Discovery of functionalized bisimidazoles bearing cyclic aliphatic-phenyl motifs as HCV NS5A inhibitors.


:This Letter describes the discovery of a number of functionalized bisimidazoles bearing a cyclohexylphenyl, piperidylphenyl, or bicyclo[2,2,2]octylphenyl motif as HCV NS5A inhibitors. Compounds 2c, 4b and 6 have demonstrated low single-digit nM potency in gt-1a replicon and double-digit pM potency in gt-1b replicon, respectively. Moreover, both 4b and 6 have, respectively, exhibited good oral bioavailability in rats with a favorable liver/plasma ratio of the drug concentration.


Bioorg Med Chem Lett


Zhong M,Peng E,Huang N,Huang Q,Huq A,Lau M,Colonno R,Li L




Has Abstract


2014-12-15 00:00:00














  • Oxidative calcium release from catechol.

    abstract::Oxidation of 4-methylcatechol previously exposed to aqueous calcium chloride was shown by ion chromatography to be associated with release of calcium ions. The catechol was oxidised to the corresponding orthoquinone by the use of tyrosinase from Agaricus bisporus. The oxidative release of calcium from the catechol is ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Riley PA,Stratford MR

    更新日期:2015-04-01 00:00:00

  • Synthesis, structural characterization and antitumor activity evaluations of copper complex with tetraazamacrocyclic ligand.

    abstract::Cu (II) complex with 1,4,7,10-tetrakis(2-cyanoethyl-)-1,4,7,10-tetraazacyclododecane was prepared and characterized by X-ray diffraction. Four nitrogen atoms of macrocyclic ligand and oxygen atom of water molecule defined a tetragonal pyramidal polyhedron surrounding the central copper atom. Preliminary pharmacologica...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kong D,Qin C,Meng L,Xie Y

    更新日期:1999-04-19 00:00:00

  • Detour of prenostodione synthesis towards pyrazolones for antibacterial activity.

    abstract::Our attempts to prepare indolyl acid (3), enroute to prenostodione (2), from phenyl-hydrazine following a reported procedure of Fischer-Indole synthesis rather lead to ethyl 2-(5-oxo-1-phenyl-2,5-dihydro-1H-pyrazol-3-yl)acetate as a major product, which underwent facile condensation with aldehydes to provide the pyraz...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Rasapalli S,Fan Y,Yu M,Rees C,Harris JT,Golen JA,Jasinski JP,Rheingold AL,Kwasny SM,Opperman TJ

    更新日期:2013-06-01 00:00:00

  • Cyclopentadienyltricarbonylrheniumbenzazepines: synthesis and binding affinity.

    abstract::Analogues of the benzazepine dopamine D1 receptor antagonist SCH-23390 incorporating the cyclo-pentadienyltricarbonyl-rhenium (CPTR) moiety were synthesized and evaluated pharmacologically. The CPTR derivatives retained affinity (0.3-2.9 nM) and D1 selectivity of the parent compound, supporting their use as neuropharm...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Tamagnan G,Baldwin RM,Kula NS,Baldessarini RJ,Innis RB

    更新日期:2000-05-15 00:00:00

  • Design, synthesis and biological evaluation of novel pyrazolo-pyrimidinones as DPP-IV inhibitors in diabetes.

    abstract::We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amon...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sagar SR,Agarwal JK,Pandya DH,Dash RP,Nivsarkar M,Vasu KK

    更新日期:2015-10-15 00:00:00

  • Substituted tetrahydro-beta-carbolines as potential agents for the treatment of human papillomavirus infection.

    abstract::The identification and optimization of a series of substituted tetrahydro-beta-carbolines with potent activity against human papillomavirus is described. Structure-activity studies focused on the substitution pattern and chirality of the beta-carboline ring system are discussed. Optimization of these parameters led to...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Miller JF,Turner EM,Sherrill RG,Gudmundsson K,Spaltenstein A,Sethna P,Brown KW,Harvey R,Romines KR,Golden P

    更新日期:2010-01-01 00:00:00

  • Parallel synthesis of 1,2,4-oxadiazoles using CDI activation.

    abstract::1,2,4-Oxadiazoles have been prepared in parallel using 1,1'-carbonyldiimidazole (CDI) as a reagent for both formation and cyclodehydration of O-acyl benzamidoximes. The use of CDI facilitates parallel purification of the oxadiazole products by simple liquid-liquid extraction and filtration. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Deegan TL,Nitz TJ,Cebzanov D,Pufko DE,Porco JA Jr

    更新日期:1999-01-18 00:00:00

  • New tetrahydronaphthalene derivatives as combined thromboxane receptor antagonists and thromboxane synthase inhibitors.

