494773-45-4Relevant academic research and scientific papers
ANTI-PARASITIC COMPOUNDS
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Paragraph 00154, (2018/03/25)
Provided are compounds, methods, and pharmaceutical compositions useful for treatment of parasites, e.g., Leishmania. For example, the compound may he represented by Ar—C(=NR1)NR2—A—X—Y—Het2, and pharmaceutically acceptable salts thereof. Ar may be an optionally substituted, aryl or nitrogen-containing heteroaryl. R1 and R2 may independently represent H, optionally substituted C1-C6 alkyl, or optionally substituted C3-C6 cycloalkyl. A may be a bond or an optionally substituted linking moiety comprising 1, 2, or 3 rings. Each ring in the optionally substituted linking moiety may independently be one of: aryl, cycloalkyl, heterocycloalkyl, and heteroaryl. X may be O, S, amide, or a bond. Y may be optionally substituted C1-C14 alkyl or optionally substituted C2-C14 alkenyl. Het2 may be an optionally substituted five-membered nitrogen-containing heteroaromatic ring comprising 1, 2, or 3 ring heteroatoms.
A scaffold merging approach to Hsp90 C-terminal inhibition: synthesis and evaluation of a chimeric library
Davis, Rachel E.,Zhang, Zheng,Blagg, Brian S. J.
supporting information, p. 593 - 598 (2017/03/31)
Inhibition of the Hsp90 C-terminus is an attractive therapeutic paradigm for the treatment of cancer, however the developmental space of C-terminal inhibitors is limited. It was hypothesized that the combination of two previously identified scaffolds into a single structure could provide a platform for which to probe the three-dimensional space within the Hsp90 C-terminal binding pocket. The resulting chimeric compounds displayed anti-proliferative activity at low micromolar concentrations and manifested inhibitory activity in an Hsp90-dependent rematuration assay. Initial structure-activity relationships suggest that this new scaffold binds Hsp90 in a conformation different from that of the parent compounds, and consequently, provides a new opportunity to develop more efficacious inhibitors of the Hsp90 C-terminal binding pocket.
Stable axial chirality in metal complexes bearing 4,4′-substituted BIPHEPs: Application to catalytic asymmetric carbon-carbon bond-forming reactions
Aikawa, Kohsuke,Miyazaki, Yoshitaka,Mikami, Koichi
supporting information; experimental part, p. 201 - 208 (2012/04/23)
Not only electronic but also steric effects of 4,4′-substituents in BIPHEP derivatives and metal (Pd, Pt, and Au) complexes are shown to influence the stability of the biphenyl single bond rotation. While electron-donating or sterically demanding substituents on the 4,4′-positions destabilize the axial chirality of BIPHEP derivatives, electron-withdrawing or sterically less demanding ones on the 4,4′-positions stabilize the axis chirality. Particularly, the axial chirality of palladium dichloride complexes bearing BIPHEP with t-Bu and CF3 substituents on the 4,4′-positions is most labile and stable, respectively (ΔG≠ = 29.22 and 30.49 kcal mol-1 at 300 K; t1/2 = 7 and 56 years at 300 K). These enantiopure dicationic BIPHEPPd complexes can be employed for catalytic enantioselective arylation, alkenylation, and ene reactions to give the corresponding products in good-to-excellent yields and enantioselectivities. Significantly, in the carbonyl-ene reaction of trifluoropyruvate with isobutene, the turnover frequency (TOF) reached 58200 h-1. The remarkable effects of 4,4′-substituents in BIPHEP derivatives can be employed as a guiding principle in the design of versatile and efficient ligands.
