Molecular Diversity (Mol Divers )

Publisher: Springer Verlag

Description

Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers perspectives news and reviews dealing with all aspects of the generation of molecular diversity application of diversity for screening against alternative targets of all types (biological biophysical technological) analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis small molecule libraries peptides proteins oligonucleotides carbohydrates structure/function/SAR computational chemistry/molecular design screening techniques and screening interfaces analytical methods robotics/automation/miniaturization new approaches/methods of library formulation and deconvolution directed evolution/origin of life/recombination theory (search techniques landscapes random chemistry). The journal will accept two types of manuscripts: (i) Full length papers giving a comprehensive description of original work. (ii) Short communications for rapid publication of novel observations. In addition Perspectives Reviews and Conference Reports are published occasionally.

  • Impact factor
    2.86
  • 5-year impact
    3.09
  • Cited half-life
    3.50
  • Immediacy index
    0.44
  • Eigenfactor
    0.00
  • Article influence
    0.64
  • Website
    Molecular Diversity website
  • Other titles
    Molecular diversity (Online)
  • ISSN
    1573-501X
  • OCLC
    41975810
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Springer Verlag

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Author's pre-print on pre-print servers such as arXiv.org
    • Author's post-print on author's personal website immediately
    • Author's post-print on any open access repository after 12 months after publication
    • Publisher's version/PDF cannot be used
    • Published source must be acknowledged
    • Must link to publisher version
    • Set phrase to accompany link to published version (see policy)
    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Nowadays most of the CNS acting therapeutic molecules are failing in clinical trials due to efflux transporters at the blood brain barrier (BBB) which imparts resistance and poor ADMET properties of these molecules. CNS acting drug molecules interact with the BBB prior to their target site, so there is a need to develop predictive models for BBB permeability which can be used in the initial phases of drug discovery process. Most of the drug molecules are transported to the brain via passive diffusion which is explored extensively; on the other hand, the role of active efflux transporters in BBB permeability is unclear. Our aim is to develop predictive models for BBB permeability that include active efflux transporters. An in silico model has been developed to assess the role of BCRP on BBB permeation. Eight descriptors were selected, which also include BCRP substrate probabilities used for model development and show a relationship between BCRP and logBB. From our analysis, it was found that 11 molecules satisfied all criteria required for BBB permeation but have low logBB values. These 11 molecules are predicted as BCRP substrates from the model developed, suggesting that the molecules are effluxed by the BCRP transporter. This predictive ability was further validated by docking of these 11 molecules into BCRP protein. This study provides a new mechanistic insight into correlation of low logBB values and efflux mechanism of BCRP in BBB.
    Molecular Diversity 12/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The reaction of racemic 2-amino-4[Formula: see text]-pyrans, such as 3-amino-1-aryl-1[Formula: see text]-benzo[Formula: see text]chromene-2-carbonitriles, with [Formula: see text]-bromosuccinimide (NBS), in [Formula: see text], at room temperature, is a very quick, regio, stereoselective, and high yielding process, affording major racemic [Formula: see text]-2-bromo-3-imino-benzo[Formula: see text]chromene or racemic [Formula: see text]-2-bromo-3-(bromoimino)-benzo[Formula: see text]chromene derivatives, when using 1.0 or 2.2 equivalents of NBS, respectively. This reaction, extended to isomeric 2-amino-4-aryl-4[Formula: see text]-benzo[Formula: see text]chromene-3-carbonitriles, showed an unexpected reactivity, affording racemic (3[Formula: see text],4[Formula: see text]-3-bromo-2-(bromoimino)-benzo[Formula: see text]chromene-3-carbonitriles or 2-oxo-2[Formula: see text]-benzo[Formula: see text]chromene-3-carbonitriles, when using 2.2 or 1.0 equivalents of NBS, respectively. The reaction of alkyl 6-amino-5-cyano-2-methyl-4[Formula: see text]-pyran-3-carboxylates has yielded unstable racemic (3[Formula: see text],4[Formula: see text]-alkyl 3-bromo-2-(bromoimino)-3-cyano-6-methyl-3,4-dihydro-2[Formula: see text]-pyran-5-carboxylates. The mechanism of these reactions has been investigated by computational methods.
    Molecular Diversity 12/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: An efficient one-pot synthesis of various 2,3-dihydroquinazolin-[Formula: see text]-one derivatives was accomplished using [Formula: see text]-catalyzed multi-component reactions between isatoic anhydride, ketones, and amines. The method has several significant advantages; mild reaction conditions, easy handling, and efficiency of catalyst.