    abstract::A pyridine group was linked to the tetrahydronaphthalene moiety of the derivatives described in the preceding paper, to afford new combined thromboxane receptor (TP-receptor) antagonists and synthase inhibitors. The most interesting compound 2f inhibits TXA2 synthase with an IC50 value of 0.64 microM and the aggregati...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Cimetière B,Dubuffet T,Landras C,Descombes JJ,Simonet S,Verbeuren TJ,Lavielle G

    更新日期:1998-06-02 00:00:00

  • Kinesin spindle protein (KSP) inhibitors. Part V: discovery of 2-propylamino-2,4-diaryl-2,5-dihydropyrroles as potent, water-soluble KSP inhibitors, and modulation of their basicity by beta-fluorination to overcome cellular efflux by P-glycoprotein.

    abstract::Installation of a C2-aminopropyl side chain to the 2,4-diaryl-2,5-dihydropyrrole series of kinesin spindle protein (KSP) inhibitors results in potent, water soluble compounds, but the aminopropyl group induces susceptibility to cellular efflux by P-glycoprotein (Pgp). We show that by carefully modulating the basicity ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Cox CD,Breslin MJ,Whitman DB,Coleman PJ,Garbaccio RM,Fraley ME,Zrada MM,Buser CA,Walsh ES,Hamilton K,Lobell RB,Tao W,Abrams MT,South VJ,Huber HE,Kohl NE,Hartman GD

    更新日期:2007-05-15 00:00:00

  • Substituted aminobenzimidazole pyrimidines as cyclin-dependent kinase inhibitors.

    abstract::A series of aminobenzimidazole-substituted pyrimidines were synthesized and evaluated for biochemical activity against CDK1. A high-speed parallel synthesis approach enabled the identification of a potent lead series having improved potency in the CDK1 assay (IC(50)<10nM). Cell cycle analysis showed that the compounds...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Verma S,Nagarathnam D,Shao J,Zhang L,Zhao J,Wang Y,Li T,Mull E,Enyedy I,Wang C,Zhu Q,Altieri M,Jordan J,Dang TT,Reddy S

    更新日期:2005-04-15 00:00:00

  • First synthesis of separable isomeric testosterone dimers showing differential activities on prostate cancer cells.

    abstract::The synthesis of two separable isomeric testosterone dimers is reported. The dimers are made from testosterone in a 5 step sequence and with 36% overall yield. The key dimerization step was performed using Hoveyda-Grubb's metathesis catalysts on 7alpha-allyltestosterone with 75% yield. The synthesis led to separable i...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Bastien D,Leblanc V,Asselin E,Bérubé G

    更新日期:2010-04-01 00:00:00

  • Novel pyrimidines as acid pump antagonists (APAs).

    abstract::A series of pyrimidine derivatives as acid pump antagonists (APAs) was synthesized and the inhibitory activities against H(+)/K(+) ATPase isolated from hog gastric mucosa were determined. After elaborating on substituents at C2 and C4 position of the pyrimidine scaffold, we have observed that the compound 7h is a pote...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Yoon YA,Park CS,Cha MH,Choi H,Sim JY,Kim JG

    更新日期:2010-10-01 00:00:00

  • Design, synthesis and biological evaluation of seco-A-pentacyclic triterpenoids-3,4-lactone as potent non-nucleoside HBV inhibitors.

    abstract::A series of seco-A-pentacyclic triterpenoids-3,4-lactone were synthesized and the anti-HBV activities were evaluated in vitro. Several compounds inhibited the secretion of HBV antigen and the replication of HBV DNA in micromolar level. Compounds D7 and D10, seco-A-oleanane-3,4-lactone, suppressed the HBeAg secretion w...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Li Z,Min Q,Huang H,Liu R,Zhu Y,Zhu Q

    更新日期:2018-05-15 00:00:00

  • Syntheses of novel antitumor dihydroxanthone derivatives with inhibitory activity against DNA topoisomerase II.

    abstract::A series of methoxycarbonyl group modified nidulalin A analogs were synthesized to improve stability against esterases. The amide derivatives showed cytotoxic activity along with inhibitory activity against DNA topoisomerase II. Among the analogs, amide 9a exhibited antitumor activity in Colon 26 murine tumor model. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sato S,Suga Y,Yoshimura T,Nakagawa R,Tsuji T,Umemura K,Andoh T

    更新日期:1999-09-20 00:00:00

  • Synthesis, antiviral activity and pharmacokinetics of P1/P1' substituted 3-aminoindazole cyclic urea HIV protease inhibitors.

