- MODIFIED PROTEINS AND PROTEIN DEGRADERS
-
Provided herein are compounds, pharmaceutical compositions, and methods for binding or degrading target proteins. Further provided herein are compounds having a DNA damage-binding protein 1 (DDB1) binding moiety. Some such embodiments include a linker. Some such embodiments include a target protein binding moiety. Further provided herein are ligand-DDB1 complexes. Further provided herein are in vivo modified DDB1 proteins.
- -
-
Paragraph 00370-00372
(2021/12/08)
-
- Triptycenyl Sulfide: A Practical and Active Catalyst for Electrophilic Aromatic Halogenation Using N-Halosuccinimides
-
A Lewis base catalyst Trip-SMe (Trip = triptycenyl) for electrophilic aromatic halogenation using N-halosuccinimides (NXS) is introduced. In the presence of an appropriate activator (as a noncoordinating-anion source), a series of unactivated aromatic compounds were halogenated at ambient temperature using NXS. This catalytic system was applicable to transformations that are currently unachievable except for the use of Br2 or Cl2: e.g., multihalogenation of naphthalene, regioselective bromination of BINOL, etc. Controlled experiments revealed that the triptycenyl substituent exerts a crucial role for the catalytic activity, and kinetic experiments implied the occurrence of a sulfonium salt [Trip-S(Me)Br][SbF6] as an active species. Compared to simple dialkyl sulfides, Trip-SMe exhibited a significant charge-separated ion pair character within the halonium complex whose structural information was obtained by the single-crystal X-ray analysis. A preliminary computational study disclosed that the πsystem of the triptycenyl functionality is a key motif to consolidate the enhancement of electrophilicity.
- Nishii, Yuji,Ikeda, Mitsuhiro,Hayashi, Yoshihiro,Kawauchi, Susumu,Miura, Masahiro
-
supporting information
p. 1621 - 1629
(2020/02/04)
-
- Cooperative Carbon Dioxide Adsorption in Alcoholamine- and Alkoxyalkylamine-Functionalized Metal–Organic Frameworks
-
A series of structurally diverse alcoholamine- and alkoxyalkylamine-functionalized variants of the metal–organic framework Mg2(dobpdc) are shown to adsorb CO2 selectively via cooperative chain-forming mechanisms. Solid-state NMR spec
- Forse, Alexander C.,Kim, Eugene J.,Lee, Jung-Hoon,Long, Jeffrey R.,Mao, Victor Y.,McGuirk, C. Michael,Milner, Phillip J.,Neaton, Jeffrey B.,Porter-Zasada, Leo B.,Reimer, Jeffrey A.,Siegelman, Rebecca L.
-
supporting information
p. 19468 - 19477
(2020/02/11)
-
- Design, synthesis, and preliminary biological evaluation of 3′,4′,5′-trimethoxy flavonoid salicylate derivatives as potential anti-tumor agents
-
According to the pharmacophore combination principle, a set of new 3′,4′,5′-trimethoxy flavonoid salicylate derivatives were designed, synthesized, and evaluated for biological activity. The cytotoxicity evaluation revealed that compound 10v exhibited higher potency than 5-Fu against HCT-116 cells. Preliminary biological activity studies showed that compound 10v could inhibit the colony formation and migration of HCT-116 cells. Besides, the Hoechst 33258 staining assay and flow cytometry revealed that treatment with compound 10v induced the apoptosis of HCT-116 cells in a concentration-dependent manner, while it had no effect on their cell cycle. The WB analysis suggested that HIF-1α, tubulin, HK-2, and PFK might be the potential pharmacophore targets of compound 10v. Tubulin was a potential drug target for compound 10v, which was explained by analyzing the crystal structure of compound 10v complexed with tubulin. These results indicated that compound 10v might be a promising anti-tumor agent candidate, deserving further optimization and evaluation.
