当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > The synthesis and SAR of novel diarylsulfone 11β-HSD1 inhibitors.

The synthesis and SAR of novel diarylsulfone 11β-HSD1 inhibitors.

Abstract：

:In this communication, human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitory activities of a novel series of diarylsulfones are described. Optimization of this series resulted in several highly potent 11β-HSD1 inhibitors with excellent pharmacokinetic (PK) properties. Compound (S)-25 showed excellent efficacy in a non-human primate ex vivo pharmacodynamic model.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Yan X,Wang Z,Sudom A,Cardozo M,DeGraffenreid M,Di Y,Fan P,He X,Jaen JC,Labelle M,Liu J,Ma J,McMinn D,Miao S,Sun D,Tang L,Tu H,Ursu S,Walker N,Ye Q,Powers JP

doi

10.1016/j.bmcl.2010.09.097

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

7071-5

issue

23

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)01406-X

journal_volume

20

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Synthesis of morpholine derivatives using the Castagnoli-Cushman reaction as BACE1 inhibitors: Unexpected binding activity of cyclic thioamides.

    abstract：:The Castagnoli-Cushman reaction between diglycolic anhydride and imines was applied for the synthesis of morpholine derivatives containing a thioamide or an amidino group. Enzyme inhibition assays towards BACE1 revealed an unexpected role of the cyclic thioamide group in providing inhibition in the micromolar range. M...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127211

    authors： Calugi L,Lenci E,Innocenti R,Trabocchi A

    更新日期：2020-07-01 00:00:00

  • N-DEVD-N'-morpholinecarbonyl-rhodamine 110: novel caspase-3 fluorogenic substrates for cell-based apoptosis assay.

    abstract：:A novel caspase-3 substrate N-Ac-DEVD-N'-MC-R110, which is a fluorogenic substrate cleavable in a single step, has been prepared. It has a significantly higher enzyme turnover rate and sensitivity for detecting caspase-3 activity both in solution and living cells than existing fluorogenic substrates. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.02.081

    authors： Wang ZQ,Liao J,Diwu Z

    更新日期：2005-05-02 00:00:00

  • Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.

    abstract：:Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.10.116

    authors： Iserloh U,Wu Y,Cumming JN,Pan J,Wang LY,Stamford AW,Kennedy ME,Kuvelkar R,Chen X,Parker EM,Strickland C,Voigt J

    更新日期：2008-01-01 00:00:00

  • N-Benzyloxycarbonyl-S-(2,4-dinitrophenyl)glutathione dibutyl diester is inhibitory to melarsoprol resistant cell lines overexpressing the T. bruceiMRPA transporter.

    abstract：:A series of glutathione derivatives 1-4, modified at the N,S and/or COOH sites, with in vitro antitrypanosomal activity were tested against bloodstream form Trypanosoma brucei 247 wild type and a T. b. brucei 247 strain over-expressing the multiple drug resistance protein (MRPA) by 50-100x to assess the susceptibility...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.05.086

    authors： Alibu VP,Daunes S,D'Silva C

    更新日期：2013-08-01 00:00:00

  • New merosesquiterpenes from a Vietnamese marine sponge of Spongia sp. and their biological activities.

    abstract：:The investigation of the Vietnamese marine sponge Spongia sp. led to the isolation of three new sesquiterpene phenols, langconols A-C (1-3), and one new sesquiterpene hydroxyquinone, langcoquinone C (4), together with two known meroterpenoids (5 and 6). Their structures were determined on the basis of spectroscopic an...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.05.060

    authors： Nguyen HM,Ito T,Kurimoto SI,Ogawa M,Win NN,Hung VQ,Nguyen HT,Kubota T,Kobayashi J,Morita H

    更新日期：2017-07-15 00:00:00

  • Bicyclic anti-VZV nucleosides: thieno analogues bearing an alkylphenyl side chain have reduced antiviral activity.

    abstract：:Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family bearing a p-alkylphenyl side chain have been synthesised and tested for their antiviral activity against Varicella-Zoster virus (VZV). While the alkyl chain analogues were shown to retain full antiviral activity against VZV, these ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.03.029

    authors： Angell A,McGuigan C,Garcia Sevillano L,Snoeck R,Andrei G,De Clercq E,Balzarini J

    更新日期：2004-05-17 00:00:00

  • Incorporation of cyclic azobenzene into oligodeoxynucleotides for the photo-regulation of DNA hybridization.

    abstract：:Cyclic azobenzene carboxylic acid was synthesized using a shortened route. After reaction with D-threolinol, the resulting cyclic azobenzene-D-threolinol (cAB-Thr) building block was transformed into the corresponding DMTr-protected phosphoramidite, and incorporated into oligodeoxynucleotides at various positions and ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.10.043

    authors： Eljabu F,Dhruval J,Yan H

    更新日期：2015-12-01 00:00:00

  • Trace amine-associated receptor 1 (TAAR1) is activated by amiodarone metabolites.

