Resorcinol derivatives
The disclosure relates to cannabinoid derivative compounds, pharmaceutical compositions made thereof, and methods for treating various diseases and disorders including cancer.
1. A compound comprising the structure of:
or a pharmaceutically acceptable salt, or prodrug thereof.
2. A pharmaceutical composition comprising a pharmaceutically acceptable carrier together with a compound of claim 1 .
3. The pharmaceutical composition of claim 2 , wherein the composition further comprises an additional therapeutic agent.
4. The pharmaceutical composition of claim 3 , wherein the additional therapeutic agent is Δ 9 -tetrahydrocannabinol (“THC”) or a THC derivative.
5. The pharmaceutical composition of claim 4 , wherein the THC derivative is selected from the group consisting of Δ 9 -tetrahydrocannabinol-C 4 , Δ 9 -tetrahydrocannabivarin, tetrahydrocannabiorcol, Δ 9 -tetrahydro-cannabinolic acid A, Δ 9 -tetrahydro-cannabinolic acid B, Δ 9 -tetrahydro-cannabinolic acid-C 4 A, Δ 9 -tetrahydro-cannabinolic acid-C 4 B, Δ 9 -tetrahydro-cannabivarinic acid A, Δ 9 -tetrahydro-cannabiorcolic acid A, Δ 9 -tetrahydro-cannabiorcolic acid B, (−)- Δ 8 -trans -(6aR,10aR)-Δ 8 -tetrahydrocannabinol, (−)- Δ 8 -trans-(6aR,10aR) -tetrahydrocannabinolic acid A, and (−)-(6aS,10aR)- Δ 9 -tetrahydrocannabinol.
6. The pharmaceutical composition of claim 3 , wherein the additional therapeutic agent is selected from the group consisting of alkylating agents, cancer immunotherapy monoclonal antibodies, anti-metabolites, mitotic inhibitors, anti-tumor antibiotics, topoisomerase inhibitors, photosensitizers, tyrosine kinase inhibitors, anti-cancer agents, chemotherapeutic agents, anti-migraine treatments, anti-tussives, mucolytics, decongestants, anti-allergic non-steroidals, expectorants, anti-histamine treatments, anti-retroviral agents, CYP3A inhibitors, CYP3A inducers, protease inhibitors, adrenergic agonists, anti-cholinergics, mast cell stabilizers, xanthines, leukotriene antagonists, glucocorticoid treatments, antibacterial agents, antifungal agents, sepsis treatments, steroidals, local or general anesthetics, NSAIDS, NRIs, DARIs, SNRIs, sedatives, NDRIs, SNDRIs, monoamine oxidase inhibitors, hypothalamic phoshpholipids, anti-emetics, ECE inhibitors, opioids, thromboxane receptor antagonists, potassium channel openers, thrombin inhibitors, growth factor inhibitors, anti-platelet agents, P2Y(AC) antagonists, anti-coagulants, low molecular weight heparins, Factor Vla inhibitors, Factor Xa inhibitors, renin inhibitors, NEP inhibitors, vasopepsidase inhibitors, squalene synthetase inhibitors, anti-atherosclerotic agents, MTP inhibitors, calcium channel blockers, potassium channel activators, alpha-muscarinic agents, beta-muscarinic agents, anti-arrhythmic agents, diuretics, thrombolytic agents, anti-diabetic agents, mineralocorticoid receptor antagonists, growth hormone secretagogues, aP2inhibitors, phophodiesterase inhibitors, anti-inflammatories, anti-proliferatives, antibiotics, farnesyl-protein transferase inhibitors, hormonal agents, plant-derived products, epipodophyllotoxins, taxanes, prenyl-protein transferase inhibitors, anti-TNF antibodies and soluble TNF receptors, and Cyclooxygenase-2inhibitors.
7. The pharmaceutical composition of claim 6 , wherein the additional therapeutic agent is selected from the group consisting of alkylating agents, cancer immunotherapy monoclonal antibodies, anti-metabolites, mitotic inhibitors, anti-tumor antibiotics, topisomerase inhibitors, photosensitizers, tyrosine kinase inhibitors, anti-cancer agents, and chemotherapeutic agents.
8. The pharmaceutical composition of claim 7 , wherein the additional therapeutic agent is an anti-cancer agent.
9. The pharmaceutical composition of claim 8 , wherein the anti-cancer agent is paclitaxel and/or temozolomide.
10. A method for modulating helix-loop-helix Id protein expression, cell proliferation, cell invasion, metastasis or a combination thereof in vivo and/or in vitro by administering a compound of claim 1 .
11. A method for treating a disease or disorder in a subject, comprising administering to a subject a therapeutically effective amount of a compound of claim 1 , wherein the disease or disorder can be ameliorated by inhibiting the expression of an Id polypeptide, by activating cannabinoid type 2 (“CB 2 ”) receptors or a combination thereof.
12. The method of claim 11 , wherein the disease or disorder is selected from the group consisting of cancer, chronic pancreatitis, psoriasis, neoplasms, angiomas, endometriosis, obesity, age-related macular degeneration, retinopathies, restenosis, scaring, fibrogenesis, fibrosis, cardiac remodeling, pulmonary fibrosis, scleroderma, failure associated with myocardial infarction, keloids, fibroid tumors, stenting, Alzheimer's Disease, Parkinson's Disease, age related dementia, Huntington's Disease, and amyotrophic lateral sclerosis.
13. The method of claim 12 , wherein cancer is selected from the group consisting of leukemia, melanoma, squamous cell carcinoma (SCC), hepatocellular carcinoma, colorectal adenocarcinoma, pancreatic cancer, lung cancer, kidney cancer, medullary thyroid cancer, papillary thyroid cancer, astrocytic tumor, neuroblastoma, Ewing's sarcoma, ovarian tumor, cervical cancer, endometrial carcinoma, breast cancer, prostate cancer, and malignant seminoma.
14. The method of claim 13 , wherein the cancer is breast cancer.
15. The method of claim 13 , wherein the cancer is brain cancer.
16. The method of claim 15 , wherein the brain cancer is glioblastoma multiforme.
17. A method of treating a disease or disorder in a subject, comprising administering to a subject a therapeutically effective amount of a compound having the structure of:
or a pharmaceutically acceptable salt, or prodrug thereof, wherein the disease or disorder can be ameliorated by inhibiting the expression of an Id polypeptide, by activating CB 2 receptors or a combination thereof.
18. The method of claim 17 , wherein the disease or disorder is selected from the group consisting of leukemia, melanoma, SCC, hepatocellular carcinoma, colorectal adenocarcinoma, pancreatic cancer, lung cancer, kidney cancer, medullary thyroid cancer, papillary thyroid cancer, astrocytic tumor, neuroblastoma, Ewing's sarcoma, ovarian tumor, cervical cancer, endometrial carcinoma, breast cancer, prostate cancer, and malignant seminoma.
19. The method of claim 18 , wherein the disease or disorder is breast cancer or brain cancer.
20. The method of claim 19 , wherein the brain cancer is glioblastoma multiforme.
21. The method of claim 17 , wherein the method further comprises administering to the subject one or more alkylating agents, cancer immunotherapy monoclonal antibodies, anti-metabolites, mitotic inhibitors, anti-tumor antibiotics, topoisomerase inhibitors, photosensitizers, tyrosine kinase inhibitors, anti-cancer agents, chemotherapeutic agents, or a combination thereof.