Protein-ligand (un)binding kinetics as a new paradigm for drug discovery at the crossroad between experiments and modelling.

abstract：:The synthesis, biological evaluation and molecular modeling of a series of pyrrole compounds related to 3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid that evaluates and optimizes C-4 substituents are reported. The key factor for microtubule depolymerization activity appears to be the presence of an ...

journal_title：MedChemComm

authors： Da C,Telang N,Hall K,Kluball E,Barelli P,Finzel K,Jia X,Gupton JT,Mooberry SL,Kellogg GE

更新日期：2013-01-01 00:00:00

abstract：:It was previously reported that 6β-aminomorphinan derivatives show high affinity for opiate receptors. Novel 6β-heteroarylamidomorphinanes were designed based on the MOR selective antagonist NAP. The 6β-aminomorphinanes were prepared with stereoselective Mitsunobu reaction and subsequently acylated with nicotinic acid...

journal_title：MedChemComm

authors： Urai Á,Váradi A,Szőcs L,Komjáti B,Le Rouzic V,Hunkele A,Pasternak GW,Majumdar S,Hosztafi S

更新日期：2017-01-01 00:00:00

abstract：:Many reports have suggested that NRP-1 acts as a co-receptor for VEGF-A165 and boosts tumour growth and metastasis. This NRP-1, due to its important role in tumour progression, triggered interest in the design of new molecules able to significantly inhibit NRP-1/VEGF-A165 interaction to suppress pathological angiogene...

journal_title：MedChemComm

authors： Puszko AK,Sosnowski P,Tymecka D,Raynaud F,Hermine O,Lepelletier Y,Misicka A

更新日期：2019-01-25 00:00:00

abstract：:Much effort has been devoted to targeting agents for imaging and chemotherapy of tumors in cancer research, but there remain significant unmet needs in that area. We have reported a series of preclinical TrkC targeting agents for diagnoses and treatment of metastatic breast cancer; however, with respect to optical ima...

journal_title：MedChemComm

authors： Yang Z,Usama SM,Li F,Burgess K,Li Z

更新日期：2018-08-03 00:00:00

abstract：:Tuberculosis (TB) is an epidemic disease and the growing burden of multidrug-resistant (MDR) TB world wide underlines the need to discover new drugs to treat the disease. Mycobacterium tuberculosis (Mtb) is the etiological agent of most cases of TB. Mtb is difficult to treat, in part, due to the presence of a sturdy h...

journal_title：MedChemComm

authors： Thanna S,Sucheck SJ

更新日期：2016-01-01 00:00:00

abstract：:In this paper, synthesis and characterization of metal complexes [Cu2(L)3]ClO4 (1), [Ga(L)2]NO3·2H2O (2) and [In(L)2]NO3·H2O (3) (HL = 2-acetylpyridine N(4)-phenylthiosemicarbazone) was carried out, including elemental analysis, spectral analysis (IR, UV-vis, NMR), and X-ray crystallography. Complex 1 contains one S-b...

journal_title：MedChemComm

authors： Wang YT,Fang Y,Zhao M,Li MX,Ji YM,Han QX

更新日期：2017-10-09 00:00:00

abstract：:Diabetes mellitus is a chronic, complex and multifactorial disease associated characteristically with hyperglycemia. One of the most recently approved antidiabetic drug classes for clinical use are sodium-glucose cotransporter type 2 (SGLT-2) inhibitors. SGLT-2 is a protein expressed in the kidneys, responsible for gl...

journal_title：MedChemComm

authors： da Silva PN,da Conceição RA,do Couto Maia R,de Castro Barbosa ML

更新日期：2018-06-06 00:00:00

abstract：:N-Acylethanolamine acid amidase (NAAA) is one of the key enzymes involved in the degradation of fatty acid ethanolamides (FAEs), especially for palmitoylethanolamide (PEA). Pharmacological blockage of NAAA restores PEA levels, providing therapeutic benefits in the management of inflammation and pain. In the current wo...

journal_title：MedChemComm

authors： Zhou P,Xiang L,Zhao D,Ren J,Qiu Y,Li Y

更新日期：2018-12-18 00:00:00

abstract：:Herein, we disclose the development of a catalyst- and protecting-group-free microwave-enhanced Friedländer synthesis which permits the single-step, convergent assembly of diverse 8-hydroxyquinolines with greatly improved reaction yields over traditional oil bath heating (increased from 34% to 72%). This rapid synthes...

journal_title：MedChemComm

authors： Garrison AT,Abouelhassan Y,Yang H,Yousaf HH,Nguyen TJ,Huigens Iii RW

更新日期：2016-07-27 00:00:00

abstract：:A series of cyclic peptides were designed and prepared to investigate the physicochemical properties that affect oral bioavailabilty of this chemotype in rats. In particular, the ionization state of the peptide was examined by the incorporation of naturally occurring amino acid residues that are charged in differing r...

journal_title：MedChemComm

authors： Rand AC,Leung SS,Eng H,Rotter CJ,Sharma R,Kalgutkar AS,Zhang Y,Varma MV,Farley KA,Khunte B,Limberakis C,Price DA,Liras S,Mathiowetz AM,Jacobson MP,Lokey RS

