Pyrazole-based factor Xa inhibitors containing N-arylpiperidinyl P4 residues.

abstract：:In HEK293 cells stably expressing alpha4beta2 nAChRs, naltrexone, but not naloxone, blocked alpha4beta2 nAChRs via an open-channel blocking mechanism. In primary hippocampal cultures, naltrexone inhibited alpha7 nAChRs up-regulated by nicotine, and in organotypic hippocampal cultures naltrexone caused a time-dependent...

journal_title：Bioorganic & medicinal chemistry letters

authors： Almeida LE,Pereira EF,Camara AL,Maelicke A,Albuquerque EX

更新日期：2004-04-19 00:00:00

abstract：:We expand the structural requirements and structure-activity relationship of a novel class of non-peptidic aryl-based thrombin inhibitors through exploration of the S1 specificity pocket of thrombin using flexible and constrained amidines. The most active compound of this class is 11 with Ki = 69 nM, which is ca. 15-f...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lu T,Tomczuk B,Bone R,Murphy L,Salemme FR,Soll RM

更新日期：2000-01-03 00:00:00

abstract：:West Nile Virus (WNV) is a potentially deadly mosquito-borne flavivirus which has spread rapidly throughout the world. Currently there is no effective vaccine against flaviviral infections. We previously reported the identification of pyrazole ester derivatives as allosteric inhibitors of WNV NS2B-NS3 proteinase. Thes...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sidique S,Shiryaev SA,Ratnikov BI,Herath A,Su Y,Strongin AY,Cosford ND

更新日期：2009-10-01 00:00:00

abstract：:The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh K,Tanui R,Gameiro A,Eisenberg G,Colas C,Schlessinger A,Grewer C

更新日期：2017-02-01 00:00:00

abstract：:Optically active phenylpropanoic acid derivatives [(S)-5, and (R)-5] were prepared, and their affinities for peroxisome proliferator-activated receptor (PPAR)alpha and PPAR gamma were evaluated. Binding assay and cell-based reporter assay indicated that the activity of these compounds is enantio-dependent, and resides...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miyachi H,Nomura M,Tanase T,Suzuki M,Murakami K,Awano K

更新日期：2002-02-11 00:00:00

abstract：:In an effort to discover potent antitumor agents, a series of novel C-7-heteroaryl-substituted camptothecin derivatives were designed and synthesized via microwave-promoted Suzuki coupling reaction. These analogs were then assessed for cytotoxicity against three human tumor cell lines, A549, HCT116, HT-29, and inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang L,Huang Y,Zhang J,Tong L,Chen Y,Lu W,Huang Q

更新日期：2014-03-15 00:00:00

abstract：:Cancer cells isolated from two patients with malignant non-Hodgkin B-cell lymphomas that became resistant to chemotherapy during clinical treatment were made ≥fourfold resistant in culture to anticancer drugs, that is cisplatin, etoposide, methotrexate and bortezomib. Because most resistant lines showed significantly ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schulz R,Emmrich T,Lemmerhirt H,Leffler U,Sydow K,Hirt C,Kiefer T,Link A,Bednarski PJ

更新日期：2012-11-01 00:00:00

abstract：:Promising anti-breast cancer agents derived from substituted quinolines were discovered. The quinolines were readily synthesized in a large scale from a sequence of reactions starting from 4-acetamidoanisole. The Michael addition product was isolated as the reaction intermediate in the ring closing reaction of 4-amino...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi A,Nguyen TA,Battina SK,Rana S,Takemoto DJ,Chiang PK,Hua DH

更新日期：2008-06-01 00:00:00

abstract：:Selective antagonism of the platelet GPIIb/IIIa receptor represents an attractive mechanism for the prevention and treatment of a number of thrombotic disease states. The antiplatelet activity of the oral GPIIb/IIIa receptor antagonists DMP 754 and DMP 802 have been disclosed. In this paper, the synthesis and biologic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sielecki TM,Liu J,Mousa SA,Racanelli AL,Hausner EA,Wexler RR,Olson RE

更新日期：2001-08-20 00:00:00

abstract：:A series of 5-HT(6) ligands derived from (R)-1-(amino)methyl-6-(phenyl)sulfonyltetralin was prepared that yielded several non-basic analogs having sub-nanomolar affinity. Ligand structure-activity relationships, receptor point mutation studies, and molecular modeling of these novel ligands all combined to reveal a new...

journal_title：Bioorganic & medicinal chemistry letters

authors： Harris RN 3rd,Stabler RS,Repke DB,Kress JM,Walker KA,Martin RS,Brothers JM,Ilnicka M,Lee SW,Mirzadegan T

