Synthesis, structure-activity, and structure-stability relationships of 2-substituted-N-(4-oxo-3-oxetanyl) N-acylethanolamine acid amidase (NAAA) inhibitors.

abstract：:The potassium channel openers flupirtine and retigabine have proven to be valuable analgesics or antiepileptics. Their recent withdrawal due to occasional hepatotoxicity and tissue discoloration, respectively, leaves a therapeutic niche unfilled. Metabolic oxidation of both drugs gives rise to the formation of electro...

journal_title：ChemMedChem

authors： Bock C,Surur AS,Beirow K,Kindermann MK,Schulig L,Bodtke A,Bednarski PJ,Link A

更新日期：2019-05-06 00:00:00

abstract：:Cellular chaperones that belong to the heat-shock protein 90 (Hsp90) family are a prerequisite for successful viral propagation for most viruses. The hepatitis C virus (HCV) uses Hsp90 for maturation, folding, and modification of viral proteins. Based on our previous discovery that marine alkaloid analogues with a 4,5...

journal_title：ChemMedChem

authors： Lillsunde KE,Tomašič T,Schult P,Lohmann V,Kikelj D,Tammela P

更新日期：2019-02-05 00:00:00

abstract：:The therapeutic potential of photoactive CO-releasing molecules (photoCORMs) have called for close examination of the roles of the ligand(s) and the central metal atoms on the overall photochemical labilization of the metal-CO bonds. Along this line, we have synthesized four metal complexes, namely, [MnBr(azpy)(CO)3 ]...

journal_title：ChemMedChem

authors： Chakraborty I,Carrington SJ,Mascharak PK

更新日期：2014-06-01 00:00:00

abstract：:Leishmaniasis is a complex disease caused by over 20 Leishmania species that primarily affects populations with poor socioeconomic conditions. Currently available drugs for treating leishmaniasis include amphotericin B, paromomycin, and pentavalent antimonials, which have been associated with several limitations, such...

journal_title：ChemMedChem

authors： Herrera-Acevedo C,Perdomo-Madrigal C,Muratov EN,Scotti L,Scotti MT

更新日期：2020-12-17 00:00:00

abstract：:In atomic force microscopy (AFM) a sharp cantilever tip is used to scan surfaces at the atomic level. One further application is force spectroscopy, in which force-distance curves between binding partners located on the cantilever and substrate surface are determined. This requires specifically immobilized molecules. ...

journal_title：ChemMedChem

authors： David R,Erdmann M,Fornof AR,Gaub HE

更新日期：2014-09-01 00:00:00

abstract：:Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis belong to a group of infectious diseases known as neglected tropical diseases and are induced by infection with protozoan parasites named trypanosomatids. Drugs in current use have several limitations, and therefore new candidate drugs are required...

journal_title：ChemMedChem

authors： Dichiara M,Marrazzo A,Prezzavento O,Collina S,Rescifina A,Amata E

更新日期：2017-08-22 00:00:00

abstract：:The serotonin transporter (SERT) is one of the neurotransmitter transporters that plays a critical role in the regulation of endogenous amine concentrations and therefore is an important target for therapeutic agents affecting the central nervous system. The recently published, high resolution X-ray structure of the c...

journal_title：ChemMedChem

authors： Jørgensen AM,Tagmose L,Jørgensen AM,Topiol S,Sabio M,Gundertofte K,Bøgesø KP,Peters GH

更新日期：2007-06-01 00:00:00

abstract：:An efficient stereocontrolled synthesis afforded alkoxymethylenephosphonate (MP) analogues of lysophosphatidic acid (LPA) and phosphatidic acid (PA). The pharmacological properties of MP-LPA and MP-PA analogues were characterized for LPA receptor subtype-specific agonist and antagonist activity using Ca(2+)-mobilizati...

journal_title：ChemMedChem

authors： Gajewiak J,Tsukahara R,Tsukahara T,Fujiwara Y,Yu S,Lu Y,Murph M,Mills GB,Tigyi G,Prestwich GD

