Syntheses of dendritic linkers containing chlorambucil residues for the preparation of antibody-multidrug immunoconjugates.

abstract：:Quinazolinone derivatives were synthesized and evaluated as non-peptidic growth hormone secretagogues. Modeling guided design of quinazolinone compound 21 led to a potency enhancement of greater than 200-fold compared to human growth hormone secretagogue affinity of a screening lead 4. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ye Z,Gao Y,Bakshi RK,Chen MH,Rohrer SP,Feighner SD,Pong SS,Howard AD,Blake A,Birzin ET,Locco L,Parmar RM,Chan WW,Schaeffer JM,Smith RG,Patchett AA,Nargund RP

更新日期：2000-01-03 00:00:00

abstract：:Herein we report the successful incorporation of a lactam as an amide replacement in the design of hepatitis C virus NS5B Site II thiophene carboxylic acid inhibitors. Optimizing potency in a replicon assay and minimizing potential risk for CYP3A4 induction led to the discovery of inhibitor 22a. This lead compound has...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barnes-Seeman D,Boiselle C,Capacci-Daniel C,Chopra R,Hoffmaster K,Jones CT,Kato M,Lin K,Ma S,Pan G,Shu L,Wang J,Whiteman L,Xu M,Zheng R,Fu J

更新日期：2014-08-15 00:00:00

abstract：:Introducing a second chiral center on our previously described 1,2,4-triazole, allowed us to increase diversity and elongate the 'C-terminal part' of the molecule. Therefore, we were able to explore mimics of the substance P analogs described as inverse agonists. Some compounds presented affinities in the nanomolar ra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Maingot M,Blayo AL,Denoyelle S,M'Kadmi C,Damian M,Mary S,Gagne D,Sanchez P,Aicher B,Schmidt P,Müller G,Teifel M,Günther E,Marie J,Banères JL,Martinez J,Fehrentz JA

更新日期：2016-05-15 00:00:00

abstract：:A protein without natural binding functions was engineered to bind HIV-1 integrase. Phage display selections applied a library of variants based on the C-terminal domain of the eye lens protein human γS-crystallin. Multiple loop regions were altered to encode libraries with ≈3.6 × 10(11) different variants. A crystall...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moody IS,Verde SC,Overstreet CM,Edward Robinson W Jr,Weiss GA

更新日期：2012-09-01 00:00:00

abstract：:COPD is a major cause of mortality in the western world. A(2A) agonists are postulated to reduce the lung inflammation that causes COPD. The cardiovascular effects of A(2A) agonists dictate that a compound needs to be delivered by inhalation to be therapeutically useful. The pharmacological and pharmacokinetic SAR of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mantell SJ,Stephenson PT,Monaghan SM,Maw GN,Trevethick MA,Yeadon M,Walker DK,Selby MD,Batchelor DV,Rozze S,Chavaroche H,Lemaitre A,Wright KN,Whitlock L,Stuart EF,Wright PA,Macintyre F

更新日期：2009-08-01 00:00:00

abstract：:A series of benzoxazole compounds containing oxamic acid were synthesized and screened for the PTP1B inhibition. Compound 31d showed best biochemical potency (Ki) of 6.7 μM. Structure-activity relationship were explained with the help of molecular modeling approach. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chandrasekharappa AP,Badiger SE,Dubey PK,Panigrahi SK,Manukonda SR

更新日期：2013-05-01 00:00:00

abstract：:Fatty acylated dipeptides homologous to Gi alpha N-termini affect ligand binding to muscarinic acetylcholine receptors. Myristylglycine-serine containing dipeptides decrease antagonist binding at both M1 and M2 muscarinic receptors. Palmitate on the serine analogous to native palmitoylated cysteine affords dipeptide w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Krishnan V,Pham WN,Messer WS Jr,Peseckis SM

更新日期：1999-12-06 00:00:00

abstract：:Inhibition of sirtuin 2 (SIRT2) is known to be protective against the toxicity of disease proteins in Parkinson's and Huntington's models of neurodegeneration. Previously, we developed SIRT2 inhibitors based on the 3-(N-arylsulfamoyl)benzamide scaffold, including3-(N-(4-bromophenyl)sulfamoyl)-N-(4-bromophenyl)benzamid...

journal_title：Bioorganic & medicinal chemistry letters

authors： Choi SH,Quinti L,Kazantsev AG,Silverman RB

更新日期：2012-04-15 00:00:00

abstract：:Potent and selective antagonists of the adenosine A2A receptor often contain a nitrogen-rich fused-ring heterocyclic core. Replacement of the core with an isomeric ring system has previously been shown to improve target affinity, selectivity, and in vivo activity. This paper describes the preparation, by a novel route...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dowling JE,Vessels JT,Haque S,Chang HX,van Vloten K,Kumaravel G,Engber T,Jin X,Phadke D,Wang J,Ayyub E,Petter RC

