Thienopyrimidine inhibitors of atypical protein kinase C
Inventors
Dorsey, Bruce D. • Learn, Keith S. • Morris, Emma L. • Ott, Gregory R. • Roffey, Jonathan R. A. • Soudy, Christelle N. • Wagner, Jason C.
Assignees
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Publication Number
US-10954251-B2
Publication Date
2021-03-23
Expiration Date
Abstract
The present application provides a compound of formula (I) or a salt thereof, wherein R1, R2, R3, R4, R5, R6, A, G, M, Q and X are as defined herein. A compound of formula (I) and its salts have a PKC inhibitory activity, and may be used to treat proliferative disorders.
Core Innovation
The invention relates to a method of treating a cancer in a subject in need thereof by administering an effective amount of a compound of Formula I or a pharmaceutically acceptable salt form thereof. Formula I is defined by substituent-variable selections for R1, R2, R3, R4, R5, R6, R7, R8, R11, and R12 through R15, with additional definitions for R19, R20, R22, R23, R24, and R30. The compound scope includes thieno[3,2-d]pyrimidine and related fused heteroaromatic ring variants, including benzo[4,5]thieno[2,3-d]pyrimidine derivatives and pyrido[3',2':4,5]thieno[3,2-d]pyrimidine derivatives.
The claimed treatment is defined as acute diminishment or alleviation of at least one symptom or characteristic associated or caused by the cancer being treated. The cancer types expressly listed include squamous cell carcinoma, leukemia, prostate cancer, non-Hodgkin's lymphoma, endometrial cancer, lung cancer, and breast cancer. The disclosed substituent classes include alkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, alkynyl, halogen, and heteroatom-containing substituent patterns.
The examples include thieno[3,2-d]pyrimidine-based diamine structures, pyridinyl substituents, and variable amine, amide, and side-chain stereochemistry. The document also describes chiral and achiral compounds, carboxamide and ester variants, and substituent variation through piperazine, piperidine, pyrrolidine, diazepane, azetidine, and other nitrogen-containing side chains, together with analytical characterization data for labeled example compounds.
Claims Coverage
The claim coverage centers on one independent claim covering a method of treating a cancer by administering an effective amount of a compound of Formula I or a pharmaceutically acceptable salt form thereof. The inventive features are the Formula I substituent framework, the defined meaning of treating a cancer, and the specified cancer types, with dependent claims narrowing selected substituent variables and cancer subtype.
Cancer treatment by administering Formula I compounds
A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula I or a pharmaceutically acceptable salt form thereof.
Defined Formula I substituent framework
Formula I is defined by the stated substituent-variable selections for R1, R2, R3, R4, R5, R6, R7, R8, R11, and R12 through R15, together with the definitions of R19, R20, R22, R23, R24, and R30.
Treating defined as acute diminishment or alleviation
Treating a cancer refers to acute diminishment or alleviation of at least one symptom or characteristic associated or caused by the cancer being treated.
Specified cancer types for treatment
The cancer is selected from squamous cell carcinoma, leukemia, prostate cancer, non-Hodgkin's lymphoma, endometrial cancer, lung cancer, and breast cancer.
R11 hydrogen constraint
Wherein R11 is H.
R12-R15 restricted to hydrogen or halogen
Wherein R12, R13, R14, and R15 are independently chosen from H and halogen.
Non-small cell lung cancer limitation
Wherein the lung cancer is non-small cell lung cancer.
Overall, the claims cover administering an effective amount of a Formula I compound or pharmaceutically acceptable salt for treating the listed cancers, with treating defined as acute diminishment or alleviation of at least one cancer-associated symptom or characteristic. The scope is further narrowed by specific substituent constraints, including R11 as H and R12 through R15 as H or halogen.
Stated Advantages
Acute diminishment or alleviation of at least one symptom or characteristic associated or caused by the cancer being treated.
Provides a method of treating a cancer in a subject by acute diminishment or alleviation of at least one symptom or characteristic associated or caused by the cancer.
Documented Applications
Treating cancer in a subject in need thereof, including squamous cell carcinoma, leukemia, prostate cancer, non-Hodgkin's lymphoma, endometrial cancer, lung cancer, and breast cancer.
Treating lung cancer specifically as non-small cell lung cancer.
Treating cancer as squamous cell carcinoma.
Treatment of squamous cell carcinoma, leukemia, prostate cancer, non-Hodgkin's lymphoma, endometrial cancer, lung cancer, and breast cancer in a subject in need thereof.
Synthetic and analytical examples of substituted thieno[3,2-d]pyrimidine and related fused derivatives, including labeled example compounds with LCMS, retention time, and 1H NMR data.
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