- Deng, Xiangping,Liu, Renbo,Li, Junjian,Li, Zhongli,Liu, Juan,Xiong, Runde,Lei, Xiaoyong,Zheng, Xing,Xie, Zhizhong,Tang, Guotao
-
p. 1874 - 1884
(2019/01/28)
-
- Sulfonamide compound and medical applications thereof
-
The invention discloses a compound containing a sulfonamide structure, a preparation method thereof, and medical applications of the compound, and more specifically discloses the compound with a structure represented by formula I, and a pharmaceutically acceptable salt or a prodrug or a solvate thereof. The compound is used for tumor treatment through inhibiting ATP-citrate lyase.
- -
-
Paragraph 0067-0070
(2019/02/13)
-
- TRICYCLIC PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
-
Described herein are tricyclic compounds with phosphoinositide-3 kinase (PI3K) modulation activity or function having the Formula I structure: or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such PI3K modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon PI3K dysregulation.
- -
-
-
- Structure-Guided Synthesis and Mechanistic Studies Reveal Sweetspots on Naphthyl Salicyl Hydrazone Scaffold as Non-Nucleosidic Competitive, Reversible Inhibitors of Human Ribonucleotide Reductase
-
Ribonucleotide reductase (RR), an established cancer target, is usually inhibited by antimetabolites, which display multiple cross-reactive effects. Recently, we discovered a naphthyl salicyl acyl hydrazone-based inhibitor (NSAH or E-3a) of human RR (hRR) binding at the catalytic site (C-site) and inhibiting hRR reversibly. We herein report the synthesis and biochemical characterization of 25 distinct analogs. We designed each analog through docking to the C-site of hRR based on our 2.7 ? X-ray crystal structure (PDB ID: 5TUS). Broad tolerance to minor structural variations preserving inhibitory potency is observed. E-3f (82% yield) displayed an in vitro IC50 of 5.3 ± 1.8 μM against hRR, making it the most potent in this series. Kinetic assays reveal that E-3a, E-3c, E-3t, and E-3w bind and inhibit hRR through a reversible and competitive mode. Target selectivity toward the R1 subunit of hRR is established, providing a novel way of inhibition of this crucial enzyme.
- Huff, Sarah E.,Mohammed, Faiz Ahmad,Yang, Mu,Agrawal, Prashansa,Pink, John,Harris, Michael E.,Dealwis, Chris G.,Viswanathan, Rajesh
-
supporting information
p. 666 - 680
(2018/02/16)
-
- Hydroxybiphenylamide GroEL/ES Inhibitors Are Potent Antibacterials against Planktonic and Biofilm Forms of Staphylococcus aureus
-
We recently reported the identification of a GroEL/ES inhibitor (1, N-(4-(benzo[d]thiazol-2-ylthio)-3-chlorophenyl)-3,5-dibromo-2-hydroxybenzamide) that exhibited in vitro antibacterial effects against Staphylococcus aureus comparable to vancomycin, an antibiotic of last resort. To follow up, we have synthesized 43 compound 1 analogs to determine the most effective functional groups of the scaffold for inhibiting GroEL/ES and killing bacteria. Our results identified that the benzothiazole and hydroxyl groups are important for inhibiting GroEL/ES-mediated folding functions, with the hydroxyl essential for antibacterial effects. Several analogs exhibited >50-fold selectivity indices between antibacterial efficacy and cytotoxicity to human liver and kidney cells in cell culture. We found that MRSA was not able to easily generate acute resistance to lead inhibitors in a gain-of-resistance assay and that lead inhibitors were able to permeate through established S. aureus biofilms and maintain their bactericidal effects.
- Kunkle, Trent,Abdeen, Sanofar,Salim, Nilshad,Ray, Anne-Marie,Stevens, McKayla,Ambrose, Andrew J.,Victorino, José,Park, Yangshin,Hoang, Quyen Q.,Chapman, Eli,Johnson, Steven M.
