Abstract:
:A series of N-methyl rac-cis-4a-aralkyl- and alkyl-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols have been prepared (2a-l) using a simple previously designed synthetic route, in order to find a ligand that would interact with both μ- and δ-opioid receptors. A C4a-phenethyl derivative 2a, was found to have modest receptor affinity both at μ- (K(i)=60 nM) and δ-opioid receptors (K(i)=64 nM). The N-methyl substituent of 2a and that of other ligands in the series was then modified to obtain compounds with different N-substituents that might provide higher affinity at both receptors. A number of compounds differently substituted at C4a and N were synthesized and evaluated. Binding studies and functional assays revealed a moderately selective δ-antagonist (2l), selective μ-δ antagonists (3d, 3g), and a μ-κ antagonist (3f).
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Iyer MR,Rothman RB,Dersch CM,Jacobson AE,Rice KCdoi
10.1016/j.bmc.2013.02.060subject
Has Abstractpub_date
2013-06-01 00:00:00pages
3298-309issue
11eissn
0968-0896issn
1464-3391pii
S0968-0896(13)00262-9journal_volume
21pub_type
杂志文章abstract::The amyloid-like fibril is considered to be a macromolecular self-assemblage with a highly-ordered quaternary structure, in which numerous beta-stranded polypeptide chains align regularly. Therefore, this kind of fibril has the potential to be engineered into proteinaceous materials, although conformational alteration...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2003.11.022
更新日期:2004-02-15 00:00:00
abstract::Several aryl substituted C-fucopeptides have been developed as sialyl Lewis X mimetics. Although the compounds have a much simpler structure compared to SLe(x), up to 3-times higher binding affinity toward E-selectin and > 1000 times toward P-selectin was observed. Furthermore, a convenient strategy for generating a n...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(98)00245-4
更新日期:1999-05-01 00:00:00
abstract::G-quadruplexes (G4s) are non-B DNA structures present in guanine-rich regions of gene regulatory areas, promoters and CpG islands, but their occurrence and functions remain incompletely understood. Thus, methodology to identify G4 sequences is needed. Here, we describe the synthesis of a novel cyclic hepta-oxazole com...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2019.02.056
更新日期:2019-04-15 00:00:00
abstract::Iron complexes (1-7) involving N6-benzyladenosine derivatives of the predominant composition [Fe(L(n))Cl(3)].H(2)O {where L(1)=N6-(2-fluorobenzyl)adenosine (1), L(2)=N6-(4-fluorobenzyl)adenosine (2), L(3)=N6-(2-trifluoromethylbenzyl)adenosine (3), L(4)=N6-(3-trifluoromethylbenzyl)adenosine (4), L(5)=N6-(4-trifluoromet...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.07.082
更新日期:2008-09-15 00:00:00
abstract::Dimethyl fumarate (DMF) is used successfully to treat psoriasis. In spite of its proven clinical efficacy, the mode of metabolism and the pharmacodynamics of DMF are still not completely understood. Some previous studies have indicated that orally applied DMF for a considerable part is quickly hydrolysed to methylhydr...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.09.053
更新日期:2007-01-01 00:00:00
abstract::A series of novel indolin-2-ones inhibitors against p90 ribosomal S6 protein kinase 2 (RSK2) were designed and synthesized and their structure-activity relationship (SAR) was studied. The most potent inhibitor, compound 3s, exhibited potent inhibition against RSK2 with an IC50 value of 0.5 μM and presented a satisfact...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.01.047
更新日期:2013-04-01 00:00:00
abstract::The discovery of the first class of potent glucose-6-phosphatase catalytic site inhibitors, substituted 4,5,6,7-tetrahydrothieno[3,2-c]- and -[2,3-c]pyridines, is described. Optimisation of this series involved solution phase combinatorial synthesis and very potent compounds were prepared with IC50 values down to 140 ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)00153-x
更新日期:2000-09-01 00:00:00
abstract::The design, synthesis, and evaluation of a series of novel inhibitors of aspartate transcarbamoylase (ATCase) are reported. Several submicromolar phosphorus-containing inhibitors are described, but all-carboxylate compounds are inactive. Compounds were synthesized to probe the postulated cyclic transition-state of the...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.09.045
更新日期:2009-11-15 00:00:00
