Abstract:
:Rigidification of the isobutyl side chain of drug-like AT2 receptor agonists and antagonists that are structurally related to the first reported selective AT2 receptor agonist 1 (C21) delivered bioactive indane derivatives. Four enantiomer pairs were synthesized and the enantiomers were isolated in an optical purity >99%. The enantiomers 7a, 7b, 8a, 8b, 9a, 9b, 10a and 10b bind to the AT2 receptor with moderate (Ki = 54-223 nM) to high affinity (Ki = 2.2-7.0 nM). The enantiomer with positive optical rotation (+) exhibited the highest affinity at the receptor. The indane derivatives 7b and 10a are among the most potent AT2 receptor antagonists reported so far. As illustrated by the enantiomer pairs 7a/b and 10a/b, an alteration at the stereogenic center has a pronounced impact on the activation process of the AT2 receptor, and can convert agonists to antagonists and vice versa.
journal_name
Medchemcommjournal_title
MedChemCommauthors
Wallinder C,Sköld C,Sundholm S,Guimond MO,Yahiaoui S,Lindeberg G,Gallo-Payet N,Hallberg M,Alterman Mdoi
10.1039/c9md00402esubject
Has Abstractpub_date
2019-11-18 00:00:00pages
2146-2160issue
12eissn
2040-2503issn
2040-2511pii
c9md00402ejournal_volume
10pub_type
杂志文章相关文献
MedChemComm文献大全abstract::Covalent probes and drugs have found widespread use as research tools and clinical agents. Covalent probes are useful because of their increased intracellular potency and because covalent labeling of cellular proteins can be tracked using click chemistry. Covalent drugs, on the other hand, can overcome drug resistance...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c5md00518c
更新日期:2016-04-01 00:00:00
abstract::A series of cyclic peptides were designed and prepared to investigate the physicochemical properties that affect oral bioavailabilty of this chemotype in rats. In particular, the ionization state of the peptide was examined by the incorporation of naturally occurring amino acid residues that are charged in differing r...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C2MD20203D
更新日期:2012-10-01 00:00:00
abstract::Urinary tract infections (UTIs) are amongst the most common and prevalent infectious diseases worldwide, with uropathogenic Escherichia coli (UPEC) reported as the main causative pathogen. Fluoroquinolone antibiotics are commonly used to treat UTIs but for infections involving UPEC biofilms, which are commonly associa...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c9md00062c
更新日期:2019-02-25 00:00:00
abstract::Bruton's tyrosine kinase (BTK) plays a critical role in B cell receptor (BCR)-mediated signaling pathways responsible for the development and function of B cells, which makes it an attractive target for the treatment of many types of B-cell malignancies. Herein, a series of N5-substituted 6,7-dioxo-6,7-dihydropteridin...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00019k
更新日期:2018-03-13 00:00:00
abstract::Two diazabicyclo analogues of maraviroc, in which the azabicyclooctane moiety is replaced by diazabicyclooctane or diazabicyclononane, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane derivative maintained a significant infectivity reduction pow...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c6md00575f
更新日期:2016-12-16 00:00:00
abstract::The dopamine D3 receptor (D3R) is a proven therapeutic target for the treatment of neurological and neuropsychiatric disorders. In particular, D3R-selective ligands that can eliminate side effects associated with dopamine D2 receptor (D2R) therapeutics have been validated. However, the high homology in signaling pathw...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00237a
更新日期:2018-06-14 00:00:00
abstract::A library of 33 compounds was screened for potentiation of the antibiotic FR 900098 against the Francisella tularensis surrogate Francisella novicida. From the screen a highly potent 2-oxazoline adjuvant was discovered capable of potentiating FR 900098 with a 1000-fold reduction in MIC against the Francisella sub-spec...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C6MD00365F
更新日期:2016-01-01 00:00:00
abstract::Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1, EC 3.1.4.1) is a metalloenzyme that belongs to the NPP family, which comprises seven subtypes (NPP1-7). NPP1 hydrolyzes a wide range of phosphodiester bonds, e.g. in nucleoside triphosphates, (cyclic) dinucleotides, and nucleotide sugars yielding nucleoside 5'...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c7md00015d
更新日期:2017-02-09 00:00:00
