554-52-9Relevant academic research and scientific papers
TARGETED BIFUNCTIONAL DEGRADERS
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, (2021/04/17)
The present invention provides, in one aspect, bifunctional compounds that can be used to promote or enhance degradation of certain circulating proteins. In another aspect, the present invention provides bifunctional compounds that can be used to promote or enhance degradation of certain autoantibodies. In certain embodiments, treatment or management of a disease and/or disorder requires degradation, removal, or reduction in concentration of the circulating protein or the autoantibody in the subject. Thus, in certain embodiments, administration of a compound of the invention to the subject removes or reduces the circulation concentration of the circulating protein or the autoantibody, thus treating, ameliorating, or preventing the disease and/or disorder. In certain embodiments, the circulating protein is TNF.
Structure–activity relationship and biological evaluation of berberine derivatives as PCSK9 down-regulating agents
Fan, Tian-Yun,Yang, Yu-Xin,Zeng, Qing-Xuan,Wang, Xue-Lei,Wei, Wei,Guo, Xi-Xi,Zhao, Li-Ping,Song, Dan-Qing,Wang, Yan-Xiang,Wang, Li,Hong, Bin
, (2021/06/01)
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein and its deficiency markedly enhanced the survival rate of patient with cardiovascular diseases (CVDs). Forty berberine (BBR) derivatives were synthesized and evaluated for their activities on down-regulating the transcription of PCSK9 in HepG2 cells, taking BBR as the lead. Structure–activity relationship (SAR) analysis revealed that 2,3-dimethoxy moiety might be beneficial for activity. Among them, 9k displayed the most potent activity with IC50 value of 9.5 ± 0.5 μM, better than that of BBR. Also, it significantly decreased PCSK9 protein level at cellular level, as well as in the liver and serum of mice in vivo. Furthermore, 9k markedly increased LDLR expression and LDL-C clearance via down-regulating PCSK9 protein. The mechanism of action of 9k is targeting HNF1α and/or Sp1 cluster modulation upstream of PCSK9, a different one from BBR. Therefore, 9k might have the potential to be a novel PCSK9 transcriptional inhibitor for the treatment of atherosclerosis, worthy for further investigation.
Chromium-Salen Complex/Nitroxyl Radical Cooperative Catalysis: A Combination for Aerobic Intramolecular Dearomative Coupling of Phenols
Nagasawa, Shota,Fujiki, Shogo,Sasano, Yusuke,Iwabuchi, Yoshiharu
, p. 6952 - 6968 (2021/05/29)
We describe an aerobic intramolecular dearomative coupling reaction of tethered phenols using a catalytic system consisting of a chromium-salen (Cr-salen) complex combined with a nitroxyl radical. This novel catalytic system enables formation of various spirocyclic dienone products including those unable to be accessed by previously reported methods efficiently under mild reaction conditions.
Copper(ii)-catalyzed and acid-promoted highly regioselective oxidation of tautomerizable C(sp3)-H bonds adjacent to 3,4-dihydroisoquinolines using air (O2) as a clean oxidant
Fan, Qi-Qi,He, Yun-Gang,Huang, Yong-Kang,Luo, Yong-Qiang,Shi, Xiao-Xin,Zheng, Bo,Zhu, Xing-Liang
, p. 29702 - 29710 (2021/10/08)
A mild, efficient and eco-friendly method for the oxidation of 1-Bn-DHIQs to 1-Bz-DHIQs without concomitant excessive oxidation of 1-Bz-DHIQs to 1-Bz-IQs is very important for the syntheses of 1-Bz-DHIQ alkaloids and analogues. In this article, we developed a novel Cu(ii)-catalyzed and acid-promoted highly regioselective oxidation of tautomerizable C(sp3)-H bonds adjacent to the C-1 positions of various 1-Bn-DHIQs. It was observed that when 0.2 equiv. of Cu(OAc)2·2H2O was used as the catalyst, 3.0 equiv. of AcOH was used as the additive and air (O2) was used as a clean oxidant, various 1-Bn-DHIQs could be efficiently oxidized to corresponding 1-Bz-DHIQs at 25 °C in DMSO. Especially, almost no concomitant excessive oxidation of 1-Bz-DHIQs to 1-Bz-IQs was observed during the above reaction. In addition, this method was successfully applied in the first total synthesis of the alkaloid canelillinoxine.