-
p. 10651 - 10664
(2019/01/04)
-
- COMPOUND HAVING ZNF143 INHIBITORY ACTIVITY AND USE THEREOF
-
PROBLEM TO BE SOLVED: To provide a compound having a ZNF143 inhibitory activity as well as to provide a ZNF143 inhibitory agent and pharmaceutical composition containing the same. SOLUTION: Provided is a compound represented by formula (I) or a salt thereof as well as a ZNF143 inhibitory agent containing the same and a pharmaceutical composition having the same as an active ingredient. A-B-C-D (I)[A is H, a methyl group, a naphthyl group, a phenyl group or a nitrogen-containing heterocyclic ring; B is as shown below, and C is an amide bond or a heteroaromatic ring containing N and O; D is a substituted/unsubstituted phenyl group or a monocyclic heteroaromatic ring containing N or S; and C and D are both fused heterocyclic ring or the like optionally having a substituent group.]. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2016,JPOandINPIT
- -
-
Paragraph 0269
(2016/10/27)
-
- Pore Environment Effects on Catalytic Cyclohexane Oxidation in Expanded Fe2(dobdc) Analogues
-
Metal-organic frameworks are a new class of heterogeneous catalysts in which molecular-level control over both the immediate and long-range chemical environment surrounding a catalytic center can be readily achieved. Here, the oxidation of cyclohexane to
- Xiao, Dianne J.,Oktawiec, Julia,Milner, Phillip J.,Long, Jeffrey R.
-
supporting information
p. 14371 - 14379
(2016/11/13)
-
- Copper-catalyzed formal c-h carboxylation of aromatic compounds with carbon dioxide through arylaluminum intermediates
-
The C-H bond carboxylation of various aromatic compounds with CO2 was achieved by the deprotonative alumination with a mixed alkyl amido lithium aluminate compound iBu3Al(TMP)Li followed by the NHC-copper-catalyzed carboxylation of the resulting arylaluminum species, which afforded the corresponding carboxylation products in high yield and high selectivity. In addition to benzene derivatives, heteroarenes such as benzofuran, benzothiophene, and indole derivatives are also suitable substrates. Functional groups such as Cl, Br, I, vinyl, amide, and CN could survive the reaction conditions. Some key reaction intermediates such as the copper aryl and isobutyl complexes and their carboxylation products were isolated and structurally characterized by X-ray crystallographic analyses, thus offering important information on the reaction mechanism.
- Ueno, Atsushi,Takimoto, Masanori,Wylie,Nishiura, Masayoshi,Ikariya, Takao,Hou, Zhaomin
-
supporting information
p. 1010 - 1016
(2015/03/31)
-
- Room-temperature ortho-alkoxylation and -halogenation of N-tosylbenzamides by using palladium(II)-catalyzed C-H activation
-
The N-tosylcarboxamide group can direct the room-temperature palladium-catalyzed C-H alkoxylation and halogenation of substituted arenes in a simple and mild procedure. The room-temperature stoichiometric cyclopalladation of N-tosylbenzamide was first studied, and the ability of the palladacycle to react with oxidants to form C-X and C-O bonds under mild conditions was demonstrated. The reaction conditions were then adapted to promote room-temperature ortho-alkoxylations and ortho-halogenations of N-tosylbenzamides using palladium as catalyst. The scope and limitation of both alkoxylations and halogenations was studied and the subsequent functional transformation of the N-tosylcarboxamide group through nucleophilic additions was evaluated. This methodology offers a simple and mild route to diversely functionalized arenes.
- Peron, Florent,Fossey, Christine,Sopkova-Deoliveirasantos, Jana,Cailly, Thomas,Fabis, Frederic
-
supporting information
p. 7507 - 7513
(2014/06/23)
-
- Selective and efficient oxidation of benzylic alcohols to benzaldehydes and methyl benzoates by dibromo-5,5-dimethylhydantoin
-
A selective and efficient method of oxidizing benzyl alcohols to benzaldehydes and methyl benzoates by using 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as oxidant is developed. One-step conversion of benzyl alcohols to methyl benzoates in methanol at room temperature for 12 hours is achieved without any catalysts. Moreover, para-substituted benzyl alcohols are obtained in 86-98% yield. When dichloromethane is used as solvent, further oxidation of benzaldehydes to esters is well controlled, selectively affording benzaldehydes in 89-99% yield within 30 minutes.
