Abstract:
:The discovery and optimization of a new class of non-peptidyl, pyridazinone derived melanocortin subtype-4 receptor agonists is disclosed.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Ujjainwalla F,Warner D,Walsh TF,Wyvratt MJ,Zhou C,Yang L,Kalyani RN,MacNeil T,Van der Ploeg LH,Rosenblum CI,Tang R,Vongs A,Weinberg DH,Goulet MTdoi
10.1016/j.bmcl.2003.09.026subject
Has Abstractpub_date
2003-12-15 00:00:00pages
4431-5issue
24eissn
0960-894Xissn
1464-3405pii
S0960894X03009806journal_volume
13pub_type
杂志文章abstract::Two new austalide meroterpenoids, named austalides V and W (1 and 2), were isolated from the fungus Aspergillus ustus VKM F-4692. Their structures were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. The main structural feature of both compounds is a tetrahydrofuranyl rin...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2019.126708
更新日期:2019-11-15 00:00:00
abstract::The halogenated and oxidized derivatives (1a-1e, 1a'-1c', 2a-2d, 2a'-2b', 3a-3e, 3' and 3a'-3b') of schizandrin (1), schizandrin B (2) and schisanhenol (3) were synthesized. The hepatoprotective effects of these dibenzocyclooctadiene lignan analogues against CCl4-induced injury were preliminarily evaluated. Most of th...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.02.020
更新日期:2014-04-01 00:00:00
abstract::The design and synthesis of a series of C28 amine-based betulinic acid derivatives as HIV-1 maturation inhibitors is described. This series represents a continuation of efforts following on from previous studies of C-3 benzoic acid-substituted betulinic acid derivatives as HIV-1 maturation inhibitors (MIs) that were e...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.03.067
更新日期:2018-05-15 00:00:00
abstract::We have developed clickable active site-directed photoaffinity probes for γ-secretase which incorporate a photoreactive benzophenone group and an alkyne handle for subsequent click chemistry mediated conjugation with azide-linked reporter tags for visualization (e.g., TAMRA-azide) or enrichment (e.g., biotin-azide) of...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.02.027
更新日期:2012-04-15 00:00:00
abstract::A novel series of 1,2,3-thiadiazole thioacetanilide (TTA) derivatives have been designed, synthesized and evaluated for its anti-HIV activities in MT-4 cells. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations. Among them, 2-[4-(2,4-dichlorophenyl)-1,2,3-thiadiaz...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.09.055
更新日期:2008-10-15 00:00:00
abstract::Inhibition of intestinal brush border DMT1 offers a novel therapeutic approach to the prevention and treatment of disorders of iron overload. Several series of diaryl and tricyclic benzylisothiourea compounds as novel and potent DMT1 inhibitors were discovered from the original hit compound 1. These compounds demonstr...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.05.129
更新日期:2012-08-01 00:00:00
abstract::The discovery of genotoxic amino acids derived from phenylglycine, and possessing halogen substituents, is described. The utility of hypervalent iodine reagents in the synthesis of this class of compounds is highlighted. The mechanism of action of the (haloaryl)glycines was studied in Saccharomyces cerevisiae. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2006.08.111
更新日期:2006-12-01 00:00:00
abstract::The SmI(2)-promoted three-component coupling reaction of thiophene-2-carboxylate, indole-2-carbaldehyde and acetophenone provides an expedient route to a series of tetracyclic carbazolothiophene compounds bearing the indole and thiophene rings. Among these samples, 9-benzyl-4-methyl-4-(4-hydroxyphenyl)-10-oxo-4,10-dih...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2003.12.067
更新日期:2004-03-08 00:00:00
abstract::4-Deacetoxyagosterol A was synthesized from ergosterol by utilizing reductive regioselective epoxy cleavage as a key reaction. This synthesized congener of agosterol A, a spongean MDR-modulator. showed similar MDR-modulating activity against KB CV-60 cells overexpressing MRP. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00502-3
更新日期:2000-11-20 00:00:00
abstract::Myelin associated glycoprotein (Siglec-4) is a myelin adhesion receptor, that is, well established for its role as an inhibitor of axonal outgrowth in nerve injury, mediated by binding to sialic acid containing ligands on the axonal membrane. Because disruption of myelin-ligand interactions promotes axon outgrowth, we...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.04.068
更新日期:2011-09-01 00:00:00
abstract::The synthesis and evaluation of tetrasubstituted aminopyridines, bearing novel azaindazole hinge binders, as potent AKT inhibitors are described. Compound 14c was identified as a potent AKT inhibitor that demonstrated reduced CYP450 inhibition and an improved developability profile compared to those of previously desc...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.11.061
更新日期:2010-01-15 00:00:00
abstract::Fourty-two thiazolyl-pyrazoline derivatives were synthesized to screen for their EGFR kinase inhibitory activity. Compound 4-(4-chlorophenyl)-2-(3-(3,4-dimethylphenyl)-5-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazole (11) displayed the most potent EGFR TK inhibitory activity with IC(50) of 0.06 μM, which was comparable ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.07.010
更新日期:2011-09-15 00:00:00
abstract::All the stereoisomers of 2-(2-carboxy-3,3-difluorocyclopropyl)glycines (F2CCGs) were synthesized in enantiomerically pure forms using (R)-2,3-O-isopropyl-ideneglyceraldehyde as a chiral precursor. L-F2CCG-I, one of the stereoisomers corresponding to an extended form of L-glutamate was found to be a potent agonist for ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(98)00338-2
更新日期:1998-08-04 00:00:00
