当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Matrix metalloproteinase inhibitors based on the 3-mercaptopyrrolidine core.

Matrix metalloproteinase inhibitors based on the 3-mercaptopyrrolidine core.

Abstract：

:New series of pyrrolidine mercaptosulfide, 2-mercaptocyclopentane arylsulfonamide, and 3-mercapto-4-arylsulfonamidopyrrolidine matrix metalloproteinase inhibitors (MMPIs) were designed, synthesized, and evaluated. Exhibiting unique properties over other MMPIs (e.g., hydroxamates), these newly reported compounds are capable of modulating activities of several MMPs in the low nanomolar range, including MMP-2 (~2 to 50 nM), MMP-13 (~2 to 50 nM), and MMP-14 (~4 to 60 nM). Additionally these compounds are selective to intermediate- and deep-pocket MMPs but not shallow-pocketed MMPs (e.g., MMP-1, ~850 to >50,000 nM; MMP-7, ~4000 to >25,000 nM). Our previous work with the mercaptosulfide functionality attached to both cyclopentane and pyrrolidine frameworks demonstrated that the cis-(3S,4R)-stereochemistry was optimal for all of the MMPs tested. However, in our newest compounds an interesting shift of preference to the trans form of the mercaptosulfonamides was observed with increased oxidative stability and biological compatibility. We also report several kinetic and biological characteristics showing that these compounds may be used to probe the mechanistic activities of MMPs in disease.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Jin Y,Roycik MD,Bosco DB,Cao Q,Constantino MH,Schwartz MA,Sang QX

doi

10.1021/jm400529f

subject

Has Abstract

pub_date

2013-06-13 00:00:00

pages

4357-73

issue

11

eissn

0022-2623

issn

1520-4804

journal_volume

56

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • 3-Fluoro-1-hydroxypropan-2-one (fluorohydroxyacetone) and some esters. Syntheses and effects in BDF mice.

    abstract：:1-(Benzoyloxy), 1-(4-nitrobenzoyloxy), and 1-(3,5-dinitrobenzoyloxy) derivatives of 3-fluoro-, 3-chloro-, and 3-bromopropan-2-one were prepared by oxidation of the 1-benzoyloxy-3-halopropan-2-ols in turn prepared from the appropriate benzoyl chloride and 3-halo-1,2-propanediols, 1-Benzoyloxy-3-fluoropropan-2-one was a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00215a005

    authors： Pero RW,Babiarz-Tracy P,Fondy TP

    更新日期：1977-05-01 00:00:00

  • Conformationally constrained tachykinin analogues: potent and highly selective neurokinin NK-2 receptor agonists.

    abstract：:The design and synthesis of potent and selective neurokinin NK-2 receptor agonists 12 (GR64349) and 31 are described, together with structure-activity relationships for related analogues. Compound 12 (EC50 = 3.7 nM at NK-2 receptors in the rat colon; selectivity > 1000- and > 300-fold with respect to NK-1 and NK-3 rec...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00100a027

    authors： Deal MJ,Hagan RM,Ireland SJ,Jordan CC,McElroy AB,Porter B,Ross BC,Stephens-Smith M,Ward P

    更新日期：1992-10-30 00:00:00

  • Flaviviral protease inhibitors identified by fragment-based library docking into a structure generated by molecular dynamics.

    abstract：:Fragment-based docking was used to select a conformation for virtual screening from a molecular dynamics trajectory of the West Nile virus nonstructural 3 protease. This conformation was chosen from an ensemble of 100 molecular dynamics snapshots because it optimally accommodates benzene, the most common ring in known...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900448m

    authors： Ekonomiuk D,Su XC,Ozawa K,Bodenreider C,Lim SP,Otting G,Huang D,Caflisch A

    更新日期：2009-08-13 00:00:00

  • Camptothecin and minor-groove binder hybrid molecules: synthesis, inhibition of topoisomerase I, and anticancer cytotoxicity in vitro.

