Elucidation of the structure-activity relationships of apelin: influence of unnatural amino acids on binding, signaling, and plasma stability.

abstract：:Different Mannich base derivatives have been studied with the aim of addressing the poor aqueous solubility of the recently disclosed 6-phenethyl-2,3,4,5-tetrahydroazepino[4,3-b]indol-1(6H)-one (1), a human butyrylcholinesterase inhibitor (hBChE, IC50 13 nM) and protective agent in NMDA-induced neurotoxicity, in in vi...

journal_title：ChemMedChem

authors： Purgatorio R,de Candia M,Catto M,Rullo M,Pisani L,Denora N,Carrieri A,Nevskaya AA,Voskressensky LG,Altomare CD

更新日期：2020-11-06 00:00:00

abstract：:A common issue during drug design and development is the discovery of novel scaffolds for protein targets. On the one hand the chemical space of purchasable compounds is rather limited; on the other hand artificially generated molecules suffer from a grave lack of accessibility in practice. Therefore, we generated a n...

journal_title：ChemMedChem

authors： Humbeck L,Weigang S,Schäfer T,Mutzel P,Koch O

更新日期：2018-03-20 00:00:00

abstract：:Oxoisoaporphine alkaloids are a family of oxoisoquinoline-derived alkaloids that were first isolated from the rhizome of Menispermum dauricum DC. (Menispermaceae). It has been demonstrated that oxoisoaporphine alkaloids possess various biological properties, such as cholinesterase and β-amyloid inhibition, acting as a...

journal_title：ChemMedChem

authors： Zhang J,Chen L,Sun J

更新日期：2018-07-06 00:00:00

abstract：:A series of new 5-alkyl-2-phenylaminocarbonylmethylthiopyrimidin-4(3H)-ones bearing variously substituted arylmethyl moieties at the C6 position of the pyrimidine ring were synthesized and evaluated for anti-HIV activity in MT-4 cells. Most of these new congeners exhibited moderate to good activities against the wild-...

journal_title：ChemMedChem

authors： Yu M,Li Z,Liu S,Fan E,Pannecouque C,De Clercq E,Liu X

更新日期：2011-05-02 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：:The histamine H1 G protein-coupled receptor (GPCR) plays an important role in allergy and inflammation. Existing drugs that address the H1 receptor differ in their chemical structure, pharmacology, and side effects. Light-controllable spatial and temporal activity regulation of photochromic H1 ligands may contribute t...

journal_title：ChemMedChem

authors： Rustler K,Pockes S,König B

更新日期：2019-03-22 00:00:00

abstract：:Modulating epigenetic mechanisms in malarial parasites is an emerging avenue for the discovery of novel antimalarial drugs. Previously we demonstrated the potent in vitro and in vivo antimalarial activity of (1-benzyl-4-piperidyl)[6,7-dimethoxy-2-(4-methyl-1,4-diazepin-1-yl)-4-quinazolinyl]amine (BIX01294; 1), a known...

journal_title：ChemMedChem

authors： Sundriyal S,Malmquist NA,Caron J,Blundell S,Liu F,Chen X,Srimongkolpithak N,Jin J,Charman SA,Scherf A,Fuchter MJ

更新日期：2014-10-01 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：:Into the fold: Prion diseases are neurodegenerative disorders characterized by the accumulation in the brain of a self-replicating, misfolded isoform (PrPSc ) of the cellular prion protein (PrPC ). No therapies are available for these pathologies. We capitalized on previously described cell-based assays to screen a li...

journal_title：ChemMedChem

authors： Massignan T,Sangiovanni V,Biggi S,Stincardini C,Elezgarai SR,Maietta G,Andreev IA,Ratmanova NK,Belov DS,Lukyanenko ER,Belov GM,Barreca ML,Altieri A,Kurkin AV,Biasini E

更新日期：2017-08-22 00:00:00

abstract：:Targeting cytokines has become an important focus in the treatment of many inflammatory disorders. p38 MAP kinase (MAPK) is the key enzyme in regulating the biosynthesis and release of pro-inflammatory cytokines such as IL-1beta and TNFalpha. Inhibition of p38 MAPK results in decreased expression of these cytokines. T...

journal_title：ChemMedChem

authors： Ziegler K,Hauser DR,Unger A,Albrecht W,Laufer SA

更新日期：2009-11-01 00:00:00

abstract：:Having oxaliplatin as archetype, several platinum complexes with a carbohydrate moiety resembling the cyclohexane-1,2-diamine ligand of oxaliplatin have been prepared. As leaving groups, the anionic ligands iodide, oxalate, and malonate were utilized, and for comparison purposes the chloro complex was employed. All co...

