Abstract:
:Discovery of a series of tert-butyl pyrrolidine derived, potent and orally bioavailable melanocortin receptor subtype-4 (MC4R) selective modulators is disclosed.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Guo L,Ye Z,Ujjainwalla F,Sings HL,Sebhat IK,Huber J,Weinberg DH,Tang R,MacNeil T,Tamvakopoulos C,Peng Q,MacIntyre E,van der Ploeg LH,Goulet MT,Wyvratt MJ,Nargund RPdoi
10.1016/j.bmcl.2008.04.049subject
Has Abstractpub_date
2008-06-01 00:00:00pages
3242-7issue
11eissn
0960-894Xissn
1464-3405pii
S0960-894X(08)00449-6journal_volume
18pub_type
杂志文章abstract::In search for a new antibacterial agent with improved antimicrobial spectrum and potency, we designed and synthesized a series of novel 3-((Z)-2-(4-nitrophenyl)-2-(1H-tetrazol-5-yl) vinyl)-4H-chromen-4-ones 7a-h by convergent synthesis approach. All the synthesized compounds were assayed for their in-vitro antibacteri...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.07.007
更新日期:2008-08-15 00:00:00
abstract::The optimization of a novel series of non-nucleoside reverse transcriptase inhibitors (NNRTI) led to the identification of pyridone 36. In cell cultures, this new NNRTI shows a superior potency profile against a range of wild type and clinically relevant, resistant mutant HIV viruses. The overall favorable preclinical...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.12.070
更新日期:2014-02-01 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
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.12.008
更新日期:2012-02-01 00:00:00
abstract::We have designed, synthesized, and evaluated the factor Xa inhibitory activities of p-amidinophenyl-sulfones, amines, and alcohols intended to take advantage of the polarity and hydrogen-bonding potential of the oxyanion hole region of the S1 specificity pocket. We demonstrate that placement of an anionic group within...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.07.054
更新日期:2004-10-18 00:00:00
abstract::A series of novel fusidic acid (FA) derivatives was synthesized by replacing the carboxylic acid group with various ester and amide groups and evaluated in vitro for their antiplasmodial activity against the chloroquine-sensitive NF54 and multidrug-resistant K1 strains of the malarial parasite Plasmodium falciparum. M...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2016.11.077
更新日期:2017-02-01 00:00:00
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
doi:10.1016/j.bmcl.2005.06.072
更新日期:2005-10-01 00:00:00
abstract::Homooligomers constructed with 4- and 6-amino acid fragments of melanocortin (alpha-MSH) bind with higher affinity and with apparent cooperativity to melanocortin receptor, compared to their constituent monomers. Individual ligands were tethered with various spacers of different length and rigidity and the influence o...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2003.09.079
更新日期:2004-01-05 00:00:00
abstract::A β-carbonic anhydrases (CAs, EC 4.2.1.1) was recently cloned, purified and characterized kinetically in the pathogen Clostridium perfringens. We report here the first inhibition study of this enzyme (CpeCA). CpeCA was poorly inhibited by iodide and bromide, and was inhibited with KIs in the range of 1-10mM by a range...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.10.037
更新日期:2013-12-15 00:00:00
abstract::S1P(1) receptor driven lymphopenia has proven utility in the treatment of an array of autoimmune disease states. As a part of our efforts to develop potent and selective S1P(1) receptor agonists, we have identified a novel chemical series of 4-oxo-4-(5-(5-phenyl-1,2,4-oxadiazol-3-yl)indolin-1-yl)butanoic acid S1P(1) r...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.05.110
更新日期:2011-10-01 00:00:00
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
doi:10.1016/j.bmcl.2013.07.007
更新日期:2013-09-15 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
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.06.031
更新日期:2014-08-15 00:00:00
abstract::Quinolizidinyl derivatives of the tricyclic systems characterizing pirenzepine and nuvenzepine, were prepared and tested as ligands for muscarinic M1, M2 and M3 receptors; 5,11-dihydro-11-[(S-lupinyl)-thioacetyl]-6H-pyrido[2,3-b][1, 4]benzodiazepin-6-one exhibited IC50 = 10 nM for M1 and 760 nM for both M2 and M3 subt...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00528-4
更新日期:1999-10-18 00:00:00
abstract::The seminal human dopamine D3 receptor (hD3R) ligand BP 897 has shown interesting properties during clinical trials. However, its lack of selectivity towards human adrenergic receptor impedes further development. Two approaches were followed to increase hD3R selectivity. The lead optimisation succeeded, we disclose he...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.12.068
更新日期:2016-02-01 00:00:00
abstract::A new class of imine derivatives of hybrid chalcone analogues containing anthraquinone scaffold was synthesized and evaluated for their in vitro cytotoxic activity against HeLa, LS174, and A549 cancer cells. The compound 5n with furan ring linked to imino group showed potent activity against all target cells with IC50...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.11.075
更新日期:2014-01-01 00:00:00
abstract::In this report we detail the evolution of our previously reported thiophene isoxazole BET inhibitor chemotype exemplified by CPI-3 to a novel bromodomain selective chemotype (the methyl isoxazoleazepine chemotype) exemplified by carboxamide 23. The methyl isoxazoleazepine chemotype provides potent inhibition of the br...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.03.045
更新日期:2015-05-01 00:00:00