    abstract：:The synthesis, characterization, inhibitory activity against topoisomerase I, and biological evaluation of a series of 14 camptothecin derivatives of polypyrrolecarboxamide (lexitropsin) conjugates of two structural classes: (A) camptothecin-NHCO-lexitropsin 44-51 and (B) camptothecin-CONH-lexitropsin 38-43 are descri...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9605804

    authors： Zhao R,al-Said NH,Sternbach DL,Lown JW

    更新日期：1997-01-17 00:00:00

  • Synthesis and antitumor activity of tropolone derivatives. 5.

    abstract：:As part of a study on the structure-activity relationship of antitumor-active tropolone derivatives, a series of bistropone analogues, related to potently active bistropolone 1a, were synthesized and tested for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. The methoxytropo...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00390a022

    authors： Yamato M,Hashigaki K,Sakai J,Takeuchi Y,Tsukagoshi S,Tashiro T,Tsuruo T

    更新日期：1987-07-01 00:00:00

  • Diverse, high-quality test set for the validation of protein-ligand docking performance.

    abstract：:A procedure for analyzing and classifying publicly available crystal structures has been developed. It has been used to identify high-resolution protein-ligand complexes that can be assessed by reconstructing the electron density for the ligand using the deposited structure factors. The complexes have been clustered a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm061277y

    authors： Hartshorn MJ,Verdonk ML,Chessari G,Brewerton SC,Mooij WT,Mortenson PN,Murray CW

    更新日期：2007-02-22 00:00:00

  • Searching for New Leads for Tuberculosis: Design, Synthesis, and Biological Evaluation of Novel 2-Quinolin-4-yloxyacetamides.

    abstract：:In this study, a new series of more than 60 quinoline derivatives has been synthesized and evaluated against Mycobacterium tuberculosis (H37Rv). Apart from the SAR exploration around the initial hits, the optimization process focused on the improvement of the physicochemical properties, cytotoxicity, and metabolic sta...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00245

    authors： Pitta E,Rogacki MK,Balabon O,Huss S,Cunningham F,Lopez-Roman EM,Joossens J,Augustyns K,Ballell L,Bates RH,Van der Veken P

    更新日期：2016-07-28 00:00:00

  • Discovery and preclinical profiling of 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a highly potent, selective, brain penetrant, and in vivo active LRRK2 kinase inhibitor.

    abstract：:Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD) by genome-wide association studies (GWAS). The most common LRRK2 mutation, G2019S, which is relatively rare in the total population, gives rise to increased kinase activity. As such, LRRK2 kinase inhibitors are potentially use...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm5014055

    authors： Henderson JL,Kormos BL,Hayward MM,Coffman KJ,Jasti J,Kurumbail RG,Wager TT,Verhoest PR,Noell GS,Chen Y,Needle E,Berger Z,Steyn SJ,Houle C,Hirst WD,Galatsis P

    更新日期：2015-01-08 00:00:00

  • Streptonigrin and related compounds. 5. Synthesis and evaluation of some isoquinoline analogues.

    abstract：:A series of analogues of streptonigrin, in which the quinoline of ring B is replaced by isoquinoline and the substituted pyridine of ring C is replaced by phenyl, nitrophenyl, aminophenyl, or benzyl functions, have been prepared. Thus, 1-substituted isoquinoline-5,8-diones with 7-amino or 6-(alkylamino) groups were pr...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00110a018

    authors： Rao KV,Beach JW

    更新日期：1991-06-01 00:00:00

  • Modulation in selectivity and allosteric properties of small-molecule ligands for CC-chemokine receptors.

    abstract：:Among 18 human chemokine receptors, CCR1, CCR4, CCR5, and CCR8 were activated by metal ion Zn(II) or Cu(II) in complex with 2,2'-bipyridine or 1,10-phenanthroline with similar potencies (EC(50) from 3.9 to 172 μM). Besides being agonists, they acted as selective allosteric enhancers of CCL3. These actions were depende...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm301121j

    authors： Thiele S,Malmgaard-Clausen M,Engel-Andreasen J,Steen A,Rummel PC,Nielsen MC,Gloriam DE,Frimurer TM,Ulven T,Rosenkilde MM

