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EP-4734969-A2 - 2-(2-ETHOXY-4-PROPYLSULFANYL-5 METHOXYPHENYL)ETHANAMINIUM CHLORIDE

EP4734969A2EP 4734969 A2EP4734969 A2EP 4734969A2EP-4734969-A2

Abstract

The disclosure relates to 2-[2-ethoxy-5-methoxy-4-(propylsulfanyl)phenyl]ethan-1-aminium chloride (2- (2-ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride), crystalline 2-(2-ethoxy-4- propylsulfanyl-5-methoxyphenyl)ethanaminium chloride, and specific crystalline forms thereof, including crystalline form 1 of 2-(2-ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride, to compositions containing the same, and to methods of treatment using them.

Inventors

  • CHADEAYNE, ANDREW R.
  • SHULGIN, ALEXANDER T.
  • COZZI, NICHOLAS V.
  • DALEY, PAUL F.

Assignees

  • Caamtech, Inc.
  • Alexander Shulgin Research Institute

Dates

Publication Date
20260506
Application Date
20240628

Claims (18)

  1. 1. 2-[2-ethoxy-5-methoxy-4-(propylsulfanyl)phenyl]ethan-l-aminiurn chloride (2-(2-ethoxy-4- propylsulfanyl-5-methoxyphenyl)ethanaminium chloride).
  2. 2. Crystalline 2-[2-ethoxy-5-methoxy-4-(propylsulfanyl)phenyl]ethan-l-aminium chloride (2-(2-ethoxy- 4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride).
  3. 3. Crystalline form 1 of 2-[2-ethoxy-5-methoxy-4-(propylsulfanyl)phenyl]ethan-l-aminium chloride (2- (2-ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride).
  4. 4. Crystalline form 1 of 2-(2-ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride according to claim 3, characterized by at least one of: a monoclinic crystal system at a temperature of about 300 K; a Pl c space group at a temperature of about 300 K; unit cell dimensions a = 17.660(3) A, b = 8.5544(10) A, c = 11.0406(14) A, a = 90°, 0 = 90.701(5)°, and y = 90°; an X-ray powder diffraction pattern substantially similar to FIG. 3; or an X-ray powder diffraction pattern characterized by at least two peaks selected from 11.5, 13.1, and 14.4 °20 ± 0.2 °29.
  5. 5. A composition comprising 2-(2-ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride according to claim 1 and an excipient.
  6. 6. A composition comprising crystalline 2-(2-ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride according to any one of claims 2-4 and an excipient.
  7. 7. A composition comprising 2-(2-ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride according to claim 1 as a first component and a second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, (d) a purified terpene, (e) an adrenergic drug, (f) a dopaminergic drug, (g) a monoamine oxidase inhibitor, (h) a purified erinacine, and (i) a purified hericenone.
  8. 8. A composition comprising crystalline 2-(2-ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride according to any one of claims 2-4 as a first component and a second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, (d) a purified terpene, (e) an adrenergic drug, (f) a dopaminergic drug, (g) a monoamine oxidase inhibitor, (h) a purified erinacine, and (i) a purified hericenone.
  9. 9. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a therapeutically effective amount of 2-(2-ethoxy-4- propylsulfanyl-5-methoxyphenyl)ethanaminium chloride according to claim 1.
  10. 10. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a therapeutically effective amount of crystalline 2-(2- ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride according to any one of claims 2-4.
  11. 11. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to claim 5 or claim 7.
  12. 12. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to claim 6.
  13. 13. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to claim 8.
  14. 14. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of 2-(2-ethoxy-4- propylsulfanyl-5-methoxyphenyl)ethanaminium chloride according to claim 1.
  15. 15. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of crystalline 2-(2- ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride according to any one of claims 2-4.
  16. 16. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a composition according to claim 5 or claim 7.
  17. 17. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a composition according to claim 6.
  18. 18. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a composition according to claim 8.

