# US RE43,688 E1 · Compositions and methods related to serotonin 5-HT1A receptors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US RE43,688 E1 - Document ID: USRE43688E1 - Status: Granted - Kind: E1 - Application number: 13/187,728 - Filed: 2011-07-21 - Granted: 2012-09-25 - Earliest claimed: 2006-01-25 - Assignees: The Regents of the University of California - Applicants: Harsh Saigal, legal representative - Inventors: Jogeshwar Mukherjee; Neil Saigal - Web page: https://patentgrep.com/patent/USRE43688E1 ## Abstract Contemplated substituted arylpiperazinyl compounds, and most preferably 18F-Mefway, exhibit desirable in vitro and in vivo binding characteristics to the 5-HT1A receptor. Among other advantageous parameters, contemplated compounds retain high binding affinity, display optimal lipophilicity, and are radiolabeled efficiently with 18F-fluorine in a single step. Still further, contemplated compounds exhibit high target to non-target ratios in receptor-rich regions both in vitro and in vivo, and selected compounds can be effectively and sensitively displaced by serotonin, thus providing a quantitative tool for measuring 5-HT1A receptors and serotonin concentration changes in the living brain. ## Claims ### Claim 1 A compound having a structure according to Formula I or a pharmaceutically acceptable salt thereof; wherein R1 is OCH3 or O11CH3 alkoxy; X is N, and W is CH; Y is O, and wherein * denotes an optional 11C isotope; Q is optionally substituted cycloalkyl or cycloalkenyl; and wherein Z is lower alkyl, and wherein 18F is covalently bound to Z when 11C is absent in *; and wherein 11C is present in at least one of R1 and * when 18F is absent and Z is CH2F. ### Claim 2 (depends on 1) The compound of claim 1 fun her comprising a pharmaceutically acceptable carrier in admixture with the compound to form a pharmaceutical composition, wherein the compound is optionally present as a salt with a pharmaceutically acceptable counter ion. ### Claim 3 A method of diagnosing or treating a panic disorder, a bipolar disorder, or a seizure disorder, comprising a step of administering a pharmaceutical composition that includes a compound having a structure according to Formula I, or a pharmaceutically acceptable salt thereof, to a mammal, wherein R1 is an optionally substituted lower alkyl, alkoxy, halogen, or hydrogen, and wherein at least one carbon atom in R1 may be 11C; X and W are independently N or CH; Y is O, NR1, or S, and wherein * denotes an optional 11C isotope; Q is optionally substituted cycloalkyl or cycloalkenyl; and wherein Z is lower alkyl, and wherein a PET detectable label is covalently bound to Z when 11C is absent in R1 and *, and wherein the PET detectable label is 11C or 18F. ### Claim 4 (depends on 3) The method of claim 3 wherein in the compound Q is cyclohexyl or cyclohexenyl, and Z is CH218 or CH2CH2 18F. ### Claim 5 (depends on 3) The method of claim 3 wherein in the compound comprises 18F-Mefway the compound is ### Claim 6 (depends on 5) The method of claim 5 wherein in the compound comprises the compound is trans-18F-Mefway ### Claim 7 (depends on 3) The method of claim 3 further comprising a step of performing at least one of a PET scan and a SPECT scan on the mammal. ### Claim 8 (depends on 3) The method of claim 3 wherein the pharmaceutical composition is parenterally administered. ### Claim 9 (depends on 3) The method of claim 3 wherein the composition comprises 18F-Mefway ### Claim 10 (depends on 3) The method of claim 3 wherein the composition comprises trans-18F-Mefway ### Claim 11 A method of quantifying serotonin in a neural tissue comprising: a step of administering a pharmaceutical composition comprising a compound having a structure according to Formula I, or a pharmaceutically acceptable salt thereof, to a mammal, wherein R1 is an optionally substituted lower alkyl, alkoxy, halogen, or hydrogen, and wherein at least one carbon atom in R1 may be 11C; X and W are independently N or CH; Y is O, NR1, or S, and wherein * denotes an optional 11C isotope; Q is optionally substituted cycloalkyl or cycloalkenyl; and wherein Z is lower alkyl, and wherein a PET detectable label is covalently bound to Z when 11C is absent in R1 to *, and wherein the PET detectable label is 11C or 18F, and wherein Z is CH2F when 11C is present in R1 or *; a step of performing a PET scan on the tissue, and a step of correlating a PET signal quantity with a serotonin concentration in the tissue. ### Claim 12 (depends on 11) The method of claim 11 wherein in the compound Q is cyclohexyl or cyclohexenyl, and Z is CH2 18F or CH2CH2 18F. ### Claim 13 A compound having a structure according to Formula II ### Claim 14 A compound having a structure according to Formula III wherein L is a leaving group. ### Claim 15 (depends on 14) The compound of claim 14 wherein L is selected from the group consisting of halogen, O-mesylate, O-tosylate, O-nosylate, and O-brosylate. ### Claim 16 A method for imaging the 5-HT1A receptor comprising: (i) administering a pharmaceutical composition comprising a compound having a structure according to Formula I to a mammal or a pharmaceutically acceptable salt thereof; wherein R1 is an optionally lower alkyl, alkoxy, halogen, or hydrogen, and wherein at least one carbon atom in R1 is optionally 11C; X and W are independently N or CH; Y is O, NR1, or S, and wherein * denotes an optional 11C isotope; Q is optionally substituted cycloalkyl or cycloalkenyl; and Z is lower alkyl, and wherein a PET detectable label is covalently bound to Z when 11C is absent in R1 and *, and wherein the PET detectable label is 11C or 18F, and wherein Z is CH2F when 11C is present in R1 or *; and (ii) performing a PET scan on said mammal. ### Claim 17 A method of quantifying serotonin in vivo comprising: (i) administering a pharmaceutical composition comprising a compound having a structure according to Formula I, or a pharmaceutically acceptable salt thereof, to a mammal wherein R1 is an optionally lower alkyl, alkoxy, halogen, or hydrogen, and wherein at least one carbon atom in R1 is optionally 11C; X and W are independently N or CH; Y is O, NR1, or S, and wherein * denotes an optional 11C isotope; Q is optionally substituted cycloalkyl; and Z is lower alkyl, and wherein a PET detectable label is covalently bound to Z when 11C is absent in R1 and * and wherein the PET detectable label is 11C or 18F, and wherein Z is CH2F when 11C is present in R1 or *; (ii) performing a PET scan on said mammal; and (iii) correlating a PET signal quantity with a serotonin concentration. ### Claim 18 A ligand-receptor complex comprising: (i) a compound having a structure according to Formula I wherein R1 is an optionally lower alkyl, alkoxy, halogen, or hydrogen, and wherein at least one carbon atom in R1 is optionally 11C; X and W are independently N or CH; Y is O, NR1, or S, and wherein * denotes an optional 11C isotope; Q is optionally substituted cycloalkyl; and Z is lower alkyl, and wherein a PET detectable label is covalently bound to Z when 11C is absent in R1 and *, and wherein the PET detectable label is 11C or 18F, and wherein Z is CH2F when 11C is present in R1 or *; and (ii) a 5-HT1A receptor.