    更新日期：2012-09-27 00:00:00

  • Bis(bioreductive) alkylating agents: synthesis and biological activity in a nude mouse human carcinoma model.

    abstract：:Chemical investigations leading to the construction of bis(bioreductive) alkylating agents having both conformationally restricted and mobile spacer regions are described. Two targets having the conformationally mobile ethylene spacer group, namely, 2,2'-ethylenebis[6-(hydroxymethyl)-p-benzoquinone] diacetate (3b) and...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00366a004

    authors： Witiak DT,Kamat PL,Allison DL,Liebowitz SM,Glaser R,Holliday JE,Moeschberger ML,Schaller JP

    更新日期：1983-12-01 00:00:00

  • Cardiotonic agents. 5. 1,2-Dihydro-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2-oxo-3- pyridinecarbonitriles and related compounds. Synthesis and inotropic activity.

    abstract：:Several 1,2-dihydro-5-(substituted phenyl)-2(1H)-pyridinones were synthesized and evaluated for inotropic activity. 1,2-Dihydro-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2-oxo-3- pyridinecarbonitrile (5a) and the corresponding unsubstituted analogue 14a were the most potent positive inotropic agents in this series. Alth...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00389a011

    authors： Sircar I,Duell BL,Bristol JA,Weishaar RE,Evans DB

    更新日期：1987-06-01 00:00:00

  • Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women's Health.

    abstract：:In 1994, following work from this laboratory, it was reported that estrone-3-O-sulfamate irreversibly inhibits a new potential hormone-dependent cancer target steroid sulfatase (STS). Subsequent drug discovery projects were initiated to develop the core aryl O-sulfamate pharmacophore that, over some 20 years, have led...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b00386

    authors： Thomas MP,Potter BV

    更新日期：2015-10-08 00:00:00

  • Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides.

    abstract：:Chemical manipulations performed on aroyl-pyrrolyl-hydroxyamides (APHAs) led to (aryloxopropenyl)pyrrolyl hydroxamates 2a-w, and their inhibition against maize HDACs and their class I or class II HDAC selectivity were determined. In particular, from these studies some benzene meta-substituted compounds emerged as high...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049002a

    authors： Mai A,Massa S,Pezzi R,Simeoni S,Rotili D,Nebbioso A,Scognamiglio A,Altucci L,Loidl P,Brosch G

    更新日期：2005-05-05 00:00:00

  • Cyclin-Dependent Kinase 2 Inhibitors in Cancer Therapy: An Update.

    abstract：:Cyclin-dependent kinase 2 (CDK2) drives the progression of cells into the S- and M-phases of the cell cycle. CDK2 activity is largely dispensable for normal development, but it is critically associated with tumor growth in multiple cancer types. Although the role of CDK2 in tumorigenesis has been controversial, emergi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/acs.jmedchem.8b01469

    authors： Tadesse S,Caldon EC,Tilley W,Wang S

    更新日期：2019-05-09 00:00:00

  • Synthesis of 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and derivatives as potent and long-acting peripheral inhibitors of catechol-O-methyltransferase.

    abstract：:A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0109964

    authors： Learmonth DA,Vieira-Coelho MA,Benes J,Alves PC,Borges N,Freitas AP,da-Silva PS

    更新日期：2002-01-31 00:00:00

  • Structure-activity studies of reduced-size gonadotropin-releasing hormone agonists derived from the sequence of an endothelin antagonist.

    abstract：:We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an endothelin antagonist, binds specifically (Ki = 1.9 microM) to the rat pituitary gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a GnRH agonistic activity, mediated directly by the GnRH receptor. We now report ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm990432o

    authors： Yahalom D,Rahimipour S,Koch Y,Ben-Aroya N,Fridkin M

    更新日期：2000-07-27 00:00:00

  • Potential antitumor agents. 49. 5-substituted derivatives of N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide with in vivo solid-tumor activity.

