Identification of a novel RAMP-independent CGRP receptor antagonist.

abstract：:A series of regioisomeric bis-fulleropyrrolidines bearing two ammonium groups have been synthesized and their activities against HIV-1 and HIV-2 have been evaluated. Two trans isomers have been endowed with interesting antiviral properties, confirming the importance of the relative positions of the substituent on the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marchesan S,Da Ros T,Spalluto G,Balzarini J,Prato M

更新日期：2005-08-01 00:00:00

abstract：:A selection of 76 nitroheterocycles and related compounds from our in-house compound library was screened in vitro against the parasite Trypanosoma brucei rhodesiense, causative agent of human African trypanosomiasis (HAT). The unspecific cytotoxicity of the compounds was also evaluated against rat myoblast L6-cells t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arán VJ,Kaiser M,Dardonville C

更新日期：2012-07-15 00:00:00

abstract：:A new series of triazole-imidazo[2,1-b][1,3,4]thiadiazole hybrids (6a-s, 7a) were designed by a molecular hybridisation approach and the target molecules were synthesized via one pot click chemistry protocol. All the intermediates and final molecules were characterised using spectral methods and one of the target comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ramprasad J,Nayak N,Dalimba U,Yogeeswari P,Sriram D

更新日期：2015-10-01 00:00:00

abstract：:The same two major CYP mediated metabolites of DG-051 were produced in the presence of rat, dog, monkey and human liver microsomes. Their respective structures were hypothesized based on mass spectrometry data correlated with the parent structure and confirmed by comparison with authentic synthetic samples. The number...

journal_title：Bioorganic & medicinal chemistry letters

authors： Enache LA,Zhang J,Sullins DW,Kennedy I,Onua E,Zembower DE,Muellner FW,Singh J,Kiselyov AS

更新日期：2009-11-15 00:00:00

abstract：:A series of novel, potent and selective pyrido[1,2-a]pyrazine dopamine D4 receptor antagonists are reported including CP-293,019 (D4 Ki = 3.4 nM, D2 Ki > 3,310 nM), which also inhibits apomorphine-induced hyperlocomotion in rats after oral dosing. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sanner MA,Chappie TA,Dunaiskis AR,Fliri AF,Desai KA,Zorn SH,Jackson ER,Johnson CG,Morrone JM,Seymour PA,Majchrzak MJ,Faraci WS,Collins JL,Duignan DB,Prete Di CC,Lee JS,Trozzi A

更新日期：1998-04-07 00:00:00

abstract：:Heteroaromatic analogs of DMU-212 (8-15) have been synthesized and evaluated for their anti-cancer activity against a panel of 60 human cancer cell lines. These novel analogs contain a trans-3,4,5-trimethoxystyryl moiety attached to the C2 position of indole, benzofuran, benzothiazole or benzothiophene ring (8, 11, 13...

journal_title：Bioorganic & medicinal chemistry letters

authors： Penthala NR,Thakkar S,Crooks PA

更新日期：2015-07-15 00:00:00

abstract：:Bergenin is an isocoumarin natural product which aides in fat loss, healthy weight maintenance, enhancing the lipolytic effects of norepinephrine, inhibiting the formation of interleukin 1α and cyclooxygenases-2. Here we describe the anti-inflammatory activity of new bergenin derivatives 1-15 in the respiratory burst ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shah MR,Arfan M,Amin H,Hussain Z,Qadir MI,Choudhary MI,VanDerveer D,Mesaik MA,Soomro S,Jabeen A,Khan IU

更新日期：2012-04-15 00:00:00

abstract：:High throughput screening of the corporate compound collection led to the discovery of a novel series of substituted aminoalkoxybenzyl pyrrolidines as human urotensin-II receptor antagonists. The synthesis, initial structure-activity relationships, and optimization of the initial hit that led to the identification of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin J,Dhanak D,Knight SD,Widdowson K,Aiyar N,Naselsky D,Sarau HM,Foley JJ,Schmidt DB,Bennett CD,Wang B,Warren GL,Moore ML,Keenan RM,Rivero RA,Douglas SA

更新日期：2005-07-01 00:00:00

abstract：:Mirror-image screening using d-proteins is a powerful approach to provide mirror-image structures of chiral natural products for drug screening. During the course of our screening study for novel MDM2-p53 interaction inhibitors, we identified that NPD6878 (R-(-)-apomorphine) inhibited both the native l-MDM2-l-p53 inte...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishiba H,Noguchi T,Shu K,Ohno H,Honda K,Kondoh Y,Osada H,Fujii N,Oishi S

更新日期：2017-06-01 00:00:00

abstract：:Spiro-carboxamides were identified as inhibitors of 11beta-hydroxysteroid-dehydrogenase type 1 by high-throughput screening. Structure-based drug design was used to optimise the initial hit yielding a sub-nanomolar IC(50) inhibitor (0.5nM) on human 11beta-HSD1 with a high binding efficiency index (BEI of 32.7) which w...

