Novel Compounds as CDK2 Inhibitors for Treating Cancer DOI Creative Commons
Ram W. Sabnis

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 16(1), P. 14 - 15

Published: Dec. 10, 2024

InfoMetricsFiguresRef. ACS Medicinal Chemistry LettersASAPArticle This publication is free to access through this site. Learn More CiteCitationCitation and abstractCitation referencesMore citation options ShareShare onFacebookX (Twitter)WeChatLinkedInRedditEmailJump toExpandCollapse Patent HighlightDecember 10, 2024Novel Compounds as CDK2 Inhibitors for Treating CancerClick copy article linkArticle link copied!Ram W. Sabnis*Ram SabnisSmith, Gambrell & Russell LLP, 1105 Peachtree Street NE, Suite 1000, Atlanta, Georgia 30309, United States*E-mail: [email protected]More by Ram Sabnishttps://orcid.org/0000-0001-7289-0581Open PDFACS LettersCite this: Med. Chem. Lett. 2024, XXXX, XXX, XXX-XXXClick citationCitation copied!https://pubs.acs.org/doi/10.1021/acsmedchemlett.4c00574https://doi.org/10.1021/acsmedchemlett.4c00574Published December 2024 Publication History Received 24 November 2024Published online 10 2024editorialPublished American Chemical Society. available under these Terms of Use. Request reuse permissionsAbstractClick section linkSection copied!High Resolution ImageDownload MS PowerPoint SlideProvided herein are novel compounds inhibitors, pharmaceutical compositions, use such in treating cancer, processes preparing compounds.This licensed personal The PublicationsPublished Society Important Compound Classes TitleCyclin-Dependent Kinase (CDK2) NumberWO 2024/171094 A1URL: https://patents.google.com/patent/WO2024171094A1/en DateAugust 22, Priority ApplicationsUS 63/485,709 US 63/580,277 DatesFebruary 17, 2023, September 1, 2023 InventorsBriner, K.; Chen, X.; Joseph, S.; Rauniyar, V.; Zecri, F. Assignee CompanyNovartis AG, Switzerland Disease AreaCancer Biological TargetCDK2 SummaryCyclic-dependent kinase 2 a serine/threonine that regulates the mammalian cell cycle. After binding cyclin-E1, cyclin-E2, cyclin-A1, or cyclin-A2, activated CDK2–cyclin complex phosphorylates variety cellular substrates. its activity often dysregulated human cancers. One dysregulation mechanism involves amplification overexpression which leads hyperactivation promotes proliferation. Cyclin-E1 also associated with poor prognosis across In many cancers, besides radiation chemotherapy, there no targeted therapy patients. Thus, development agent against would potentially benefit cancer patients.The present application describes series inhibitors treatment cancer. Further, discloses compounds, their preparation, use, composition, treatment. DefinitionsY1 = bond CH2;Y2 bond, O, NR5 CR6R7;R1 R2 H, halo, C1–C6alkyl C1–C6haloalkyl;R3 hydroxy, C1–C6haloalkyl;R4 C1–C6haloalkyl;ring A 5 membered heteroaryl comprising 1 3 heteroatoms selected from N, O S, said being substituted 0 substituents RA;m 5; n 3. Key Structures AssayThe biochemical assay was performed. described were tested ability inhibit CDK2. IC50 values (μM) shown following table. DataThe table below shows representative inhibition biological data obtained testing examples. ClaimsTotal claims: 49Compound 42Pharmaceutical composition 1Method 3Method modulation 1Use compound Recent Review ArticlesSee refs (1−5).Author InformationClick copied!Corresponding AuthorRam Sabnis, Smith, States, https://orcid.org/0000-0001-7289-0581, Email: protected]NotesThe author declares competing financial interest.ReferencesClick copied! references other publications. 1Patel, D. A.; Patel, S. H. Advances synthesis evaluation therapy. Bioorg. 143, 107045, DOI: 10.1016/j.bioorg.2023.107045 Google ScholarThere corresponding record reference.2Gerosa, R.; De Sanctis, Jacobs, F.; Benvenuti, C.; Gaudio, M.; Saltalamacchia, G.; Torrisi, Masci, Miggiano, Agustoni, Pedrazzoli, P.; Santoro, Zambelli, A. Cyclin-dependent others CDK (CDKi) breast cancer: clinical trials, current impact, future directions. Crit. Rev. Oncol. Hematol. 196, 104324, 10.1016/j.critrevonc.2024.104324 reference.3Morrison, L.; Loibl, Turner, N. C. CDK4/6 inhibitor revolution – game-changing era Nat. Clin. 21, 89– 105, 10.1038/s41571-023-00840-4 reference.4Areewong, Suppramote, O.; Prasopporn, Jirawatnotai, Exploiting acquired vulnerability develop treatments cholangiocarcinoma. Cancer Cell Int. 24, 362, 10.1186/s12935-024-03548-2 reference.5Sabnis, R. Sulfonylamide Cancer. 2021, 12, 1528– 1529, 10.1021/acsmedchemlett.1c00471 reference.Cited By Click copied!This has not yet been cited publications.Download PDFFiguresReferences Get e-AlertsGet e-AlertsACS copied!https://doi.org/10.1021/acsmedchemlett.4c00574Published permissionsArticle Views225Altmetric-Citations-Learn about metrics closeArticle Views COUNTER-compliant sum full text downloads since 2008 (both PDF HTML) all institutions individuals. These regularly updated reflect usage leading up last few days.Citations number articles citing article, calculated Crossref daily. Find more information counts.The Altmetric Attention Score quantitative measure attention research received online. Clicking on donut icon will load page at altmetric.com additional details score social media presence given article. how calculated.Recommended Articles FiguresReferencesAbstractHigh SlideReferences There reference.