abstract::N-Myristoyltransferase (NMT) represents an attractive drug target in parasitic infections such as malaria due to its genetic essentiality and amenability to inhibition by drug-like small molecules. Scaffold simplification from previously reported inhibitors containing bicyclic cores identified phenyl derivative 3, pro...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c5md00242g
更新日期:2015-10-08 00:00:00
abstract::The cytotoxic drug gemcitabine (GEM) has been conjugated to receptor-binding peptides to target melanoma tumors. A hexapeptide having a Lys-Gly-His-Lys sequence (pep-1), an octapeptide with an Arg-Gly-Asp-Lys-Gly-His-Lys sequence (pep-2), a GEM-conjugated Lys-Gly-His-Lys peptide (GEM-pep-3) and a GEM-conjugated Asp-Gl...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00638a
更新日期:2018-03-06 00:00:00
abstract::Fungal infections directly affect millions of people each year. In addition to the invasive fungal infections of humans, the plants and animals that comprise our primary food source are also susceptible to diseases caused by these eukaryotic microbes. The need for antifungals, not only for our medical needs, but also ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C6MD00222F
更新日期:2016-07-01 00:00:00
abstract::Herein we continued our previous work on the development of CB2 ligands, reporting the design and synthesis of a series of benzimidazole-containing derivatives that were explored as selective CB2 ligands with binding affinity towards both CB1 and CB2 receptors. Seven out of eighteen compounds exhibited preferential bi...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00461g
更新日期:2018-10-10 00:00:00
abstract::A series of 4-thiazolidinone derivatives were synthesized and evaluated as novel human dihydroorotate dehydrogenase (hDHODH) inhibitors. Compounds 26 and 31 displayed IC50 values of 1.75 and 1.12 μM, respectively. The structure-activity relationship was summarized. Further binding mode analysis revealed that compound ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00081b
更新日期:2017-04-26 00:00:00
abstract::Bile acids have emerged as strong signaling molecules capable of influencing various biological processes like inflammation, apoptosis, cancer progression and atherosclerosis depending on their chemistry. In the present study, we investigated the effect of major hydrophobic bile acids lithocholic acid (LCA) and deoxyc...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00475c
更新日期:2017-10-31 00:00:00
abstract::In the present work, coumarin based pyrazolines (7a-g) have been synthesized and investigated for their in vitro and in vivo anti-inflammatory potential. Amongst the synthesized compounds, compounds 7a, 7d and 7f exhibited significant in vitro anti-inflammatory activity as compared to the standard etoricoxib. Keeping ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00457a
更新日期:2019-01-23 00:00:00
abstract::Periodontal disease is an oral chronic immune-inflammatory disease highly prevalent worldwide that is initiated by specific oral bacterial species leading to local and systemic effects. The development of new preventive/therapeutic strategies to specifically target oral periodontopathogens without perturbing oral micr...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c9md00074g
更新日期:2019-06-10 00:00:00
abstract::Zampanolide and dactylolide are microtubule-stabilizing polyketides possessing potent cytotoxicity towards a variety of cancer cell lines. Using our understanding of the conformational preferences of the macrolide core in both natural products, we hypothesized that analogues lacking the C17-methyl group would maintain...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c9md00164f
更新日期:2019-04-09 00:00:00
abstract::Human African trypanosomiasis (HAT), also known as African sleeping sickness, is caused by parasitic protozoa of the genus Trypanosoma. As the disease progresses, the parasites cross the blood brain barrier and are lethal for the patients if the disease is left untreated. Current therapies suffer from several drawback...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c7md00280g
更新日期:2017-07-31 00:00:00
abstract::We used quantum mechanics/molecular mechanics calculations to test if antimalarial primaquine (PQ) and its derivatives aid the conversion of hemoglobin to methemoglobin by binding to hemoglobin and merely lowering hemoglobin's ionization potential (IP). Our results showed that PQ and its derivatives do not significant...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C3MD00045A
更新日期:2013-08-01 00:00:00
abstract::[This corrects the article DOI: 10.1039/C7MD00637C.]. ...