    abstract：:Amiodarone (Cordarone, Wyeth-Ayerst Pharmaceuticals) is a clinically available drug used to treat a wide variety of cardiac arrhythmias. We report here the synthesis and characterization of a panel of potential amiodarone metabolites that have significant structural similarity to thyroid hormone and its metabolites th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.08.013

    authors： Snead AN,Miyakawa M,Tan ES,Scanlan TS

    更新日期：2008-11-15 00:00:00

  • Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide as an agonist of the alpha7 nicotinic acetylcholine receptor: in vitro and in vivo activity.

    abstract：:A novel alpha7 nAChR agonist, N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (3a, PHA-709829), has been identified for the potential treatment of cognitive deficits in schizophrenia. The compound shows potent and selective alpha7 in vitro activity, excellent brain penetration, good rat oral b...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.04.070

    authors： Acker BA,Jacobsen EJ,Rogers BN,Wishka DG,Reitz SC,Piotrowski DW,Myers JK,Wolfe ML,Groppi VE,Thornburgh BA,Tinholt PM,Walters RR,Olson BA,Fitzgerald L,Staton BA,Raub TJ,Krause M,Li KS,Hoffmann WE,Hajos M,Hurst RS,

    更新日期：2008-06-15 00:00:00

  • The development of monocyclic pyrazolone based cytokine synthesis inhibitors.

    abstract：:4-Aryl-5-pyrimidyl based cytokine synthesis inhibitors that contain a novel monocyclic, pyrazolone heterocyclic core are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-alpha production. One of the compounds (6e) was found to be efficacious in the rat iodoacetate (RIA) in vivo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.03.007

    authors： Golebiowski A,Townes JA,Laufersweiler MJ,Brugel TA,Clark MP,Clark CM,Djung JF,Laughlin SK,Sabat MP,Bookland RG,VanRens JC,De B,Hsieh LC,Janusz MJ,Walter RL,Webster ME,Mekel MJ

    更新日期：2005-05-02 00:00:00

  • Novel pyrrolidine melanin-concentrating hormone receptor 1 antagonists with reduced hERG inhibition.

    abstract：:We discovered novel pyrrolidine MCHR1 antagonist 1 possessing moderate potency. Profiling of pyrrolidine 1 demonstrated that it was an inhibitor of the hERG channel. Investigation of the structure-activity relationship of this class of pyrrolidines allowed us to optimize the MCHR1 potency and decrease the hERG inhibit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.02.046

    authors： Fox BM,Natero R,Richard K,Connors R,Roveto PM,Beckmann H,Haller K,Golde J,Xiao SH,Kayser F

    更新日期：2011-04-15 00:00:00

  • Investigation of novel 7,8-disubstituted-5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-ones as potent Chk1 inhibitors.

    abstract：:The synthesis and structure-activity relationships (SAR) of Chk1 inhibitors based on a 5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-one core are described. Specifically, an exploration of the 7 and 8 positions on this previously disclosed core afforded compounds with improved enzymatic and cellular potency. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.02.080

    authors： Hasvold LA,Wang L,Przytulinska M,Xiao Z,Chen Z,Gu WZ,Merta PJ,Xue J,Kovar P,Zhang H,Park C,Sowin TJ,Rosenberg SH,Lin NH

    更新日期：2008-04-01 00:00:00

  • Synthesis and biological evaluation of novel 4-(hetero) aryl-2-piperazino quinazolines as anti-leishmanial and anti-proliferative agents.

    abstract：:A series of new class of 4-(hetero)aryl-2-piperazino quinazolines were synthesized and assessed for in vitro activity against extracellular promastigotes and intracellular amastigotes of Leishmania donovani. Among the compounds evaluated, compound 4bb and 4cb showed the selectivity index (SI) value>8.03 and 4.21, resp...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.03.020

    authors： Kumar S,Shakya N,Gupta S,Sarkar J,Sahu DP

    更新日期：2009-05-01 00:00:00

  • Synthesis of a novel universal opioid receptor agonist with the 1,3,5-trioxazatriquinane skeleton and its pharmacologies.

    abstract：:We designed and synthesized of 1,3,5-trioxazatriquinanes with o- or p-hydroxyphenyl rings as analogs of the κ opioid receptor agonist SYK-146 with m-hydroxyphenyl groups. Although almost all tested compounds did not bind to the opioid receptors, only 17b (SYK-524) with two o-hydroxyphenyl rings showed moderate or pote...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.08.012

    authors： Hirayama S,Wada N,Kuroda N,Iwai T,Yamaotsu N,Hirono S,Fujii H,Nagase H

    更新日期：2014-10-15 00:00:00

  • Synthesis and inhibitory activity of ubiquinone-acetogenin hybrid inhibitor with bovine mitochondrial complex I.