- Li, Zhongzhou,Zhu, Wei,Bao, Jinlong,Zou, Xinzhuo
-
supporting information
p. 1155 - 1164
(2014/04/03)
-
- Bromination of arenes using I2O5-KBr in water
-
An efficient and environmentally benign bromination of various aromatic compounds using aN aqueous I2O5-KBr system at room temperature has been developed in this work. A series of aromatic compounds such as acetophenones, benzaldehydes, benzoic acids, anilines, amides, and aminopyridine have been successfully brominated in excellent regioselectivities and good yields under the typical reaction conditions. The features of KBr as brominating reagent, water as solvent, and mild conditions make this system an attractive synthetic procedure. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]
- Hou, Jieping,Li, Zejiang,Jia, Xiao-Dong,Liu, Zhong-Quan
-
supporting information
p. 181 - 187
(2013/12/04)
-
- 1,3,5-TRIAZINE-2-AMINE DERIVATIVES, PREPARATION THEREOF AND DIAGNOSTIC AND THERAPEUTIC USE THEREOF
-
The present invention relates to compounds corresponding to formula (I) in which: - R1 represents a substituted phenyl; - R2 represents: - a substituted phenyl; - a heteroaromatic group, the said group being unsubstituted or substituted one or more times; - R3 represents a group Alk; - R4 represents a hydrogen atom or a (C1-C4)alkyl; - R5 represents a hydrogen atom, a (C3-C6)cycloalkyl or a (C1-C4)alkyl-O-Alk; - or alternatively R4 and R5, together with the nitrogen atom to which they are attached, constitute a heterocyclic radical chosen from: azetidin-1-yl, pyrrolidin-1-yl, piperid-1-yl, morpholin-4-yl; - R6 represents a group -COOAlk, a group -CONH2 or a group -NHSO2 Alk; - Alk represents a (C1-C4)alkyl, which is unsubstituted or substituted one or more times with a halogen atom; in the form of the base or of an acid-addition salt. Preparation process and diagnostic and therapeutic use
- -
-
Page/Page column 21
(2013/07/05)
-
- LONG CHAIN BASE SPHINGOSINE KINASE INHIBITORS
-
The invention relates to inhibitors of sphingosine kinase enzymatic activity, compounds and pharmaceutical compositions that inhibit sphingosine kinase 1 and sphingosine kinase 2 (SphK1 and SphK2) enzymes and further relates to methods of treating diseases and disorders mediated by sphingosine 1 phosphate activity, comprising administering an effective amount of sphingosine kinase inhibitors.
- -
-
Paragraph 0311; 0204; 0323
(2013/08/28)
-
- BENZOFURANE DERIVATIVES FOR THE TREATMENT OF HEPATITITS C
-
The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and maybe useful in treating those infected with HCV.
- -
-
Page/Page column 52
(2012/06/30)
-
- Gold-catalyzed halogenation of aromatics by N-halosuccinimides
-
(Chemical Equation Presented) Golden bromination: A highly efficient and mild AuCl3-catalyzed bromination of aromatic rings with Nbromosuccinimide (NBS) has been developed. This method works with a low catalyst loading (down to 0.01 mol %) and can be combined with transition metal catalyzed transformations to deliver various aryl products.