更新日期：2007-12-01 00:00:00

abstract：:ABC, it's easy as 1 2 3! Bioisosteric replacement of the anilide core by an indole moiety considerably increased stability and gave potent and selective ABCG2 (BCRP) inhibitors. Some compounds are superior to the reference substances fumitremorgin C and Ko143 in terms of potency and efficacy and are the most potent AB...

journal_title：ChemMedChem

authors： Bauer S,Ochoa-Puentes C,Sun Q,Bause M,Bernhardt G,König B,Buschauer A

更新日期：2013-11-01 00:00:00

abstract：:The application of covalent inhibitors has experienced a renaissance within drug discovery programs in the last decade. To leverage the superior potency and drug target residence time of covalent inhibitors, there have been extensive efforts to develop highly specific covalent modifications to decrease off-target liab...

journal_title：ChemMedChem

authors： Vance NR,Witkin KR,Rooney PW,Li Y,Pope M,Spies MA

更新日期：2018-12-06 00:00:00

abstract：:A class of compounds with a common thiazolo[3,2-a]pyrimidinone motif has been developed as general inhibitors of Bcl-2 family proteins. The lead compound was originally identified in a random screening of a small compound library using a fluorescence polarization-based competitive binding assay. Its binding to the Bcl...

journal_title：ChemMedChem

authors： Zhou B,Li X,Li Y,Xu Y,Zhang Z,Zhou M,Zhang X,Liu Z,Zhou J,Cao C,Yu B,Wang R

更新日期：2011-05-02 00:00:00

abstract：:Disturbances of neutrotransmission at the dopamine D3 receptor are related to several neuropsychiatric diseases and in particular to drug addiction. Herein, we report the computer-assisted prediction of D3 selectivities of new fluoroalkoxy-substituted receptor ligands by means of 3D-QSAR analysis. As close analogues o...

journal_title：ChemMedChem

authors： Hocke C,Prante O,Salama I,Hübner H,Löber S,Kuwert T,Gmeiner P

更新日期：2008-05-01 00:00:00

abstract：:The three databases of PubChem, ChemSpider, and UniChem capture the majority of open chemical structure records with February 2018 totals of 95, 63, and 154 million, respectively. Collectively, they constitute a massively enabling resource for cheminformatics, chemical biology, and drug discovery. As meta-portals, the...

journal_title：ChemMedChem

authors： Southan C

更新日期：2018-03-20 00:00:00

abstract：:This is, to our knowledge, the most comprehensive analysis to date based on generative topographic mapping (GTM) of fragment-like chemical space (40 million molecules with no more than 17 heavy atoms, both from the theoretically enumerated GDB-17 and real-world PubChem/ChEMBL databases). The challenge was to prove tha...

journal_title：ChemMedChem

authors： Lin A,Horvath D,Afonina V,Marcou G,Reymond JL,Varnek A

更新日期：2018-03-20 00:00:00

abstract：:Over the years, the 2-substituted imidazoline nucleus has been demonstrated to be a bioversatile structural motif. In this study, novel imidazoline derivatives bearing a 3- and/or 4-hydroxy- or methoxy-substituted phenyl ring, linked by an ethylene bridge to position 2 of an N-benzyl- or N-phenethyl-substituted imidaz...

journal_title：ChemMedChem

authors： Mammoli V,Bonifazi A,Dal Ben D,Giannella M,Giorgioni G,Piergentili A,Pigini M,Quaglia W,Thomas A,Newman AH,Ferré S,Sanchez-Soto M,Keck TM,Del Bello F

更新日期：2016-08-19 00:00:00

abstract：:With the widespread occurrence of bacterial resistance to antibiotics, the development of new strategies beyond conventional treatments is a pursuit taken by public health institutions worldwide. LasR, a transcription factor that controls quorum sensing in Pseudomonas aeruginosa, has emerged as an attractive therapeut...

