US 12,343,337 B2
Compounds for increasing neural plasticity
David E. Olson, Davis, CA (US)
Assigned to THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, Oakland, CA (US)
Appl. No. 16/337,698
Filed by THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, Oakland, CA (US)
PCT Filed Sep. 29, 2017, PCT No. PCT/US2017/054277
§ 371(c)(1), (2) Date Mar. 28, 2019,
PCT Pub. No. WO2018/064465, PCT Pub. Date Apr. 5, 2018.
Claims priority of provisional application 62/401,641, filed on Sep. 29, 2016.
Prior Publication US 2020/0030309 A1, Jan. 30, 2020
Int. Cl. A61K 31/4045 (2006.01); A61K 31/404 (2006.01); A61K 31/4196 (2006.01); A61K 31/422 (2006.01); A61K 31/454 (2006.01)
CPC A61K 31/454 (2013.01) [A61K 31/4045 (2013.01); A61K 31/4196 (2013.01); A61K 31/422 (2013.01)] 4 Claims
OG exemplary drawing
 
1. A method of treating depression in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of a non-hallucinogenic analog of dimethyltryptamine (DMT) having the structure of Formula (IIa-1):

OG Complex Work Unit Chemistry
thereby treating depression in the subject in need thereof,
wherein:
L3 is a bond, —C(O)NRb—, —NRbC(O)—, —NHC(O)NRb—, —C(O)O—, —OC(O)—, —NHC(O)O—, —SO2NRb—, —NHSO2—, —SO2—, —S—, or —NRb—;
R8 is hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C8 cycloalkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 aminoalkyl, heterocycloalkyl, aryl, or heteroaryl;
Rb is hydrogen, or C1-C6 alkyl;
R11 is di-(C1-C6 alkyl)amino;
R12 is hydrogen, halogen, —OH, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or C1-C6 alkoxy;
subscript p is 2; and
subscript q is an integer from 0 to 3, and
wherein the non-hallucinogenic analog of DMT produces a maximum number of dendritic crossings with an increase of greater than 1.0 fold by a Sholl Analysis,
wherein the non-hallucinogenic analog of DMT produces an area-under-curve (AUC) of a Sholl plot with an increase of greater than 1.0 fold,
wherein the non-hallucinogenic analog of DMT produces a number of dendritic branches with an increase of greater than 1.0 fold,
wherein the non-hallucinogenic analog of DMT produces a total dendritic length with an increase of greater than 1.0 fold,
wherein the non-hallucinogenic analog of DMT produces a density of dendritic spines with an increase of greater than 1.0 fold, or
wherein the non-hallucinogenic analog of DMT produces a density of synapses with an increase of greater than 1.0 fold.