专利号:US-12441733-B2 优先权日:2018-03-26 标题:Substituted 2,4-dioxotetrahydropyrimidines as intermediates in the synthesis of bruton's tyrosine kinase inhibitors 发明人:ARISTA LUCA; HEBACH CHRISTINA; HOLLINGWORTH GREGORY JOHN; HOLZER PHILIPP; IMBACH-WEESE PATRICIA; LORBER JULIEN; MACHAUER RAINER; SCHMIEDEBERG NIKO; VULPETTI ANNA; ZOLLER THOMAS 权利人:NOVARTIS AG 摘要:The invention relates to compounds of the formulae (I), (III), (IIIa), (XXIa), (XXIII), and/or (XLVI)or a pharmaceutically acceptable salt thereof, wherein the substituents are as defined in the specification; to intermediates in the preparation of the compounds, to pharmaceutical compositions comprising the compounds and to use of the compounds in the treatment of disease.
专利号:US-2025289827-A1 优先权日:2022-12-02 标 题:Morphic forms of a mutant braf degrader and methods of manufacture thereof 发明人:YU ROBERT T; HE MINSHENG; SCHNADERBECK MATTHEW J; KREGER BRIDGET; POLLOCK ROY MACFARLANE; JIANG SIYI; LI MEIQI; CHEN BOLU; LU JIANNAN 权利人:C4 THERAPEUTICS INC 摘要:Advantageous isolated morphic forms of (3R)-3-[6-[2-cyano-3-[[ethyl(methyl)sulfamoyl]amino]-6-fluorophenoxy]-4-oxoquinazolin-3-yl]-8-[2-[1-[3-(2,4-dioxo-1,3-diazinan-1-yl)-5-fluoro-1-methylindazol-6-yl]-4-hydroxypiperidin-4-yl]acetyl]-1-oxa-8-azaspiro[4.5]decane (Compound 1), which is a mutant BRAF degrader, and methods to prepare Compound 1 morphic forms for therapeutic applications are provided in the invention. The invention also provides improved methods for the synthesis of Compound 1, new pharmaceutical compositions comprising Compound 1, and new uses of Compound 1.
专利号:US-2024066133-A1 优先权日:2020-03-06 标 题 :Therapeutic agents and conjugates thereof 发明人:SONG YUNTAO; LI ANRONG; LI HUI; LI XIANFENG; YANG JUNBAO 权利人:BEIJING XUANYI PHARMASCIENCES CO LTD 摘要:The present disclosure provides a class of conjugates of general formula (X), a class of TLR9 agonist derivatives, such as formula (I), (XX), and (XXI), certain diastereomers of STING agonists, a class of STING agonist derivatives, such as formula (XXVIV), a class of heterocyclic compounds of general formula (II), a class of heterocyclic compounds of general formula (III), as defined herein. A 1 , A 2 , T, Z 1 , Z 2 , Z 3 , b 1 , and b 2 , in formula (X) are defined herein. The conjugate provides unique properties that are based upon the properties of the therapeutic agents that are part of the conjugate. Also provided are methods of synthesis and use of compounds.
1: Witkowski J, Polak S, Pawelec D, Rogulski Z. In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part III. Int J Mol Sci. 2023 Jan 23;24(3):2239. doi: 10.3390/ijms24032239. 2: Witkowski J, Polak S, Rogulski Z, Pawelec D. In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part I. Int J Mol Sci. 2022 Oct 26;23(21):12984. doi: 10.3390/ijms232112984. 3: Witkowski J, Polak S, Rogulski Z, Pawelec D. In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part II. Int J Mol Sci. 2022 Oct 8;23(19):11939. doi: 10.3390/ijms231911939.
合成参考文献
参考文献:10.1007/s00044-023-03102-1 摘要:Aguilar A, Thomas JE, Wang S. Targeting MDM2 for the development of a new cancer therapy: progress and challenges. Med Chem Res. 2023 Jun 23;32(7):1334–44. doi: 10.1007/s00044-023-03102-1. 参考文献:10.1007/978-981-99-3810-0_12 摘要:Gill H. Next-Generation FLT3 Inhibitors for the Treatment of FLT3-Positive AML. 2023. In: Pathogenesis and Treatment of Leukemia. 参考文献:10.1186/s43042-024-00616-0 摘要:Wang F, Chen L, Zhang L, Du S, Feng Y. Inhibition of JAK2 and MDM2 to treat secondary acute myeloid leukemia evolving from myelofibrosis. Egypt J Med Hum Genet. 2024 Dec 16;25(1). doi: 10.1186/s43042-024-00616-0. 参考文献:10.1007/978-981-95-6099-8_6 摘要:Soni S, Tiwari AN, Upadhyay A. Ubiquitin-Proteasome System in the Cellular Proteostasis. 2026. In: Ubiquitin Proteasome System in CNS Neurodegenerative Diseases. 参考文献:10.1016/j.ejca.2019.12.012 摘要:Decaudin D, Frisch Dit Leitz E, Nemati F, Tarin M, Naguez A, Zerara M, Marande B, Vivet-Noguer R, Halilovic E, Fabre C, Jochemsen A, Roman-Roman S, Alsafadi S. Preclinical evaluation of drug combinations identifies co-inhibition of Bcl-2/XL/W and MDM2 as a potential therapy in uveal melanoma. Eur J Cancer. 2020 Feb;126():93–103. doi: 10.1016/j.ejca.2019.12.012.