更新日期：2005-11-01 00:00:00

abstract：:The 2,4,6-trimethylpyridinium derivative of histamine is an effective activator of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). However, unlike other CA activators, which bind at the entrance of the active site cavity, an X-ray crystal structure of hCA II in complex with the 1-[2-(1H-imidazol-4-yl)-ethyl]-2,4,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dave K,Ilies MA,Scozzafava A,Temperini C,Vullo D,Supuran CT

更新日期：2011-05-01 00:00:00

abstract：:A series of 1-aminotetralin scaffolds was synthesized via metal-catalyzed ring-opening reactions of heterobicyclic alkenes. Small libraries of amides and amines were made using the amino group of each scaffold as a handle. Screening of these libraries against human opioid receptors led to the identification of (S)-(S)...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dockendorff C,Jin S,Olsen M,Lautens M,Coupal M,Hodzic L,Spear N,Payza K,Walpole C,Tomaszewski MJ

更新日期：2009-02-15 00:00:00

abstract：:A series of new coumarin-based 1,2,4-triazole derivatives were designed, synthesized and evaluated for their antimicrobial activities in vitro against four Gram-positive bacteria (Staphylococcus aureus, MRSA, Bacillus subtilis and Micrococcus luteus), four Gram-negative bacteria (Escherichia coli, Proteus vulgaris, Sa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi Y,Zhou CH

更新日期：2011-02-01 00:00:00

abstract：:Structure- and ligand-based virtual-screening methods (docking, 2D- and 3D-similarity searching) were analyzed for their effectiveness in virtual screening against FFAR2. To evaluate the performance of these methods, retrospective virtual screening was performed. Statistical quality of the methods was evaluated by BED...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fells JI,Ai X,Weinglass A,Feng W,Lei Y,Finley M,Hoveyda HR,Fraser GL,Machacek M

更新日期：2020-11-01 00:00:00

abstract：:Apparent kinetic constants k(cat) and K(m) were determined for tyrocidine thioesterase (TycC TE) using randomized peptide N-acetylcysteamine thioesters as substrate analogues. The enzyme has been found to be adequately active for the synthesis of positional-scanning libraries for novel antibiotic screening with reduce...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xie G,Uttamchandani M,Chen GY,Bu X,Lin SS,Wong KM,Yan W,Yao SQ,Guo Z

更新日期：2002-03-25 00:00:00

abstract：:To overcome the chemical and metabolic instability of the secondary fatty acyl residues in the AGP class of lipid A mimetics, the secondary ether lipid analogs of the potent TLR4 agonist CRX-527 (2) and TLR4 antagonist CRX-526 (3) were synthesized and evaluated along with their ester counterparts for agonist/antagonis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bazin HG,Murray TJ,Bowen WS,Mozaffarian A,Fling SP,Bess LS,Livesay MT,Arnold JS,Johnson CL,Ryter KT,Cluff CW,Evans JT,Johnson DA

更新日期：2008-10-15 00:00:00

abstract：:Benzylamides of pentanedioic acid were identified as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) by high-throughput screening. Optimisation to 2-adamantyl amides yielded inhibitors with single digit nanomolar IC(50)s on the 11beta-HSD1 human isoform. The hydroxy adamantyl amide lead compound...

journal_title：Bioorganic & medicinal chemistry letters

authors： Roche D,Carniato D,Leriche C,Lepifre F,Christmann-Franck S,Graedler U,Charon C,Bozec S,Doare L,Schmidlin F,Lecomte M,Valeur E

更新日期：2009-05-15 00:00:00

abstract：:Over 195 4-alkyl and 4,4-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione derivatives were synthesized, utilizing microwave accelerated synthesis, for evaluation as new inhibitors of bacterial cell wall biosynthesis. Many of them demonstrated good activity against MurB in vitro and low MIC values against gram-pos...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kutterer KM,Davis JM,Singh G,Yang Y,Hu W,Severin A,Rasmussen BA,Krishnamurthy G,Failli A,Katz AH

更新日期：2005-05-16 00:00:00

abstract：:Urea-based inhibitors of human glutamate carboxypeptidase II (GCPII) have advanced into clinical trials for imaging metastatic prostate cancer. In parallel efforts, agents with increased lipophilicity have been designed and evaluated for targeting GCPII residing within the neuraxis. Here we report the structural and c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pavlicek J,Ptacek J,Cerny J,Byun Y,Skultetyova L,Pomper MG,Lubkowski J,Barinka C

更新日期：2014-05-15 00:00:00

abstract：:The synthesis of novel C6-aryl substituted derivatives of 3-(dimethylamino)chroman is described. The novel derivatives display 5-HT(7) receptor affinities that varies from nM to muM, indicating that this small set of derivatives constitute a novel and interesting starting point for further structure-serotonin 5-HT(7) ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Holmberg P,Tedenborg L,Rosqvist S,Johansson AM

更新日期：2005-02-01 00:00:00

abstract：:New Lp-PLA(2) inhibitors were synthesized by the bioisosteric replacement of the amide group of Darapladib with an imidazole or a triazole. Unfortunately, the inhibitory activities of these derivatives were lower than that of Darapladib. But interestingly, a series of quaternary ammonium salts that were isolated as by...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang K,Xu W,Liu Y,Zhang W,Wang W,Shen J,Wang Y

