journal
MENU ▼
Read by QxMD icon Read
search

Bioorganic & Medicinal Chemistry Letters

journal
https://www.readbyqxmd.com/read/28108251/discovery-of-7-3-piperazin-1-yl-phenyl-pyrrolo-2-1-f-1-2-4-triazin-4-amine-derivatives-as-highly-potent-and-selective-pi3k%C3%AE-inhibitors
#1
Lan-Ying Qin, Zheming Ruan, Robert J Cherney, T G Murali Dhar, James Neels, Carolyn A Weigelt, John S Sack, Anurag S Srivastava, Lyndon A M Cornelius, Joseph A Tino, Kevin Stefanski, Xiaomei Gu, Jenny Xie, Vojkan Susulic, Xiaoxia Yang, Melissa Yarde-Chinn, Stacey Skala, Ruth Bosnius, Christine Goldstein, Paul Davies, Stefan Ruepp, Luisa Salter-Cid, Rajeev S Bhide, Michael A Poss
As demonstrated in preclinical animal models, the disruption of PI3Kδ expression or its activity leads to a decrease in inflammatory and immune responses. Therefore, inhibition of PI3Kδ may provide an alternative treatment for autoimmune diseases, such as RA, SLE, and respiratory ailments. Herein, we disclose the identification of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent, selective and orally bioavailable PI3Kδ inhibitors. The lead compound demonstrated efficacy in an in vivo mouse KLH model...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28108250/synthesis-of-vorinostat-and-cholesterol-conjugate-to-enhance-the-cancer-cell-uptake-selectivity
#2
Nethrie D Idippily, Chunfang Gan, Paul Orefice, Jane Peterson, Bin Su
Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar levels. It will be ideal to selectively deliver SAHA into cancer cells. Rapidly growing cancer cells have a great need of cholesterol. Low-density lipoprotein (LDL) is the major cholesterol carrier in plasma and its uptake is mediated by LDL-receptor (LDL-R), a glycoprotein overexpressed on the surface of cancer cells...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28108249/synthesis-and-biological-evaluation-of-thiazole-derivatives-as-novel-usp7-inhibitors
#3
Chao Chen, Jiemei Song, Jinzheng Wang, Chang Xu, Caiping Chen, Wei Gu, Hongbin Sun, Xiaoan Wen
Herpesvirus-associated Ubiquitin-Specific Protease (HAUSP, also called USP7) interacts with and stabilizes Mdm2, and represents one of the first examples that deubiquitinases oncogenic proteins. USP7 has been regarded as a potential drug target for cancer therapy. Inhibitors of USP7 have been recently shown to suppress tumor cell growth in vitro and in vivo. Based on leading USP7 inhibitors P5091 and P22077, we designed and synthesized a series of thiazole derivatives. The results of in vitro assays showed that the thiazole compounds exhibited low micromolar inhibition activity against both USP7 enzyme and cancer cell lines...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28108248/a-new-efficient-method-of-generating-photoaffinity-beads-for-drug-target-identification
#4
Yoichi Nishiya, Tomoko Hamada, Masayuki Abe, Michio Takashima, Kyoko Tsutsumi, Katsuya Okawa
Affinity purification is one of the most prevalent methods for the target identification of small molecules. Preparation of an appropriate chemical for immobilization, however, is a tedious and time-consuming process. A decade ago, a photoreaction method for generating affinity beads was reported, where compounds are mixed with agarose beads carrying a photoreactive group (aryldiazirine) and then irradiated with ultraviolet light under dry conditions to form covalent attachment. Although the method has proven useful for identifying drug targets, the beads suffer from inefficient ligand incorporation and tend to shrink and aggregate, which can cause nonspecific binding and low reproducibility...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28094183/discovering-novel-7-azaindole-based-series-as-potent-axl-kinase-inhibitors
#5
Clémence Feneyrolles, Léa Guiet, Mathilde Singer, Nathalie Van Hijfte, Bénédicte Daydé-Cazals, Bénédicte Fauvel, Gwénaël Chevé, Abdelaziz Yasri
AXL is a receptor tyrosine kinase that plays a key role in tumor growth and proliferation. The scientific community has validated AXL as therapeutic target in the treatment of cancers for several years now, and several AXL inhibitors have been developed but none of them are approved. In this context, we started to design new kinase inhibitors targeting AXL from the 7-azaindole scaffold well known to interact with the ATP binding site of the kinase. Focused screening and chemical diversification around 7-azaindole scaffold were developed, based on modeling studies and medicinal chemistry rational, leading to the discovery of a new family of hits with potent inhibitory activity against AXL...