更新日期：2010-06-01 00:00:00

abstract：:The stereochemistry of the tubulin inhibitors taltobulin HTI-286 (2) and HTI-042 (3) was determined by utilizing the DPFGSE 1D NOE experiment. Single crystal X-ray diffraction analysis further confirmed the absolute configuration of these two compounds, which carry the (S,S,S)-configuration necessary for biological ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Niu C,Ho DM,Williamson RT,Zask A,Ayral-Kaloustian S

更新日期：2010-03-01 00:00:00

abstract：:Activators of the pyruvate kinase M2 (PKM2) are currently attracting significant interest as potential anticancer therapies. They may achieve a novel antiproliferation response in cancer cells through modulation of the classic 'Warburg effect' characteristic of aberrant metabolism. In this Letter, we describe the opti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu Y,Liu XH,Saunders M,Pearce S,Foulks JM,Parnell KM,Clifford A,Nix RN,Bullough J,Hendrickson TF,Wright K,McCullar MV,Kanner SB,Ho KK

更新日期：2014-01-15 00:00:00

abstract：:Hydroxy urea moieties are introduced as a new class of bradykinin B(1) receptor antagonists. First, the SAR of the lead compound was systematically explored. Subsequent optimization resulted in the identification of several biaryl-based hydroxyurea bradykinin B(1) receptor antagonists with low-nanomolar activity and v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schnatbaum K,Schaudt M,Stragies R,Pfeifer JR,Gibson C,Locardi E,Scharn D,Richter U,Kalkhof H,Dinkel K,Zischinsky G

更新日期：2010-02-01 00:00:00

abstract：:A series of novel oxime-containing pyrazole derivatives were synthesized by the reaction of ethyl 3-phenyl-1H-pyrazole-5-carboxylate derivatives and 2-bromo-1-phenylethanone followed by the reaction with hydroxylamine hydrochloride. The structures were determined by IR, (1)H NMR, HRMS, and X-ray analysis. A dose- and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng LW,Li Y,Ge D,Zhao BX,Liu YR,Lv HS,Ding J,Miao JY

更新日期：2010-08-15 00:00:00

abstract：:The enediyne natural products have been explored for their phenomenal cytotoxicity. The development of enediynes into anticancer drugs has been successfully achieved through the utilization of polymer- and antibody-drug conjugates (ADCs) as drug delivery systems. An increasing inventory of enediynes would benefit curr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shen B,Hindra,Yan X,Huang T,Ge H,Yang D,Teng Q,Rudolf JD,Lohman JR

更新日期：2015-01-01 00:00:00

abstract：:Telomerase and telomere maintenance are emerging targets for the treatment of human cancers. We report here on the targeting of the telomere-telomerase complex with a series of small molecules based on an acridine platform. A series of 3,6-bisamidoacridines with extended 9-anilino sidechains were designed and synthesi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schultes CM,Guyen B,Cuesta J,Neidle S

更新日期：2004-08-16 00:00:00

abstract：:A series of N-2-(4-(4-(2-substitutedthiazol-4-yl) piperazin-1-yl)-2-oxoethyl)acetamides were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were synthesized by either microwave irradiation technique or by conventional synthesis and were characterized by spectral data (IR, (1)H N...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sekhar KV,Rao VS,Devambatla RKV,Kumar MM

更新日期：2008-12-01 00:00:00

abstract：:Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiong H,Brugel TA,Balestra M,Brown DG,Brush KA,Hightower C,Hinkley L,Hoesch V,Kang J,Koether GM,McCauley JP Jr,McLaren FM,Panko LM,Simpson TR,Smith RW,Woods JM,Brockel B,Chhajlani V,Gadient RA,Spear N,Sygowski LA

更新日期：2010-12-15 00:00:00

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

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

更新日期：2008-11-15 00:00:00

abstract：:A library of natural and semi-synthetic Amaryllidaceae alkaloids was screened for cytochrome P450 3A4 (CYP3A4) inhibitory activity. Of the crinane, lycorane and galanthamine representatives examined two semi-synthetic silylated lycorane analogues, accessed via a chemoselective silylation strategy from lycorine, and th...

journal_title：Bioorganic & medicinal chemistry letters

authors： McNulty J,Nair JJ,Singh M,Crankshaw DJ,Holloway AC,Bastida J

更新日期：2009-06-15 00:00:00

abstract：:KIAA1363 is a serine hydrolase whose activity has been shown to be positively associated with tumor cell invasiveness. Thus, inhibitors of KIAA1363 represent a novel targeted therapy approach towards cancer. AX11890 ((1-bromo-2-naphthyl) N,N-dimethylcarbamate) was identified as a KIAA1363 inhibitor with an IC(50) valu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shreder KR,Lin EC,Wu J,Cajica J,Amantea CM,Hu Y,Okerberg E,Brown HE,Pham LM,Chung de M,Fraser AS,McGee E,Rosenblum JS,Kozarich JW