更新日期：2013-03-01 00:00:00

abstract：:A set of 31 DNA minor groove binders (MGBs) with diverse structural features relating to both physical chemical properties and DNA binding sequence preference has been evaluated as potential drugs to treat Plasmodium falciparum infections using a chloroquine sensitive strain (3D7) and a chloroquine resistant strain (D...

journal_title：Bioorganic & medicinal chemistry letters

authors： Scott FJ,Khalaf AI,Duffy S,Avery VM,Suckling CJ

更新日期：2016-07-15 00:00:00

abstract：:Positioning of reactive functional groups within a DNA duplex can enable chemical reactions that otherwise would not occur to an appreciable extent. However, few studies have quantitatively defined the extent to which the enforced proximity of reaction partners in duplex DNA can favor chemical processes. Here, we meas...

journal_title：Bioorganic & medicinal chemistry letters

authors： Catalano MJ,Price NE,Gates KS

更新日期：2016-06-01 00:00:00

abstract：:Eight new isocoumarin glycosides (1-8) were obtained from the solid culture of the wetland soil-derived fungus Metarhizium anisopliae (No. DTH12-10). Their chemical structures were elucidated by analyses of HR ESI-TOF MS, (1)H, (13)C NMR, (1)H-(1)H COSY, HSQC, and HMBC spectra. The absolute configurations were determi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tian JF,Li PJ,Li XX,Sun PH,Gao H,Liu XZ,Huang P,Tang JS,Yao XS

更新日期：2016-03-01 00:00:00

abstract：:Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipide...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu P,Liu W,Ren J,Wang Y,Ning Y,Huang M,Hu X,Wei L,Ji M,Cai J

更新日期：2019-08-15 00:00:00

abstract：:Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as potentially gastric-sparing NSAIDs. Herein, we report a novel class of '1-(nitrooxy)ethyl ester' group-containing NSAIDS as efficient NO releasing 'true' prodrugs of aspirin and naproxen. While an aspirin prodrug exhibite...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gund M,Gaikwad P,Borhade N,Burhan A,Desai DC,Sharma A,Dhiman M,Patil M,Sheikh J,Thakre G,Tipparam SG,Sharma S,Nemmani KVS,Satyam A

更新日期：2014-12-15 00:00:00

abstract：:A series of 1-benzoyl isoquinolines, based on compound 1, was synthesized and evaluated for their ability to displace IGF-I from its complex with IGF-binding protein-3. Successful modifications of 1 included the replacement of the 3,4-dihydroxybenzoyl group with a substituted benzyl group. These alternations culminate...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhu YF,Wilcoxen K,Gross T,Connors P,Strack N,Gross R,Huang CQ,McCarthy JR,Xie Q,Ling N,Chen C

更新日期：2003-06-02 00:00:00

abstract：:A series of 4-amino-pyrido[2,3-d]pyrimidin-5(8H)-ones were designed and synthesized as a novel class of inhibitors of NAD(+)-dependent DNA ligase that possess potency against Gram-positive bacteria. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang T,Duncan L,Gu W,O'Dowd H,Wei Y,Perola E,Parsons J,Gross CH,Moody CS,Arends SJ,Charifson PS

更新日期：2012-06-01 00:00:00

abstract：:Several chemically modified analogues to a tightly binding ligand for the second PDZ domain of MAGI-3 were synthesized and evaluated for their ability to compete with native peptide ligands. N-methyl scanning of the ligand backbone amides revealed the energetically important hydrogen bonds between the ligand backbone ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Novak KA,Fujii N,Guy RK

更新日期：2002-09-02 00:00:00

abstract：:A series of 2,6-dimethoxylpyridinyl phosphine oxides have been synthesized and examined for their antitumor activity. 2,6-Dimethoxy-3-phenyl-4-diphenylphosphinoylpyridine 2 has been employed as the lead compound for this study. We found out that the presence of phosphine oxide on the 2,6-dimethoxylpyridine ring is imp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lam KH,Gambari R,Yuen MC,Kan CW,Chan P,Xu L,Tang W,Chui CH,Cheng GY,Wong RS,Lau FY,Tong CS,Chan AK,Lai PB,Kok SH,Cheng CH,Chan AS,Tang JC

更新日期：2009-04-15 00:00:00

abstract：:Modification of the biphenyl portion of MMP inhibitor 2a gave analogue 2i which is greater than 1000-fold selective against MMP-2 versus MMP-1. The stereospecific synthesis of both enantiomers of 2i was achieved beginning with (S)- or (R)-benzyl glycidyl ether. The (S)-enantiomer, 11 (ABT-770), is orally bioavailable ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Curtin ML,Florjancic AS,Heyman HR,Michaelides MR,Garland RB,Holms JH,Steinman DH,Dellaria JF,Gong J,Wada CK,Guo Y,Elmore IB,Tapang P,Albert DH,Magoc TJ,Marcotte PA,Bouska JJ,Goodfellow CL,Bauch JL,Marsh KC,Morgan

更新日期：2001-06-18 00:00:00