January 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28094184/in-vivo-evaluation-of-igf1r-ir-pet-ligand-18-f-bms-754807-in-rodents
#6
Jaya Prabhakaran, Stephen L Dewey, Richard McClure, Norman R Simpson, Mohammed N Tantawy, J John Mann, Wellington Pham, J S Dileep Kumar
In vivo evaluation of [(18)F]BMS-754807 binding in mice and rats using microPET and biodistribution methods is described herein. The radioligand shows consistent binding characteristics, in vivo, in both species. Early time frames of the microPET images and time activity curves of brain indicate poor penetration of the tracer across the blood brain barrier (BBB) in both species. However, microPET experiments in mice and rats show high binding of the radioligand outside the brain to heart, pancreas and muscle, the organs known for higher expression of IGF1R/1R...
January 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28094182/dna-duplex-linker-for-afm-selex-of-dna-aptamer-against-human-serum-albumin
#7
Musashi Takenaka, Yuzo Okumura, Tomokazu Amino, Yusuke Miyachi, Chiaki Ogino, Akihiko Kondo
DNA-duplex interactions in thymines and adenins are used as a linker for the novel methodology of Atomic Force Microscope-Systematic Evolution of Ligands by EXpotential enrichment (AFM-SELEX). This study used the hydrogen bonds in 10 mer of both thymines (T10) and adenines (A10). Initially, the interactive force in T10-A10 was measured by AFM, which returned an average interactive force of approximately 350pN. Based on this result, DNA aptamers against human serum albumin could be selected in the 4th round, and 15 different clones could be sequenced...
January 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28094181/the-oxidative-induction-of-dna-lesions-in-cancer-cells-by-5-thio-d-glucose-and-6-thio-d-fructopyranose-and-their-genotoxic-effects-part-3
#8
Anna Czubatka-Bienkowska, Anna Macieja, Joanna Sarnik, Zbigniew J Witczak, Tomasz Poplawski
Thio-sugars have been described as potent inhibitors of cancer cell growth but the detailed mechanism of action remains unknown. Herein we investigated the mechanism of their anticancer action in the HeLa cell line. We investigated two thio-sugars: 5-thio-d-glucose (FCP1) and 6-thio-β-d-fructopyranose (FCP2). We have observed that FCP1 as well as FCP2 clearly induced oxidative DNA lesions in cancer cells and increased the level of cellular ROS. A spin trap and antioxidants have decreased the level of DNA lesions induced by FCPs...
January 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28094186/nardonaphthalenones-a-and-b-from-the-roots-and-rhizomes-of-nardostachys-chinensis-batal
#9
Xu Deng, Yi-Jing Wu, Ying-Peng Chen, Hong-Hong Zheng, Zhong-Ping Wang, Yan Zhu, Xiu-Mei Gao, Yan-Tong Xu, Hong-Hua Wu
Nardonaphthalenones A and B (1-2), one new apo-α-carotenone (3) and four new monoterpenoids (4, 8-9 and 11), along with six known compounds (5-7, 10, 12-13) were isolated from the dried roots and rhizomes of Nardostachys chinensis Batal. Their structures were elucidated by analysis of the spectroscopic data including NMR, HRESIMS and circular dichroism data. Furthermore, the serotonin transporter (SERT)-regulating activities of these isolates were evaluated, among them compound 3 showed the strongest enhancement activity while compound 12 showed a moderate inhibition activity on SERT...