journal_title：ChemMedChem

authors： Berger I,Nazarov AA,Hartinger CG,Groessl M,Valiahdi SM,Jakupec MA,Keppler BK

更新日期：2007-04-01 00:00:00

abstract：:Selectivity is a central aspect of lead optimization in the drug discovery process. Medicinal chemists often try to decrease molecular flexibility to improve selectivity, given the common belief that the two are interdependent. To investigate the relationship between polypharmacology and conformational flexibility, we...

journal_title：ChemMedChem

authors： He MW,Lee PS,Sweeney ZK

更新日期：2015-02-01 00:00:00

abstract：:Many methods have been developed to capture the biological similarity between two compounds for use in drug discovery. A variety of similarity metrics have been introduced, the Tanimoto coefficient being the most prominent. Many of the approaches assume that molecular features or descriptors that do not relate to the ...

journal_title：ChemMedChem

authors： Abdo A,Salim N

更新日期：2009-02-01 00:00:00

abstract：:HIV protease is a promising drug target for AIDS therapy, and several potent HIV-1 protease inhibitors have been reported to date. Although existing inhibitors exhibit high selectivity, they have also been associated with severe side effects and the possible emergence of therapeutic resistance. As HIV protease cleaves...

journal_title：ChemMedChem

authors： Bhattacharya AK,Rana KC,Pannecouque C,De Clercq E

更新日期：2012-09-01 00:00:00

abstract：:Global pharmaceutical and biotechnology companies have been building increasingly on the skills and services offered by Indian biotech companies through strategic collaborative partnerships and alliances to fuel their in-house discovery and development pipelines. With the exception of generic press releases, however, ...

journal_title：ChemMedChem

authors： Differding E

更新日期：2014-01-01 00:00:00

abstract：:A series of new substituted 7-phenyl-3H-pyrrolo[3,2-f]quinolin-9-ones were synthesized and evaluated for their antiproliferative activity. The most active derivatives showed high selectivity against human leukemia cell lines and potently inhibited their growth, with GI(50) values in the nanomolar range. The active com...

journal_title：ChemMedChem

authors： Ferlin MG,Bortolozzi R,Brun P,Castagliuolo I,Hamel E,Basso G,Viola G

更新日期：2010-08-02 00:00:00

abstract：:The NLRP3 inflammasome is an important regulator of the sterile inflammatory response, and its activation by host-derived sterile molecules leads to the intracellular activation of caspase-1, processing of the pro-inflammatory cytokines interleukin-1β (IL-1β)/IL-18, and pyroptotic cell death. Inappropriate activation ...

journal_title：ChemMedChem

authors： Baldwin AG,Tapia VS,Swanton T,White CS,Beswick JA,Brough D,Freeman S

更新日期：2018-02-20 00:00:00

abstract：:PH-797804 ((aS)-3-{3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl}-N,4-dimethylbenzamde) is a diarylpyridinone inhibitor of p38 mitogen-activated protein (MAP) kinase derived from a racemic mixture as the more potent atropisomer (aS), first proposed by molecular modeling and subsequently confirmed ...

journal_title：ChemMedChem

authors： Xing L,Devadas B,Devraj RV,Selness SR,Shieh H,Walker JK,Mao M,Messing D,Samas B,Yang JZ,Anderson GD,Webb EG,Monahan JB

更新日期：2012-02-06 00:00:00

abstract：:Here we report the synthesis of a number of compounds structurally related to arginine methyltransferase inhibitor 1 (AMI-1). The structural alterations that we made included: 1) the substitution of the sulfonic groups with the bioisosteric carboxylic groups; 2) the replacement of the ureidic function with a bis-amidi...

journal_title：ChemMedChem

authors： Castellano S,Milite C,Ragno R,Simeoni S,Mai A,Limongelli V,Novellino E,Bauer I,Brosch G,Spannhoff A,Cheng D,Bedford MT,Sbardella G

更新日期：2010-03-01 00:00:00

abstract：:Iridium(III) complexes of the type [Ir(η(5) -C5 Me5 )Cl2 {Ph2 PCH2 CH2 CH2 S(O)x Ph-κP}] (x=0-2; 1-3) and [Ir(η(5) -C5 Me5 )Cl{Ph2 PCH2 CH2 CH2 S(O)x Ph-κP,κS}][PF6 ] (x=0-1; 4 and 5) with 3-(diphenylphosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph2 PCH2 CH2 CH2 S(O)x Ph were designed, synthesized, a...

journal_title：ChemMedChem

authors： Ludwig G,Ranđelović I,Maksimović-Ivanić D,Mijatović S,Bulatović MZ,Miljković D,Korb M,Lang H,Steinborn D,Kaluđerović GN