    abstract：:Derivatives of N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide bearing a wide variety of different groups at the 5-position (and for comparative purposes at the 7-position) have been prepared, and their physicochemical properties and biological activities have been determined. Although both 5- and 7-substitut...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00387a013

    authors： Denny WA,Atwell GJ,Rewcastle GW,Baguley BC

    更新日期：1987-04-01 00:00:00

  • Synthesis of some 1, 8- and 2, 8-disubstituted derivatives of adenosine cyclic 3', 5'-phosphate and their interaction with some enzymes of cAMP metabolism.

    abstract：:1, 8-Disubstituted derivatives of adenosine cyclic 3', 5'-phosphate (cAMP) were synthesized by N-oxidation or N-methylation of previously reported 8-substituted cAMP derivatives to yield 8-bromoadenosine cyclic 3', 5'-phosphate 1-oxide and 8-(benzylthio)-1-methyladenosine cyclic 3', 5'-phosphate. Substituents were int...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00225a017

    authors： Uno H,Meyer RB,Shuman DA,Robins RK,Simon LN,Miller JP

    更新日期：1976-03-01 00:00:00

  • Discovery of a bulky 2-tert-butyl group containing primaquine analogue that exhibits potent blood-schizontocidal antimalarial activities and complete elimination of methemoglobin toxicity.

    abstract：:To eliminate an unwarranted metabolic pathway of the quinoline ring, a set of two compounds, where C-2 position of the antimalarial drug primaquine is blocked by metabolically stable bulky alkyl group are synthesized. Compound 2 [R = C(CH(3))(3)] of the series has produced excellent antimalarial efficacy against P. be...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0304562

    authors： Jain M,Vangapandu S,Sachdeva S,Singh S,Singh PP,Jena GB,Tikoo K,Ramarao P,Kaul CL,Jain R

    更新日期：2004-01-15 00:00:00

  • Heterocyclic-Fused Pyrimidines as Novel Tubulin Polymerization Inhibitors Targeting the Colchicine Binding Site: Structural Basis and Antitumor Efficacy.

    abstract：:We report the design, synthesis, and biological evaluation of heterocyclic-fused pyrimidines as tubulin polymerization inhibitors targeting the colchicine binding site with significantly improved therapeutic index. Additionally, for the first time, we report high-resolution X-ray crystal structures for the best compou...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b01858

    authors： Banerjee S,Arnst KE,Wang Y,Kumar G,Deng S,Yang L,Li GB,Yang J,White SW,Li W,Miller DD

    更新日期：2018-02-22 00:00:00

  • Simple selection criteria for drug-like chemical matter.

    abstract：:A simple pharmacophore point filter has been developed that discriminates between drug-like and nondrug-like chemical matter. It is based on the observation that nondrugs are often underfunctionalized. Therefore, a minimum count of well-defined pharmacophore points is required to pass the filter. The application of th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm015507e

    authors： Muegge I,Heald SL,Brittelli D

    更新日期：2001-06-07 00:00:00

  • Hotspots in an obligate homodimeric anticancer target. Structural and functional effects of interfacial mutations in human thymidylate synthase.

    abstract：:Human thymidylate synthase (hTS), a target for antiproliferative drugs, is an obligate homodimer. Single-point mutations to alanine at the monomer-monomer interface may enable the identification of specific residues that delineate sites for drugs aimed at perturbing the protein-protein interactions critical for activi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b00137

    authors： Salo-Ahen OM,Tochowicz A,Pozzi C,Cardinale D,Ferrari S,Boum Y,Mangani S,Stroud RM,Saxena P,Myllykallio H,Costi MP,Ponterini G,Wade RC

    更新日期：2015-04-23 00:00:00

  • Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activity.

    abstract：:The discovery of an exceptionally potent series of thrombin receptor (PAR-1) antagonists based on the natural product himbacine is described. Optimization of this series has led to the discovery of 4 (SCH 530348), a potent, oral antiplatelet agent that is currently undergoing Phase-III clinical trials for acute corona...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm800180e

    authors： Chackalamannil S,Wang Y,Greenlee WJ,Hu Z,Xia Y,Ahn HS,Boykow G,Hsieh Y,Palamanda J,Agans-Fantuzzi J,Kurowski S,Graziano M,Chintala M

