144340-21-6Relevant articles and documents
A Palladium(II)-Catalyzed C-H Activation Cascade Sequence for Polyheterocycle Formation
Cooper, Stephen P.,Booker-Milburn, Kevin I.
supporting information, p. 6496 - 6500 (2015/06/02)
Polyheterocycles are found in many natural products and are useful moieties in functional materials and drug design. As part of a program towards the synthesis of Stemona alkaloids, a novel palladium(II)-catalyzed C-H activation strategy for the construction of such systems has been developed. Starting from simple 1,3-dienyl-substituted heterocycles, a large range of polycyclic systems containing pyrrole, indole, furan and thiophene moieties can be synthesized in a single step. Don't overdo it: A palladium(II)-catalyzed C-H activation cascade sequence for the synthesis of polyheterocycles is reported. Aromatization of the initially formed dihydro species occurred with a quinone oxidant. In some cases the use of one equivalent of the oxidant enabled isolation of the dihydro species as a single isomer (see scheme; X=NMe, O, S).
Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083)
Zhou, Han-Jie,Wang, Jinhai,Yao, Bing,Wong, Steve,Djakovic, Stevan,Kumar, Brajesh,Rice, Julie,Valle, Eduardo,Soriano, Ferdie,Menon, Mary-Kamala,Madriaga, Antonett,Kiss Von Soly, Szerenke,Kumar, Abhinav,Parlati, Francesco,Yakes, F. Michael,Shawver, Laura,Le Moigne, Ronan,Anderson, Daniel J.,Rolfe, Mark,Wustrow, David
, p. 9480 - 9497 (2016/01/12)
The AAA-ATPase p97 plays vital roles in mechanisms of protein homeostasis, including ubiquitin-proteasome system (UPS) mediated protein degradation, endoplasmic reticulum-associated degradation (ERAD), and autophagy. Herein we describe our lead optimization efforts focused on in vitro potency, ADME, and pharmaceutical properties that led to the discovery of a potent, ATP-competitive, D2-selective, and orally bioavailable p97 inhibitor 71, CB-5083. Treatment of tumor cells with 71 leads to significant accumulation of markers associated with inhibition of UPS and ERAD functions, which induces irresolvable proteotoxic stress and cell death. In tumor bearing mice, oral administration of 71 causes rapid accumulation of markers of the unfolded protein response (UPR) and subsequently induces apoptosis leading to sustained antitumor activity in in vivo xenograft models of both solid and hematological tumors. 71 has been taken into phase 1 clinical trials in patients with multiple myeloma and solid tumors.
Synthesis and quantitative structure-activity relationship (QSAR) study of novel N-arylsulfonyl-3-acylindole arylcarbonyl hydrazone derivatives as nematicidal agents
Che, Zhiping,Zhang, Shaoyong,Shao, Yonghua,Fan, Lingling,Xu, Hui,Yu, Xiang,Zhi, Xiaoyan,Yao, Xiaojun,Zhang, Rui
, p. 5696 - 5705 (2013/07/26)
In continuation of our program aimed at the discovery and development of natural-product-based pesticidal agents, 54 novel N-arylsulfonyl-3-acylindole arylcarbonyl hydrazone derivatives were prepared, and their structures were well characterized by 1
Positive allosteric modulators of nicotinic acetylcholine receptor
-
Page/Page column 20, (2012/10/08)
The present invention relates to compounds useful in therapy, to compositions comprising said compounds, and to methods of treating diseases comprising administration of said compounds. The compounds referred to are positive allosteric modulators (PAMs) of the nicotinic acetylcholine α7 receptor.
Synthesis of novel PPARα/γ dual agonists as potential drugs for the treatment of the metabolic syndrome and diabetes type II designed using a new de novo design program PROTOBUILD
Bhurruth-Alcor, Yushma,Rost, Therese,Jorgensen, Michael R.,Kontogiorgis, Christos,Skorve, Jon,Cooper, Robert G.,Sheridan, Joseph M.,Hamilton, William D. O.,Heal, Jonathan R.,Berge, Rolf K.,Miller, Andrew D.
experimental part, p. 1169 - 1188 (2011/04/15)
Peroxisome proliferator activated receptors (PPARs) have been shown to have critical roles in fatty acid oxidation, triglyceride synthesis, and lipid metabolism - making them an important target in drug discovery. Here we describe the in silico design, sy
INDOLE COMPOUNDS
-
Page/Page column 23-24, (2010/04/03)
Novel indole compounds which interact with peroxisome proliferator-activated receptors (PPARs) are disclosed. The compounds have an influence on metabolic diseases, obesity and diabetes.
NOVEL COMPOUNDS EFFECTIVE AS XANTHINE OXIDASE INHIBITORS, METHOD FOR PREPARING THE SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
-
Paragraph 810-814, (2010/09/03)
The present invention relates to novel compounds which are effective as an inhibitor for xanthine oxidase, a process for preparing the same, and a pharmaceutical composition comprising a therapeutically effective amount of the same.
Anti HIV-1 agents 5: Synthesis and anti-HIV-1 activity of some N-arylsulfonyl-3-acetylindoles in vitro
Ran, Jun-Qiang,Huang, Ning,Xu, Hui,Yang, Liu-Meng,Lv, Min,Zheng, Yong-Tang
supporting information; experimental part, p. 3534 - 3536 (2010/08/21)
In continuation of our program aimed at the discovery and development of compounds with superior anti-human immunodeficiency virus type 1 (HIV-1) activity, 21N-arylsulfonyl-3-acetylindole analogs (2a-u) were synthesized and preliminarily evaluated as HIV-
Derivatives of 5-amidine indole as inhibitors of thrombin catalytic activity
Iwanowicz, Edwin J.,Lau, Wan F.,Lin, James,Roberts, Daniel G. M.,Seiler, Steven M.
, p. 1339 - 1344 (2007/10/03)
Substituted 5-amidine indoles were constructed based upon a computational analysis of putative modes of binding to thrombin utilizing coordinates from the crystal structure of BMS-183,507-α-thrombin complex. These analogs display competitive kinetics for
5-heteroyl indole derivatives
-
, (2008/06/13)
Compounds of the formula STR1 which are useful in treating migraine and other disorders, and intermediates used in the preparation of said compounds.
