- Design, synthesis, and evaluation of A-ring-modified lamellarin N analogues as noncovalent inhibitors of the EGFR T790M/L858R mutant
-
A series of A-ring-modified lamellarin N analogues were designed, synthesized, and evaluated as potential noncovalent inhibitors of the EGFR T790M/L858R mutant, a causal factor in the drug-resistant non-small cell lung cancer. Several water-soluble ammonium- or guanidinium-tethered analogues exhibited good kinase inhibitory activities. The most promising analogue, 14f, displayed an excellent inhibitory profile against the T790M/L858R mutant [IC50 (WT) = 31.8 nM; IC50 (T790M/L858R) = 8.9 nM]. The effects of A-ring-substituents on activity were rationalized by docking studies.
- Fukuda, Tsutomu,Umeki, Teppei,Tokushima, Keiji,Xiang, Gao,Yoshida, Yuki,Ishibashi, Fumito,Oku, Yusuke,Nishiya, Naoyuki,Uehara, Yoshimasa,Iwao, Masatomo
-
-
Read Online
- TRICYCLIC SUBSTITUTED PIPERIDINE DIONE COMPOUND
-
Disclosed is a series of tricyclic substituted piperidine dione compounds, and applications thereof in the preparation of medicines for treating diseases related to CRBN protein; specifically disclosed are the derivative compound represented by formula (I) or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0083-0084
(2021/07/17)
-
- Enantioselective Ni-Catalyzed Electrochemical Synthesis of Biaryl Atropisomers
-
A scalable enantioselective nickel-catalyzed electrochemical reductive homocoupling of aryl bromides has been developed, affording enantioenriched axially chiral biaryls in good yield under mild conditions using electricity as a reductant in an undivided cell. Common metal reductants such as Mn or Zn powder resulted in significantly lower yields in the absence of electric current under otherwise identical conditions, underscoring the enhanced reactivity provided by the combination of transition metal catalysis and electrochemistry.
- Chen, Song,Chen, Yue-Gang,Gao, Pei-Sen,Liu, Dong,Ma, Hong-Xing,Mei, Tian-Sheng,Qiu, Hui,Shuai, Bin,Wang, Yun-Zhao
-
supporting information
p. 9872 - 9878
(2020/06/27)
-
- Design, synthesis and characterization of potent microtubule inhibitors with dual anti-proliferative and anti-angiogenic activities
-
Microtubule has been an important target for anticancer drug development. Here we report the discovery and characterization of a series of fused 4-aryl-4H-chromene-based derivatives as highly potent microtubule inhibitors. Among a total of 37 derivatives synthesized, 23 exhibited strong in vitro anti-proliferative activities against A375 human melanoma cells. The relationship between the biological activities of these microtubule inhibitors and their chemical structure variations was analyzed. Studies of compounds 27a, 19a and 9a in parallel with colchicine as the positive control compound in a panel of biological assays revealed that these compounds blocked cell cycle progression, increased apoptosis, and inhibited HUVEC capillary tube formation at low nanomolar concentrations. The most potent compound 27a was also tested in eight additional cancer cell lines besides A375 cells and two non-cancer cells and showed potent and selective activity on these cancer cells. To understand the molecular and structure mechanism of action of these compounds, tubulin polymerization and molecular docking studies were carried out for 27a as the representative. The results were consistent with the mechanism by which 27a interacts with the colchicine binding site on tubulin and disrupts tubulin polymerization. With potent dual actions of microtubule destabilization and vascular disruption described above, this small molecule can serve as a valuable research probe of the function and role of microtubules in human diseases and promising lead for developing new therapeutic agents.
- Zhang, Huijun,Fang, Xiong,Meng, Qian,Mao, Yujia,Xu, Yan,Fan, Tingting,An, Jing,Huang, Ziwei
-
supporting information
p. 380 - 396
(2018/08/17)
-
- HEMOGLOBIN MODIFIER COMPOUNDS AND USES THEREOF
-
Described herein are compounds, including pharmaceutically acceptable salts thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat, prevent or diagnose blood-based diseases, disorders or conditions.
- -
-
Paragraph 00398
(2018/02/28)
-
- BENZO-FUSED HETEROCYCLIC DERIVATIVES USEFUL AS AGONISTS OF GPR120
-
The present invention is directed to benzo-fused heterocyclic derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by GPR120. More particularly, the compounds of the present invention are agonists of GPR120, useful in the treatment of, such as for example, Type II diabetes mellitus.
