| 摘要 |
[Problem];A compound which is useful as an agent for treating breast cancer is provided.;[Means for Solution];As a result of intensive studies on a compound having a Complex I inhibitory effect and an AMPK activation effect, the present inventors found that a bicyclic nitrogen-containing aromatic heterocyclic amide compounds of the present invention has an excellent Complex I inhibitory effect and the AMPK activation effect, furthermore, has a cell proliferation inhibitory effect with respect to not only human PIK3CA mutation-positive breast cancer cell lines in which MCT4 is not expressed but also human breast cancer cell lines which do not have mutation of PIK3CA in which MCT4 is not expressed, and exhibits an anti-tumor effect in a human PIK3CA mutation-positive breast cancer cell line MDA-MB-453 cell in a cancer-bearing mouse in which the MCT4 is not expressed, thereby completing the present invention. A bicyclic nitrogen-containing aromatic heterocyclic amide compound of the present invention can be used as an agent for treating breast cancer, in particular, breast cancer in which the MCT4 is not expressed, and among others, PIK3CA mutation-positive breast cancer in which the MCT4 is not expressed. |
| 主权项 |
1. A compound of the formula (I) or a salt thereof: wherein R1 is aryl or monocyclic nitrogen-containing heteroaryl, optionally substituted with at least one substituent selected from the group consisting of halogen, lower alkyl, —O-lower alkyl, halogeno-lower alkyl, —O-halogeno-lower alkyl, —CN, dimethylamino, and cycloalkyl; wherein X is CH, N, or C; the following:is a single bond if X is CH or N or is a double bond if X is C;
Y is a cyclic group of any of formulae Y-1 to Y-11: Y1 is CRh or N; Y2 is CRi or N; Y1 and Y2 are not both N; Ra, Rh, and Ri are each independently H or halogen; Rb is H or lower alkyl; Rc is lower alkyl; Y3 is CH or N; Rd and Re are each independently H or lower alkyl; Rf is H or lower alkyl; Y4 is P or S; Y5 is CH or N; Y6 is CH or N; Rg is H or lower alkyl; R2 is H or lower alkyl; and either R3 and R4 are each independently H, halogen, lower alkyl, —O-lower alkyl, halogeno-lower alkyl, —O-halogeno-lower alkyl, cycloalkyl, or —CN, or R3 and R4 form 2,2-difluoro-1,3-benzodioxole with the benzene ring to which R3 and R4 are bonded. |