- Mo, Fanyang,Yan, Jerry Mingtao,Qiu, Di,Li, Fei,Zhang, Yan,Wang, Jianbo
-
supporting information; experimental part
p. 2028 - 2032
(2010/06/17)
-
- Anion binding of N-(o-Methoxybenzamido)thioureas: Contribution of the intramolecular hydrogen bond in the N-benzamide moiety
-
N-(o-Methoxybenzamido)- thioureas (2X/2Y) are found to show an enhanced anion binding affinity with binding constants over 107 mol -1L orders of magnitude for AcO- and a redshifted absorption of the anion binding complexes in acetonitrile (MeCN) relative to those of N-benzamidothioureas (1) that bear no o- OMe in the N-benzamide moiety, despite the electron-donating character of o-OMe. Absorption of the anion-2X/ 2Y complex was shown to be of the same charge-transfer nature as that of the anion-1 complex, but its dependence on substituent X is interestingly influenced by the o-MeO···HNC=O six-membered-ring intramolecular hydrogen bond identified in 2X/2Y. Such an intramolecular hydrogen bond is suggested to be responsible for the enhanced anion binding affinity. In the presence of this intramolecular hydrogen bond, the anion binding constant of 2X was found to be independent of substituent X at the N-phenyl ring, as in the case of 1, whereas that of 2Y showed an amplified dependence on substituent Y at the N′-phenyl ring, but to a lower extent than that of 1. A similar ring intramolecular hydrogen bond was purported to exist in 2Za, 2Zd, and 2Ze, which bear NHMe, F, and Cl as the ortho substituent in the N-benzamide moiety. In terms of the current roles of thiourea in not only anion recognition and sensing but also organocatalysis and crystal engineering, the present finding would be of significance for a wider structural diversity of smart thiourea derivatives with predesigned functions.
- Jiang, Qian-Qian,Darhkijav, Burenkhangai,Liu, Hao,Wang, Fang,Li, Zhao,Jiang, Yun-Bao
-
experimental part
p. 543 - 549
(2010/08/20)
-
- BENZAMIDE DERIVATIVE
-
To provide compounds which have high angiogenesis inhibiting activity, and are useful as agents for effective treatment and prevention of diseases involving pathologic angiogenesis, for example, cancer and cancer metastasis, methods for producing the comp
- -
-
Page/Page column 31-32
(2010/11/23)
-
- Bromodecarbonylation and bromodecarboxylation of electron-rich benzaldehydes and benzoic acids with oxone and sodium bromide
-
Benzaldehydes and benzoic acids bearing ortho- and paraelectron donating substituents having unshared electron-pair have undergone bromodecarbonylation or bromodecarboxylation on treatment with sodium bromide in the presence of Oxone in aqueous methanol.
- Koo, Bon-Suk,Kim, Eun-Hoo,Lee, Kee-Jung
-
p. 2275 - 2286
(2007/10/03)
-
- Preparation and photochemical rearrangements of 2-phenyl-2,5-cyclohexadien-1-ones. an efficient route to highly substituted phenols.
-
[reaction: see text]. The synthesis of 2-phenyl-2,5-cyclohexadien-1-ones 1a-c and 2a-b from methyl 3-phenylbenzoate 4 and methyl 2-methoxy-5-phenylbenzoate 8 by the Birch reduction alkylation methodology is described. 1a-c and 2a-b undergo regiospecific photorearrangements at 300 nm to give tetrasubstituted phenols 14a-c and pentasubstituted phenols 18a-b, respectively. The type A photoproducts 17a-b resulting from irradiation of 2a-b at 366 nm have been isolated as approximately 1:1 diastereomer mixtures. When an optimized condition is applied, a single diastereomer of 17a is obtained.
- Guo,Schultz,Antoulinakis
-
p. 1177 - 1180
(2007/10/03)
-
- Synthesis of a carbon-14 labelled version of benzofuran GR151004B
-
The 5HT1 receptor agonist GR1510048 (2b), labelled with carbon-14 at C-3 of the benzofuran ring, was prepared in 19% overall yield in five steps from 5-bromo-2-methoxybenzoic [14C]acid (3b).
- Wadsworth, Alan H.,Mitchell, Heather A.,Fellows, Lan,Sutherland, Derek R.
-
p. 863 - 871
(2007/10/03)
-
- Benzoguanamine derivatives
-
2,4-Diamino-6-phenyl-s-triazine derivatives which are substituted in the 3-position of the phenyl ring and optionally further substituted in the 6-position demonstrate anti-ulcer and diuretic properties. A representative embodiment is 2,4-diamino-6-(3-tri
- -
-
-
