Cycloalkane-1,3-diamine derivative

Inventors

Yoshikawa, Kenji • Haginoya, Noriyasu • Hamada, Tomoaki • Kanada, Ryutaro • Watanabe, Jun • Kagoshima, Yoshiko • TOKUMARU, Eri • Murata, Kenji • Baba, Takayuki • KITAGAWA, Mayumi • Kurimoto, Akiko • Numata, Masashi • Shiroishi, Machiko • Shinozaki, Taeko

Assignees

Daiichi Sankyo Co Ltd

Abstract

The present invention provides a compound or a pharmaceutically acceptable salt thereof having an inhibitory action on the interaction between menin and an MLL protein. The compound represented by the formula (1) or a pharmaceutically acceptable salt thereof.wherein, in the formula (1), the dotted circle, R1, R2, R3, R4, R5, R6, R7, R8, Ring Q1, W, m and n are each as defined in the description.

Core Innovation

The patent discloses compounds represented by formula (1), or pharmaceutically acceptable salts thereof, where the dotted circle indicates that the ring is aromatic and connectivity is defined by attachment sites marked with * and **. The scaffold is built from variable groups R1 through R12, ring fragments Ring Q1, Ring Q2, and Ring Q3, and linker options W, Y, and Z, with X defined as CH or a nitrogen atom.

The structural definition constrains R1 and R2 to hydrogen or a C1-6 alkyl group, and constrains R3 and R4 to selected combinations of hydrogen, hydroxy, halogen, C1-6 alkoxy, di(C1-6 alkyl) carbamoyl, or oxazolyl. R5 and R6 are likewise limited to defined substituent classes, and R7 and R8 taken together with the carbon atoms to which they are bonded form any of formulas (2A) to (2C). Ring Q1, Ring Q2, and Ring Q3 are selected from enumerated aromatic, heteroaromatic, saturated heterocycle, cycloalkane, cycloalkene, and bicyclic ring classes with optional substituents from Groups A through F.

The scaffold further defines W as formula (4A) or (4B), Y as a single bond or an oxygen atom, and Z as a single bond, oxygen atom, —NH—, —SO2—, a C1-6 alkylene group, or specified *-bonded linkage patterns. The examples emphasize thieno[2,3-d]pyrimidinyl and cyclopentyl or cyclopentan-1-ol based compounds, including stereochemically defined members, hydrochloride salt forms, and other pharmaceutically acceptable salts.

Claims Coverage

The consolidated claim coverage includes a broad independent claim to a compound represented by formula (1) or a pharmaceutically acceptable salt thereof, and a narrower independent claim to specific stereochemically defined compounds and pharmaceutically acceptable salts. In total, the claims center on the formula (1) scaffold with constrained substituent, ring, and linker options, plus an enumerated compound set.

The claims cover a broadly defined formula (1) scaffold with explicit aromatic-ring connectivity, constrained substituent definitions, selected ring fragments, and defined linker options. In portions that include the narrower independent claim, the coverage is further limited to a listed set of specific stereodefined compounds and salts.

Stated Advantages

Documented Applications