Language: Английский

Novel Bicyclic Amines as CDK2 Inhibitors for Treating Metastatic Breast Cancer or Metastatic Lung Cancer DOI Creative Commons
Ram W. Sabnis

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: 16(2), P. 198 - 199

Published: Jan. 16, 2025

Provided herein are novel bicyclic amines as CDK2 inhibitors, pharmaceutical compositions, use of such compounds in treating metastatic breast cancer or lung and processes for preparing compounds.

Language: Английский

Citations

0
Novel Compounds as CDK2 Inhibitors for Treating Cancer DOI Creative Commons
Ram W. Sabnis

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 16(1), P. 14 - 15

Published: Dec. 10, 2024

InfoMetricsFiguresRef. ACS Medicinal Chemistry LettersASAPArticle This publication is free to access through this site. Learn More CiteCitationCitation and abstractCitation referencesMore citation options ShareShare onFacebookX (Twitter)WeChatLinkedInRedditEmailJump toExpandCollapse Patent HighlightDecember 10, 2024Novel Compounds as CDK2 Inhibitors for Treating CancerClick copy article linkArticle link copied!Ram W. Sabnis*Ram SabnisSmith, Gambrell & Russell LLP, 1105 Peachtree Street NE, Suite 1000, Atlanta, Georgia 30309, United States*E-mail: [email protected]More by Ram Sabnishttps://orcid.org/0000-0001-7289-0581Open PDFACS LettersCite this: Med. Chem. Lett. 2024, XXXX, XXX, XXX-XXXClick citationCitation copied!https://pubs.acs.org/doi/10.1021/acsmedchemlett.4c00574https://doi.org/10.1021/acsmedchemlett.4c00574Published December 2024 Publication History Received 24 November 2024Published online 10 2024editorialPublished American Chemical Society. available under these Terms of Use. Request reuse permissionsAbstractClick section linkSection copied!High Resolution ImageDownload MS PowerPoint SlideProvided herein are novel compounds inhibitors, pharmaceutical compositions, use such in treating cancer, processes preparing compounds.This licensed personal The PublicationsPublished Society Important Compound Classes TitleCyclin-Dependent Kinase (CDK2) NumberWO 2024/171094 A1URL: https://patents.google.com/patent/WO2024171094A1/en DateAugust 22, Priority ApplicationsUS 63/485,709 US 63/580,277 DatesFebruary 17, 2023, September 1, 2023 InventorsBriner, K.; Chen, X.; Joseph, S.; Rauniyar, V.; Zecri, F. Assignee CompanyNovartis AG, Switzerland Disease AreaCancer Biological TargetCDK2 SummaryCyclic-dependent kinase 2 a serine/threonine that regulates the mammalian cell cycle. After binding cyclin-E1, cyclin-E2, cyclin-A1, or cyclin-A2, activated CDK2–cyclin complex phosphorylates variety cellular substrates. its activity often dysregulated human cancers. One dysregulation mechanism involves amplification overexpression which leads hyperactivation promotes proliferation. Cyclin-E1 also associated with poor prognosis across In many cancers, besides radiation chemotherapy, there no targeted therapy