    Molecular Diversity 11/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mer kinase is a novel therapeutic target for many cancers, and overexpression of Mer receptor tyrosine kinase has been observed in several kinds of tumors. To deeply understand the structure-activity correlation of a series of pyridine/pyrimidine analogs as potent Mer inhibitors, a combined molecular docking and three-dimensional quantitative structure-activity relationship modeling was carried out. A comparative molecular similarity indices analysis model was developed based on the maximum common substructure alignment. The optimum model exhibited statistically significant results: the cross-validated correlation coefficient [Formula: see text] was 0.599, and non-cross-validated [Formula: see text] value was 0.984. Furthermore, the results of internal validation such as bootstrapping, Y-randomization as well as external validation (the external predictive correlation coefficient [Formula: see text] confirmed the rationality and good predictive ability of the model. Using the crystal structure of Mer kinase, the selected pyridine/pyrimidine compounds were docked into the enzyme active site. Some key amino acid residues were determined, and hydrogen bonding and hydrophobic interactions between Mer kinase and inhibitors were identified. The satisfactory results from this study may aid in the research and development of novel potent Mer kinase inhibitors.
    Molecular Diversity 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: This report provides a brief overview of the various representative literature procedures for the synthesis of 1,5-disubstituted tetrazoles (1,5-DSTs) and fused 1,5-disubstituted tetrazoles with more than 120 references. Most of the published methods for the synthesis of 1,5-DSTs include the use of nitriles, amides, thioamides, imidoyl chlorides, heterocumulenes, isocyanates, isothiocyanates, carbodiimides, ketenimines, ketones, amines, and alkenes as the starting materials. The transformation of 1- and 5-substituted tetrazoles into 1,5-DSTs is also covered in this report.
    Molecular Diversity 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Influenza is an acute respiratory infectious disease caused by influenza viruses. Its subtype can be distinguished based on the antigenicity of two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). One of the main challenges in anti-influenza drug development is the quick evolution of drug resistance due to virus mutations. One solution to this problem is to develop dual-targeting anti-influenza agents. In this paper, a new rationally designed virtual screening protocol that combines structure-based approaches (molecular docking and molecular dynamic simulations) and ligand-based approaches (support vector machines and 3D shape & electrostatic similarity algorithms) is reported for the virtual screening of dual-targeting agents against HA and NA. The final hits came from the consensus of the ligand- and receptor-based knowledge of HA and NA and were tested using ADMET predictions. Evidence from the binding energy calculations and binding mode analyses suggested that several of the hits are promising as dual-targeting anti-influenza agents. The virtual screening protocol may also lead to the identification of innovative drugs in other fields.
    Molecular Diversity 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: An effective and practical method has been developed for the diversity-oriented synthesis of fully substituted cyclohexene [Formula: see text]-aminoester via a pseudo five-component reaction between nitromethane, aromatic aldehydes, and substituted cyanoacetate for the generation of a wide range of structurally relevant and highly functionalized compounds. The attractive range and features of the method, which enables the facile preparation of highly substituted cyclohexenes, are its simple and straightforward procedure, mild reaction conditions, and ideal yields. The mechanism involves a double Michael addition reaction followed by intramolecular ring closure. The fully substituted cyclohexene [Formula: see text]-aminoesters with potential bioactivities could be of impact in medical chemistry.
    Molecular Diversity 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: A general synthetic route for the exclusive preparation of tetrasubstituted imidazoles, possessing benzylic methyl groups has been developed using [Formula: see text] via solvent-free, one-pot reaction conditions. Detailed results from our investigation on the bromination of the benzylic methyl groups of imidazoles are described. The products generated during this study were utilized as substrates for the synthesis of organosilicon-containing imidazoles. Synthesis of tris(triorganosilyl)methylimidazole derivatives was carried out using organolithium reagents [Formula: see text] (R= H, Me, Ph) prepared via metalation of [Formula: see text] with lithiumdiisopropylamide or methyllithium in THF, in excellent yields. [Formula: see text], (R= Me, Ph) were treated with formylated imidazole to afford imidazole containing 2,2-bis(organosilyl)ethenyl groups. 2-(4-(2,2-bis(trimethylsilyl)vinyl)phenyl)-1,4,5-triphenyl-1[Formula: see text]-imidazole was obtained via Peterson reaction in high yield. However, compound 2-(4-(2,2-bis(dimethyl(phenyl)silyl)vinyl)phenyl)-1,4,5-triphenyl-1[Formula: see text]-imidazole was obtained in low yield likely because of the steric hindrance of the [Formula: see text]- group.