    abstract：:To elucidate the inhibitory action of acetogenins, the most potent inhibitors of mitochondrial complex I, we synthesized an acetogenin analogue which possesses a ubiquinone ring (i.e., the physiological substrate of complex I) in place of the alpha,beta-unsaturated gamma-lactone ring of natural acetogenins, and named ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00439-6

    authors： Yabunaka H,Abe M,Kenmochi A,Hamada T,Nishioka T,Miyoshi H

    更新日期：2003-07-21 00:00:00

  • Discovery of dimeric inhibitors by extension into the entrance channel of HIV-1 reverse transcriptase.

    abstract：:Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase is being pursued with computational guidance. Extension of azine-containing inhibitors into the entrance channel between Lys103 and Glu138 has led to the discovery of potent and structurally novel derivatives including dimeric inhibitors in an NNRTI-li...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.12.132

    authors： Ekkati AR,Bollini M,Domaoal RA,Spasov KA,Anderson KS,Jorgensen WL

    更新日期：2012-02-15 00:00:00

  • Development of an automated assay for accelerated in vitro detection of DNA adduct-inducing and crosslinking agents.

    abstract：:Current techniques for the identification of DNA adduct-inducing and DNA interstrand crosslinking agents include electrophoretic crosslinking assays, electrophoretic gel shift assays, DNA and RNA stop assays, mass spectrometry-based methods and 32P-post-labelling. While these assays provide considerable insight into t...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2021.127813

    authors： Medan J,Sleebs BE,Lackovic K,Watson KG,Evison BJ,Phillips DR,Cutts SM

    更新日期：2021-01-21 00:00:00

  • Discovery of a novel class of selective human CB1 inverse agonists.

    abstract：:Ligand-based virtual screening led to the discovery of a new class of potent inverse agonists of the human cannabinoid receptor 1, hCB(1), which are selective versus hCB(2). These CB(1) ligands present intriguing departures from a classical CB(1) antagonist pharmacophore. Elements of SAR are discussed in this context....

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.11.133

    authors： Foloppe N,Allen NH,Bentley CH,Brooks TD,Kennett G,Knight AR,Leonardi S,Misra A,Monck NJ,Sellwood DM

    更新日期：2008-02-01 00:00:00

  • N-Heteroaryl glycinamides and glycinamines as potent NPY5 antagonists.

    abstract：:Subtype specific ligands are needed to evaluate the therapeutic potential of modulating the brain's neuropeptide Y system. The benzothiazepine glycinamide 1a was identified as an NPY5 antagonist lead. While having acceptable solubility, the compound was found to suffer from high clearance and poor exposure. Optimizati...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.06.078

    authors： Wu L,Lu K,Desai M,Packiarajan M,Joshi A,Marzabadi MR,Jubian V,Andersen K,Chandrasena G,Boyle NJ,Walker MW

    更新日期：2011-09-15 00:00:00

  • 4-(Alkylthio)- and 4-(arylthio)-benzonitrile derivatives as androgen receptor antagonists for the topical suppression of sebum production.

    abstract：:The first examples of thioether-substituted benzonitriles as potential soft-drug androgen receptor antagonists are reported. A number of 4-(alkylthio)- and of 4-(arylthio)-benzonitrile analogs were evaluated in human androgen receptor binding and cellular functional assays. Analogs with potent in vitro binding and cel...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.01.063

    authors： Mitchell L,Wang Z,Hu LY,Kostlan C,Carroll M,Dettling D,Du D,Pocalyko D,Wade K

    更新日期：2009-03-01 00:00:00

  • 5-Carboxamido-1,3,2-dioxaphosphorinanes, potent inhibitors of MTP.

    abstract：:5-Carboxamido-1,3,2-dioxaphosphorinanes have been identified as potent inhibitors of microsomal triglyceride-transfer protein. The 1,3,2-dioxaphosphorine functionality acted as a neutral and stable replacement for piperidine and piperidine N-oxide. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.07.069

    authors： Sulsky R,Robl JA,Biller SA,Harrity TW,Wetterau J,Connolly F,Jolibois K,Kunselman L

    更新日期：2004-10-18 00:00:00

  • A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 to identify new inhibitors of gp120-CD4 protein-protein interactions.

    abstract：:A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 was built and used to identify new hits able to inhibit gp120-CD4 protein-protein interactions. Two compounds showed micromolar inhibition of HIV-1 replication in cells attributable to an interference with the entry step of infecti...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.09.029

    authors： Caporuscio F,Tafi A,González E,Manetti F,Esté JA,Botta M

    更新日期：2009-11-01 00:00:00

  • Discovery of pyrrolidine-based β-secretase inhibitors: lead advancement through conformational design for maintenance of ligand binding efficiency.