    更新日期：2008-06-12 00:00:00

  • PRO_LIGAND: an approach to de novo molecular design. 2. Design of novel molecules from molecular field analysis (MFA) models and pharmacophores.

    abstract：:A computational approach for molecular design, PRO_LIGAND, has been developed within the PROMETHEUS molecular design and simulation system in order to provide a unified framework for the de novo generation of diverse molecules which are either similar or complementary to a specified target. In this instance, the targe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00049a019

    authors： Waszkowycz B,Clark DE,Frenkel D,Li J,Murray CW,Robson B,Westhead DR

    更新日期：1994-11-11 00:00:00

  • 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine: an improved serotonin transporter imaging agent.

    abstract：:Imaging serotonin transporters (SERT) is an emerging research tool potentially useful to cast light on the mechanisms of drug action as well as to monitor the treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2-(dimethylaminometh...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049917p

    authors： Kung HF,Newman S,Choi SR,Oya S,Hou C,Zhuang ZP,Acton PD,Plössl K,Winkler J,Kung MP

    更新日期：2004-10-07 00:00:00

  • Potent and Orally Bioavailable Inverse Agonists of RORγt Resulting from Structure-Based Design.

    abstract：:Retinoic acid receptor related orphan receptor γt (RORγt), has been identified as the master regulator of TH17-cell function and development, making it an attractive target for the treatment of autoimmune diseases by a small-molecule approach. Herein, we describe our investigations on a series of 4-aryl-thienyl acetam...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b00783

    authors： Narjes F,Xue Y,von Berg S,Malmberg J,Llinas A,Olsson RI,Jirholt J,Grindebacke H,Leffler A,Hossain N,Lepistö M,Thunberg L,Leek H,Aagaard A,McPheat J,Hansson EL,Bäck E,Tångefjord S,Chen R,Xiong Y,Hongbin G,Hansson

    更新日期：2018-09-13 00:00:00

  • Synthesis and structure-activity relationships of antitubercular 2-nitroimidazooxazines bearing heterocyclic side chains.

    abstract：:Recently described biphenyl analogues of the antituberculosis drug PA-824 displayed improved potencies against M. tuberculosis but were poorly soluble. Heterobiaryl analogues of these, in which the first phenyl ring was replaced with various 5-membered ring heterocycles, were prepared with the aim of identifying poten...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm901378u

    authors： Sutherland HS,Blaser A,Kmentova I,Franzblau SG,Wan B,Wang Y,Ma Z,Palmer BD,Denny WA,Thompson AM

    更新日期：2010-01-28 00:00:00

  • Synthesis, Biological Activities, and X-ray Crystal Structural Analysis of 25-Hydroxy-25(or 26)-adamantyl-17-[20(22),23-diynyl]-21-norvitamin D Compounds.

    abstract：:Novel 19-norvitamin D analogues (ADYW1-4, 5a-d) in which an adamantyl diyne side chain is attached directly to the 17-position of the D ring are designed and stereoselectively synthesized. The adamantane ring of these analogues was expected to interfere with helix 12 (H12, activation function 2) of the vitamin D recep...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b00792

    authors： Watarai Y,Ishizawa M,Ikura T,Zacconi FC,Uno S,Ito N,Mouriño A,Tokiwa H,Makishima M,Yamada S

    更新日期：2015-12-24 00:00:00

  • Phenylalanyl transfer ribonucleic acid synthetase from Escherichia coli B. Potent inhibition by analogues of N-benzyl-2-phenylethylamine.

    abstract：:A potent new class of inhibitors of phenylalanyl-tRNA synthetase from Escherichia coli B is described. N-Benzyl-2-phenylethylamine is a competitive inhibitor with respect to L-phenylalanine and appears to possess the structural features required for near-optimal binding. Hydrophobic substituents at the ortho position ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00233a002

    authors： Anderson RT Jr,Santi DV

    更新日期：1976-11-01 00:00:00