January 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28094185/anticomplement-triterpenoids-from-the-roots-of-ilex-asprella
#10
Quan Wen, Yan Lu, Zhi Chao, Dao-Feng Chen
Five new (1-5) and twenty-eight known (6-33) triterpenoids were isolated from the roots of Ilex asprella. The structures of the new compounds were elucidated by the detailed spectral analysis. The ursane and oleanane triterpenoids were found to show anticomplement activity with some structure-activity relationships. Several triterpenoids (1-3, 6-7) exhibited potent anticomplement activity with the CH50 and AP50 values of 0.058-0.131mg/mL and 0.080-0.444mg/mL, respectively. It was found that caffeoyl group could enhance activity remarkably, followed by coumaroyl and feruloyl group...
January 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28094180/antifungal-activity-of-substituted-aurones
#11
Caleb L Sutton, Zachary E Taylor, Mary B Farone, Scott T Handy
Novel antifungals are in high demand as there is a growing resistance to antifungals currently in use. In particular, opportunistic fungal infections caused by Candida spp. are on the rise with infections by this genus accounting for the most severe fungal infections following chemotherapy, implantation procedures, and in patients with HIV/AIDS. A series of simple aurone analogs were synthesized and screened for antifungal activity versus Candida spp. Several compounds displayed activity at 100μM, with two having IC50 values below 20μM for three species of Candida...
January 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28094179/synthesis-and-antiviral-evaluation-of-novel-heteroarylpyrimidines-analogs-as-hbv-capsid-effectors
#12
Sebastien Boucle, Xiao Lu, Leda Bassit, Tugba Ozturk, Olivia Ollinger Russell, Franck Amblard, Steven J Coats, Raymond F Schinazi
New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored. The anti-HBV activity in the HepAD38 system, and cytotoxicity profiles of each of the new compounds has been assessed. Among them, five new iodo- and bromo-heteroarylpyrimidines analogs displayed anti-HBV activity in the low micromolar range.
January 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28089700/new-synthetic-route-to-ethynyl-dutp-a-means-to-avoid-formation-of-acetyl-and-chloro-vinyl-base-modified-triphosphates-that-could-poison-selex-experiments
#13
Pascal Röthlisberger, Fabienne Levi-Acobas, Marcel Hollenstein
5-Ethynyl-2'-deoxyuridine is a common base-modified nucleoside analogue that has served in various applications including selection experiments for potent aptamers and in biosensing. The synthesis of the corresponding triphosphates involves a mild acidic deprotection step. Herein, we show that this deprotection leads to the formation of other nucleoside analogs which are easily converted to triphosphates. The modified nucleoside triphosphates are excellent substrates for numerous DNA polymerases under both primer extension and PCR conditions and could thus poison selection experiments by blocking sites that need to be further modified...
January 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28087274/study-of-antileishmanial-activity-of-2-aminobenzoyl-amino-acid-hydrazides-and-their-quinazoline-derivatives
#14
Sherine Nabil Khattab, Nesreen Saied Haiba, Ahmed Mosaad Asal, Adnan A Bekhit, Aida A Guemei, Adel Amer, Ayman El-Faham
A new small library of 2-aminobenzoyl amino acid hydrazide derivatives and quinazolinones derivatives was synthesized and fully characterized by IR, NMR, and elemental analysis. The activity of the prepared compounds on the growth of Leishmania aethiopica promastigotes was evaluated. 2-Benzoyl amino acid hydrazide showed higher inhibitory effect than the quinazoline counterpart. The in vitro antipromastigote activity demonstrated that compounds 2a, 2b, 2f and 4a had IC50 better than standard drug miltefosine and comparable activity to amphotericin B deoxycholate, which indicates their high antileishmanial activity against Leishmania...
January 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28087271/mesoionic-pyrido-1-2-a-pyrimidinones-discovery-of-dicloromezotiaz-as-a-lepidoptera-insecticide-acting-on-nicotinic-acetylcholine-receptors-1-2
#15
Wenming Zhang, Caleb W Holyoke, James Barry, Daniel Cordova, Robert M Leighty, My-Hanh T Tong, Kenneth A Hughes, George P Lahm, Thomas F Pahutski, Ming Xu, Twyla A Briddell, Stephen F McCann, Yewande T Henry, Yuzhong Chen
A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species. In this communication, we report the part of the optimization program that led to the identification of dicloromezotiaz as a potent insecticide to control a broad range of lepidoptera. Our efforts in discovery, synthesis, structure-activity relationship elucidation, and biological activity evaluation are also presented.
