubstituted C 2 -C 10 heterocyclic group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted C 1 -C 8 acyl group, substituted or unsubstituted arylacyl group, and substituted or unsubstituted heteroaryl acyl,
or R 6 and R 7 , together with N atom to which R 6 and R 7 are connected, form a substituted or unsubstituted 3 to 10-membered monocyclic or bicyclic structure,
wherein a group is substituted means that the group is substituted by a substituent selected from OH; NH 2 ; C 1 -C 10 alkyl, alkenyl or alkynyl group; C 1 -C 10 alkylamine group; sulfhydryl group; C 1 -C 10 alkylsulfhydryl group; C 1 -C 20 alkoxy group; C 1 -C 10 carbonyl group; C 3 -C 10 cycloalkyl group; 3 to 10-membered heterocyclic group with one or more heteroatoms selected from N, S, O and P; C 6 -C 20 aryl group; C 2 -C 20 heteroaryl group; nitrocyano; and halogen.
2 . The compound, stereoisomer or tautomer thereof according to claim 1 , wherein the compound is represented by Formula II:
3 . The compound, stereoisomer or tautomer thereof according to claim 1 , wherein the compound is represented by Formula III:
4 . The compound, or a salt, stereoisomer or tautomer thereof according to claim 1 , wherein the compound is represented by Formula IV:
5 . The compound, or a salt, stereoisomer or tautomer thereof according to claim 1 , wherein the compound is shown below:
6 . The compound, or a salt, stereoisomer or tautomer thereof according to claim 1 , wherein the compound is shown below:
7 . A compound, or a salt, stereoisomer or tautomer thereof, wherein the compound is shown below:
wherein R 8 is H or a protecting group.
8 . The compound, or a salt, stereoisomer or tautomer thereof according to claim 7 , wherein the compound is shown below:
9 . The compound, or a salt, stereoisomer or tautomer thereof according to claim 7 , wherein the compound is shown below:
or
10 . A pharmaceutical composition, comprising the compound, or a salt, stereoisomer or tautomer thereof according to claim 1 , and optionally a pharmaceutically acceptable carrier.
11 . A pharmaceutical composition, comprising the compound, or a salt, stereoisomer or tautomer thereof according to claim 7 , and optionally a pharmaceutically acceptable carrier.
12 . A method for anesthesia, alleviating pain, improving cognitive function, lung protection, anti-depression, mitigating anxiety and post-traumatic stress syndrome, or treating amyotrophic lateral sclerosis or complex regional pain syndrome of a subject, comprising administrating therapeutic effective amount of the compound, or a salt, stereoisomer or tautomer thereof according to claim 1 to the subject.
13 . The method of claim 12 , wherein the pain comprises chronic pain or neuropathic pain; the depression comprises bipolar depression or major depressive disorder; and improving of cognitive function comprises preventing or treating Alzheimer's, dementia, or Parkinson's disease.
14 . A method for anesthesia, alleviating pain, improving cognitive function, lung protection, anti-depression, mitigating anxiety and post-traumatic stress syndrome, or treating amyotrophic lateral sclerosis or complex regional pain syndrome of a subject, comprising administrating therapeutic effective amount of the compound, or a salt, stereoisomer or tautomer thereof according to claim 7 to the subject.
15 . The method of claim 14 , wherein the pain comprises chronic pain or neuropathic pain; the depression comprises bipolar depression or major depressive disorder; and improving of cognitive function comprises preventing or treating Alzheimer's, dementia, or Parkinson's disease.