journal_title：Bioorganic & medicinal chemistry letters

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

更新日期：2009-07-01 00:00:00

abstract：:A series of multisubstituted indole-acrylonitrile hybrids were designed, synthesized and evaluated for their potential cytotoxic activities. The bio-evaluation results indicated that some of the target compounds (such as 3a, 3f, 3k, 3n) exhibited good to moderate cytotoxic effect on HepG2, BCG-823, BEL-7402, and HL-77...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ke S,Yang Z,Zhang Z,Liang Y,Wang K,Liu M,Shi L

更新日期：2014-04-15 00:00:00

abstract：:Peroxisome proliferator-activated receptors (PPARs) are attractive targets for the treatment of the metabolic syndrome. Especially a combination of PPARα and PPARγ agonistic activity seems worthwhile to be pursued. Herein we present the design and synthesis of a series of pirinixic acid derivatives as potent PPARα par...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lamers C,Dittrich M,Steri R,Proschak E,Schubert-Zsilavecz M

更新日期：2014-08-15 00:00:00

abstract：:A series of 4-substituted (benzo[b]thiophene-2-carbonyl)guanidines was synthesized and evaluated for the NHE-1 inhibitory activity and cardioprotective efficacy both in vitro and in vivo. Several analogs exhibited a strong inhibition on NHE-1, and which was generally well correlated with their cardioprotective efficac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee S,Lee H,Yi KY,Lee BH,Yoo SE,Lee K,Cho NS

更新日期：2005-06-15 00:00:00

abstract：:A new class of O-arylmandelic acid PPAR agonists show excellent anti-hyperglycemic efficacy in a db/db mouse model of DM2. These PPARalpha-weighted agonists do not show the typical PPARgamma associated side effects of BAT proliferation and cardiac hypertrophy in a rat tolerability assay. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Adams AD,Hu Z,von Langen D,Dadiz A,Elbrecht A,MacNaul KL,Berger JP,Zhou G,Doebber TW,Meurer R,Forrest MJ,Moller DE,Jones AB

更新日期：2003-10-06 00:00:00

abstract：:The syntheses of 7-chloro-4-(substituted amino) quinolines (2-22) and their antifilarial activities are delineated. Some of the screened compounds have shown promising filarial response and sterilization effect on female Acanthocheilonema viteae in rodents. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tewari S,Chauhan PM,Bhaduri AP,Fatima N,Chatterjee RK

更新日期：2000-07-03 00:00:00

abstract：:Tyrosine kinase inhibitor (TKI) therapy is the standard treatment for chronic phase (CP)-chronic myeloid leukemia (CML), yet patients in blast crisis (BC) phase of CML are unlikely to respond to TKI therapy. The transcription factor E2F1 is a down-stream target of the tyrosine kinase BCR-ABL1 and is up-regulated in TK...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hayatigolkhatmi K,Padroni G,Su W,Fang L,Gómez-Castañeda E,Hsieh YC,Jackson L,Pellicano F,Burley GA,Jørgensen HG

更新日期：2019-09-15 00:00:00

abstract：:A novel class of Growth Hormone Secretagogues (GHS), based on a tetrazole template, has been discovered. In vitro SAR and in vivo potency within this new class of GHS are described. The tetrazole 9q exhibits good oral bioavailability in rats and dogs as well as efficacy following an oral 10 mg/kg dose in dogs. Solutio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hernández AS,Cheng PT,Musial CM,Swartz SG,George RJ,Grover G,Slusarchyk D,Seethala RK,Smith M,Dickinson K,Giupponi L,Longhi DA,Flynn N,Murphy BJ,Gordon DA,Biller SA,Robl JA,Tino JA

更新日期：2007-11-01 00:00:00

abstract：:Group II metabotropic glutamate receptors (mGluRs) have been implicated in a variety of neurological and psychiatric disorders in recent studies. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers the possibility to visualize and study gro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang JQ,Zhang Z,Kuruppu D,Brownell AL

更新日期：2012-03-01 00:00:00

abstract：:A quantitative structure-activity relationship (QSAR) modeling of the antimold activity of cinnamaldehyde analogues against of Aspergillus niger and Paecilomyces variotii was presented. The molecular descriptors of cinnamaldehyde analogues were calculated by the CODESSA program, and these descriptors were selected by ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang Y,Li S,Kong X

更新日期：2013-03-01 00:00:00

abstract：:Following the promising activity of Q2FA15 on axonal growth, two new series of N/O-substituted QFAs were synthesized, based on a SN2-type reaction. O-alkylated QFA bearing 14 carbon atoms on the side chain (n=14) shows a very potent activity on axonal growth though lowered when compared to Q2FA15. While O-alkylation a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanbali M,Bagnard D,Luu B

更新日期：2006-08-01 00:00:00

abstract：:In order to improve the analgesic activity of lead compound 7a, two series of dispirocyclopiperazinium (DSPZ) salts 9a-h, 10a-e and compounds 14, 15 were synthesized and evaluated for their in vivo analgesic activity both by acetic acid induced writhing test and hot plate test. Compounds 9h, 14, and 15 exhibited bette...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li A,Wang X,Yue CQ,Ye J,Li CL,Li RT