    abstract::A series of P1/P1' substituted cyclic urea analogues were prepared in an attempt to increase the intra-cellular antiviral potency of the nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851. The effect of alkyl substitution of the P1/P1' residues on cellular antiviral potency, protein binding, resistance profile and ph...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kaltenbach RF 3rd,Patel M,Waltermire RE,Harris GD,Stone BR,Klabe RM,Garber S,Bacheler LT,Cordova BC,Logue K,Wright MR,Erickson-Viitanen S,Trainor GL

    更新日期:2003-02-24 00:00:00

  • Substrate and inhibitor specificity of kynurenine monooxygenase from Cytophaga hutchinsonii.

    abstract::Kynurenine monooxygenase (KMO) is a potential drug target for treatment of neurodegenerative disorders such as Huntington's and Alzheimer's diseases. We have evaluated substituted kynurenines as substrates or inhibitors of KMO from Cytophaga hutchinsonii. Kynurenines substituted with a halogen at the 5-position are ex...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Phillips RS,Anderson AD,Gentry HG,Güner OF,Bowen JP

    更新日期:2017-04-15 00:00:00

  • Synthesis and preliminary cytotoxicity of nitrogen mustard derivatives of distamycin A.

    abstract::Distamycin and nitrogen mustard conjugates, in which the nitrogen mustard unit was coupled to the C-terminus of the pyrrole, were synthesized. The switching of the nitrogen mustard unit from the N-terminus to the C-terminus did not compromise the compound's cytotoxicity. Compound 3, bearing three pyrrole units, was hi...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Wang Y,Wright SC,Larrick JW

    更新日期:2003-02-10 00:00:00

  • Transformation of 8-prenylnaringenin by Absidia coerulea and Beauveria bassiana.

    abstract::Beauveria bassiana AM278 and Absidia coerulea AM93 converted 8-prenylnaringenin (1) into two glycoside derivatives (7-O-β-D-glucopyranoside) (2) and 7-O-β-D-4'''-O-methylglucopyranoside) (3) in high yields in processes conducted in Saboraud medium. 8-Prenylnaringenin 7-O-β-D-4'''-O-methylglucopyranoside (3) is a new c...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Bartmańska A,Tronina T,Huszcza E

    更新日期:2012-10-15 00:00:00

  • A new strategy for the synthesis of crucigasterin A, and cytotoxic activity of this compound and its related analogues.

    abstract::Stereoselective total synthesis of bioactive marine natural product crucigasterin A has been accomplished from commercially available and inexpensive L-(-)-malic acid as a starting material. Julia olefination and chelation controlled Grignard additions are the key steps involved in the present synthesis. Cytotoxic pro...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kumar JN,Reddy PR,Das B,Kumar CG,Sujitha P

    更新日期:2013-09-15 00:00:00

  • Successful bridging from a peptide to a non peptide antagonist at the human tachykinin NK-2 receptor.

    abstract::Non peptide products have been found to show nanomolar binding and functional affinities at the human tachykinin NK-2 receptor. The new antagonists do not possess stereogenic centers and their thermal behaviour in solution is featured by a peculiar set of conformational stereoisomers. A macroscopic viewpoint is prefer...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Altamura M,Canfarini F,Catalioto RM,Guidi A,Pasqui F,Renzetti AR,Triolo A,Maggi CA

    更新日期:2002-10-21 00:00:00

  • A facile, click chemistry-based approach to assembling fluorescent chemosensors for protein tyrosine kinases.

    abstract::A group of fluorophore-labeled peptide substrates of Src kinases have been synthesized with the aid of click chemistry. Some of the generated peptides exhibit an increase in fluorescence upon phosphorylation and are capable of detecting Src kinases with high sensitivity and specificity. Their availability permits real...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kamaruddin MA,Ung P,Hossain MI,Jarasrassamee B,O'Malley W,Thompson P,Scanlon D,Cheng HC,Graham B

    更新日期:2011-01-01 00:00:00

  • Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 1.

    abstract::Structure-activity relationship (SAR) efforts around our initial lead compound 1 led to the identification of potent P2X(7) receptor antagonists with improved pharmacokinetic profiles. These compounds were potent and selective at the P2X(7) receptor in both human and rodent. Compound (entry 31) exhibited oral efficacy...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Matasi JJ,Brumfield S,Tulshian D,Czarnecki M,Greenlee W,Garlisi CG,Qiu H,Devito K,Chen SC,Sun Y,Bertorelli R,Geiss W,Le VD,Martin GS,Vellekoop SA,Haber J,Allard ML

    更新日期:2011-06-15 00:00:00

  • 4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives as non-peptidic selective delta-opioid agonists with potential anxiolytic/antidepressant properties. Part 2.

    abstract::Novel 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives have been prepared and their synthesis described herein. In vitro affinities for delta-, micro-, and kappa-opioid receptors are reported. Evaluation of some representative compounds from this series in the mouse neonatal ultrasonic vocalization test and the mo...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Trabanco AA,Aerts N,Alvarez RM,Andrés JI,Boeckx I,Fernández J,Gómez A,Janssens FE,Leenaerts JE,De Lucas AI,Matesanz E,Steckler T,Pullan S

