Use of fluorinated derivatives of 4-aminopyridine in therapeutics and medical imaging
AssigneeThe University of Chicago
InventorsPedro Brugarolas, Brian POPKO, Daniel APPELBAUM, Chin-Tu CHEN
Life of this patent
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Abstract
The present disclosure provides novel compounds, including compounds that bind to potassium channels, methods for their manufacture, and methods for their use, including their use to diagnose and/or assess traumatic brain injury and use to treat dymeylinating diseases, and/or in vivo imaging of the central nervous system, and to diagnose and/or assess the progression of MS or other diseases.
Claims30
A compound of Formula (I):
- wherein:
- R1, R2, R3, and R4 are each independently selected from the group consisting of H, (CH2)nX, CH2OCH2CH2X, NH2, CH2OH, CF3, OCH3, OCH2F, OCHF2, OCF3 and
- R5 is selected from the group consisting of H, (CH2)mX, OH, COOCF3, COOC(CH3)3, and COO(CH2)mX;
- wherein n=0, 1, 2, 3, 4, or 5 and m=1, 2, 3, 4, or 5;
- wherein X represents a fluorine atom or an isotope thereof;
- wherein at least one of R1, R2, R3, R4 and R5 is not hydrogen;
- wherein at least one of R1, R2, R3, R4 and R5 contains a fluorine atom or an isotope thereof;
- wherein when R2 is NH2 or CH2OH or a nonradioactive fluorine or CF3, at least one of R1, R3, R4, and R5 is not hydrogen;
- wherein when R4 is NH2 or CH2OH or a nonradioactive fluorine or CF3, at least one of R1, R2, R4, and R5 is not hydrogen;
- and
- wherein any of C, N, O is optionally replaced by the isotope 11C, 13N, 15O, respectively;
- or a pharmaceutical acceptable salt thereof, or a deuterated version thereof.
(canceled)
5-6. (canceled)
12-13. (canceled)
15-23. (canceled)
An imaging agent comprising the compound of Formula (I):
- wherein:
- R1, R2, R3, and R4 are each independently selected from the group consisting of H, (CH2)nX, CH2OCH2CH2X, NH2, CH2OH, CF3, OCH3, OCH2F, OCHF2, OCF3 and
- R5 is selected from the group consisting of H, (CH2)mX, OH, COOCF3, COOC(CH3)3, and COO(CH2)mX;
- wherein n=0, 1, 2, 3, 4, or 5 and m=1, 2, 3, 4, or 5;
- wherein X represents a fluorine atom or an isotope thereof;
- wherein at least one of R1, R2, R3, R4 and R5 is not hydrogen;
- wherein at least one of R1, R2, R3, R4 and R5 contains a fluorine atom or an isotope thereof;
- wherein when R2 is NH2 or CH2OH or a nonradioactive fluorine or CF3, at least one of R1, R3, R4, and R5 is not hydrogen;
- wherein when R4 is NH2 or CH2OH or a nonradioactive fluorine or CF3, at least one of R1, R2, R4, and R5 is not hydrogen;
- and
- wherein any of C, N, O is optionally replaced by the isotope 11C, 13N, 15O, respectively;
- or a pharmaceutical acceptable salt thereof, or a deuterated version thereof.
27-32. (canceled)
34-57. (canceled)
A method for diagnosing traumatic brain injury or evaluating the progression of traumatic brain injury in a subject comprising administering to the subject an imaging agent and detecting a compound comprised in the imaging agent in the subject, wherein the imaging agent comprises the compound of Formula (I):
- wherein:
- R1, R2, R3, and R4 are each independently selected from the group consisting of H, (CH2)nX, CH2OCH2CH2X, NH2, CH2OH, CF3, OCH3, OCH2F, OCHF2, OCF3 and
- R5 is selected from the group consisting of H, (CH2)mX, OH, COOCF3, COOC(CH3)3, and COO(CH2)mX;
- wherein n=0, 1, 2, 3, 4, or 5 and m=1, 2, 3, 4, or 5;
- wherein X represents a fluorine atom or an isotope thereof;
- wherein at least one of R1, R2, R3, R4 and R5 is not hydrogen;
- wherein at least one of R1, R2, R3, R4 and R5 contains a fluorine atom or an isotope thereof;
- wherein when R2 is NH2 or CH2OH or a nonradioactive fluorine or CF3, at least one of R1, R3, R4, and R5 is not hydrogen;
- wherein when R4 is NH2 or CH2OH or a nonradioactive fluorine or CF3, at least one of R1, R2, R4, and R5 is not hydrogen;
- and
- wherein any of C, N, O is optionally replaced by the isotope 11C, 13N, 15O, respectively;
- or a pharmaceutical acceptable salt thereof, or a deuterated version thereof.
(canceled)
62-63. (canceled)
(canceled)
67-79. (canceled)
A method for treating traumatic brain injury (TBI) or mitigating a symptom of TBI in a subject, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula (I):
- wherein:
- R1, R2, R3, and R4 are each independently selected from the group consisting of H, (CH2)nX, CH2OCH2CH2X, NH2, CH2OH, CF3, OCH3, OCH2F, OCHF2, OCF3 and
- R5 is selected from the group consisting of H, (CH2)mX, OH, COOCF3, COOC(CH3)3, and COO(CH2)mX;
- wherein n=0, 1, 2, 3, 4, or 5 and m=1, 2, 3, 4, or 5;
- wherein X represents a fluorine atom;
- wherein at least one of R1, R2, R3, R4 and R5 is not hydrogen;
- wherein at least one of R1, R2, R3, R4 and R5 contains a fluorine atom;
- wherein when R2 is NH2 or CH2OH or a nonradioactive fluorine or CF3, at least one of R1, R3, R4, and R5 is not hydrogen;
- wherein when R4 is NH2 or CH2OH or a nonradioactive fluorine or CF3, at least one of R1, R2, R4, and R5 is not hydrogen;
- or a pharmaceutical acceptable salt thereof, or a deuterated version thereof.
81-93. (canceled)
Dependencies are inferred from the claim text.