patients. Thus, development agent against would potentially benefit cancer patients.The present application describes series inhibitors treatment cancer. Further, discloses compounds, their preparation, use, composition, treatment. DefinitionsY1 = bond CH2;Y2 bond, O, NR5 CR6R7;R1 R2 H, halo, C1–C6alkyl C1–C6haloalkyl;R3 hydroxy, C1–C6haloalkyl;R4 C1–C6haloalkyl;ring A 5 membered heteroaryl comprising 1 3 heteroatoms selected from N, O S, said being substituted 0 substituents RA;m 5; n 3. Key Structures AssayThe biochemical assay was performed. described were tested ability inhibit CDK2. IC50 values (μM) shown following table. DataThe table below shows representative inhibition biological data obtained testing examples. ClaimsTotal claims: 49Compound 42Pharmaceutical composition 1Method 3Method modulation 1Use compound Recent Review ArticlesSee refs (1−5).Author InformationClick copied!Corresponding AuthorRam Sabnis, Smith, States, https://orcid.org/0000-0001-7289-0581, Email: protected]NotesThe author declares competing financial interest.ReferencesClick copied! references other publications. 1Patel, D. A.; Patel, S. H. Advances synthesis evaluation therapy. Bioorg. 143, 107045, DOI: 10.1016/j.bioorg.2023.107045 Google ScholarThere corresponding record reference.2Gerosa, R.; De Sanctis, Jacobs, F.; Benvenuti, C.; Gaudio, M.; Saltalamacchia, G.; Torrisi, Masci, Miggiano, Agustoni, Pedrazzoli, P.; Santoro, Zambelli, A. Cyclin-dependent others CDK (CDKi) breast cancer: clinical trials, current impact, future directions. Crit. Rev. Oncol. Hematol. 196, 104324, 10.1016/j.critrevonc.2024.104324 reference.3Morrison, L.; Loibl, Turner, N. C. CDK4/6 inhibitor revolution – game-changing era Nat. Clin. 21, 89– 105, 10.1038/s41571-023-00840-4 reference.4Areewong, Suppramote, O.; Prasopporn, Jirawatnotai, Exploiting acquired vulnerability develop treatments cholangiocarcinoma. Cancer Cell Int. 24, 362, 10.1186/s12935-024-03548-2 reference.5Sabnis, R. Sulfonylamide Cancer. 2021, 12, 1528– 1529, 10.1021/acsmedchemlett.1c00471 reference.Cited By Click copied!This has not yet been cited publications.Download PDFFiguresReferences Get e-AlertsGet e-AlertsACS copied!https://doi.org/10.1021/acsmedchemlett.4c00574Published permissionsArticle Views225Altmetric-Citations-Learn about metrics closeArticle Views COUNTER-compliant sum full text downloads since 2008 (both PDF HTML) all institutions individuals. These regularly updated reflect usage leading up last few days.Citations number articles citing article, calculated Crossref daily. Find more information counts.The Altmetric Attention Score quantitative measure attention research received online. Clicking on donut icon will load page at altmetric.com additional details score social media presence given article. how calculated.Recommended Articles FiguresReferencesAbstractHigh SlideReferences There reference.

Language: Английский

Citations

0