MACROCYCLIC INDOLE DERIVATIVES FOR THE TREATMENT OF HEPATITIS C INFECTIONS
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Page/Page column 37, (2009/03/07)
A class of macrocyclic compounds of formula (I), wherein R7, R9, B, F, M, Q, W, Y and Z are defined herein, that are useful as inhibitors of viral proteases, particularly the hepatitis C virus (HCV) NS3 protease, are provided. Also p
TETRACYCLIC INDOLE DERIVATIVES AS ANTIVIRAL AGENTS
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Page/Page column 29, (2008/06/13)
The present invention relates to tetracyclic indole derivatives of formula (I); wherein Ar, D1, D2, D3, D4, W, X, Y and Z are defined herein, and pharmaceutically acceptable salts thereof, pharmaceutical composi
1,4-Addition of arylboronic acids to β-aryl-α,β-unsaturated ketones and esters catalyzed by a rhodium(I)-chiraphos complex for catalytic and enantioselective synthesis of selective endothelin A receptor antagonists
Itoh, Takahiro,Mase, Toshiaki,Nishikata, Takashi,Iyama, Tetsuji,Tachikawa, Hiroto,Kobayashi, Yuri,Yamamoto, Yasunori,Miyaura, Norio
, p. 9610 - 9621 (2007/10/03)
An enantioselective synthesis of acyclic β-diaryl ketones and esters via 1,4-addition of arylboronic acids to β-aryl-α,β-unsaturated ketones or esters is described. The complex in situ prepared from [Rh(nbd)2]BF4 and chiraphos was fo
An efficient synthesis of coumestrol and coumestans by iodocyclization and Pd-catalyzed intramolecular lactonization
Yao, Tuanli,Yue, Dawei,Larock, Richard C.
, p. 9985 - 9989 (2007/10/03)
The iodocyclization of acetoxy-containing 2-(1-alkynyl)anisoles and subsequent direct palladium-catalyzed carbonylation/lactonization provide an efficient route to naturally occurring coumestan and coumestrol, and their related analogues.
ERβ ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene scaffold to achieve ERβ selectivity
Mewshaw, Richard E.,Edsall Jr., Richard J.,Yang, Cuijian,Manas, Eric S.,Xu, Zhang B.,Henderson, Ruth A.,Keith Jr., James C.,Harris, Heather A.
, p. 3953 - 3979 (2007/10/03)
The 2-phenylnaphthalene scaffold was explored as a simplified version of genistein in order to identify ER selective ligands. With the aid of docking studies, positions 1, 4, and 8 of the 2-phenylnaphthalene template were predicted to be the most potentially influential positions to enhance ER selectivity using two different binding orientations. Both orientations have the phenol moiety mimicking the A-ring of genistein. Several compounds predicted to adopt orientations similar to that of genistein when bound to ERβ were observed to have slightly higher ER affinity and selectivity than genistein. The second orientation we exploited, which was different from that of genistein when bound to ERβ, resulted in the discovery of several compounds that had superior ER selectivity and affinity versus genistein. X-ray structures of two ER selective compounds (i.e., 15 and 47) confirmed the alternate binding mode and suggested that substituents at positions 1 and 8 were responsible for inducing selectivity. One compound (i.e., 47, WAY-202196) was further examined and found to be effective in two models of inflammation, suggesting that targeting ER may be therapeutically useful in treating certain chronic inflammatory diseases.
Total syntheses of three natural products, vignafuran, 2-(4-hydroxy-2-methoxyphenyl)-6-methoxybenzofuran-3-carboxylic acid methyl ester, and coumestrol from a common starting material
Hiroya, Kou,Suzuki, Naoyuki,Yasuhara, Akito,Egawa, Yuya,Kasano, Atsushi,Sakamoto, Takao
, p. 4339 - 4346 (2007/10/03)
Vignafuran 2, 2-(4-hydroxy-2-methoxyphenyl)-6-methoxybenzofuran-3-carboxylic acid methyl ester 3, and coumestrol 4 were efficiently synthesized from the same starting material, 4-bromoresorcinol 14a, through the common intermediate, diarylacetylene 7. The key steps of these syntheses were the tetrabutylammonium fluoride (TBAF)-catalyzed benzo[b]furan ring formation for 2 and the carbonylative ring closure methodology catalyzed by a Pd complex for 3 and 4. The Royal Society of Chemistry 2000.
Substrate regulation of product distribution in the reactions of aryl chromium carbene complexes with alkynes
Bos, Mary Ellen,Wulff, William D.,Miller, Ross A.,Chamberlin, Steven,Brandvold, Timothy A.
, p. 9293 - 9319 (2007/10/02)
The reactions of arylcarbene complexes with alkynes were examined for six of the nine possible substitution patterns for mono- and dioxygenated aryl substituents of the carbene carbon. The product distributions were found to be highly dependent on a numbe