更新日期：2014-07-01 00:00:00

abstract：:Structural preorganization to fix bioactive conformations at protein binding sites is a popular strategy to enhance binding affinity during late-stage optimization. The rationale for this enhancement relates to entropic advantages assigned to rigidified versus flexible ligands. We analyzed a narrow series of peptidomi...

journal_title：ChemMedChem

authors： Rühmann EH,Rupp M,Betz M,Heine A,Klebe G

更新日期：2016-02-04 00:00:00

abstract：:Pharmaceutical companies are facing an increasing interest in new target identification and validation. In particular, extensive efforts are being made in the field of protein kinase inhibitors research and development, and the past ten years of effort in this field have altered our perception of the potential of kina...

journal_title：ChemMedChem

authors： Margutti S,Laufer SA

更新日期：2007-08-01 00:00:00

abstract：:The tropical diseases human African trypanosomiasis, Chagas disease, and the various forms of leishmaniasis are caused by parasites of the family of trypanosomatids. These protozoa possess a unique redox metabolism based on trypanothione and trypanothione reductase (TR), making TR a promising drug target. We report th...

journal_title：ChemMedChem

authors： De Gasparo R,Brodbeck-Persch E,Bryson S,Hentzen NB,Kaiser M,Pai EF,Krauth-Siegel RL,Diederich F

更新日期：2018-05-08 00:00:00

abstract：:Nitrogen mustards are an important class of bifunctional alkylating agents routinely used in chemotherapy. They react with DNA as electrophiles through the formation of highly reactive aziridinium ion intermediates. The antibiotic 593A, with potential antitumor activity, can be considered a naturally occurring piperid...

journal_title：ChemMedChem

authors： Zuravka I,Roesmann R,Sosic A,Wende W,Pingoud A,Gatto B,Göttlich R

更新日期：2014-09-01 00:00:00

abstract：:A DNA-encoded chemical library (DECL) with 1.2 million compounds was synthesized by combinatorial reaction of seven central scaffolds with two sets of 343×492 building blocks. Library screening by affinity capture revealed that for some target proteins, the chemical nature of building blocks dominated the selection re...

journal_title：ChemMedChem

authors： Favalli N,Biendl S,Hartmann M,Piazzi J,Sladojevich F,Gräslund S,Brown PJ,Näreoja K,Schüler H,Scheuermann J,Franzini R,Neri D

更新日期：2018-07-06 00:00:00

abstract：:We previously found that p97 ATPase inhibitors 2-(2-amino-1H-benzo[d]imidazol-1-yl)-N-benzyl-8-methoxyquinazolin-4-amine (ML240) and 2-(2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-benzyl-5,6,7,8-tetrahydroquinazolin-4-amine (ML241) specifically target the D2 domain of wild-type p97. In addition, one of the major p97 cofactors,...

journal_title：ChemMedChem

authors： Fang CJ,Gui L,Zhang X,Moen DR,Li K,Frankowski KJ,Lin HJ,Schoenen FJ,Chou TF

更新日期：2015-01-01 00:00:00

abstract：:β-Lactamases (BLs) are important antibiotic-resistance determinants that significantly compromise the efficacy of valuable β-lactam antibacterial drugs. Thus, combinations with BL inhibitor were developed. Avibactam is the first non-β-lactam BL inhibitor introduced into clinical practice. Ceftazidime-avibactam represe...

journal_title：ChemMedChem

authors： Pozzi C,Di Pisa F,De Luca F,Benvenuti M,Docquier JD,Mangani S

更新日期：2018-07-18 00:00:00

abstract：:Discovered as a modulator of the toxic response to environmental pollutants, aryl hydrocarbon receptor (AhR) has recently gained attention for its involvement in various physiological and pathological pathways. AhR is a ligand-dependent transcription factor activated by a large array of chemical compounds, which inclu...

journal_title：ChemMedChem

authors： Dolciami D,Gargaro M,Cerra B,Scalisi G,Bagnoli L,Servillo G,Fazia MAD,Puccetti P,Quintana FJ,Fallarino F,Macchiarulo A

更新日期：2018-02-06 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：:New geiparvarin derivatives modified at the unsaturated alkenyloxy bridge, where a hydrogen atom replaces the 3'-methyl group, were synthesized and evaluated against a panel of human tumor cell lines in vitro. These compounds demonstrated an increase in growth inhibitory activity relative to the parent compound, geipa...

journal_title：ChemMedChem

authors： Chimichi S,Boccalini M,Salvador A,Dall'Acqua F,Basso G,Viola G

更新日期：2009-05-01 00:00:00