January 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28089348/shape-based-virtual-screening-synthesis-and-evaluation-of-novel-pyrrolone-derivatives-as-antiviral-agents-against-hcv
#16
Marcella Bassetto, Pieter Leyssen, Johan Neyts, Mark M Yerukhimovich, David N Frick, Andrea Brancale
A ligand-based approach was applied to screen in silico a library of commercially available compounds, with the aim to find novel inhibitors of the HCV replication starting from the study of the viral NS3 helicase. Six structures were selected for evaluation in the HCV subgenomic replicon assay and one hit was found to inhibit the HCV replicon replication in the low micromolar range. A small series of new pyrrolone compounds was designed and synthesised, and novel structures were identified with improved antiviral activity...
January 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28082038/design-synthesis-and-biological-activity-evaluation-of-novel-2-6-difluorobenzamide-derivatives-through-ftsz-inhibition
#17
Fangchao Bi, Liwei Guo, Yinhu Wang, Henrietta Venter, Susan J Semple, Fang Liu, Shutao Ma
Novel series of 3-substituted 2,6-difluorobenzamide derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their in vitro antibacterial activity against various phenotype of Gram-positive and Gram-negative bacteria, and their cell division inhibitory activity against three representative strains. As a result, 3-chloroalkoxy derivative 7, 3-bromoalkoxy derivative 12 and 3-alkyloxy derivative 17 were found to exhibit the best antibacterial activity against Bacillus subtilis with MICs of 0...
January 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28082040/discovery-of-medium-ring-thiophosphorus-based-heterocycles-as-antiproliferative-agents
#18
Wei Feng, Wisna Novera, Kaye Peh, Donavan Neo, Pondy Murugappan Ramanujulu, Philip K Moore, Lih-Wen Deng, Brian W Dymock
Hydrogen sulfide (H2S) has been investigated for its potential in therapy. Recently, we reported novel H2S donor molecules based on a thiophosphorus core, which slowly release H2S and have improved anti-proliferative activity in cancer cell lines compared to the most widely studied H2S donor GYY4137 (1). Herein, we have prepared new thiophosphorus organic H2S donors with different ring sizes and evaluated them in two solid tumor cell lines and one normal cell line. A seven membered ring compound, 17, was found to be the most potent with sub-micromolar IC50s in breast (0...
January 2, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28108247/design-synthesis-and-bioactivities-of-novel-oxadiazole-substituted-pyrazole-oximes
#19
Hong Dai, Jia Chen, Gang Li, Shushan Ge, Yujun Shi, Yuan Fang, Yong Ling
A series of novel pyrazole oxime derivatives containing a substituted oxadiazole group were designed and synthesized. The bioassay results indicated that some title compounds displayed good acaricidal and insecticidal activities against Tetranychus cinnabarinus, Aphis medicaginis, Oriental armyworm, and Nilaparvata lugens. Especially, compounds 7a, 7b, and 7c had 80%, 90%, and 90% insecticidal activities against A. medicaginis at 20μg/mL, respectively. Interestingly, some of the designed compounds displayed wonderful fungicidal activities in vivo against cucumber Pseudoperonospora cubensis...
December 31, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28089698/novel-2-4-dichlorophenoxy-acetic-acid-substituted-thiazolidin-4-ones-as-anti-inflammatory-agents-design-synthesis-and-biological-screening
#20
Yakub Ali, Mohammad Sarwar Alam, Hinna Hamid, Asif Husain, Abhijeet Dhulap, Sameena Bano, Chetna Kharbanda
A library of fourteen 2-imino-4-thiazolidinone derivatives (1a-1n) has been synthesized and evaluated for in vivo anti-inflammatory activity and effect on ex-vivo COX-2 and TNF-α expression. Compounds 1k (5-(2,4-dichloro-phenooxy)-acetic acid (3-benzyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) and 1m (5-(2,4-dichloro-phenooxy)-acetic acid (3-cyclohexyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) exhibited in vivo inhibition of 81.14% and 78.80% respectively after 5h in comparison to indomethacin which showed 76...
December 31, 2016: Bioorganic & Medicinal Chemistry Letters
journal
journal
30732
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"