abstract::We synthesized homologated truncated 4'-thioadenosine analogues 3 in which a methylene (CH(2)) group was inserted in place of the glycosidic bond of a potent and selective A(3) adenosine receptor antagonist 2. The analogues were designed to induce maximum binding interaction in the binding site of the A(3) adenosine r...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.08.018
更新日期:2010-10-01 00:00:00
abstract::Fibrosarcoma is one of the fatal cancer types and there is still not satisfactory success in its treatment despite new drugs. Therefore, the search for a new compound has been going on. It is currently known that some palladium-based anti-cancer compounds seem to have powerful apoptosis-inducing effects in cancer cell...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.05.023
更新日期:2013-08-01 00:00:00
abstract::Thirty three derivatives of 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine analogues were synthesized by molecular modification of a reported antimycobacterial molecule (GSK163574A). Compounds were evaluated in vitro against actively replicative and nutrient starved non-replicative Mycobacter...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.09.012
更新日期:2016-11-01 00:00:00
abstract::We examined effects of alpha-, beta-galactosylceramides (CalCers) and alpha-, beta-glucosylceramides (GlcCers) on the syngeneic mixed leukocyte reaction (MLR) using spleen cells (responder cells) and dendritic cells (DC, stimulator cells). The DC pretreated with these alpha-monoglycosylceramides markedly stimulated th...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(98)00112-6
更新日期:1998-10-01 00:00:00
abstract::Using hydroxy-/dihydroxybenzoic acids as leads, a series of methyl, ethyl and iso-propyl esters of 4-hydroxy-benzoic acid, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-dihydroxybenzoic acids and of coumaric acid, were obtained and investigated for the inhibition of six mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that i...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2012.05.019
更新日期:2013-03-15 00:00:00
abstract::Two zinc(II) phthalocyanines bearing either four methoxy (ZnPc 3) or trifluoromethylbenzyloxy (ZnPc 4) substituents have been synthesized by a two-step procedure starting from 4-nitrophthalonitrile. Absorption and fluorescence spectroscopic studies were analyzed in different media. These compounds are essentially non-...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2004.10.003
更新日期:2005-01-03 00:00:00
abstract::Several benzaldoximes, benzaldehyde-O-ethyloximes, and acetophenonoximes were synthesized and evaluated as tyrosinase inhibitors by an assay based on tyrosinase catalyzed L-DOPA oxidation. Whereas benzaldoxime itself is only a weak inhibitor, its derivatives with one or two hydroxy or methoxy moieties in para and meta...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(01)00084-0
更新日期:2001-07-01 00:00:00
abstract::Recent knowledge about the determinants of beta-sheet formation and stability has notably been improved by the structural analysis of model peptides with beta-hairpin structure in aqueous solution. Several experimental studies have shown that the turn region residues can not only determine the stability, but also the ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(98)00215-6
更新日期:1999-01-01 00:00:00
abstract::5-Bromouracil ((Br)U) was incorporated into three types of synthetic RNA and the products of the photoirradiated (Br)U-containing RNAs were investigated using HPLC and MS analysis. The photoirradiation of r(GCA(Br)UGC)(2) and r(CGAA(Br)UUGC)/r(GCAAUUCG) in A-form RNA produced the corresponding 2'-keto adenosine ((keto...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2012.11.010
更新日期:2013-01-15 00:00:00
abstract::The design, synthesis, and biological evaluation of new phosphodiesterase type 4 inhibitors, which possess new templates instead of a cyclohexane ring, are described. The mode of interaction with the enzyme is discussed based on the structure-activity relationship (SAR) data obtained for the synthesized inhibitors. Fu...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2004.07.040
更新日期:2004-10-01 00:00:00
abstract::Several derivatives out of a series of antifungal agents exhibited a good inhibitory potency against aromatase as well as a fairly good selectivity toward CYP17, even if lacking H-bond accepting substituents. Their common structural feature is a flexible backbone that did not fit into previously reported CYP19 models....
