US 12,421,276 B2
Methods of treating neurodegenerative disease with substituted n-hexanoic-l-tyrosine-l-isoleucine-(6)-aminohexanoic amide analogues
Leen H. Kawas, Seattle, WA (US); Jasbir Singh, Seattle, WA (US); Lansing Joseph Stewart, Seattle, WA (US); and William R. Baker, Seattle, WA (US)
Assigned to Athira Pharma, Inc., Bothell, WA (US)
Filed by Athira Pharma, Inc., Seattle, WA (US)
Filed on Apr. 12, 2021, as Appl. No. 17/228,481.
Application 17/228,481 is a division of application No. 16/306,277, granted, now 11,021,514, previously published as PCT/US2017/035547, filed on Jun. 1, 2017.
Claims priority of provisional application 62/344,305, filed on Jun. 1, 2016.
Prior Publication US 2021/0340176 A1, Nov. 4, 2021
Int. Cl. C07K 5/065 (2006.01); A61K 9/00 (2006.01); C07K 5/02 (2006.01)
CPC C07K 5/06078 (2013.01) [A61K 9/0019 (2013.01); C07K 5/021 (2013.01)] 57 Claims
 
1. A method for treating a neurogenerative disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula (I):

OG Complex Work Unit Chemistry
or a tautomer or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer, wherein:
n is 1, 2, 3, 4, 5, 6, 7, 8, or 9;
m is 0, 1, 2, 3, or 4;
R1 is C1-C12 alkyl or C1-C12 substituted alkyl;
R2 is selected from

OG Complex Work Unit Chemistry
each Y is independently —Z—(CH2)q—W—Rb;
q is 0-4;
Z and W are independently selected from CH2, NRc, and Rb,
or Z and W are taken together to form a C3-C8 heterocycloalkyl;
each Rc is independently hydrogen or C1-C4 alkyl;
each Rb is independently selected from hydrogen, C1-C12 alkyl, C1-C12 substituted alkyl, C3-C8 heterocycloalkyl, and C3-C8 substituted heterocycloalkyl;
r is 0-5;
U is heterocycloalkyl;
R3 and R4 are independently hydrogen or C1-C12 alkyl,
or R3 and R4 are taken together to form a spirocyclic ring system;
R5 is hydrogen; and
each R6 is independently selected from hydrogen, deuterium, CH3, F, 19F, and 18F;
wherein each heterocyclic ring contains up to four heteroatoms selected from O, N, and S;
with the proviso that when both Z and W are heteroatoms, the value of q cannot be 1.