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US 12,734,159 B2Granted
Methods of treating spinal cord injury or damage
AssigneeSpinogenix, Inc.
InventorsStella T. Sarraf, Vincent F. Simmon, Peter W. Vanderklish
Life of this patent
Estimating the term…
Abstract
In some embodiments, a method of treating spinal cord injury or damage, or a complication thereof, in a patient is provided, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I, Ia, Ik, or II.
Claims17
A method of treating a spinal cord injury or damage, or a complication thereof, in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I or Ia:
- or a pharmaceutically acceptable salt, solvate, and/or an N-oxide thereof, wherein:
- subscripts n and p are independently selected from 0, 1, or 2;
- each R1 is independently selected from the group consisting of hydrogen, halo, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, acyl, acylamino, aminocarbonyl, aminosulfonyl, amino, substituted amino, aryl, substituted aryl, carboxyl, carboxyl esters, cyano, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, hydroxyl, sulfonyl, substituted sulfonyl, thiol, thioalkyl, and nitro;
- A is an arylene or heteroarylene, having 1 to 4 heteroatoms;
- W is selected from the group consisting of —O—, —S—, —SO—, —S(O)2—, and —NR2—, wherein R2 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, and substituted heterocyclyl;
- X is selected from the group consisting of —O—, —S—, —SO—, —S(O)2—, and —NR2—, provided that when A is arylene, and Y is —S— or —NR2—, then X is not —S—;
- Y is selected from the group consisting of —O—, —S—, —SO—, S(O)2—, and —NR2—;
- and
- Z is selected from the group consisting of —N(CH3)CH2CH2OC(O)CH3 and —(CH2CH(R3)O)q-T, wherein subscript q is an integer selected from 1 to 100, R3 is selected from the group consisting of hydrogen and methyl, and T is selected from the group consisting of hydrogen, alkyl, substituted alkyl, -L-monosaccharide, and -L-oligosaccharide, wherein L is selected from the group consisting of a bond, phosphate, and sulfate;
- and
- wherein the complication of spinal cord injury or damage is a respiratory complication, cardiovascular complication, hypotension, bradycardia, neurogenic shock, an autonomic dysreflexia, secondary immunodeficiency, syringomyelia, neuropathic joint arthropathy, Charcot joint arthropathy, loss of motor control, loss of sensory function, tetraplegia, paraplegia, loss of bladder control, spasm, loss of sexual function, numbness, loss of balance, autonomic dysreflexia, deep vein thrombosis, spasticity, pain, neuropathic pain, syringomyelia, neurogenic heterotopic ossification, shock, bradyarrhythmias, hypotension, ectopic beats, abnormal temperature regulation, changes in sweat secretion, vasodilatation, autonomic dysreflexia, thromboembolism, pressure ulcer, or heterotopic ossification, or a combination thereof.
8 more elements
A method of treating a spinal cord injury or damage, or a complication thereof, in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula II:
- or a pharmaceutically acceptable salt, solvate, and/or an N-oxide thereof, wherein:
- Y is —NR33— or —S—;
- each R31 is independently halogen, —CX313, —CHX312, —CH2X31, —OCX313, —OCHX312, —OCH2X31, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —C(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
- each R32 is independently halogen, —CX323, —CHX322, —CH2X32, —OCX323, —OCHX322, —OCH2X32, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
- R33 is H, alkyl, or substituted alkyl;
- each of X31 and X32 is independently halogen;
- each of z1 and z2 is independently an integer from 0 to 4;
- and
- z3 is an integer from 1 to 12;
- and
- wherein the complication of spinal cord injury or damage is a respiratory complication, cardiovascular complication, hypotension, bradycardia, neurogenic shock, an autonomic dysreflexia, secondary immunodeficiency, syringomyelia, neuropathic joint arthropathy, Charcot joint arthropathy, loss of motor control, loss of sensory function, tetraplegia, paraplegia, loss of bladder control, spasm, loss of sexual function, numbness, loss of balance, autonomic dysreflexia, deep vein thrombosis, spasticity, pain, neuropathic pain, syringomyelia, neurogenic heterotopic ossification, shock, bradyarrhythmias, hypotension, ectopic beats, abnormal temperature regulation, changes in sweat secretion, vasodilatation, autonomic dysreflexia, thromboembolism, pressure ulcer, or heterotopic ossification, or a combination thereof.
8 more elements
Dependencies are inferred from the claim text.