623935-92-2Relevant articles and documents
Site-Specific Photochemical Desaturation Enables Divergent Syntheses of Illicium Sesquiterpenes
Shen, Yang,Li, Linbin,Xiao, Xiaoxia,Yang, Sihan,Hua, Yuhui,Wang, Yinglu,Zhang, Yun-Wu,Zhang, Yandong
, p. 3256 - 3263 (2021)
Desaturation of unactivated alkanes remains a challenging yet desirable strategy to make olefins. The Illicium sesquiterpenes usually possess highly oxygenated cage-like architectures, and some of them exhibit prominent neurotrophic effects. Here, we disclose a unique photochemical desaturation strategy for the efficient, highly stereocontrolled total syntheses of five Illicium sesquiterpenes from inexpensive (R)-pulegone, featuring a 13-step gram-scale synthesis of (-)-merrilactone A. The efficiency of the syntheses derives from an expedient construction of a tetracyclic framework via two annulations, a site-specific photoinduced single-step desaturation in a complex hydrocarbon system, and diverse oxygenation manipulations around the resultant olefin intermediate. This work highlights how late-stage desaturation can dramatically streamline the synthesis of complex terpenes and diverse non-natural analogues for establishing the structure-activity relationship and elucidating their molecular mechanisms of bioactivity.
Cyclopenta [d] pyrimidine compound, pharmaceutically acceptable salt, solvate or prodrug thereof and application
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Paragraph 0219-0224, (2020/07/15)
The invention discloses a cyclopenta [d] pyrimidine compound, a pharmaceutically acceptable salt, solvate or prodrug thereof, and an application of the cyclopenta [d] pyrimidine compound, the pharmaceutically acceptable salt, the solvate or the prodrug. T
COMBINATIONS OF AKT INHIBITOR COMPOUNDS AND VEMURAFENIB, AND METHODS OF USE
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, (2012/10/18)
The invention provides a combination of a) a compound of Formula Ia: [insert Formula Ia], or a pharmaceutically acceptable salt thereof, and b) vemurafenib or a pharmaceutically acceptable salt thereof for the prophylactic or therapeutic treatment of a hy
Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors
Blake, James F.,Xu, Rui,Bencsik, Josef R.,Xiao, Dengming,Kallan, Nicholas C.,Schlachter, Stephen,Mitchell, Ian S.,Spencer, Keith L.,Banka, Anna L.,Wallace, Eli M.,Gloor, Susan L.,Martinson, Matthew,Woessner, Richard D.,Vigers, Guy P.A.,Brandhuber, Barbara J.,Liang, Jun,Safina, Brian S.,Li, Jun,Zhang, Birong,Chabot, Christine,Do, Steven,Lee, Leslie,Oeh, Jason,Sampath, Deepak,Lee, Brian B.,Lin, Kui,Liederer, Bianca M.,Skelton, Nicholas J.
, p. 8110 - 8127 (2012/11/13)
The discovery and optimization of a series of 6,7-dihydro-5H-cyclopenta[d] pyrimidine compounds that are ATP-competitive, selective inhibitors of protein kinase B/Akt is reported. The initial design and optimization was guided by the use of X-ray structures of inhibitors in complex with Akt1 and the closely related protein kinase A. The resulting compounds demonstrate potent inhibition of all three Akt isoforms in biochemical assays and poor inhibition of other members of the cAMP-dependent protein kinase/protein kinase G/protein kinase C extended family and block the phosphorylation of multiple downstream targets of Akt in human cancer cell lines. Biological studies with one such compound, 28 (GDC-0068), demonstrate good oral exposure resulting in dose-dependent pharmacodynamic effects on downstream biomarkers and a robust antitumor response in xenograft models in which the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin pathway is activated. 28 is currently being evaluated in human clinical trials for the treatment of cancer.
Synthesis of the reported structure of trans-africanan-1α-ol
Taber, Douglass F.,Bai, Sha,Tian, Weiwei
experimental part, p. 9733 - 9737 (2012/01/04)
A trisubstituted cyclopentane chiron has been prepared by dynamic kinetic reduction of a pulegone-derived β-keto ester. This chiron served as the starting material for the synthesis of the reported structure of the tricyclic sesquiterpene trans-africanan-
5H-CYCLOPENTA[D]PYRIMIDINES AS AKT PROTEIN KINASE INHIBITORS
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Page/Page column 49-50, (2009/09/04)
Compounds of Formula I are useful for inhibiting AKT protein kinases. Methods of using compounds of Formula I and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed. Formula (I).
PYRIMIDYL CYCLOPENTANES AS AKT PROTEIN KINASE INHIBITORS
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Page/Page column 75, (2009/09/04)
The present invention provides compounds of Formula (I) including tautomers, resolved enantiomers, resolved diastereomers, solvates, metabolites, salts and pharmaceutically acceptable prodrugs thereof. Also provided are methods of using the compounds of this invention as Akt protein kinase inhibitors and for the treatment of Akt-mediated diseases, for example, hyperproliferative diseases such as cancer.
CYCLOPENTA [D] PYRIMIDINES AS AKT PROTEIN KINASE INHIBITORS
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, (2008/06/13)
The present invention provides compounds of Formula I, including tautomers, resolved enantiomers, diastereomers, solvates, metabolites, salts and pharmaceutically acceptable prodrugs thereof. Formula (I). Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.
HYDROXYLATED AND METHOXYLATED CYCLOPENTA [D] PYRIMIDINES AS AKT PROTEIN KINASE INHIBITORS
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Page/Page column 41; 75-76; 87, (2008/06/13)
The present invention provides compounds, including resolved enantiomers, resolved diastereomers, solvates and pharmaceutically acceptable salts thereof, comprising the Formula (I). Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.