Fused tricyclic ring derivatives as Src homology-2 phosphate inhibitors

Inventors

Fu, Jiping • Lou, Yan • HE, Yigang

Assignees

Nikang Therapeutics Inc

Abstract

The present disclosure provides certain fused tricyclic ring derivatives that are Src Homology-2 phosphatase (SHP2) inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of SHP2. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Core Innovation

The disclosure describes substituted heterocyclic compounds defined by Formula (A) and related formulae, including fused pyrido[3,2-b]pyrrolo[1,2-d][1,4]oxazine, pyridyl–oxazine, and spirocyclic amine structures. The compounds are characterized by variable substituent selections, stereochemically defined examples, and thioether-linked heteroaryl motifs, including pyrazine and pyrazole fragments. The text also describes intermediates and named examples with fluorine-, iodine-, hydroxy-, ether-, carbonitrile-, carbamate-, and thio-containing variants.

The described chemical space includes defined choices for X, Y, Z, and R, with X limited to halogen or thiol, Y limited to null, CH2, O, or C(=O)/C≡O as written in the inputs, Z limited to CH2 or O, and R selected from null, hydrogen, alkyl, alkoxy, hydroxyl, methoxyalkoxy, heterocyclylmethyloxy, and cycloalkylmethoxymethyl. The disclosure further includes formulae and ring definitions involving Q1, Q2, L, ring C, ring D, and ring E, together with pharmaceutically acceptable salts. Representative embodiments are reported as stereochemically defined members of the claimed scaffold.

The document also presents synthetic intermediates and product elaborations associated with the same scaffold, including iodinated and fluorinated oxazine intermediates, protected ether substituents, and thioether formation to pyrazine derivatives. Multiple examples are identified by numbering or naming, and the text references analytical characterization such as MS values and specific stereochemical designations. Across the examples, the common theme is elaboration of a fused heteroaromatic core into structurally defined derivatives within the stated formula constraints.

Claims Coverage

The independent claim coverage centers on one Formula (A) scaffold with four inventive variables: X, Y, Z, and R. Across the input items, the family is consistently narrowed by dependent claims that select halogen or iodine/bromine for X, fix Y or Z to O in specific cases, and identify at least one stereochemically defined example compound.

Overall, the claim set defines a Formula (A) compound family by restricting X, Y, Z, and R to stated options, with dependent claims further narrowing X to halogen or iodine/bromine, fixing Y or Z to O, and providing a stereochemically defined named example.

Stated Advantages

Documented Applications