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.
Palladium-catalyzed chelation-assisted aromatic C-H nitration: Regiospecific synthesis of nitroarenes free from the effect of the orientation rules
Zhang, Wei,Lou, Shaojie,Liu, Yunkui,Xu, Zhenyuan
, p. 5932 - 5948 (2013/07/26)
A palladium-catalyzed chelation-assisted ortho-nitration of aryl C-H bond is described. A range of azaarenes such as 2-arylquinoxalines, pyridines, quinoline, and pyrazoles were nitrated with excellent chemo- and regioselectivity. Using the O-methyl oximyl group as a removable directing group, the regiospecific synthesis of a variety of o-nitro aryl ketones was achieved starting from aryl ketones via a three-step process involving the Pd-catalyzed ipso-nitration of C-H bond as a key step. Mechanistic investigations support a silver-mediated radical mechanism involving Pd((II/III) and/or Pd(II/IV) catalytic cycles under oxidizing conditions.
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.
Regiospecific synthesis of nitroarenes by palladium-catalyzed nitrogen-donor-directed aromatic C-H nitration
Liu, Yun-Kui,Lou, Shao-Jie,Xu, Dan-Qian,Xu, Zhen-Yuan
, p. 13590 - 13593 (2011/03/18)
Nitration of N-heteroaromatics: The first example of palladium-catalyzed direct ortho-nitration of aryl C-H bonds is described. A range of azaarenes, such as 2-arylquinoxalines, pyridines, pyrazoles, and O-methyl oximes, were nitrated with excellent chemo- and regioselectivity (see scheme; DCE=1,2-dichloroethane). Preliminary mechanistic investigations support a silver-mediated radical mechanism involving palladium(II/III) and/or palladium(II/IV) catalytic cycles under oxidizing conditions. Copyright
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.
4(1H)-Oxocinnoline-3-carboxylic acid derivatives
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, (2008/06/13)
Amide and ester derivatives of substituted-4(1H)-oxocinnoline-3-carboxylic acids have antibacterial activity and are useful for inhibiting the growth of disease causing bacteria.