更新日期：2012-10-01 00:00:00

abstract：:Previous studies have demonstrated that natural steroid compounds containing a peroxide bridge exhibited potential anti-hepatitis B virus activity. To continue our research, a simple and regioselective methodology, using Eosin Y as a clean photosensitized oxidation catalyst, was developed for the synthesis of a peroxi...

journal_title：MedChemComm

authors： Jia M,Zhao R,Xu B,Yan W,Chu F,Gu H,Xie T,Xiang H,Ren J,Chen D,Wang P,Lei H

更新日期：2016-10-19 00:00:00

abstract：:A focused library of 24 N-aryl urea derivatives was prepared and evaluated against serine esterases of Mycobacterium tuberculosis (Mtb) Rv3802c and Mtb Ag85C. The members of the library were evaluated for both selectivity and mode of inhibition. Furan-based urea derivative 6c was found to be the most potent non-covale...

journal_title：MedChemComm

authors： Vartak A,Goins C,de Moura VCN,Schreidah CM,Landgraf AD,Lin B,Du J,Jackson M,Ronning DR,Sucheck SJ

更新日期：2019-06-04 00:00:00

abstract：:Intrinsic and acquired resistance to conventional and targeted therapeutics is a fundamental reason for treatment failure in many cancer patients. Targeted approaches to overcome chemoresistance as well as resistance to targeted approaches require in depth understanding of the underlying molecular mechanisms. The anti...

journal_title：MedChemComm

authors： Ferreira BI,Lie MK,Engelsen AST,Machado S,Link W,Lorens JB

更新日期：2016-10-21 00:00:00

abstract：:Two diazabicyclo analogues of maraviroc, in which the azabicyclooctane moiety is replaced by diazabicyclooctane or diazabicyclononane, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane derivative maintained a significant infectivity reduction pow...

journal_title：MedChemComm

authors： Legnani L,Colombo D,Venuti A,Pastori C,Lopalco L,Toma L,Mori M,Grazioso G,Villa S

更新日期：2016-12-16 00:00:00

abstract：:The cytotoxic drug gemcitabine (GEM) has been conjugated to receptor-binding peptides to target melanoma tumors. A hexapeptide having a Lys-Gly-His-Lys sequence (pep-1), an octapeptide with an Arg-Gly-Asp-Lys-Gly-His-Lys sequence (pep-2), a GEM-conjugated Lys-Gly-His-Lys peptide (GEM-pep-3) and a GEM-conjugated Asp-Gl...

journal_title：MedChemComm

authors： Gaonkar RH,Baishya R,Paul B,Dewanjee S,Ganguly S,Debnath MC,Ganguly S

更新日期：2018-03-06 00:00:00

abstract：:Human African trypanosomiasis (HAT), also known as African sleeping sickness, is caused by parasitic protozoa of the genus Trypanosoma. As the disease progresses, the parasites cross the blood brain barrier and are lethal for the patients if the disease is left untreated. Current therapies suffer from several drawback...

journal_title：MedChemComm

authors： Berninger M,Schmidt I,Ponte-Sucre A,Holzgrabe U

更新日期：2017-07-31 00:00:00

abstract：:The dopamine D3 receptor (D3R) is a proven therapeutic target for the treatment of neurological and neuropsychiatric disorders. In particular, D3R-selective ligands that can eliminate side effects associated with dopamine D2 receptor (D2R) therapeutics have been validated. However, the high homology in signaling pathw...

journal_title：MedChemComm

authors： Cao Y,Sun N,Zhang J,Liu Z,Tang YZ,Wu Z,Kim KM,Cheon SH

更新日期：2018-06-14 00:00:00

abstract：:Malaria is a serious tropical disease that kills thousands of people every year, mainly in Africa, due to Plasmodium falciparum infections. Salirasib is a promising cancer drug candidate that interferes with the post-translational modification of Ras. This S-farnesyl thiosalicylate inhibits isoprenylcysteine carboxyl ...

journal_title：MedChemComm

authors： Porta EOJ,Bofill Verdaguer I,Perez C,Banchio C,Ferreira de Azevedo M,Katzin AM,Labadie GR

更新日期：2019-06-21 00:00:00

abstract：:[This corrects the article DOI: 10.1039/C7MD00637C.]. ...

journal_title：MedChemComm

authors： Okombo J,Chibale K

更新日期：2018-03-02 00:00:00

abstract：:Recognition of nucleosides at adenosine receptors (ARs) is supported by multiple X-ray structures, but the structure of an adenine complex is unknown. We examined the selectivity of predicted A1AR and A3AR adenine antagonists that incorporated known agonist affinity-enhancing N6 and C2 substituents. Adenines with A1AR...

journal_title：MedChemComm

authors： Yu J,Mannes P,Jung YH,Ciancetta A,Bitant A,Lieberman DI,Khaznadar S,Auchampach JA,Gao ZG,Jacobson KA