- -
-
Paragraph 0618
(2014/09/30)
-
- Synthesis and structure revision of goupiolone A: A benzotropolone natural product
-
Goupiolone A, a benzotropolone natural product, has been synthesized by assembling a benzocyclobutene derivative and a silyl-substituted cyclopropane unit, followed by thermal ring enlargement. The synthetic sample did not correspond to the reported data. On the basis of biogenetic considerations, an alternative structure with a catechol moiety was proposed, and the synthesis established it as the correct structure.
- Fukui, Nobuaki,Ohmori, Ken,Suzuki, Keisuke
-
p. 2194 - 2217
(2013/02/22)
-
- Sporolide B: Synthetic studies
-
Studies directed toward the synthesis of the architecturally complex marine natural product sporolide B are described. Synthetic analysis suggested advanced hydroquinone and benzodiquinane fragments, which upon elaboration were successfully united via an
- Gladding, Jeffery A.,Bacci, James P.,Shaw, Scott A.,Smith III, Amos B.
-
scheme or table
p. 6697 - 6706
(2011/10/01)
-
- Synthesis and SAR study of N-(4-hydroxy-3-(2-hydroxynaphthalene-1-yl)phenyl)-arylsulfonamides: Heat shock protein 90 (Hsp90) inhibitors with submicromolar activity in an in vitro assay
-
Heat shock protein 90 is emerging as an important target in cancer chemotherapy. In a program directed toward identifying novel chemical probes for Hsp90, we found N-(4-hydroxy-3-(2-hydroxynaphthalene-1-yl)phenyl)benzene sulfonamide as an Hsp90 inhibitor with very weak activity. In this report, we present a new and general method for the synthesis of a variety of analogs around this scaffold, and discuss their structure-activity relationships.
- Ganesh, Thota,Thepchatri, Pahk,Li, Lian,Du, Yuhong,Fu, Haian,Snyder, James P.,Sun, Aiming
-
scheme or table
p. 4982 - 4987
(2009/05/26)
-
- Solvent-controlled leaving-group selectivity in aromatic nucleophilic substitution
-
(Figure Presented) A solvent-controlled inversion of leaving group ability allows selective access to either of two internal substitution products in SNAr reactions of substrates with competing leaving groups. Application of this principle in a
- Hintermann, Lukas,Masuo, Ritsuki,Suzuki, Keisuke
-
supporting information; experimental part
p. 4859 - 4862
(2009/05/31)
-
- Synthetic studies on Ecteinascidin-743: synthesis of building blocks through Sharpless asymmetric dihydroxylation and aza-Michael reactions
-
A practical and an efficient synthesis of three building blocks of tetrahydroisoquinoline alkaloid Ecteinascidin-743 was accomplished, starting from readily available piperonal, 2-methyl anisole, and veratraldehyde. A combination of Vilsmeier-Haack reaction and Sharpless asymmetric dihydroxylation was employed for the synthesis of building blocks A and B whereas a Heck reaction in PEG-2000 and aza-Michael reactions were employed for the synthesis of building block C.
- Chandrasekhar,Reddy, N. Ramakrishna,Rao, Y. Srinivasa
-
p. 12098 - 12107
(2007/10/03)
-
- Total synthesis of ecteinascidin 743
-
A convergent total synthesis of ecteinascidin 743 is realized from five building blocks of almost equal size. It takes 23 steps from l-3-hydroxy-4-methoxy-5-methyl phenylalanol (5) with an overall yield of 3%. Copyright
- Chen, Jinchun,Chen, Xiaochuan,Bois-Choussy, Michele,Zhu, Jieping
-
-
- PROCESS FOR TOTAL SYNTHESIS OF ECTEINASCIDINS AND INTERMEDIATES THEREFOR
-
An intermediate compound for total synthesis of ecteinascidins comprising, a compound represented by general formula 2 having thioether group at C4 site, and the substituent R2 of N12 site is trichloroethoxicarbonyl (Troc) to which various substituents can be introduced by mild condition, further having 10 members ring structure which can be converted to a ring of other numbered members.
