Abstract:
:We report a three-dimensional model of the alpha5beta1 integrin headgroup bound to the most potent and selective ligand (SJ749) known to date. The model was built using the comparative protein modeling method, and it is consistent with experimental data. From this study, we identified two potentially important regions in the alpha5beta1 receptor that are peculiar to this integrin and might be worth considering for drug targeting.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Marinelli L,Meyer A,Heckmann D,Lavecchia A,Novellino E,Kessler Hdoi
10.1021/jm040224ikeywords:
subject
Has Abstractpub_date
2005-06-30 00:00:00pages
4204-7issue
13eissn
0022-2623issn
1520-4804journal_volume
48pub_type
杂志文章abstract::As part of our studies to develop novel retinoids with increased affinity and selectivity for the retinoid X receptor (RXR) subfamily, we have designed and synthesized a series of (E,E,E)-7-(1,2,3, 4-tetrahydroquinolin-6-yl)-7-alkyl-6-fluoro-3-methylhepta-2, 4, 6-trienoic acid derivatives. These tetrahydroquinolines, ...
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abstract::The bradykinin B1 receptor is rapidly induced upon tissue injury and inflammation, stimulating the production of inflammatory mediators resulting in plasma extravasation, leukocyte trafficking, edema, and pain. We have previously reported on sulfonamide and sulfone-based B1 antagonists containing a privileged bicyclic...
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更新日期:2011-10-27 00:00:00
abstract::A novel series of substituted (pyrroloamino)pyridines was synthesized, and the compounds were evaluated for cholinomimetic-like properties in vitro (inhibition of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine-induced dementia) as potential agents for the treatment of Alzheimer's disease. Co...
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abstract::Thymidylate synthase X (ThyX) represents an attractive target for tuberculosis drug discovery. Herein, we selected 16 compounds through a virtual screening approach. We solved the first X-ray crystal structure of Thermatoga maritima (Tm) ThyX in complex with a nonsubstrate analog inhibitor. Given the active site simil...
journal_title:Journal of medicinal chemistry
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doi:10.1021/acs.jmedchem.6b00977
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abstract::5-(2,2-Difluorovinyl)uracil (IV) was synthesized from 2,4-dimethoxy-5-bromopyrimidine by sequential formylation, difluoromethylenation, and removal of the 2- and 4-methyl groups. Condensation of the trimethylsilyl derivative of IV with protected D-erythro-pentofuranosyl chloride followed by separation of anomers and d...
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pub_type: 杂志文章
doi:10.1021/jm00391a036
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abstract::We have synthesized a set of bis-pyranobenzoquinones through a direct and highly efficient approach based on a double intramolecular domino Knoevenagel hetero Diels-Alder reaction. These bis-pyranobenzoquinone derivatives are compounds whose skeletons have similarities to those of some anticancerous and leishmanicidal...
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pub_type: 杂志文章
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abstract::Several derivatives of erythro-beta-hydroxy-DL-aspartic acid (1) were prepared as a potential inhibitors of L-asparagine synthetase (ASase) from rat Novikoff hepatoma. Benzylation of 1 gave the dibenzyl ester 2 which upon coupling with carbobenzoxyglycine afforded the blocked dipeptide 3. Deblocking of 3 gave glycl-er...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
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更新日期:1975-04-01 00:00:00
abstract::A series of N-substituted 3-aminoglutarimides have been synthesized and tested for inhibitory activity against a range of chemokines in vitro and for suppression of lipopolysaccharide-induced inflammation in vivo. The results show that they represent the first class of small molecules with broad-spectrum chemokine inh...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm010984i
更新日期:2002-01-17 00:00:00
abstract::The discovery of a new zinc binding chemotype from screening a nonbiased fragment library is reported. Using the orthogonal fragment screening methods of native state mass spectrometry and surface plasmon resonance a 3-unsubstituted 2,4-oxazolidinedione fragment was found to have low micromolar binding affinity to the...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.7b00606
更新日期:2017-09-14 00:00:00
abstract::We report the esterification of the carboxyl groups of the cyclic peptide toxins nodularin-R and microcystin-LA to produce stable diacetoxymethyl and dipropionyloxymethyl ester derivatives. The derivatives had no activity but were reactivated upon esterase treatment. When injected into cells, the acyloxymethyl moietie...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm900502e
更新日期:2009-09-24 00:00:00
abstract::The academic setting provides an environment that may foster success in the discovery of certain types of small molecule tools while proving less suitable in others. For example, small molecule probes for poorly understood systems, those that exploit a specific resident expertise, and those whose commercial return is ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1021/jm400132d
更新日期:2013-09-26 00:00:00
abstract::N,N-Dialkylated leucine enkephalin analogues containing melphalan (Mel) in place of Phe4 were synthesized as potentially irreversible antagonists of the delta opioid receptor. These compounds, along with the corresponding Phe4 peptides, were tested for both agonist and antagonist activity in the GPI and MVD smooth mus...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00392a025
更新日期:1987-09-01 00:00:00
abstract::In this study, we described a series of N-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine derivatives as selective JAK2 (Janus kinase 2) inhibitors. Systematic exploration of the structure-activity relationship though cyclization modification based on previously reported compound 18e led to the discovery of the...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c01488
更新日期:2020-12-10 00:00:00