journal_title：ChemMedChem

authors： Skovstrup S,Le Quement ST,Hansen T,Jakobsen TH,Harmsen M,Tolker-Nielsen T,Nielsen TE,Givskov M,Taboureau O

更新日期：2013-01-01 00:00:00

abstract：:In an approach to design drugs with higher affinity for π-π stacking and electrostatic interactions with targeted biomolecules, complexes of the type [{cis-Pt(A)2 (L)}2 -μ-{trans-1,4-dach}](NO3 )4 ((A)2 =(NH3 )2 or ethylenediamine (en), L=quinoline (quin) or benzothiazole (bztz), dach=trans-1,4-diaminocyclohexane) wer...

journal_title：ChemMedChem

authors： Ma ES,Daniel AG,Farrell NP

更新日期：2014-06-01 00:00:00

abstract：:The spider polyamine toxins Joro spider toxin-3 (JSTX-3) and Nephila polyamine toxins-1 and -8 (NPTX-1 and NPTX-8) are isolated from the venom of the orb-weaver spider Nephila clavata (Joro spider). They share a high degree of structural resemblance, their aromatic head groups being the only difference, and were recen...

journal_title：ChemMedChem

authors： Xiong XF,Poulsen MH,Hussein RA,Nørager NG,Strømgaard K

更新日期：2014-12-01 00:00:00

abstract：:Up to 45 % of deaths in developed nations can be attributed to chronic fibroproliferative diseases, highlighting the need for effective therapies. The RGD (Arg-Gly-Asp) integrin αvβ1 was recently investigated for its role in fibrotic disease, and thus warrants therapeutic targeting. Herein we describe the identificati...

journal_title：ChemMedChem

authors： Hatley RJD,Barrett TN,Slack RJ,Watson ME,Baillache DJ,Gruszka A,Washio Y,Rowedder JE,Pogány P,Pal S,Macdonald SJF

更新日期：2019-07-17 00:00:00

abstract：:The role of beta-aminovinyl ketones as synthetic intermediates has been well categorised, but recent developments have shown an interesting array of applications and new chemotherapeutic potential, both in the preparation of biologically active heterocycles and as pharmacophores in their own right.Medicinal chemists a...

journal_title：ChemMedChem

authors： Gaber HM,Bagley MC

更新日期：2009-07-01 00:00:00

abstract：:Better control of postprandial hyperglycemia can be achieved by delaying the absorption of glucose resulting from carbohydrate digestion. Because α-amylase initiates the hydrolysis of polysaccharides, the design of α-amylase inhibitors can lead to the development of new treatments for metabolic disorders such as type ...

journal_title：ChemMedChem

authors： Al-Asri J,Gyémánt G,Fazekas E,Lehoczki G,Melzig MF,Wolber G,Mortier J

更新日期：2016-11-07 00:00:00

abstract：:TIBO- and TBO-like sulfone derivatives 1 and 2 were designed, synthesized, and tested for their ability to block the replication cycle of HIV-1 in infected cells. The anti-HIV-1 activities of sulfones 3, which were intermediates in the syntheses of 1 and 2, were also evaluated. Surprisingly, the sulfone analogues of T...

journal_title：ChemMedChem

authors： Di Santo R,Costi R,Artico M,Ragno R,Lavecchia A,Novellino E,Gavuzzo E,La Torre F,Cirilli R,Cancio R,Maga G

更新日期：2006-01-01 00:00:00

abstract：:A small library of 17 organoruthenium compounds with the general formula [RuII (fcl)(chel)(L)]n+ (in which fcl=face capping ligand, chel=chelating bidentate ligand, and L=monodentate ligand) were screened for inhibitory activity against cholinesterases and glutathione-S-transferases of human and animal origins. Compou...

journal_title：ChemMedChem

authors： Ristovski S,Uzelac M,Kljun J,Lipec T,Uršič M,Zemljič Jokhadar Š,Žužek MC,Trobec T,Frangež R,Sepčić K,Turel I

