Ras/raf binding inhibitor compound
AssigneeNational University Corporation Kobe University
InventorsFumi SHIMA, Yoko YOSHIKAWA, Shigeyuki MATSUMOTO, Yoshiteru MAKINO, Hirokazu KUBOTA, Hitomi YUKI, Takashi KUMASAKA, Takashi KAWAMURA, Ko KIKUZATO
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Abstract
The object of the present invention is to provide a Ras/Raf binding inhibitory compound exhibiting a Ras/Raf signaling inhibitory action even against cancer cells bearing proved drug resistance and those with a variety of Ras mutations. The Ras/Raf binding inhibitory compound of the present invention is represented by the following formula (I) (wherein A, B, X, and R1 to R4 are as defined in the present description).
Claims15
A compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof, or an isomer thereof:
- wherein
- A represents a benzene ring or a pyridine ring,
- B represents a C6-10 aryl group, or a heteroaryl group containing 1 to 4 atoms selected from N, S and O,
- X represents —NR5—,
- R1 represents H, a C1-6 alkyl group optionally substituted with a NHCOCH3 group, or halogen,
- R2, R3 and R4, which are the same or different, each represent (provided that at least any one of them is not H)
- H;
- C1-6 alkyl-SO2—;
- cyano;
- halogen;
- nitro;
- azide;
- a —CO—R11 group (wherein the R1 represents
- OH,
- an R12 group (wherein the R12 group represents a heterocyclyl group containing 1 or 2 atoms (groups) selected from N, S, SO, SO2 and O, and optionally having a substituent),
- NH2, NHR12, or N(R12)R12, or
- C6-10 arylamino);
- an —O—CH2—CO—R11 group;
- a C1-6 alkyl group optionally having a substituent
- (wherein the substituent represents
- —CONH2,
- an R12 group,
- OH,
- —NR13R14 (wherein the R13 represents C1-6 alkyl-SO2—, C1-6 alkyl-CO—, or an R12 group, and the R14 represents H, a C1-6 alkyl group, or an R12 group),
- R12—CO—, or
- R12—C1-6 alkyl-CONH—);
- an —OR15 group
- (wherein the R15 represents
- H,
- a C1-6 alkyl group optionally having a substituent
- (wherein the substituent represents OH, C1-6 alkoxy, C6-10 aryl, C6-10 aryloxy, R12, cyano, C1-6 alkyl-SO2—, or methylsulfinyl),
- C1-6 alkyl-SO2—, or
- a heteroaryl group containing 1 to 4 atoms selected from N, S and O);
- an —NR16R17 group
- (wherein the R16 and R17, which are the same or different, each represent
- H,
- C1-6 alkyl-CO—,
- an R12 group, or
- R12—C1-6 alkyl-CO—, or R16 and R17 may form an R12 group, together with N);
- a C6-10 aryl group optionally having a substituent
- (wherein the substituent represents C6-10 aryloxy, a heteroaryl group containing 1 to 4 atoms selected from N, S and O, and optionally having a substituent, or phenyl optionally annelated with R12);
- a heteroaryl group containing 1 to 4 atoms selected from N, S and O, and optionally having a substituent;
- or
- —(CH═CH)—R18 (wherein the R18 represents —CO—R19 or —SO2—R19, and the R19 represents NH2, or an R12 group);
- wherein
- R5 represents C1-6 alkyl, —COR6, —COOR6, —CONR6R7, —SOnR6, or SOnNR6R7, wherein n represents 0, 1 or 2, and
- R6 and R7, which are the same or different, each represent H, a C1-6 alkyl group, or a C6-10 aryl group, and the wavy line represents a geometrical isomer.
Dependencies are inferred from the claim text.