- -
-
Page 14 - 15
(2008/06/13)
-
- Synthetic studies on ecteinascidin 743: Rapid access to the fully functionalized tetrahydroisoquinoline with a bridged 10-membered sulfur containing macrocycle
-
Synthesis of tetrahydroisoquinoline with a 1,4-bridged 10-membered sulfur containing macrolactone (5) is described. Phenolic aldolisation, Pictet-Spengler cyclisation of an acid sensitive amino diol under newly developed conditions (LiBr, toluene-TFE, 80°
- De Paolis, Michael,Chiaroni, Angele,Zhu, Jieping
-
p. 2896 - 2897
(2007/10/03)
-
- Development of novel antioxidants: Design, synthesis, and reactivity
-
We are attempting to develop novel synthetic antioxidants aimed at retarding the effects of free-radical induced cell damage. In this paper we discuss the design strategy and report the synthesis of seven novel antioxidants, including six catechols and a
- Hussain, Helmi H.,Babic, Gordana,Durst, Tony,Wright, James S.,Flueraru, Mihaela,Chichirau, Alexandru,Chepelev, Leonid L.
-
p. 7023 - 7032
(2007/10/03)
-
- Total synthesis of ecteinascidin 743
-
The total synthesis of ecteinascidin 743 (1), an extremely potent antitumor agent, has been accomplished. The synthesis features Ugi's 4CC reaction, intramolecular Heck reaction, phenol-aldehyde cyclization, and acid-induced intramolecular sulfide formation. Copyright
- Endo, Atsushi,Yanagisawa, Arata,Abe, Masanao,Tohma, Shigemitsu,Kan, Toshiyuki,Fukuyama, Tohru
-
p. 6552 - 6554
(2007/10/03)
-
- New syntheses of dillapiol [4,5-dimethoxy-6-(2-propenyl)-1,3-benzodioxole], its 4-methylthio and other analogs
-
Three syntheses of the natural synergist dillapiol from the natural, commercially available sesamol as starting material, are described. A major difference between these is the order of introduction of the additional methoxy and allyl substituents. In one
- Majerus, Sherry L.,Alibhai, Najma,Tripathy, Sasmita,Durst, Tony
-
p. 1345 - 1355
(2007/10/03)
-
- Synthetic study on ecteinascidin 743 starting from D-glucose
-
During the course of synthetic study on ecteinascidin 743 (1), key intermediate 5 was prepared. Stereocontrolled synthesis of 5 from D-glucose was accomplished using incorporation of two nitrogen atoms and stereoselective addition of a phenol to an imine
- Endo, Atsushi,Kann, Toshiyuki,Fukuyama, Tohru
-
p. 1103 - 1105
(2007/10/03)
-
- Synthetic approaches toward ecteinascidins. Part 1. Preparation of an (E)-2-arylidene-3-benzyl-1,5-imino-3-benzazocin-4-one having a protected phenol in the E-ring
-
A synthetic strategy for the preparation of ecteinascidins isolated from the Caribbean tunicate Ecteinascidia turbinata and an efficient synthesis of a key tricyclic lactam intermediate 32 are described.The key step is the intramolecular cyclization of the allylic alcohol 15 to the (E)-1,5-imino-3-benzazocine 16.Cyclization of 15 (R = Me, Bn) afforded the desired product 16 in good yield.However, treatment of 15 (R = MOM) under acidic conditions gave compound 18 in high yield, the structure of which was determined by X-ray crystallography.Finally, 16 was converted into (E)-N-methyltricyclic lactam 32 that can serve as a synthetic precursor of ecteinascidins.
- Saito, Naoki,Tashiro, Kyoichi,Maru, Yukie,Yamaguchi, Kentaro,Kubo, Akinori
-
-
- A general synthesis of dihydrobenzofurans by intramolecular conjugate addition
-
ortho Iodophenoxy crotonates 3e-7e cyclize to dihydrobenzofurans 1 and 9-12 when subjected to lithium-iodine exchange at -100 deg C.Naphtofuran 13 can be similarly obtained from α-iodonaphtoxy crotonate 8e.Methylation of this reaction mixture in
- Weeratunga, Gamini,Jaworska-Sobiesiak, Alina,Horne, Stephen,Rodrigo, Russel
-
p. 2019 - 2023
(2007/10/02)
-