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.08.046
更新日期:2008-09-15 00:00:00
abstract::Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group between nitrogen atoms (N(1) and N(2)) in the P-gp inhibitor XR9576 ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.03.014
更新日期:2007-06-01 00:00:00
abstract::The combination of berberine and baicalein may have a better therapeutic effect against disease. To explore the combined effect of baicalein and berberine in the treatment of obesity, we designed and synthesized a hybrid compound, and its biological activities were evaluated in 3T3-L1 adipocytes. The structures of the...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.08.013
更新日期:2017-10-15 00:00:00
abstract::The imidazoquinoxalinones 1 and 2 are benzimidazole analogues of indole-based marine natural products called makaluvamins. The stabilized cation 1 and the zwitterion 2 were prepared in approximately 9 steps from readily available starting materials. Compound 1 is more cytostatic and cytotoxic than 2 and also shows act...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2004.10.016
更新日期:2005-01-17 00:00:00
abstract::In the present article, we have synthesized three different series of pyrazolo[3,4-b]pyridines and their structural analogues using novel synthetic strategy involving one-pot condensation of 5,6-dihydro-4H-pyran-3-carbaldehyde/2-formyl-3,4,6-tri-O-methyl-D-glucal/chromone-3-carbaldehyde with heteroaromatic amines. All...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.06.042
更新日期:2008-08-01 00:00:00
abstract::Two new series of new compounds containing a 6-amino-substituted group or 6-acrylamide-substituted group linked to a 4-anilinoquinazoline nucleus have been discovered as potential EGFR inhibitors. These compounds proved efficient effects on antiproliferative activity and EGFR-TK inhibitory activity. Especially, N(6)-(...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.06.070
更新日期:2013-10-01 00:00:00
abstract::The 3C-like main proteinase of the severe acute respiratory syndrome (SARS) coronavirus, SARS-CoV M(pro), is widely considered to be a major drug target for the development of anti-SARS treatment. Based on the chemical structure of a lead compound from a previous screening, we have designed and synthesized a number of...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.09.034
更新日期:2008-01-01 00:00:00
abstract::Two novel C(27)N(3)-type Lycopodium alkaloids, cryptadines A (1) and B (2) consisting of two octahydroquinoline rings (C(11)N) and a piperidine ring (C(5)N), have been isolated from the club moss Lycopodium cryptomerinum, and their structures and relative stereochemistry were elucidated on the basis of spectroscopic d...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.08.043
更新日期:2007-12-15 00:00:00
abstract::Green tea and (-)-epigallocatechin gallate (EGCG: one of the main components of green tea) are reported to have cancer-preventive activity in humans. A previous SAR study of EGCG and derivatives indicated that a galloyl group is essential for the activity. To test this hypothesis, we synthesized various alkyl gallate ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.07.063
更新日期:2008-09-01 00:00:00
abstract::A new series of 5-glycylamino-2-substituted-phenyl-1,3-dioxacycloalkanes were designed and synthesized. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model. Sixteen of these new compounds exhibited comparable or better anti-inflammatory activities than aspirin...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.11.017
更新日期:2008-02-15 00:00:00
abstract::The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient P...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.02.001
更新日期:2011-03-15 00:00:00
abstract::Thionation of estrogen-like active cyclic peptides, segetalins A (1) and B (2), with Lawesson's reagent provided each two thiosegetalins; thiosegetalin A1 [Gly-1-psi(CS-NH)-Val-2; Trp-5-psi (CS-NH)-Ala-6]segetalin A, thiosegetalin A2 [Gly-1-psi(CS-NH)-Val-2; Ala-6-psi(CS-NH)-Gly-1]segetalin A, thiosegetalin B1 [Gly-1-...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(97)00001-1
更新日期:1997-03-01 00:00:00