US 11,866,409 B2
Apoptosis related protein in the tgf-beta signaling pathway (ARTS) mimetic compounds, compositions, methods and uses thereof in induction of differentiation and/or apoptosis of premalignant and malignant cells, thereby restoring their normal-like phenotype
Sarit Larisch, Zichron Yaakov (IL); and Dalit Barkan, Zichron Yaakov (IL)
Assigned to CARMEL-HAIFA UNIVERSITY ECONOMIC CORPORATION LTD., Haifa (IL)
Appl. No. 15/772,699
Filed by CARMEL-HAIFA UNIVERSITY ECONOMIC CORPORATION LTD., Haifa (IL)
PCT Filed Nov. 2, 2016, PCT No. PCT/IL2016/051187
§ 371(c)(1), (2) Date May 1, 2018,
PCT Pub. No. WO2017/077535, PCT Pub. Date May 11, 2017.
Claims priority of provisional application 62/249,446, filed on Nov. 2, 2015.
Prior Publication US 2018/0230096 A1, Aug. 16, 2018
Int. Cl. C07D 209/42 (2006.01); C07D 231/14 (2006.01); C07D 217/02 (2006.01); A61K 31/496 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01)
CPC C07D 209/42 (2013.01) [A61K 31/496 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07D 217/02 (2013.01); C07D 231/14 (2013.01)] 18 Claims
 
1. A method for inducing differentiation and/or apoptosis in a cell, wherein said method comprises the step of contacting said cell with an effective amount of at least one ARTS mimetic compound, any combination thereof any vehicle, matrix, nano- or micro-particle, or any composition comprising said at least one ARTS mimetic compound, wherein said ARTS mimetic compound having the general formula (I) or a pharmaceutically acceptable salt or hydrate thereof or any stereoisomer or salt thereof:

OG Complex Work Unit Chemistry
wherein:
R1 is independently selected from H, C1-C3 alkyl;
R2 is independently selected from —C(═O)—X—R3, —S(═O)—X—R3′;
X is a heteroatom independently selected from O;
R3 and R3′, independently of each other may be selected independently from H, C1-C3 alkyl;
R5 is -L1-R7-L2-R8;
L1 and L2, independently of each other, are selected independently from —(CH2)n; —NH—C(═O)—(CH2)n—, —C(═O)—NH—(CH2)n—; —S—S—(CH2)n—; —O—(CH2)n—; —NH—(CH2)n—; C(═O)—(CH2)n—; —S—(CH2)n—; —NH—S(═O)n—(CH2)n—;
n is independently 1 to 3;
R7 is a carbocyclic ring or a heterocyclic ring;
R8 is a mono cyclic ring system having 5 to 12, optionally substituted with at least one of OH, CF3, halogen, —COOH, —NH2, CN, C1-C3alkyl; and
R6 is independently selected from H, halogen, CN, NO2, C1-C3 alkoxy, straight or branched C1-C3 alkyl.