abstract::Novel indole-3-heterocycles were designed and synthesized and found to be potent CB1 receptor agonists. Starting from a microsomally unstable lead 1, a bioisostere approach replacing a piperazine amide was undertaken. This was found to be a good strategy for improving stability both in vitro and in vivo. This led to t...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.10.093
更新日期:2011-01-01 00:00:00
abstract::New carbon-11 and fluorine-18 labeled N-acetyl-1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives were designed and synthesized as potential positron emission tomography AMPA (2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid) receptor ligands to image brain diseases. The single crystal structure ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2006.01.042
更新日期:2006-04-15 00:00:00
abstract::Based on our earlier reported neuropeptide FF receptors antagonist (RF9), we carried out an extensive structural exploration of the N-terminus part of the amidated dipeptide Arg-Phe-NH(2) in order to establish a structure-activity relationships (SAR) study towards both NPFF receptor subtypes. This SAR led to the disco...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.10.049
更新日期:2012-12-15 00:00:00
abstract::Structure-activity relationship studies directed toward improving the metabolic stability of compound 1 resulted in the identification of 3-[5-(3,5-difluorophenyl)-3-({[(1S,3R)-3-fluorocyclopentyl]amino}methyl)-4-methyl-1H-pyrazol-1-yl]propanenitrile 39 (MK-1925) as a selective, orally available and brain-penetrable o...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.06.051
更新日期:2009-08-15 00:00:00
abstract::A number of analogues of the recently described compound nematophin were prepared and studied for antibacterial activity. The 2-phenyl derivative was found to exhibit exceptional activity against methicillin resistant Staphylococcus aureus (MRSA) whereas the isosteric benzimidazole analogue was much less active. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00331-0
更新日期:2000-08-07 00:00:00
abstract::Four stereoisomeric hybrids of the polyketide natural products callystatin A and leptomycin B have been prepared by parallel synthetic routes involving chiral allenylstannane methodology. Like their natural counterparts, these hybrids exhibit nanomolar levels of cytotoxicity toward HCT-116 human colon cancer cells. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.09.084
更新日期:2006-01-15 00:00:00
abstract::A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (3...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.08.075
更新日期:2015-10-15 00:00:00
abstract::A series of benzoxazole/benzothiazole-2,3-dihydrobenzo[b][1,4]dioxine derivatives (5a-5d and 8a-8j) was synthesized. Compounds were evaluated for binding affinities at the 5-HT1A and 5-HT2A receptors. Antidepressant activities of the compounds were screened using the forced swimming test (FST) and the tail suspension ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.02.031
更新日期:2014-04-01 00:00:00
abstract::Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which exhibits selective cytotoxicity against a tumorigenic cell line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)-methanone (18m) was designed and synthesized as a biologically stable derivative c...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2003.10.039
更新日期:2004-01-19 00:00:00
abstract::The Keap1-Nrf2 system is involved not only in biological defense but also in malignancy progression and chemoresistance. The ubiquitin-binding protein p62/Sqstm1 (p62), which is highly expressed in several cancers, competes with Nrf2 for Keap1 binding, leading to activation of Nrf2-mediated gene expression and surviva...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2016.10.083
更新日期:2016-12-15 00:00:00
abstract::Structure-activity studies on the oxytocin antagonist 1 (L-371,257; Ki = 9.3 nM) have led to the identification of a related series of compounds containing an ortho-trifluoroethoxyphenylacetyl core which are orally bioavailable and have significantly improved potency in vitro and in vivo, e.g., compound 8 (L-374,943; ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00181-x
更新日期:1999-05-03 00:00:00
abstract::Two nemadectin congeners 1 and 2 were isolated from the fermentation broth of a mutant strain (Y-3) of Streptomyces microflavus neau3. Their structures were determined on the basis of extensive spectroscopic analysis and comparison with data from the literature. Compound 2 possessed a 5-membered ring lactone that is u...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.08.002
更新日期:2013-10-15 00:00:00
abstract::Pholasin is a bioluminescent photoprotein of Pholas dactylus. Pholasin is a commercially available photoprotein used to measure intracellular reactive oxygen species. Although extensive efforts have been carried out to determine the chemical structure of the prosthetic (chromophore) group, it still remains unclear to ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.08.113
更新日期:2008-10-15 00:00:00
abstract::A series of oxazole-substituted indanylacetic acids were prepared which show a spectrum of activity as ligands for PPAR nuclear receptor subtypes. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.10.008
更新日期:2006-01-15 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::We report an efficient approach for the chemical synthesis of Rhesus θ-defensin-1 (RTD-1) using Fmoc-based solid-phase peptide synthesis in combination with an intramolecular version of native chemical ligation. The corresponding linear thioester precursor was cyclized and folded in a one-pot reaction using reduced gl...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.02.080
更新日期:2012-04-15 00:00:00
abstract::A series of pentapeptides, based on hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)), was prepared in which either DPhe(7) or Trp(9) residue was systematically substituted. A number of interesting DPhe surrogates (D-Thi, D-3-CF(3)Phe, D-2-Nal and D-3,4-diClPhe) as well as Trp surrogates (2-Na...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(02)01052-1
更新日期:2003-02-24 00:00:00