更新日期：2018-10-18 00:00:00

abstract：:β-Carbolines have been assessed for osteoclastogenesis. However, their effect on osteoblasts during estrogen deficiency is still unclear. Here, a series of novel piperazine and tetrazole tag β-carbolines have been synthesized and examined for osteoblast differentiation in vitro. In vitro data suggest that compound 8g ...

journal_title：MedChemComm

authors： Karvande A,Khan S,Khan I,Singh D,Khedgikar V,Kushwaha P,Ahmad N,Kothari P,Dhasmana A,Kant R,Trivedi R,Chauhan PMS

更新日期：2018-06-12 00:00:00

abstract：:The type III secretion system injectisome is a syringe-like multimembrane spanning nanomachine that is essential to the pathogenicity but not viability of many clinically relevant Gram-negative bacteria, such as enteropathogenic Escherichia coli, Salmonella enterica and Pseudomonas aeruginosa. Due to the rise in antib...

journal_title：MedChemComm

authors： Lyons BJE,Strynadka NCJ

更新日期：2019-06-20 00:00:00

abstract：:Receptor mediated gene delivery to the liver offers advantages in treating genetic disorders such as hemophilia and hereditary tyrosinemia type I (HTI). Prior findings demonstrated that tethering the d-galactose head group to cationic lipids directs genes to the liver via asialoglycoprotein receptors (ASGPRs). In our ...

journal_title：MedChemComm

authors： Muripiti V,Lohchania B,Marepally SK,Patri SV

更新日期：2017-12-06 00:00:00

abstract：:Sphingosine 1-phosphate (S1P) is involved in hyper-proliferative diseases such as cancer and pulmonary arterial hypertension. We have synthesized inhibitors that are selective for the two isoforms of sphingosine kinase (SK1 and SK2) that catalyze the synthesis of S1P. A thiourea adduct of sphinganine (F02) is selectiv...

journal_title：MedChemComm

authors： Byun HS,Pyne S,Macritchie N,Pyne NJ,Bittman R

更新日期：2013-01-01 00:00:00

abstract：:Previous studies on the large-scale glycomics of more than 3500 human serum samples revealed that the serum glycoproteins of cancer patients often have more dominant and specific glycoforms, namely, branched tri- and tetra-antennary N-glycans, most cancer patient groups than normal control groups. We herein establishe...

journal_title：MedChemComm

authors： Yogesh KV,Kamiyama T,Ohyama C,Yoneyama T,Nouso K,Kimura S,Hinou H,Nishimura SI

更新日期：2018-06-29 00:00:00

abstract：:Tuberculosis is an ever-evolving infectious disease that urgently needs new drugs. In the search for new antituberculosis agents, a library of 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-ones (CHPs) (2a-2y) was synthesized and evaluated against a standard virulent laboratory strain of Mycobacterium tuberculosis H37Rv. O...

journal_title：MedChemComm

authors： Bhat ZS,Ul Lah H,Rather MA,Maqbool M,Ara T,Ahmad Z,Yousuf SK

更新日期：2017-12-06 00:00:00

abstract：:2-Arylethynyl derivatives of (N)-methanocarba adenosine 5'-uronamides are selective A3AR (adenosine receptor) agonists. Here we substitute a 1,2,3-triazol-1-yl linker in place of the rigid, linear ethynyl group to eliminate its potential metabolic liability. Docking of nucleosides containing possible short linker moie...

journal_title：MedChemComm

authors： Tosh DK,Paoletta S,Chen Z,Crane S,Lloyd J,Gao ZG,Gizewski ET,Auchampach JA,Salvemini D,Jacobson KA

更新日期：2015-01-01 00:00:00

abstract：:The natural products colchicine and combretastatin A-4 (CA4) have provided inspiration for the discovery and development of a wide array of derivatives and analogues that inhibit tubulin polymerization through a binding interaction at the colchicine site on β-tubulin. A water-soluble phosphate prodrug salt of CA4 (ref...

journal_title：MedChemComm

authors： Maguire CJ,Chen Z,Mocharla VP,Sriram M,Strecker TE,Hamel E,Zhou H,Lopez R,Wang Y,Mason RP,Chaplin DJ,Trawick ML,Pinney KG

更新日期：2018-08-24 00:00:00

abstract：:Rigidification of the isobutyl side chain of drug-like AT2 receptor agonists and antagonists that are structurally related to the first reported selective AT2 receptor agonist 1 (C21) delivered bioactive indane derivatives. Four enantiomer pairs were synthesized and the enantiomers were isolated in an optical purity >...

journal_title：MedChemComm

authors： Wallinder C,Sköld C,Sundholm S,Guimond MO,Yahiaoui S,Lindeberg G,Gallo-Payet N,Hallberg M,Alterman M

更新日期：2019-11-18 00:00:00

abstract：:The potential for carbon monoxide-releasing molecules (CO-RMs) as antimicrobials represents an exciting prospective in the fight against antibiotic resistance. Trypto-CORM, a tryptophan-containing manganese(i) carbonyl, is toxic against E. coli following photo-activation. Here, we demonstrate that Trypto-CORM is toxic...

journal_title：MedChemComm

authors： Ward JS,Morgan R,Lynam JM,Fairlamb IJS,Moir JWB

更新日期：2016-12-06 00:00:00