# US 8,772,330 B2 · Inhibitor(s) of transporters or uptake of monoaminergic neurotransmitters > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,772,330 B2 - Document ID: US8772330B2 - Status: Granted - Kind: B2 - Application number: 13/355,371 - Filed: 2012-01-20 - Published: 2012-07-26 - Granted: 2014-07-08 - Earliest claimed: 2009-07-23 - Assignees: State of Oregon acting by and through the State Board of Higher Education on behalf of Oregon State University - Applicants: James David White; David T. Wong; David B. Chan; Jongtae Yang; Rajan Juniku - Inventors: James David White; David T. Wong; David B. Chan; Jongtae Yang; Rajan Juniku - Web page: https://patentgrep.com/patent/US8772330B2 ## CPC - A61K 31/381: having five-membered rings - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 3/04: Anorexiants; Antiobesity agents - A61P 13/00: Drugs for disorders of the urinary system - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/06: Antimigraine agents - A61P 25/08: Antiepileptics; Anticonvulsants - A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia - A61P 25/16: Anti-Parkinson drugs - A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia - A61P 25/22: Anxiolytics - A61P 25/24: Antidepressants - A61P 25/30: for treating abuse or dependence - A61P 25/32: Alcohol-abuse - A61P 25/34: Tobacco-abuse - A61P 25/36: Opioid-abuse - C07D 333/16: by oxygen atoms - C07D 333/20: by nitrogen atoms (nitro, nitroso radicals C07D333/12) - C07D 333/24: 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 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract The present disclosure concerns a compound, or a pharmaceutically acceptable salt thereof, having a formula: where at least one of R1-R4 is a heterocycle, at least one of R1-R4 is an aryl group coupled to the ring by a linker atom, functional group, or other moiety, or where none of R1-R4 is an amide, and any and all combinations thereof. Remaining R1-R4 substituents independently are aliphatic, substituted aliphatic, amine, substituted amine, aryl, substituted aryl, cyclic, substituted cyclic, halide, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, hydrogen or hydroxyl. A method for treating a subject also is provided comprising administering a disclosed compound or compounds, or a prodrug that is converted into the disclosed compound or compounds, or a composition comprising the compound, compounds, or prodrugs thereof, to a subject. A method for making disclosed compounds also is provided. ## Claims ### Claim 1 A compound having a formula or a pharmaceutically acceptable salt thereof, where n is from 1 to 10, R groups independently are aliphatic, substituted aliphatic, aryl, substituted aryl,-cyclic, substituted cyclic, halide, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, hydrogen or hydroxyl, R1 substituents independently are aliphatic, substituted aliphatic, cyclic, substituted cyclic, heterocyclic, substituted heterocyclic, or hydrogen, X1 is carbon, oxygen, nitrogen or sulfur, and X2 is a bond to the 3-membered ring, or is selected from a carbon, oxygen, nitrogen or sulfur atom. ### Claim 2 (depends on 1) The compound according to claim 1 where X2 is selected from a carbon atom, nitrogen atom, oxygen atom or sulfur atom. ### Claim 3 (depends on 1) The compound according to claim 1 having a formula or a pharmaceutically acceptable salt thereof, where n is from 1 to 10, R independently are aliphatic, substituted aliphatic, amine, cyclic, substituted cyclic, halide, heterocyclic, substituted heterocyclic, hydrogen or hydroxyl, and R1 substituents independently are aliphatic, substituted aliphatic, cyclic, substituted cyclic, heterocyclic, substituted heterocyclic, or hydrogen. ### Claim 4 A compound, or a biological active salt thereof, having a formula ### Claim 5 A composition, comprising: a compound or pharmaceutically acceptable salt thereof, having a formula where n is from 1 to 10, R groups independently are aliphatic, substituted aliphatic, cyclic, substituted cyclic, halide, heterocyclic, substituted heterocyclic, hydrogen or hydroxyl, R1 substituents independently are aliphatic, substituted aliphatic, cyclic, substituted cyclic, heterocyclic, substituted heterocyclic, or hydrogen, X1 is carbon, oxygen, nitrogen or sulfur, and X2 is a bond to the 3-membered ring, or is selected from a carbon, oxygen, nitrogen or sulfur atom; and at least one additional material useful for making a pharmaceutically acceptable composition. ### Claim 6 A method for making a compound having a formula where n is from 1 to 10, R groups independently are aliphatic, substituted aliphatic, cyclic, substituted cyclic, halide, heterocyclic, substituted heterocyclic, hydrogen or hydroxyl, R1 substituents independently are aliphatic, substituted aliphatic, cyclic, substituted cyclic, heterocyclic, substituted heterocyclic, or hydrogen, and X1 is carbon, oxygen, nitrogen or sulfur, the method comprising: forming an ester by reacting a carboxylic acid with an aryl alcohol, wherein the carboxylic acid has a formula and the aryl alcohol has a formula performing a Tebbe or Wittig methylenation reaction on the ester to provide an olefin; and forming a 3-membered ring from the olefin using a diazo compound. ### Claim 7 An in vitro method, comprising contacting a neurotransmitter transporter with an amount of a compound effective to inhibit an activity of the neurotransmitter transporter, the compound having a formula or a pharmaceutically acceptable salt thereof, where n is from 1 to 10, R groups independently are aliphatic, substituted aliphatic, cyclic, substituted cyclic, halide, heterocyclic, substituted heterocyclic, hydrogen or hydroxyl, R1 substituents independently are aliphatic, substituted aliphatic, cyclic, substituted cyclic, heterocyclic, substituted heterocyclic, or hydrogen, X1 is carbon, oxygen, nitrogen or sulfur, and X2 is a bond to the 3-membered ring, or is selected from a carbon, oxygen, nitrogen or sulfur atom. ### Claim 8 A method of treating a subject, comprising: administering to the subject a compound having a formula or a pharmaceutically acceptable salt thereof, where n is from 1 to 10, R groups independently are aliphatic, substituted aliphatic, cyclic, substituted cyclic, halide, heterocyclic, substituted heterocyclic, hydrogen or hydroxyl, R1 substituents independently are aliphatic, substituted aliphatic, cyclic, substituted cyclic, heterocyclic, substituted heterocyclic, or hydrogen, X1 is carbon, oxygen, nitrogen or sulfur, and X2 is a bond to the 3-membered ring, or is selected from a carbon, oxygen, nitrogen, or sulfur atom; and wherein the subject is suffering from a disease, or a symptom thereof, selected from diabetic peripheral neuropathy, major depressive disorder (MDD), generalized anxiety disorder (GAD), or posttraumatic stress disorder. ### Claim 9 (depends on 7) The method according to claim 7 where the compound has a binding affinity from greater than 0 nM to about 40 nM for the serotonin transporter. ### Claim 10 (depends on 9) The method according to claim 9 where the compound has a binding affinity from about 1 nM to about 10 nM. ### Claim 11 (depends on 7) The method according to claim 7 where the compound has a binding affinity of greater than 0 nM to about 500 nM for the norepinephrine transporter. ### Claim 12 (depends on 11) The method according to claim 11 where the compound has a binding affinity of 1 nM to about 200 nM.