更新日期：2018-10-22 00:00:00

abstract：:Designed multitarget ligands are a popular approach to generating efficient and safe drugs, and fragment-based strategies have been postulated as a versatile avenue to discover multitarget ligand leads. To systematically probe the potential of fragment-based multiple ligand discovery, we have employed a large fragment...

journal_title：ChemMedChem

authors： Brunst S,Kramer JS,Kilu W,Heering J,Pollinger J,Hiesinger K,George S,Steinhilber D,Merk D,Proschak E

更新日期：2020-12-06 00:00:00

abstract：:A historical overview of key events that led, 50 years ago, to the foundation of the European Federation for Medicinal Chemistry (EFMC), and the impact this had on promoting and structuring medicinal chemistry as a discipline in Europe. EFMC, together with the growing number of newly established national medicinal che...

journal_title：ChemMedChem

authors： Differding E

更新日期：2020-12-15 00:00:00

abstract：:Natural products containing the α,β-unsaturated δ-lactone skeleton have been shown to possess a variety of biological activities. The natural product (-)-tarchonanthuslactone (1) possessing this privileged scaffold is a popular synthetic target, but its biological activity remains underexplored. Herein, the total synt...

journal_title：ChemMedChem

authors： Toneto Novaes LF,Martins Avila C,Pelizzaro-Rocha KJ,Vendramini-Costa DB,Pereira Dias M,Barbosa Trivella DB,Ernesto de Carvalho J,Ferreira-Halder CV,Pilli RA

更新日期：2015-10-01 00:00:00

abstract：:Disulfide bridges that stabilize the native conformation of conotoxins pose a challenge in the synthesis of smaller conotoxin analogues. Herein we describe the synthesis of a minimized analogue of the analgesic mu-conotoxin KIIIA that blocks two sodium channel subtypes, the neuronal Na(V)1.2 and skeletal muscle Na(V)1...

journal_title：ChemMedChem

authors： Han TS,Zhang MM,Walewska A,Gruszczynski P,Robertson CR,Cheatham TE 3rd,Yoshikami D,Olivera BM,Bulaj G

更新日期：2009-03-01 00:00:00

abstract：:Salecan is a water-soluble bacterial polysaccharide consisting of glucopyranosyl units linked by α-1,3 and β-1,3 glycosidic bonds. salecan is suitable for the development of hydrogels for biomedical applications, given its outstanding physicochemical and biological profiles. In this study we designed a new semi-interp...

journal_title：ChemMedChem

authors： Qi X,Li J,Wei W,Su T,Zuo G,Pan X,Zhang J,Dong W

更新日期：2017-01-20 00:00:00

abstract：:N-Acylethanolamine acid amidase (NAAA) is a cysteine hydrolase that catalyzes the hydrolysis of endogenous lipid mediators such as palmitoylethanolamide (PEA). PEA has been shown to exert anti-inflammatory and antinociceptive effects in animals by engaging peroxisome proliferator-activated receptor α (PPAR-α). Thus, p...

journal_title：ChemMedChem

authors： Fiasella A,Nuzzi A,Summa M,Armirotti A,Tarozzo G,Tarzia G,Mor M,Bertozzi F,Bandiera T,Piomelli D

更新日期：2014-07-01 00:00:00

abstract：:A series of 1,3,3,4-tetrasubstituted pyrrolidine containing CCR5 receptor antagonists were designed, which were elaborated either by condensation of a lithium salt of 3-(N,N-dibenzyl)aminopropionic acid methyl ester with ethyl benzoformate or by Baylis-Hillman reaction of ethyl acrylate with ethyl benzoformate and sub...

journal_title：ChemMedChem

authors： Ma D,Yu S,Li B,Chen L,Chen R,Yu K,Zhang L,Chen Z,Zhong D,Gong Z,Wang R,Jiang H,Pei G

更新日期：2007-02-01 00:00:00