SUBSTITUTED 1-METHYL-1,2,3,4-TETRAHYDROISOQUINOLINE MOLECULES AS PCSK9 ALLOSTERIC BINDERS
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, (2018/04/20)
The present invention relates to PCSK9 allosteric binding compounds of Formula I: (Formula (I)) and pharmaceutically acceptable salts thereof, wherein X1, X2, Y, R1, R2, RA, RB and n are as defined herein. The present invention also relates to compositions which comprise an allosteric binding compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The invention further relates, inter alia, to methods for inducing PCSK9 protein degradation in a subject, and methods for treating atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions, comprising administering to a subject an effective amount of a compound or a pharmaceutically acceptable salt of the invention. The invention also provides a means for the in vitro labeling, detection and/or quantification of PCSK9 in biological samples.
TETRAHYDROPROTOBERBINE COMPOUNDS AND USES THEREOF IN THE TREATMENT OF NEUROLOGICAL, PSYCHIATRIC AND NEURODEGENERATIVE DISEASES
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Paragraph 0193, (2013/03/26)
Tetrahydroprotoberbine (THPB) compounds and their use in the treatment of neurological, psychiatric and neurodegenerative diseases is provided. The compounds include d-govadine, l-govadine and racemic govadine, as well as d-THPBs of general formula (I). Enantioselective processes for preparing compounds of formula (I), and d- and l-govadine are also provided.(I)
Studies on the synthesis, pungency and anti-biofouling performance of capsaicin analogues
Peng, Bixian,Wang, Junlian,Peng, Zhenghong,Zhou, Shengze,Wang, Fengqi,Ji, Yongliang,Ye, Zhangji,Zhou, Xiangfeng,Lin, Tong,Zhang, Xiaobin
body text, p. 435 - 442 (2012/10/07)
Ten capsaicin analogues were synthesized and their pungency degrees were determined through Scoville Organoleptic Test. The relationship between the structure and pungency degree of these capsaicin analogues was discussed. Then four of these capsaicin analogues with higher pungency degree were picked out and added to anti-biofouling paints as repellents to study their anti-biofouling performance by shallow sea buoyant raft hung-plate experimentation. The results showed that capsaicin and dihydrocapsaicin exhibited equally good anti-biofouling performance while nordihydrocapsaicin and N-vanillylnonanamide had poor anti-biofouling performance. Experimental results also showed that the paints with only 0.1% capsaicin or dihydrocapsaicin as repellent without any other biocides had also exhibited good anti-biofouling performance, which provided a new idea for developing novel, more environment-friendly and Cu 2O-free antifouling paints.
Drug metabolism-based design, synthesis, and bioactivities of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane hydrochloride (DDPH) analogs as α1-adrenoceptors antagonists
Xi, Bao-Min,Jiang, Zhen-Zhou,Zou, Jian-Wei,Ni, Pei-Zhou,Chen, Wen-Hua
, p. 783 - 788 (2011/03/19)
1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane hydrochloride (DDPH) is a potent α1-adrenoceptor antagonist that is currently under Phase II clinic trials. However, the fast metabolism has restricted its further use. In this paper, 11 DDPH analogs were designed according to the probable metabolism pathways of DDPH, and featured the structures of halogen, methyl, and cyano groups at the 3-, or 4-position of aromatic ring A to block the hydroxylation, and one hydroxyl group at the 3-, or 4-position of aromatic ring B to extend the duration time. These compounds were synthesized in moderate to good yields from the reductive amination of substituted phenoxyacetones with substituted phenylethylamines, and fully characterized with 1H NMR, IR, and HRMS. Biological evaluation indicated that most of the compounds exhibited strong blocking and moderate to good antihypertensive activities. It is clear that the compounds having 4-OH/3-OMe on group B exhibited higher blocking activities and longer duration time than their corresponding analogs having 4-OMe/3-OMe (and also 3-OH/4-OMe). Among them, compound 13 having bromo group at the 4-position of ring A and 4-OH/3-OMe on group B, exhibited the highest blocking activity, whereas compound 17 that had a methyl group at the 4-position of ring A and a hydroxyl group at the 4-position of ring B, was more active than potent DDPH in terms of both blocking and antihypertensive activities. In addition, the possible correlations between the blocking and antihypertensive activities are also briefly discussed.
The palladium-catalyzed preparation of condensed tetracyclic heterocycles and their application to the synthesis of rac-mangochinine
Vincze, Zoltan,Biro, A. Beatrix,Csekei, Marton,Timari, Geza,Kotschy, Andras
, p. 1375 - 1385 (2007/10/03)
Dihydroisoquinoline derivatives and their analogues, prepared by the Bischler-Napieralsky reaction, were converted to their indole-fused derivatives. Scope and limitations of the palladium-catalyzed reaction, proceeding through the tautomeric enamine forms of these compounds, were studied and the process was extended to the preparation of racemic mangochinine. Georg Thieme Verlag Stuttgart.