    Molecular Diversity 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The translational failure between preclinical animal models and clinical outcome has alarmed us to search for a new strategy in the treatment of Alzheimer’s disease (AD). Interlink between Pregnane X Receptor (PXR) and P-glycoprotein (Pgp) at the blood brain barrier (BBB) has raised hope toward a new disease modifying therapy in AD. Pgp is a major efflux transporter for beta amyloid (A β) at human BBB. A literature survey reveals diminished expression of Pgp transporter at the BBB in AD patients. Pregnane X Receptor is a major transcriptional regulator of Pgp. Restoration of Pgp at the BBB enhances the elimination of the A β from brain alongside and inhibits the apical to basolateral movement of A β from the circulatory blood. This review concentrates on in vitro, in vivo, and in silico advancements on the study of the PXR in context to Pgp and discusses the substrate and inhibitor specificity between PXR and Pgp.
    Molecular Diversity 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: A highly efficient, catalyst-free group-assisted purification chemical protocol for the construction of pyrimidine containing poly-functionalized pyrroles from a four-component domino reaction of acyclic-1,3-dicarbonyls or electron deficient alkynes, aromatic amines, barbituric acid and arylglyoxal hydrates under mild reaction conditions has been developed. The prominent features of the present protocol are environmentally benign, mild reaction conditions, atom economy, no column chromatography separation, easy isolation of products and excellent yields.
    Molecular Diversity 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: A small library of 30 thiomarinol analogues was successfully synthesised using as a key step-a catalytic enantioselective tandem oxa[4+2] cycloaddition/aldehyde allylboration methodology. With this method, highly substituted [Formula: see text]-hydroxyalkyl dihydropyrans were assembled in a single three-component reaction utilizing three different enol ethers and a wide variety of aldehydes, such as aromatic, heteroaromatic, unsaturated and aliphatic aldehydes. In a second operation, a mild and direct method for reducing an acetal unit in the [Formula: see text]-hydroxyalkyl dihydropyrans was optimised without the need for protecting a nearby hydroxyl group. This procedure facilitated the synthetic sequence, which was completed by a dihydroxylation of the residual olefin of [Formula: see text]-hydroxyalkyl 2[Formula: see text]-pyrans to provide the desired library of dihydroxylated pyran analogues reminiscent of the thiomarinol antibiotics. The relative stereochemistry of the resulting library compounds was demonstrated by X-ray crystallography on one of the analogues.
    Molecular Diversity 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: An efficient synthesis of novel 3-oxotetrahyrothiazolo[3,2-[Formula: see text]]pyrimidine-8-carboxylate derivatives was developed by reacting 4-oxothiazolidines with formaldehyde and amines under very mild conditions. A variety of novel thiazolopyrimidine carboxylates were attained rapidly by double Mannich/intramolecular cyclisation reactions in very good yields.
    Molecular Diversity 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: An efficient and diastereoselective synthetic procedure for highly functionalized tetrahydroacenaphtho[1,2-[Formula: see text]]indolone derivatives was successfully developed by the three-component reaction of acenaphthequinone, enaminones, and barbituric acid in the presence of a catalytic amount of L-proline. This method has the advantages of convenient operation, excellent yields, mild reaction conditions, and environmental friendliness.
    Molecular Diversity 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The three-component reaction of [Formula: see text]-benzylbenzimidazole, dialkyl acetylenedicarboxylate, and [Formula: see text]-alkylisatins in tetrahydrofuran at room temperature afforded the novel functionalized benzimidazole[2.1-b][1,3]oxazine spirooxindoles in good yields. [Formula: see text]H NMR spectra indicated that two diastereoisomers with a ratio of 1:3-1:6 exist in the obtained spirooxindole derivatives. .
    Molecular Diversity 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The synthesis of bis(1,2,4-oxadiazoles), 1,2,4-oxadiazolyl-quinazolines, and 1,2,4-oxadiazolyl-benzothiazinones has been investigated by the reaction of diaminoglyoxime with various ketones and methyl 2-aminobenzoate, 2-amino-5-chlorophenyl)(phenyl)methanone, and 2-mercapto benzoic acid in acetic acid either a catalyst or solvent at 100 [Formula: see text]C.
    Molecular Diversity 08/2014;