13991-36-1Relevant articles and documents
Development of resin-to-resin transfer reactions (RRTR) using Sonogashira chemistry
Tulla-Puche, Judit,Barany, George
, p. 2195 - 2201 (2005)
Sonogashira chemistry can be used according to the 'resin-to-resin transfer reaction' (RRTR) concept. Two fragments, one containing the halide moiety and the second one incorporating the alkyne functionality, are anchored on different solid supports using
Enantioselective desymmetrization of prochiral cyclohexanones by organocatalytic intramolecular michael additions to α,β-unsaturated esters
Gammack Yamagata, Adam D.,Datta, Swarup,Jackson, Kelvin E.,Stegbauer, Linus,Paton, Robert S.,Dixon, Darren J.
, p. 4899 - 4903 (2015)
A new catalytic asymmetric desymmetrization reaction for the synthesis of enantioenriched derivatives of 2-azabicyclo[3.3.1]nonane, a key motif common to many alkaloids, has been developed. Employing a cyclohexanediamine-derived primary amine organocatalyst, a range of prochiral cyclohexanone derivatives possessing an α,β-unsaturated ester moiety linked to the 4-position afforded the bicyclic products, which possess three stereogenic centers, as single diastereoisomers in high enantioselectivity (83-99 % ee) and in good yields (60-90 %). Calculations revealed that stepwise C-C bond formation and proton transfer via a chair-shaped transition state dictate the exclusive endo selectivity and enabled the development of a highly enantioselective primary amine catalyst.
Biosynthesis of salinosporamides from α,β-unsaturated fatty acids: Implications for extending polyketide synthase diversity
Liu, Yuan,Hazzard, Christopher,Eustaquio, Alessandra S.,Reynolds, Kevin A.,Moore, Bradley S.
, p. 10376 - 10377 (2009)
(Chemical Equation Presented) A new series of coenzyme A-tethered polyketide synthase extender units were discovered in relation to the biosynthesis of the salinosporamide family of anticancer agents from the marine bacterium Salinispora tropica. In vivo and in vitro experiments revealed that the crotonyl-CoA reductase/carboxylase SalG has broad substrate tolerance toward 2-alkenyl-CoAs that give rise to the salinosporamide C-2 substitution pattern.
Convenient synthesis of (RS)-4-amino-3-hydroxybutyric acid.
Pinza,Pifferi
, p. 120 - 121 (1978)
A new three-step synthesis of 4-amino-3-hydroxybutyric acid from an inexpensive starting material and under mild reaction conditions is described. Crotonic acid was brominated by the Wohl-Ziegler reaction to 4-bromocrotonic acid, which, in turn, was converted with ammonium hydroxide into 4-aminocrotonic acid. This compound, refluxed in water in the presence of a strong acid resin, afforded 4 amino-3-hydroxybutyric acid in good yields.
Design and synthesis of novel benzothiophene analogs as selective estrogen receptor covalent antagonists against breast cancer
Bai, Chengfeng,Ren, Shengnan,Wu, Shuangjie,Zhu, Meiqi,Luo, Guoshun,Xiang, Hua
, (2021/05/27)
Endocrine therapy (ET) has benefited patients with estrogen receptor alpha (ERα) positive breast cancer for decades. Selective estrogen receptor modulator (SERM) such as Tamoxifen represents the clinical standard of care (SoC). Despite the therapeutic importance of current SoC agents, 30–50% of prolonged treatment patients inevitably generated resistant tumor cells, usually eventually suffered tumor relapse and developed into metastatic breast cancer (MBC), which was the leading cause of female cancer-related mortality. Among these, most resistant tumors remained dependent on ERα signaling, which reignited the need for the next generation of ERα related agents. We hypothesized that selective estrogen receptor covalent antagonists targeting ERα would provide a therapeutic alternative. In the current work, series of novel benzothiophene hybrids bearing electrophile moieties were synthesized and biologically evaluated. The representative analogue 15c exhibited potent anti-proliferative effect in MCF-7 cell lines in vitro, and further mechanism studies confirmed the necessity of covalent bonding. More importantly, 15c could attenuate the expression of TFF-1, GREB-1 and downregulate the levels of cellular ERα protein.
