Claims for Patent: 11,077,098

Summary for Patent: 11,077,098

Title:	Opioid receptor ligands and methods of using and making same
Abstract:	This application describes compounds that can act as opioid receptor ligands, which compounds can be used in the treatment of, for example, pain and pain related disorders.
Inventor(s):	Yamashita; Dennis (Cambridge, MA), Gotchev; Dimitar (Hatboro, PA), Pitis; Philip (North Wales, PA), Chen; Xiao-Tao (Furlong, PA), Liu; Guodong (Jamison, PA), Yuan; Catherine C. K. (King of Prussia, PA)
Assignee:	Trevena, Inc. (King of Prussia, PA)
Application Number:	15/828,695
Patent Claims:	1. A pharmaceutically acceptable salt of [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine, wherein the pharmaceutically acceptable salt is a non-toxic inorganic or organic acid salt. 2. The pharmaceutically acceptable salt of claim 1, wherein the pharmaceutically acceptable salt is: [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine 2-hydroxyethanesulfonate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine 2-acetoxybenzoate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine acetate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine ascorbate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine benzenesulfonate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine benzoate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine bicarbonate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine carbonate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine citricate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine edetic acid salt; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine ethanedisulfonate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine ethanesulfonate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine fumate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine glucoheptonate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine gluconate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine glutamate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine glycolate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine glycollyarsanilate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine hexylresorcinol acid salt; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine hydrabamate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine hydrobromide salt; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine hydrocloride salt; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine hydroiodide salt; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine hydroxymaleate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine hydroxynaphthoate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine isethionate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine lactate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine lactobionate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine laurylsulfonate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine maleate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine malate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine mandelate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine methanesulfonate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine napsylate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine nitrate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine oxalate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine pamoate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine pantothenate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine phenyl acetate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine phosphate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine polygalacturonate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine propionate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine salicylate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine stearate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine subacetate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine succinate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine sulfamate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine sulfanilate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine sulfate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine tannate; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine tartrate; or [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine toluenesulfonate. 3. The compound of claim 1, wherein the pharmaceutically acceptable salt is [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[- 4.5]decan-9-yl]ethyl})amine fumarate. 4. A pharmaceutical composition comprising the pharmaceutically acceptable salt of claim 1 and a pharmaceutically acceptable carrier or excipient. 5. A pharmaceutical composition comprising the pharmaceutically acceptable salt of claim 2 and a pharmaceutically acceptable carrier or excipient. 6. A pharmaceutical composition comprising the pharmaceutically acceptable salt of claim 3 and a pharmaceutically acceptable carrier or excipient. 7. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition comprises an enantiomeric excess of at least 90% of [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine fumarate. 8. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition comprises an enantiomeric excess of at least 95% of [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine fumarate. 9. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition comprises an enantiomeric excess of at least 98% of [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine fumarate. 10. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition comprises an enantiomeric excess of at least 99% of [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5- ]decan-9-yl]ethyl})amine fumarate. 11. A method of treating pain in a subject comprising administering to the subject the pharmaceutical composition of claim 4. 12. A method of treating pain in a subject comprising administering to the subject the pharmaceutical composition of claim 5. 13. A method of treating pain in a subject comprising administering to the subject the pharmaceutical composition of claim 6. 14. A method of treating pain in a subject comprising administering to the subject the pharmaceutical composition of claim 7. 15. A method of treating pain in a subject comprising administering to the subject the pharmaceutical composition of claim 8. 16. A method of treating pain in a subject comprising administering to the subject the pharmaceutical composition of claim 9. 17. A method of treating pain in a subject comprising administering to the subject the pharmaceutical composition of claim 10. 18. A method of treating pain in a subject comprising administering to the subject the pharmaceutically acceptable salt of claim 1. 19. A method of treating pain in a subject comprising administering to the subject the pharmaceutically acceptable salt of claim 2. 20. A method of treating pain in a subject comprising administering to the subject the pharmaceutically acceptable salt of claim 3.