abstract::We describe the preparation and evaluation of a novel series of glycine transporter 1 (GlyT1) inhibitors derived from a high-throughput screening hit. The SAR studies resulted in the discovery of 3-biphenyl-4-yl-4-(2-fluorophenyl)-5-isopropyl-4H-1,2,4-triazole (6p). A pharmacokinetic study was also conducted and revea...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm101031u
更新日期:2011-01-13 00:00:00
abstract::A series of novel (1,3-dialkyl-5-amino-1H-pyrazol-4-yl)arylmethanones was synthesized. Pharmacological evaluation of these compounds demonstrated central nervous system depressant activity, potential anticonvulsant properties, and a low order of acute toxicity. In addition, selected compounds showed potential antipsyc...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00377a003
更新日期:1984-11-01 00:00:00
abstract::Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been developed using comparative molecular field analysis (CoMFA) on a large data set (118 compounds) of diverse cyclic urea derivatives as protease inhibitors against the human immunodeficiency virus type 1 (HIV-1). X-ray crystal str...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm980369n
更新日期:1999-01-28 00:00:00
abstract::The 18 kDa translocator protein (TSPO) is a mitochondrial protein whose basal density is altered in several diseases, with the result that the evaluation of its expression levels by means of molecular imaging techniques represents a promising diagnostic approach. Experimental procedures using a labeled ligand often ca...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm100100q
更新日期:2010-05-27 00:00:00
abstract::Conjugation of pleuromutilin is an attractive strategy for the development of novel antibiotics and the fight against multiresistant bacteria as the class is associated with low rates of resistance and cross-resistance development. Herein, the preparation of 35 novel (+)-pleuromutilin conjugates is reported. Their des...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c01328
更新日期:2020-12-24 00:00:00
abstract::There is reported the first four members of heteroarotinoids, the names of which are ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate (1b), ethyl (E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoate (1c), ethyl (E)-p-[2-(4,4-dimethyl-1-oxothiochroman-6-yl)propenyl]benzoate (1d), and (E)-p-[2-(4,4-dimethy...
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pub_type: 杂志文章
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abstract::New analogues of human cholecystokinin in which the Tyr(SO3H) has been replaced by Phe(p-CH2SO3Na), methionines by norleucines, and tryptophan by 2-naphthylalanine([Phe(p-CH2- SO3Na)27,Nle28,31,Nal30]-CCK26-33 and [Phe(p-CH2SO3Na)27,Nle7,28,31,Nal30]-CCK-33) were synthesized by Fmoc solid phase methodology on two diff...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00064a001
更新日期:1993-06-11 00:00:00
abstract::The N-2 atoms of phosphorus 2,2-dimethylhydrazides, contrary to a previous report, can be methylated by iodomethane. Treatment of the resulting dihydrazinium iodides with aqueous sodium hydroxide results in mono- instead of didehydroiodination, apparently due to resonance stabilization of the inner salt form. The phos...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm50001a010
更新日期:1985-05-01 00:00:00
abstract::4-(Phenylamino)-5-phenyl-7-(5-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 1 and related compounds known as "diaryltubercidin" analogues are potent inhibitors of adenosine kinase (AK) and are orally active in animal models of pain such as the rat formalin paw model (GP3269 ED50= 6.4 mg/kg). However, the utility...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm050394a
更新日期:2005-12-01 00:00:00
abstract::The synthesis and biological evaluation of the two known phenolic metabolites of paclitaxel are described. The C3'-phenolic metabolite 2 of paclitaxel was prepared from 7-(triethylsilyl)-baccatin III (8) and enantioenriched N-benzoyl-2-azetidinone 7. The C2-phenolic metabolite 3 was synthesized from paclitaxel (1a) vi...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
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abstract::A series of 5-alkyl-2-(alkylthio)-6-(1-(2,6-difluorophenyl)propyl)-3,4-dihydropyrimidin-4(3H)-one derivatives (3a-h) belonging to the F(2)-DABOs class of non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) are endowed with a strong antiproliferative effect and induce cytodifferentiation in A375 melanoma cel...
journal_title:Journal of medicinal chemistry
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更新日期:2011-08-25 00:00:00
abstract::The intense intrinsic fluorescence emissions from several clinically relevant camptothecin drugs have been exploited in order to study the structural basis of drug binding to human serum albumin. Both HPLC and time-resolved fluorescence spectroscopic methodologies were employed to characterize the associations of camp...
journal_title:Journal of medicinal chemistry
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更新日期:1994-01-07 00:00:00
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journal_title:Journal of medicinal chemistry
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更新日期:1984-02-01 00:00:00
abstract::Establishing quantitative relationships between molecular structure and broad biological effects has been a long-standing goal in drug discovery. Evaluation of the capacity of molecules to modulate protein functions is a prerequisite for understanding the relationship between molecular structure and in vivo biological...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
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更新日期:2005-11-03 00:00:00
abstract::Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary b...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm070307+
更新日期:2007-09-06 00:00:00
abstract::A series of tetrazole amide derivatives of (+/-)-2-dodecyl-alpha-phenyl-N-(2,4,6-trimethoxyphenyl)-2H-tetrazole-5- acetamide (1) was prepared and evaluated for their ability to inhibit acyl-CoA: cholesterol O-acyltransferase (ACAT) in vitro and to lower plasma total cholesterol in vivo. For this series of compounds, o...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
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更新日期:1996-06-07 00:00:00