Benzothiophene derivatives as selective estrogen receptor covalent antagonists: Design, synthesis and anti-ERα activities
Bai, Chengfeng,Luo, Guoshun,Ren, Shengnan,Wu, Shuangjie,Xiang, Hua,Zhu, Meiqi
, (2021/09/13)
Estrogen receptor α emerged as a well validated therapeutic target of breast cancer for decades. However, approximately 50% of patients who initially responding to standard-of-care (SoC), such as undergo therapy of Tamoxifen, generally inevitably progress to an endocrine-resistance ER+ phenotype. Recently, selective estrogen receptor covalent antagonists (SERCAs) targeted to ERα have been demonstrated as a therapeutic alternative. In the present study, series of novel 6-OH-benzothiophene (BT) derivatives targeting ERα and deriving from Raloxifene were designed, synthesized, and biologically evaluated as covalent antagonists. Driven by the antiproliferative efficacy in ER+ breast cancer cells, our chemical optimization finally led to compound 19d that with potent antagonistic activity in ER+ tumor cells while without agonistic activity in endometrial cells. Moreover, the docking simulation was carried out to elucidate the binding mode, revealing 19d as an antagonist and covalently binding to the cysteine residue at the 530 position of ER helix H11.
SUMO INHIBITOR COMPOUNDS AND USES THEREOF
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Paragraph 0187, (2020/10/09)
The present invention relates to compounds and compositions capable of acting as inhibitors of small ubiquitin-like modifier (SUMO) family of proteins. The compounds and compositions may be used in the treatment of cancer. There are disclosed, inter alia, methods of inhibiting an E1 enzyme, and compounds useful for inhibiting an E1 enzyme.
Live-cell imaging and profiling of c-Jun N-terminal kinases using covalent inhibitor-derived probes
Qian, Linghui,Pan, Sijun,Lee, Jun-Seok,Ge, Jingyan,Li, Lin,Yao, Shao Q.
supporting information, p. 1092 - 1095 (2019/01/29)
c-Jun N-terminal kinases (JNKs) are involved in critical cellular functions. Herein, small-molecule JNK-targeting probes are reported based on a covalent inhibitor. Together with newly developed two-photon fluorescence Turn-ON reporters and chemoproteomic studies, we showed that some probes may be suitable for live-cell imaging and profiling of JNKs.
ALKYNYL-SUBSTITUTED HETEROCYCLIC COMPOUND, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF
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Paragraph 0181; 0182; 0183, (2019/07/23)
The present invention relates to an alkynyl-substituted heterocyclic compound acting as an FGFR inhibitor, a preparation method therefor and a medical use thereof. In particular, the present invention relates to a compound as shown in general formula (I) and a pharmaceutically acceptable salt thereof; a pharmaceutical composition including the compound or a pharmaceutically acceptable salt thereof; a method for treating and/or preventing FGFR-associated diseases, particularly tumors, by using the compound or a pharmaceutically acceptable salt thereof; and a preparation method for the compound or a pharmaceutically acceptable salt thereof. The present invention also relates to the use of the compound or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition including the compound or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating and/or preventing FGFR-associated diseases, particularly tumors, wherein the definition of each substituent group in general formula (I) is the same as that in the description.
Alkynyl-substituted heterocyclic compound, preparation method therefor and medical use therefor for effectively treating and/or preventing FGFR-related diseases such as tumors
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Page/Page column 50-51, (2020/02/18)
The present invention relates to an alkynyl-substituted heterocyclic compound serving as an FGFR inhibitor, a preparation method therefor and a medical use therefor. In particular, the present invention relates to a compound represented by the general formula (I) and its pharmaceutically acceptable salt, a pharmaceutical composition including the compound or its pharmaceutically acceptable salt, a method for treating and/or preventing FGFR-related diseases, particularly tumors, by using the compound or its pharmaceutically acceptable salt, and a preparation method of the compound or its pharmaceutically acceptable salt. The present invention also relates to an use of the compound or its pharmaceutically acceptable salt, or an pharmaceutical composition including the compound or its pharmaceutically acceptable salt in the preparation of a drug for treating and/or preventing FGFR-related diseases, particularly tumors, wherein the definition of each substituent in the general formula (I) is the same as that in the specification.
