Pyrrolopyrazole derivative

Inventors

Namiki, Hidenori • Saitou, Masanori • Matsui, Satoshi • Shibata, Yoshihiro • Kawamoto, Yoshito • ICHIKAWA, Rie • YOSHIHAMA, Yohei • OTSUKA, Akiko

Assignees

Daiichi Sankyo Co Ltd

Abstract

The present invention provides a low molecular compound that inhibits phosphatidylserine synthase 1 or a pharmaceutically acceptable salt thereof, a pharmaceutical containing thereof, and a therapeutic agent for cancer having a suppressed function of phosphatidylserine synthase 2. The compound represented by formula (1) or a pharmaceutically acceptable salt thereof, wherein R1, ring Q1, ring Q2, and W are as defined in the specification.

Core Innovation

The invention is directed to compounds represented by general formula (1) or pharmaceutically acceptable salts thereof, including tetrahydropyrrolo[3,4-c]pyrazol-1,3-benzoxazol-2(3H)-one derivatives and benzoxazolyl-tetrahydropyrrolo[3,4-c]pyrazol-6-one derivatives. The structural framework is defined by restricted options for R1, ring Q1, ring Q2, ring Q3, W, Y, R2, R3, and R4, with ring Q1 expressed by formulas (2A) to (2C) and substituent groups restricted to enumerated halogen, alkyl, halogenoalkyl, halogenoalkoxy, cycloalkyl, alkylsulfanyl, and alkylsulfonyl options.

The compound represented by formula (1) may include its tautomer represented by formula (1′) in any ratio, including 100% for either formula (1) or formula (1′). The disclosure also includes named stereodefined 7-substituted 1,3-benzoxazol-2(3H)-one embodiments, including formula (13A) and the related form represented by formula (13B), with explicit tautomer exclusion in some embodiments and a 2-methylpropane-2-amine salt form in others.

The disclosure further includes crystalline embodiments of the 2-methylpropane-2-amine salt of the specified benzoxazol-2(3H)-one derivative, characterized by at least five powder X-ray diffraction peaks at stated 2θ values measured with copper Kα radiation. The provided material also recites phosphatidylserine synthase 1 inhibitor embodiments and states that some compounds are described in relation to cancer treatment.

Claims Coverage

The consolidated claim coverage includes one broad independent claim directed to a general formula (1) compound or pharmaceutically acceptable salt thereof, with multiple dependent refinements. Across the provided items, the inventive features center on restricted structural variables, optional tautomer inclusion in specified ratios, specific named benzoxazol-2(3H)-one derivatives, a 2-methylpropane-2-amine salt, crystalline characterization by powder X-ray diffraction peak positions, and stated phosphatidylserine synthase 1 inhibition context.

Overall, the claim coverage is centered on a general-formula compound family with tightly restricted structural variables and optional tautomer inclusion, then narrows to specific stereodefined benzoxazol-2(3H)-one derivatives, a 2-methylpropane-2-amine salt, crystalline forms defined by PXRD peak constraints, and a phosphatidylserine synthase 1 inhibitor context.

Stated Advantages

Documented Applications