SYNTHESIS OF 20-NOR-SALVINORIN A

• US 20200131162A1
• Filed: 06/07/2018
• Published: 04/30/2020
• Est. Priority Date: 06/14/2017
• Status: Active Grant

• Current Assignee: The Scripps Research Institute
• Original Assignee: The Scripps Research Institute
• Inventors: Shenvi, Ryan, Roach, Jeremy, Sasano, Yusuke, Bohn, Laura, Schmid, Cullen
• Granted Patent: US 11,512,075 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2602/28 Hydrogenated naphthalenes
• CPC Class Codes: C07C 69/757 having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
• CPC Class Codes: C07D 307/54 Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 407/04 directly linked by a ring-member-to-ring-member bond

Abstract

The invention provides 20-nor-salvinorin A, an analog of the kappa-opioid agonist salvinorin A. The 20-nor-salvinorin A is an active kappa-opioid modulator and can be used for treatment of medical conditions wherein modulation of the kappa-opioid receptor is medically indicated, such as pain, pruritis, depression, or inflammation, or conditions implicating perception and consciousness. 20-nor-salvinorin A can be less additive when used in treatment compared to a mu-opioid receptor agonist, and 20-nor-salvinorin A is more stable in vivo than is parent compound salvinorin A. The invention further provides synthetic intermediates and procedures for preparation of 20-nor-salvinorin A.

Claims

1. A compound of formula 20-nor-salvinorinA

2. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

3. A method of modulating a kappa-opioid receptor, comprising contacting the kappa-opioid receptor with an effective amount or concentration of a compound of claim 1.

4. A method of treating a medical condition in a patient, wherein modulation of a kappa-opioid receptor is medically indicated, comprising administering to the patient an effective dose of the compound of claim 1.

5. The method of claim 4, wherein the medical condition comprises pain, pruritis, depression, or inflammation, or conditions implicating perception and consciousness.

6. The method of claim 4, wherein the compound of claim 1 is less addictive to the patient during the course of the treatment than is a modulator of opioid receptors other than the kappa-opioid receptor, including but not restricted to a mu-opioid receptor or a delta-opioid receptor.

10. A method of synthesis of compound S12,

20. A method for treatment of a medical condition in a patient, comprising administering to the patient an effective dose of the compound of claim 1, wherein the medical condition comprises pain, pruritis, depression, or inflammation, or conditions implicating perception and consciousness.

7-8. -8. (canceled)

9. A compound of formula S11

11-12. -12. (canceled)

13. A compound of formula S9

14. A method of synthesis of a compound of formula S10

15-19. -19. (canceled)