abstract::We have developed two novel series of tetrasubstituted pyrazoles, embodying 1,3-diaryl-4,5-dialkyl or 3,5-diaryl-1,4-dialkyl substitution patterns. The scope of a regioselective method, developed by us earlier, was expanded to allow the synthesis of the first series of these tetrasubstituted pyrazoles directly from al...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(02)00057-4
更新日期:2002-03-25 00:00:00
abstract::A series of transdermal permeation enhancers based on dicarboxylic acid esters was studied. Single-chain amphiphiles were markedly more effective than the double-chain ones. Monododecyl maleate, that is a cis derivative, was a more potent enhancer than its trans isomer, while the activity of succinates strongly depend...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.11.083
更新日期:2009-01-15 00:00:00
abstract::During development of nitroheterocycles with potential antimycobacterial activities we have tested against Mycobacterium tuberculosis a number of pyrroles strictly related to pyrrolnitrin, an antifungal antibiotic isolated from Streptomyces pyrrocinia. Some of the tested arylpyrrole derivatives and pyrrolnitrin have s...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(98)00526-5
更新日期:1998-10-20 00:00:00
abstract::Natural inhibitors of fatty acid synthase (FAS) are emerging as potential therapeutic agents to treat cancer and obesity. The bioassay-guided chemical investigation of the hulls of Garcinia mangostana led to the isolation of 13 phenolic compounds (1-13) mainly including xanthone and benzophenone, in which compounds 7,...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.08.061
更新日期:2010-10-15 00:00:00
abstract::The design, synthesis, and biological evaluation of arylsulfonamidooxazoles as 11beta-HSD1 inhibitors and the serendipitous discovery of beta-keto sulfones as potent 11beta-HSD1 inhibitors are described here. These two classes of compounds are not active against 11beta-HSD2 and therefore may have significant therapeut...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.03.093
更新日期:2005-06-02 00:00:00
abstract::A novel series of aminopyrimidinylisoindoline derivatives 1a-w having an aminopyrimidine scaffold as a hinge region binding motif were designed and synthesized. Among them, six compounds showed potent inhibitory activities against AXL kinase with IC50 values of submicromolar range. Especially, compound 1u possessing (...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.10.013
更新日期:2018-12-15 00:00:00
abstract::A new series of 3,6-diaryl-1H-pyrazolo[3,4-b]pyridine compounds have been discovered as potent anaplastic lymphoma kinase (ALK) inhibitors. The 4-hydroxyphenyl in the 6-position of 1H-pyrazolo[3,4-b]pyridine were crucial and a fluorine atom substitution could give promising inhibitory activity. The IC50 of compound 9v...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2019.01.037
更新日期:2019-04-01 00:00:00
abstract::A novel series of imidazo[1,5-a]pyrazines was synthesized and evaluated as corticotropin releasing hormone (CRH) receptor ligands. SAR studies focused primarily on dialkylamino side chain optimization. SAR of the aryl and small alkyl substituents was also explored. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(01)00741-7
更新日期:2002-02-11 00:00:00
abstract::By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 μM; MIC = 0.48 μM) than the positive controls AHA (IC50 = 17.2 μM) and Metronidazole (MIC = 31.3 ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.08.025
更新日期:2018-10-15 00:00:00
abstract::Prothrombin is a vitamin K-dependent serine protease and plays pivotal roles in both procoagulant and anticoagulant pathway of hemostasis. In this study, prothrombin purified from porcine plasma was modified through PEGylation at N-terminal residue using 40 kDa PEG-phenyl-isothiocyanate (PIT-PEG40K). The monoPEGylated...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.04.037
更新日期:2011-06-01 00:00:00
abstract::Following the discovery of N-acyl-1,4-diazepan-2-one as a novel pharmacophore for potent and selective DPP-4 inhibitors, optimization of this new lead with different substitution on the seven-membered ring resulted in several highly potent and selective, orally bioavailable, and efficacious DPP-4 inhibitors, such as 3...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.01.039
更新日期:2007-04-01 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
pub_type: 杂志文章
doi:10.1016/s0960-894x(01)00032-4
更新日期:2001-06-18 00:00:00
abstract::Iminium quaternary protoberberine alkaloids (QPA) have been found to be novel P2X(7) antagonists. To assess their structure-activity relationships, these compounds were modified at their R(1) and R(2) groups and assayed for their ability to inhibit the 2'(3')-O-(4-benzoylbenzoyl)-ATP (BzATP)-induced uptake of fluoresc...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.11.088
更新日期:2009-02-01 00:00:00
abstract::A novel series of 5-HT(7) receptor ligands has been identified and evaluated, providing compounds showing a broad spectrum of functional activities and good selectivity over selected receptors and ion channels. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.11.067
更新日期:2006-03-01 00:00:00
abstract::A potent, selective series of MMP-13 inhibitors has been derived from a weak (3.2 microM) inhibitor that did not bear a zinc chelator. Structure-based drug design strategies were employed to append a Zn-chelating group to one end of the molecule and functionality to enhance selectivity to the other. A compound from th...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.06.019
更新日期:2005-09-15 00:00:00