    abstract：:We have developed a novel series of pyrrolidine derived BACE-1 inhibitors. The potency of the weak initial lead structure was enhanced using library-based SAR methods. The series was then further advanced by rational design while maintaining a minimal ligand binding efficiency threshold. Ultimately, the co-crystal str...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.11.024

    authors： Stachel SJ,Steele TG,Petrocchi A,Haugabook SJ,McGaughey G,Katharine Holloway M,Allison T,Munshi S,Zuck P,Colussi D,Tugasheva K,Wolfe A,Graham SL,Vacca JP

    更新日期：2012-01-01 00:00:00

  • Optimization of allosteric MEK inhibitors. Part 2: Taming the sulfamide group balances compound distribution properties.

    abstract：:Recently, we had identified an unexplored pocket adjacent to the known binding site of allosteric MEK inhibitors which allowed us to design highly potent and in vivo efficacious novel inhibitors. We now report that our initial preclinical candidate, featuring a phenoxy side chain with a sulfamide capping group, displa...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.11.004

    authors： Hartung IV,Hammer S,Hitchcock M,Neuhaus R,Scholz A,Siemeister G,Bohlmann R,Hillig RC,Pühler F

    更新日期：2016-01-01 00:00:00

  • Identification of potent, nonabsorbable agonists of the calcium-sensing receptor for GI-specific administration.

    abstract：:Modulation of gastrointestinal nutrient sensing pathways provides a promising a new approach for the treatment of metabolic diseases including diabetes and obesity. The calcium-sensing receptor has been identified as a key receptor involved in mineral and amino acid nutrient sensing and thus is an attractive target fo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.09.008

    authors： Sparks SM,Spearing PK,Diaz CJ,Cowan DJ,Jayawickreme C,Chen G,Rimele TJ,Generaux C,Harston LT,Roller SG

    更新日期：2017-10-15 00:00:00

  • Synthesis of (Z)-2-((1H-indazol-3-yl)methylene)-6-[¹¹C]methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one as a new potential PET probe for imaging of the enzyme PIM1.

    abstract：:(Z)-2-((1H-Indazol-3-yl)methylene)-6-methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one is a potent and selective proviral integration site in moloney murine leukemia virus kinase 1 (PIM1) inhibitor with an IC₅₀ value of 3 nM. (Z)-2-((1H-Indazol-3-yl)methylene)-6-[(11)C]methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.05.091

    authors： Gao M,Wang M,Miller KD,Zheng QH

    更新日期：2013-08-01 00:00:00

  • Cathepsin B inhibitory activities of phthalates isolated from a marine Pseudomonas strain.

    abstract：:Two cathepsin B inhibitors were isolated from the culture supernatant of a marine Pseudomonas sp. PB01 (GenBank Accession No. EU126129). Their structures were elucidated by spectroscopic analyses as dibutyl phthalate and di-(2-ethylhexyl) phthalate. Both dibutyl phthalate and di-(2-ethylhexyl) phthalate showed dose-de...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.01.097

    authors： Hoang VL,Li Y,Kim SK

    更新日期：2008-03-15 00:00:00

  • Synthesis, iron binding and antimicrobial properties of hexadentate 3-hydroxypyridinones-terminated dendrimers.

    abstract：:Macromolecular chelators have potential applications in the medical area, for instance, in treatment of iron overload-related disorders and in the treatment of external infections. In this investigation, several novel iron(III)-selective hydroxypyridinone hexadentate-terminated first and second generation dendrimeric ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.05.058

    authors： Zhou T,Chen K,Kong LM,Liu MS,Ma YM,Xie YY,Hider RC

    更新日期：2018-08-01 00:00:00

  • Discovery of potent and selective histamine H3 receptor inverse agonists based on the 3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one scaffold.

    abstract：:A novel series of potent histamine H(3) receptor inverse agonists based on the 3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one scaffold has been discovered. Several compounds display high selectivity over other histamine receptor subtypes and have favorable physicochemical properties, low potential for CYP450 enzyme inhibit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.08.009

    authors： Richter HG,Freichel C,Huwyler J,Nakagawa T,Nettekoven M,Plancher JM,Raab S,Roche O,Schuler F,Taylor S,Ullmer C,Wiegand R

    更新日期：2010-10-01 00:00:00

  • Synthesis of potent taxoids for tumor-specific delivery using monoclonal antibodies.

    abstract：:The targeted delivery of taxoids, in the form of taxane-antibody immunoconjugates, requires the preparation of taxoids containing moieties suitable for their conjugation to monoclonal antibodies. A series of taxoids incorporating a disulfide-containing linker at various positions of the taxoid framework have been prep...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.05.027

    authors： Miller ML,Roller EE,Wu X,Leece BA,Goldmacher VS,Chari RV,Ojima I

    更新日期：2004-08-02 00:00:00