更新日期：2012-09-01 00:00:00

abstract：:The diacylglycerol acyltransferase enzyme, DGAT1, presents itself as a potential target for obesity as this enzyme is dedicated to the final committed step in triglyceride biosynthesis. Biphenyl ureas, exemplified by compound 4, have been reported to be potent hDGAT1 inhibitors. We have synthesized and evaluated 2-pyr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Motiwala H,Kandre S,Birar V,Kadam KS,Rodge A,Jadhav RD,Mahesh Kumar Reddy M,Brahma MK,Deshmukh NJ,Dixit A,Doshi L,Gupte A,Gangopadhyay AK,Vishwakarma RA,Srinivasan S,Sharma M,Nemmani KV,Sharma R

更新日期：2011-10-01 00:00:00

abstract：:Drug-induced QT prolongation arising from drugs' blocking of hERG channel activity presents significant challenges in drug development. Many, but not all, of our benzamidine-containing factor Xa inhibitors were found to have high hERG binding propensity. However, incorporation of a carboxylic acid group into these ben...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhu BY,Jia ZJ,Zhang P,Su T,Huang W,Goldman E,Tumas D,Kadambi V,Eddy P,Sinha U,Scarborough RM,Song Y

更新日期：2006-11-01 00:00:00

abstract：:Human kallikrein 1 (KLK1) is the most extensively studied member of this family and plays a major role in inflammation processes. From Ugi multicomponent reactions, isomannide-based peptidomimetic 10 and 13 where synthesized and showed low micromolar values of IC50 for KLK1 The most active compound (10) presented comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barros TG,Santos JAN,de Souza BEG,Sodero ACR,de Souza AMT,da Silva DP,Rodrigues CR,Pinheiro S,Dias LRS,Abrahim-Vieira B,Puzer L,Muri EMF

更新日期：2017-01-15 00:00:00

abstract：:In the course of ongoing research on protein tyrosine phosphatase 1B (PTP1B) inhibitory compounds from Antarctic lichens, four new diterpene furanoids, hueafuranoids A-D (1-4) have been isolated from the MeOH extract of Antarctic lichen Huea sp. by various chromatographic methods. The structures of these compounds wer...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cui Y,Yim JH,Lee DS,Kim YC,Oh H

更新日期：2012-12-15 00:00:00

abstract：:The effects of PEGylation of glucose-dependent insulinotropic polypeptide (GIP) on potency and dipeptidyl peptidase IV (DPPIV) stability are reported. N-terminal modification of GIP(1-30) with 40 kDa polyethylene glycol (PEG) abrogates functional activity. In contrast, C-terminal PEGylation of GIP(1-30) maintains full...

journal_title：Bioorganic & medicinal chemistry letters

authors： Salhanick AI,Clairmont KB,Buckholz TM,Pellegrino CM,Ha S,Lumb KJ

更新日期：2005-09-15 00:00:00

abstract：:The 1,3-dipolar cycloaddition of azomethine ylides derived from acenaphthenequinone and alpha-amino acids viz. sarcosine, phenylglycine, 1,3-thiazolane-4-carboxylic acid and proline to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones afforded novel spiro-heterocycles chemo-, regio- and stereoselectively in quant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ranjith Kumar R,Perumal S,Manju SC,Bhatt P,Yogeeswari P,Sriram D

更新日期：2009-07-01 00:00:00

abstract：:An indole compound with a strong purple-red color was produced by boiling a solution of indican under acidic conditions and purified by chromatographies on DEAE-650S Toyopearl TSK-gel and silica-gel columns. The purple-red compound purified was identified as indoxyl red, on the basis of FAB Mass, (13)C NMR, (1)H NMR, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song J,Kitamatsu M,Imamura K,Ohmori H,Watanabe K,Nakanishi K

更新日期：2013-02-01 00:00:00

abstract：:Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms. Previous studies have shown aplysinopsin analogs to possess a variety of biological activities, including modulation of neurotransmissions. A series of fifty aplysinopsin analogs was synthesized and assaye...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lewellyn K,Bialonska D,Chaurasiya ND,Tekwani BL,Zjawiony JK

更新日期：2012-08-01 00:00:00

abstract：:We report the discovery of a novel series of ATP-competitive Janus kinase 3 (JAK3) inhibitors based on the 5H-pyrrolo[2,3-b]pyrazine scaffold. The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family. Computational and crystal...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jaime-Figueroa S,De Vicente J,Hermann J,Jahangir A,Jin S,Kuglstatter A,Lynch SM,Menke J,Niu L,Patel V,Shao A,Soth M,Vu MD,Yee C

更新日期：2013-05-01 00:00:00