US 10,376,480 B2
Biguanide derivative, a preparation method thereof, and a pharmaceutical composition containing the biguanide derivative as an active ingredient
Sung Wuk Kim, Gyeonggi-do (KR); Sung Soo Jun, Gyeonggi-do (KR); Chang Hee Min, Seoul (KR); Young Woong Kim, Daejeon (KR); Min Seok Kang, Gyeonggi-do (KR); Byung Kyu Oh, Daejeon (KR); Se Hwan Park, Daejeon (KR); Yong Eun Kim, Daejeon (KR); Duck Kim, Daegu (KR); Ji Sun Lee, Daejeon (KR); and Ju Hoon Oh, Gangwon-do (KR)
Assigned to ImmunoMet Therapeutics Inc., Houston, TX (US)
Filed by Immunomet Therapeutics Inc., Houston, TX (US)
Filed on May 10, 2018, as Appl. No. 15/976,613.
Application 15/976,613 is a division of application No. 15/206,780, filed on Jul. 11, 2016, granted, now 9,993,446.
Application 15/206,780 is a division of application No. 13/520,902, granted, now 9,416,098, issued on Aug. 16, 2016, previously published as PCT/KR2011/000097, filed on Jan. 6, 2011.
Claims priority of application No. 10-2010-0001021 (KR), filed on Jan. 6, 2010; and application No. 10-2011-0001438 (KR), filed on Jan. 6, 2011.
Prior Publication US 2018/0256520 A1, Sep. 13, 2018
Int. Cl. A61K 31/155 (2006.01); A61K 31/341 (2006.01); A61K 31/472 (2006.01); C07C 277/04 (2006.01); C07C 279/04 (2006.01); C07C 279/06 (2006.01); C07C 279/08 (2006.01); C07C 279/16 (2006.01); C07C 279/18 (2006.01); C07C 279/26 (2006.01); C07D 213/38 (2006.01); C07D 307/52 (2006.01); C07D 317/58 (2006.01); C07D 333/20 (2006.01); A61K 31/4406 (2006.01)
CPC A61K 31/155 (2013.01) [A61K 31/341 (2013.01); A61K 31/4406 (2013.01); A61K 31/472 (2013.01); C07C 277/04 (2013.01); C07C 279/04 (2013.01); C07C 279/06 (2013.01); C07C 279/08 (2013.01); C07C 279/16 (2013.01); C07C 279/18 (2013.01); C07C 279/26 (2013.01); C07D 213/38 (2013.01); C07D 307/52 (2013.01); C07D 317/58 (2013.01); C07D 333/20 (2013.01); C07C 2601/08 (2017.05); C07C 2601/14 (2017.05); C07C 2601/18 (2017.05); C07C 2603/74 (2017.05)] 6 Claims
 
1. A method of activating AMPKα(5′-AMP-activated protein kinase alpha) in cells, the method comprising:
administering a therapeutically effective amount of a compound of Formula 1 below or a pharmaceutically acceptable salt to a subject in need thereof:

OG Complex Work Unit Drawing
wherein R1is C5-12aryl, or C1-12 alkyl unsubstituted or substituted with C5-12 aryl, and
the aryl is unsubstituted or substituted with at least one non-hydrogen substituent selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, hydroxyl, and halogen;
R2 is hydrogen, or C1-12 alkyl unsubstituted or substituted with at least one non-hydrogen substituent selected from the group consisting of C3-10 cycloalkyl, C5-12 aryl, C5-12 heteroaryl, hydroxyl, halogen, and C1-4 alkoxycarbonyl, and
the aryl and heteroaryl are unsubstituted or substituted with at least one non-hydrogen substituent selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, hydroxyl, and halogen;
R3is hydrogen, C5-12 aryl, or C1-12 alkyl unsubstituted or substituted with at least one non-hydrogen substituent selected from the group consisting of C3-10 cycloalkyl, C5-12 aryl, C5-12 heteroaryl, hydroxyl, halogen, and C1-4 alkoxycarbonyl, and
the aryl and heteroaryl are unsubstituted or substituted with at least one non-hydrogen substituent selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, hydroxyl, and halogen; and
R4 is C3-10 cycloalkyl, C5-12 alkoxy, C5-12 aryl, C5-12 heteroaryl, hydroxyl, halogen, or C1-12 alkyl unsubstituted or substituted with at least one non-hydrogen substituent selected from the group consisting of C3-10 cycloalkyl, C5-12 aryl, C5-12 heteroaryl, hydroxyl, halogen, and C1-4 alkoxycarbonyl, and
the aryl and heteroaryl are unsubstituted or substituted with at least one non-hydrogen substituent selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, hydroxyl, and halogen.