23082-51-1Relevant articles and documents
INHIBITORS OF KRAS G12C
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, (2015/04/28)
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
Discovery of a novel series of 4-quinolone JNK inhibitors
Gong, Leyi,Tan, Yun-Chou,Boice, Genevieve,Abbot, Sarah,McCaleb, Kristen,Iyer, Pravin,Zuo, Fengrong,Porto, Joseph Dal,Wong, Brian,Jin, Sue,Chang, Alice,Tran, Patricia,Hsieh, Gary,Niu, Linghao,Shao, Ada,Reuter, Deborah,Lukacs, Christine M.,Ursula Kammlott,Kuglstatter, Andreas,Goldstein, David
, p. 7381 - 7387 (2013/02/21)
A novel series of highly selective JNK inhibitors based on the 4-quinolone scaffold was designed and synthesized. Structure based drug design was utilized to guide the compound design as well as improvements in the physicochemical properties of the series. Compound (13c) has an IC50 of 62/170 nM for JNK1/2, excellent kinase selectivity and impressive efficacy in a rodent asthma model.
Dihydroquinone and dihydronaphthridine inhibitors of JNK
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Page/Page column 39, (2008/12/09)
Compounds of formula I are effective modulators of JNK: wherein X is CR11 or N;Y is —C(O)R3, 5-membered heteroaryl, or 5-membered heterocyclyl;Z is phenyl, cycloalkyl, heterocyclyl or heteroaryl, and is substituted with R1 and R2;R1 and R2 are each independently H, halo, CN, lower alkyl, or —Y1—Y2—Y3—R8, or R1 and R2 together form —O(CH2)nO—, where n is 1 or 2; Y1 is —O—, —C(O)—, —C(O)O—, —C(O)NR9—, —NR9C(O)—, —S—, —SO2—, or a bond;Y2 is cycloalkylene, heterocycloalkylene, lower alkylene or a bond;Y3 is —O—, —C(O)—, —C(O)O—, —C(O)NR9—, —NR9C(O)—, —SO2—, or a bond;R8 is H, lower alkyl, lower alkoxy, cycloalkyl, heterocycloalkyl, or —NR9R10, wherein R8 other than H is optionally substituted with lower alkyl, halo, —CF3, or —OH; R9 and R10 are each independently H or lower alkyl;R3 is OH, lower alkyl, lower alkoxy, (lower alkoxy)-lower alkoxy, or —NR9R10;R4 is lower alkyl, phenyl, heterocyclyl, cycloalkyl, heterocycloalkyl, or heteroaryl, and is optionally substituted with lower alkyl, hydroxy, lower alkoxy, halo, nitro, amino, cyano, or halo-lower alkyl;R5 and R6 are each independently H, halo, cyano, lower alkyl, —CF3, lower alkoxy, —OCHF2, —NO2, or —NR9R10;R7 is H, F, Cl, methyl, or OH;R11 is H, lower alkyl, lower cycloalkyl, or phenyl;or a pharmaceutically acceptable salt thereof.
