US 12,280,038 B2
L-pag derivatives for treatment of sleep disordered breathing (SDB)
Michael J. Kates, Philadelphia, PA (US); Nanduri R. Prabhakar, Chicago, IL (US); David L. McCormick, Chicago, IL (US); and Miguel Muzzio, Chicago, IL (US)
Assigned to The University of Chicago, Chicago, IL (US); and IIT Research Institute, Chicago, IL (US)
Filed by The University of Chicago, Chicago, IL (US); and IIT Research Institute, Chicago, IL (US)
Filed on Jun. 24, 2022, as Appl. No. 17/808,645.
Application 17/808,645 is a continuation of application No. 15/929,512, filed on May 6, 2020, abandoned.
Application 15/929,512 is a continuation of application No. 16/470,445, abandoned, previously published as PCT/US2017/067689, filed on Dec. 20, 2017.
Claims priority of provisional application 62/436,942, filed on Dec. 20, 2016.
Prior Publication US 2022/0323415 A1, Oct. 13, 2022
Int. Cl. A61K 31/4164 (2006.01); A61K 31/197 (2006.01); A61K 31/198 (2006.01); A61K 31/216 (2006.01); A61K 31/221 (2006.01); A61K 31/275 (2006.01); A61K 31/381 (2006.01); A61K 45/06 (2006.01); A61P 11/00 (2006.01); C07C 229/30 (2006.01); C07C 255/07 (2006.01); C07D 277/30 (2006.01); C07D 333/24 (2006.01)
CPC A61K 31/4164 (2013.01) [A61K 31/197 (2013.01); A61K 31/198 (2013.01); A61K 31/216 (2013.01); A61K 31/221 (2013.01); A61K 31/275 (2013.01); A61K 31/381 (2013.01); A61K 45/06 (2013.01); A61P 11/00 (2018.01); C07C 229/30 (2013.01); C07C 255/07 (2013.01); C07D 277/30 (2013.01); C07D 333/24 (2013.01)] 25 Claims
 
1. A method of treating or reducing a sleep-related breathing disorder in an individual in need thereof comprising administering to the individual a therapeutically effective amount of a cystathionine-γ-lyase (CSE) antagonist, wherein the CSE antagonist is a propargylglycine analog compound of the formula

OG Complex Work Unit Chemistry
wherein:
R1 and R3 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heterocycle;
R2 is hydrogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heterocycle; and
X is hydrogen, halide, CN, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heterocycle;
or a pharmaceutically acceptable salt, enantiomer, diastereomer, or prodrug thereof, wherein R1, R2, R3, and X are not all hydrogen, and wherein the individual is suffering from or having symptoms of a sleep-related breathing disorder selected from central sleep apnea (CSA), Cheyne-Stokes breathing-central sleep apnea (CSB-CSA), obesity hypoventilation syndrome (OHS), congenital central hypoventilation syndrome (CCHS), obstructive sleep apnea (OSA), idiopathic central sleep apnea (ICSA), narcotic-induced CSA, high altitude periodic breathing, chronic mountain sickness, impaired respiratory motor control associated with stroke, upper airway resistance syndrome (UARS), or impaired respiratory motor control associated with a neurologic disorder.