    更新日期:2007-07-15 00:00:00

  • Synthesis and insecticidal activity of new oxime derivatives of podophyllotoxin-based phenazines against Mythimna separata Walker.

    abstract::To discover new natural-product-based insecticidal agents, a series of novel oxime derivatives of podophyllotoxin-based phenazines modified in the C, D and E rings of podophyllotoxin were prepared and tested as insecticidal agents against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Zhi X,Yang C,Yu X,Xu H

    更新日期:2014-12-15 00:00:00

  • Design and synthesis of tetracyclic nonpeptidic biaryl nitrile inhibitors of cathepsin K.

    abstract::The synthesis and biological profile of a novel series of potent and selective inhibitors of cysteine protease cathepsin K (Cat K) are described. Pharmacokinetic evaluation of 12 indicated that some members of this series could be suitable candidates to develop new orally active therapeutic agents for the treatment of...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Setti EL,Venkatraman S,Palmer JT,Xie X,Cheung H,Yu W,Wesolowski G,Robichaud J

    更新日期:2006-08-15 00:00:00

  • Synthesis and anti-influenza virus activity of 7-O-alkylated derivatives related to zanamivir.

    abstract::A series of 7-alkyl ether derivatives related to zanamivir were synthesized using direct alkylation of the C-7 alcohol of sialic acid. Alkyl ether moiety of less than 12 carbons in length showed low nanomolar inhibitory activity against influenza A virus sialidase. Furthermore, their moiety improved influenza A virus ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Honda T,Masuda T,Yoshida S,Arai M,Kaneko S,Yamashita M

    更新日期:2002-08-05 00:00:00

  • Preparation and optimization of new 4-(2-(indolin-1-yl)-2-oxoethyl)-2-morpholinothiazole-5-carboxylic acid and amide derivatives as potent and selective PI3Kβ inhibitors.

    abstract::In our continuous efforts to identify and develop novel targeted cancer treatments, a new morpholino-thiazole scaffold active against PI3Kβ has been identified. This Letter reports the optimization of this compound class to develop PI3Kβ isoform-selective inhibitors with suitable pharmacological properties. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Certal V,Halley F,Virone-Oddos A,Filoche-Rommé B,Carry JC,Gruss-Leleu F,Bertin L,Guizani H,Pilorge F,Richepin P,Karlsson A,Charrier V,Abecassis PY,Vincent L,Nicolas JP,Lengauer C,Garcia-Echeverria C,Schio L

    更新日期:2014-03-15 00:00:00

  • Acetylenic TACE inhibitors. Part 2: SAR of six-membered cyclic sulfonamide hydroxamates.

    abstract::The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a butynyloxy P1' group was explored. In particular, compound 5k has excellent in vitro potency against TACE enzyme and in cells, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Levin JI,Chen JM,Laakso LM,Du M,Du X,Venkatesan AM,Sandanayaka V,Zask A,Xu J,Xu W,Zhang Y,Skotnicki JS

    更新日期:2005-10-01 00:00:00

  • Construction and functionalization of pyranone ring fused with pyran moiety: design and synthesis of novel pyrano[4,3-b]pyran-5(4H)-ones as potential inhibitors of sirtuins.

    abstract::Novel pyrano[4,3-b]pyran-5(4H)-one based small molecules were designed as potential inhibitors of sirtuins (i.e., yeast sir2, a homolog of human SIRT1). Elegant synthesis of these compounds was performed via a multi-step sequence consisting of MCR, Sandmeyer type iodination, Sonogashira type coupling followed by iodoc...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Nakhi A,Rahman MS,Archana S,Kishore R,Seerapu GP,Kumar KL,Haldar D,Pal M

    更新日期:2013-07-15 00:00:00

  • Design and synthesis of functionalized piperazin-1yl-(E)-stilbenes as inhibitors of 17α-hydroxylase-C17,20-lyase (Cyp17).

    abstract::The synthesis of steroid hormones is critical to human physiology and improper regulation of either the synthesis of these key molecules or activation of the associated receptors can lead to disease states. This has led to intense interest in developing compounds capable of modulating the synthesis of steroid hormones...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Blass BE,Iyer P,Abou-Gharbia M,Childers WE,Gordon JC,Ramanjulu M,Morton G,Arumugam P,Boruwa J,Ellingboe J,Mitra S,Reddy Nimmareddy R,Paliwal S,Rajasekhar J,Shivakumar S,Srivastava P,Tangirala RS,Venkataramanaiah K,Bob

    更新日期:2018-07-15 00:00:00