N-pyridinyl acetamide derivatives as Wnt signalling pathway inhibitors
Inventors
Bhamra, Inder • Mathieson, Michael • Donoghue, Craig • Testar, Richard
Assignees
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Publication Number
US-10793562-B2
Publication Date
2020-10-06
Expiration Date
Abstract
Disclosed are compounds useful as inhibitors of the Wnt signalling pathway. Specifically, inhibitors of Porcupine (Porcn) are contemplated by the invention. In addition, the invention contemplates processes to prepare the compounds and uses of the compounds. The compounds of the invention may therefore be used in treating conditions mediated by the Wnt signalling pathway, for example, in treating cancer, sarcoma, melanoma, skin cancer, haematological tumors, lymphoma, carcinoma, and leukemia; or enhancing the effectiveness of an anti-cancer treatment.
Core Innovation
The invention relates to compounds of formula (VIa) and formula (Ma) together with a pharmaceutically acceptable excipient. The compounds include substituted or unsubstituted heteroaryl ring systems with defined heterocyclic ring sizes and substitution options, including an unsubstituted azaindole in formula (Ma), and the disclosed subject matter is directed to Wnt signalling pathway-mediated conditions.
The disclosed chemistry defines N-pyridinyl acetamide derivative inhibitors and substituted acetamide derivatives containing fused pyrrolo/pyridopyrimidine/pyrazolopyridine cores. The structures are further defined by heteroaryl fragments, ring-size variables, and allowed substituents, with pharmaceutically acceptable salts and pharmaceutically acceptable excipients included in the definitions.
The invention addresses treatment of a condition mediated by the Wnt signalling pathway by administering a therapeutic amount of the pharmaceutical formulation. The condition is selected from cancer and related disease categories, and the compounds are intended to modulate or inhibit the Wnt signalling pathway via porcupine (Porcn) inhibition.
Claims Coverage
The independent claims cover four inventive features: a pharmaceutical formulation of formula (VIa), a treatment method using formula (VIa), a compound of formula (Ma), and a treatment method using formula (Ma). The claim scope is defined by heteroaryl ring variables, substituent lists, and constrained variables R3, R4, and n.
Pharmaceutical formulation of formula (VIa)
A pharmaceutical formulation comprising a compound of formula (VIa) and a pharmaceutically acceptable excipient, with het1 as a substituted or unsubstituted 9 membered bicyclic heteroaryl group, het2 as an aromatic, saturated or unsaturated 6 membered heterocyclic ring, and R3, R4, n, and multiple labeled R substituents defined by enumerated options.
Wnt-signalling-pathway mediated treatment using formula (VIa)
A method of treatment of a condition mediated by the Wnt signalling pathway selected from cancer, sarcoma, melanoma, skin cancer, haematological tumours, lymphoma, carcinoma, and leukaemia, by administering a therapeutic amount of a pharmaceutical formulation comprising a compound of formula (VIa) and a pharmaceutically acceptable excipient.
Compound of formula (Ma)
A compound of formula (Ma), wherein het1 represents unsubstituted azaindole, het2 is a 5 or 6 membered heterocyclic ring, het3 is a 6 membered heterocyclic ring, and R3, R4, n, and multiple labeled R substituents are defined by enumerated options.
Wnt-signalling-pathway mediated treatment using formula (Ma)
A method of treatment of a condition mediated by the Wnt signalling pathway selected from cancer, sarcoma, melanoma, skin cancer, haematological tumours, lymphoma, carcinoma, and leukaemia, by administering a therapeutic amount of a compound of formula (Ma) and a pharmaceutically acceptable excipient.
The claims cover defined compounds of formula (VIa) and formula (Ma), pharmaceutical formulations containing those compounds with pharmaceutically acceptable excipients, and methods of treating Wnt-signalling-pathway-mediated conditions by administering those formulations or compounds.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating a condition mediated by the Wnt signalling pathway selected from cancer, sarcoma, melanoma, skin cancer, haematological tumours, lymphoma, carcinoma, and leukaemia by administering a therapeutic amount of a pharmaceutical formulation comprising a compound of formula (VIa) and a pharmaceutically acceptable excipient.
Treating a condition mediated by the Wnt signalling pathway selected from cancer, sarcoma, melanoma, skin cancer, haematological tumours, lymphoma, carcinoma, and leukaemia by administering a therapeutic amount of a compound of formula (Ma) and a pharmaceutically acceptable excipient.
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