Description

2-(2-ETHOXY-4-PROPYLSULFANYL-5-METHOXYPHENYL)ETHANAMINIUM CHLORIDE Cross-Reference to Related Applications [001] This application claims priority to U.S. Provisional Application No. 63/511,260, filed on June 30, 2023; the disclosure of which is incorporated herein by reference. Technical Field [002] This disclosure relates to 2-[2-ethoxy-5-methoxy-4-(propylsulfanyl)phenyl]ethan-l-aminium chloride (2-(2-ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride or 2CT7-2EtO chloride), crystalline 2CT7-2EtO chloride, and specific crystalline forms thereof, including crystalline form 1 of 2CT7-2EtO chloride; to pharmaceutical compositions containing 2CT7-2EtO chloride or crystalline 2CT7- 2EtO chloride, including crystalline form 1 of 2CT7-2EtO chloride; and to methods of treatment/therapeutic uses of 2CT7-2EtO chloride or crystalline 2CT7-2EtO chloride, including crystalline form 1 of 2CT7-2EtO chloride. Background of the Invention [003] Obtaining specific salts or crystalline forms of an active pharmaceutical ingredient (API) is extremely useful in drug development. It permits better characterization of the drug candidate's chemical and physical properties. Crystalline forms often have better chemical and physical properties than the API in its amorphous state. Such crystalline forms may possess more favorable pharmaceutical and pharmacological properties or be easier to process. Additionally, preparing a crystalline API and solving its crystal structure provides the gold standard for chemical characterization and determining the molecular formula (and molecular weight) of the API. Accordingly, preparing a crystalline form with an accompanying crystal structure thereof prevents potential ambiguities and/or inaccuracies in the API's molecular weight. This is important because the API's molecular weight is used to calculate the concentration of compositions comprising that API. Thus, inaccuracies in molecular weight may lead to errors in the calculations pertaining to dosing, potency, toxicity, etc. in all downstream in vitro and in vivo assays that correlated the concentration of the API with a measured property. Accordingly, there remains a need to obtain and characterize crystalline forms of APIs, such as tryptamines and other psychedelic drug compounds. Summary of the Invention [004] This disclosure relates to 2-[2-ethoxy-5-methoxy-4-(propylsulfanyl)phenyl]ethan-l-aminium chloride (2-(2-ethoxy-4-propylsulfanyl-5-methoxyphenyl)ethanaminium chloride or 2CT7-2EtO chloride), crystalline 2CT7-2EtO chloride, and specific crystalline forms thereof. In one embodiment, this disclosure pertains to particular crystalline forms of 2CT7-2EtO chloride, including crystalline form 1 of 2CT7-2EtO chloride. In one embodiment, crystalline form 1 of 2CT7-2EtO chloride is characterized by at least one of: a monoclinic, P2i/c space group at a temperature of about 300(2) K; unit cell dimensions a = 17.660(3) A, b = 8.5544(10) A, c = 11.0406(14) A, a = 90°, = 90.701(5)°, and y = 90°; an X-ray powder diffraction (XRPD) pattern substantially similar to FIG. 3; and an X-ray powder diffraction pattern characterized by at least two peaks selected from 11.5, 13.1, and 14.4 °20 ± 0.2 °20. [005] The disclosure further relates to a composition comprising 2CT7-2EtO chloride, crystalline 2CT7-2EtO chloride, or specific crystalline forms thereof, such as crystalline form 1 of 2CT7-2EtO chloride, and at least one excipient. [006] The disclosure also provides a composition comprising 2CT7-2EtO chloride, crystalline 2CT7- 2EtO chloride, or specific crystalline forms thereof, such as crystalline form 1 of 2CT7-2EtO chloride, as a first component and a second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, (d) a purified terpene, (e) an adrenergic drug, (f) a dopaminergic drug, (g) a monoamine oxidase inhibitor, (h) a purified erinacine, and (i) a purified hericenone; and at least one excipient. [007] The disclosure also relates to a method of preventing or treating a psychological disorder comprising the step of administering to a subject in need thereof a therapeutically effective amount of 2CT7-2EtO chloride, crystalline 2CT7-2EtO chloride, or specific crystalline forms thereof, such as crystalline form 1 of 2CT7-2EtO chloride, or a composition according to this disclosure. [008] The disclosure further relates to a method of preventing or treating inflammation and/or pain, preventing or treating a neurological disorder, modulating activity of a mitogen-activated protein kinase (MARK), modulating neurogenesis, or modulating neurite outgrowth comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of 2CT7- 2EtO chloride, crystalline 2CT7-2EtO chloride, or specific crystalline forms thereof, such as crystalline form 1 of 2CT7-2EtO chloride, and to administering a pharmaceutical composition or a composi