journal_title:MedChemComm
pub_type: 杂志文章,已发布勘误
doi:10.1039/c8md90009d
更新日期:2018-03-02 00:00:00
abstract::Recently, there has been an emergence of significant interest in silver-based antimicrobials. Our goal was to develop a radioactive tracer for investigating the biological fate of such compounds. Purified 111Ag was incorporated into the methylated caffeine analogue, IC1 to yield the silver carbene complex designated a...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C3MD00082F
更新日期:2013-06-01 00:00:00
abstract::Previous studies have demonstrated that natural steroid compounds containing a peroxide bridge exhibited potential anti-hepatitis B virus activity. To continue our research, a simple and regioselective methodology, using Eosin Y as a clean photosensitized oxidation catalyst, was developed for the synthesis of a peroxi...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c6md00344c
更新日期:2016-10-19 00:00:00
abstract::It was previously reported that 6β-aminomorphinan derivatives show high affinity for opiate receptors. Novel 6β-heteroarylamidomorphinanes were designed based on the MOR selective antagonist NAP. The 6β-aminomorphinanes were prepared with stereoselective Mitsunobu reaction and subsequently acylated with nicotinic acid...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C6MD00450D
更新日期:2017-01-01 00:00:00
abstract::New derivatives of aminoglycosides containing 6'-carboxylic acid or 6'-amide on their ring I were designed, synthesized and their ability to readthrough nonsense mutations was examined in vitro, along with the protein translation inhibition in prokaryotic and eukaryotic systems. The observed structure-activity relatio...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00001h
更新日期:2018-02-02 00:00:00
abstract::Classical aminoglycoside antibiotics are obsolete or hampered by the emergence of drug resistant bacteria. Recent discoveries of antifungal amphiphilic kanamycins offer new strategies for reviving and repurposing these old drugs. A simple structural modification turns the clinically obsolete antibacterial kanamycin in...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c8md00155c
更新日期:2018-04-17 00:00:00
abstract::Based on the scaffold of astemizole, three novel turn-on fluorescent probes (N1-N3) for human ether-a-go-go-related gene (hERG) potassium channel were developed herein. These probes have reasonable fluorescence properties, acceptable cell toxicity, and potent inhibitory activity, all of which contribute to cell imagin...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00562a
更新日期:2019-02-26 00:00:00
abstract::Malaria is a serious tropical disease that kills thousands of people every year, mainly in Africa, due to Plasmodium falciparum infections. Salirasib is a promising cancer drug candidate that interferes with the post-translational modification of Ras. This S-farnesyl thiosalicylate inhibits isoprenylcysteine carboxyl ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c9md00298g
更新日期:2019-06-21 00:00:00
abstract::The natural products colchicine and combretastatin A-4 (CA4) have provided inspiration for the discovery and development of a wide array of derivatives and analogues that inhibit tubulin polymerization through a binding interaction at the colchicine site on β-tubulin. A water-soluble phosphate prodrug salt of CA4 (ref...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00322j
更新日期:2018-08-24 00:00:00
abstract::Three series of compounds were designed, synthesized and evaluated for their in vitro anticancer activity against a procaspase-3 over-expression cancer cell line (U937) and a procaspase-3 no-expression cancer cell line (MCF-7) to rule out off-target effects. Biological evaluation led to the identification of a series ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00624e
更新日期:2019-02-25 00:00:00
abstract::2-Arylethynyl derivatives of (N)-methanocarba adenosine 5'-uronamides are selective A3AR (adenosine receptor) agonists. Here we substitute a 1,2,3-triazol-1-yl linker in place of the rigid, linear ethynyl group to eliminate its potential metabolic liability. Docking of nucleosides containing possible short linker moie...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C4MD00571F
更新日期:2015-01-01 00:00:00