Small molecule modulators of sigma-1 and sigma-2 receptors and uses thereof
This invention is in the field of medicinal chemistry. In particular, the invention relates to anew class of small-molecules having a tetrahydroindazole structure which function as modulators (e.g., activators or inhibitors) of sigma-1 and/or sigma-2 receptors, and their use as therapeutics for the treatment of cancer and other diseases (e.g., neurological conditions) characterized with sigma-1 and/or sigma-2 receptor activity.
1 . A compound described by Formulas I, II, III, IV, V, or VI:
including pharmaceutically acceptable salts, solvates, and/or prodrugs thereof;
wherein X is either CH or Nitrogen;
wherein R 1 is selected from
wherein R 2 is selected from Hydrogen,
wherein R 3 is selected from
wherein R 4 is Hydrogen or methyl;
wherein if the compound is described by Formula I
then R 2 cannot be
2 . The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and a pharmaceutically acceptable carrier.
3 . The compound of claim 1 , wherein the compound is comprised within a pharmaceutical composition.
4 . A method of treating, ameliorating, or preventing a disease or condition characterized with sigma-1 receptor activity, sigma-2 receptor activity or both sigma-1 receptor activity and sigma-2 receptor activity, comprising administering to a patient a therapeutically effective amount of a compound of claim 1 ;
wherein the disease or condition is
a neurological or CNS disease or condition, or
a hyperproliferative disease or condition,
wherein the neurological or CNS disease or condition is one or more of traumatic brain injury, depression, stroke, pain, alcohol addiction, substance abuse, ALS, and Alzheimer's disease,
wherein the hyperproliferative disease is any type of cancer characterized with sigma-1 and/or sigma-2 receptor activity selected from liver cancer, esophageal cancer, prostate cancer, breast cancer, pancreatic cancer, and colon cancer.
5 . The method of claim 4 , wherein the patient is a human patient.
6 . The method of claim 4 , further comprising administering to said patient one or more anticancer agents, wherein said anticancer agent is selected from one or more of a chemotherapeutic agent and radiation therapy.
7 . A compound selected from the group consisting of:
or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and a pharmaceutically acceptable carrier.