更新日期：2007-09-15 00:00:00

abstract：:The hit-to-lead optimization of the HNE inhibitor 5-methyl-2-(2-phenoxy-pyridin-3-yl)-benzo[d][1,3]oxazin-4-one is described. A structure-activity relationship study that focused on the 5 and 7 benzoxazinone positions yielded the optimized 5-ethyl-7-methoxy-benzo[d][1,3]oxazin-4-one core structure. 2-[2-(4-Methyl-pipe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shreder KR,Cajica J,Du L,Fraser A,Hu Y,Kohno Y,Lin EC,Liu SJ,Okerberg E,Pham L,Wu J,Kozarich JW

更新日期：2009-08-15 00:00:00

abstract：:The alpha7 subtype of the neuronal nicotinic acetylcholine receptors (nAChRs) was targeted for the design of selective agonists deriving from the quinuclidine scaffold. Arylidene groups at the 3-position and N-methyl quinuclidine were found to be selective agonists with EC(50)s of 1.5 and 40 microM, respectively. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Leonik FM,Papke RL,Horenstein NA

更新日期：2007-03-15 00:00:00

abstract：:Cell penetrating peptide TAT was introduced into doxorubicin structure. Synthesized doxorubicin-TAT conjugate showed different intracellular distribution pattern and cell killing activity from those of free doxorubicin. Unlike free doxorubicin, doxorubicin-TAT conjugate was highly permeable to drug-resistant cells and...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liang JF,Yang VC

更新日期：2005-11-15 00:00:00

abstract：:Imidazo[1,2-a]pyrimidines and imidazo[1,2-b][1,2,4]triazines are ligands for the benzodiazepine binding site of GABA(A) receptors that are functionally selective for the alpha2/alpha3 subtypes over the alpha1 subtype. SAR studies to optimise this functional selectivity, pharmacokinetic and behavioural data are describ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jennings AS,Lewis RT,Russell MG,Hallett DJ,Street LJ,Castro JL,Atack JR,Cook SM,Lincoln R,Stanley J,Smith AJ,Reynolds DS,Sohal B,Pike A,Marshall GR,Wafford KA,Sheppard WF,Tye SJ

更新日期：2006-03-15 00:00:00

abstract：:The synthesis and receptor binding of novel adenosine receptor antagonists is described. We found that non-xanthine 4-phenyl-2-(phenylcarboxamido)-1,3-thiazole derivatives may have high affinity and substantial selectivity for the adenosine A(1) receptor. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： van Tilburg EW,van der Klein PA,de Groote M,Beukers MW,IJzerman AP

更新日期：2001-08-06 00:00:00

abstract：:Using structure-based optimization procedures on in silico hits, dibenzosuberyl- and benzoate substituted tropines were designed as ligands for acetylcholine-binding protein (AChBP). This protein is a homolog to the ligand binding domain of the nicotinic acetylcholine receptor (nAChR). Distinct SAR is observed between...

journal_title：Bioorganic & medicinal chemistry letters

authors： Edink E,Akdemir A,Jansen C,van Elk R,Zuiderveld O,de Kanter FJ,van Muijlwijk-Koezen JE,Smit AB,Leurs R,de Esch IJ

更新日期：2012-02-01 00:00:00

abstract：:We have identified a novel series of alpha-methylene carbonyl compounds through structure-activity relationship (SAR) studies with high levels of anti-proliferative activities. The lead molecule, 3-methylene-2-norbornanone (3) showed potent activity (LC(50)=3-8 microM) against mutant p53 cell types and many fold selec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Reddy NL,Hill J,Ye L,Fernandes PB,Stout DM

更新日期：2004-11-15 00:00:00

abstract：:Starting from a thiazolidin-4-one HTS hit, a novel series of substituted lactams was identified and developed as dual orexin receptor antagonists. In this Letter, we describe our initial efforts towards the improvement of potency and metabolic stability. These investigations delivered optimized lead compounds with CNS...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sifferlen T,Boller A,Chardonneau A,Cottreel E,Hoecker J,Aissaoui H,Williams JT,Brotschi C,Heidmann B,Siegrist R,Gatfield J,Treiber A,Brisbare-Roch C,Jenck F,Boss C

更新日期：2014-02-15 00:00:00

abstract：:A structure-activity relationship (SAR) study on the benzimidazole series of opioid receptor-like 1 (ORL1) antagonists related to 1 is described. Optimization of 1 by introduction of a hydrophilic substituent into the thioether part resulted in identification of potent ORL1 antagonists with high selectivity over bindi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kobayashi K,Kato T,Yamamoto I,Shimizu A,Mizutani S,Asai M,Kawamoto H,Ito S,Yoshizumi T,Hirayama M,Ozaki S,Ohta H,Okamoto O

更新日期：2009-06-01 00:00:00