Abstract：
:The effect of a variety of aryl substituents on the potency and selectivity of 19 analogues of 1,3-dipropyl-8-phenylxanthine as antagonists at A1- and A2-adenosine receptors in brain tissue was determined. The 4-sulfamoylphenyl and 4-carbamoylphenyl analogues are potent and somewhat selective for the A1 receptor. None of the dihydroxyphenyl analogues are remarkably potent, but all are selective for the A1 receptor. 1,3-Dipropyl-8-(2-hydroxy-4-methoxyphenyl)xanthine is the most selective A1 antagonist of the analogues with a A1/A2 potency ratio of about 90.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Daly JW,Padgett WL,Shamim MTdoi
10.1021/jm00158a034subject
Has Abstractpub_date
1986-08-01 00:00:00pages
1520-4issue
8eissn
0022-2623issn
1520-4804journal_volume
29pub_type
杂志文章abstract：:A series of 1-(p-nitrophenyl)-2-aminoethanol derivatives and their morpholine analogues have been synthesized and pharmacologically investigated in order to confirm some pharmacological observations made with the N-isopropyl-substituted compounds. In agreement with the previously obtained results, the weak alpha-adren...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00192a023
更新日期：1979-06-01 00:00:00
abstract：:Recently, it has been reported that 5-HT2 receptor agonists effectively reduce intraocular pressure (IOP) in a nonhuman primate model of glaucoma. Although 1-[(2S)-2-aminopropyl]indazol-6-ol (AL-34662) was shown to have good efficacy in this nonhuman primate model of ocular hypertension as well as a desirable physicoc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00857
更新日期：2015-11-25 00:00:00
abstract：:We present and thoroughly characterize a large collection of 3,4-dihydropyrimidin-2(1H)-ones as A2BAR antagonists, an emerging strategy in cancer (immuno) therapy. Most compounds selectively bind A2BAR, with a number of potent and selective antagonists further confirmed by functional cyclic adenosine monophosphate exp...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01431
更新日期：2021-01-14 00:00:00
abstract：:Targeted imaging requires contrast agents that remain in the vasculature for extended periods of time. A new contrast agent is described in which gadolinium is encapsulated within an extremely stable carbon sphere, thus allowing for safe extended residence. Water solubility and small particle size is achieved with nov...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800521j
更新日期：2008-07-10 00:00:00
abstract：:Six new analogues of 1α,25-dihydroxy-19-norvitamin D(3) (3a-4b, 5, and 6) were prepared by a convergent synthesis applying the Wittig-Horner reaction as a key step. The influence of methyl groups at C-22 on their biological activity was examined. It was established that both in vitro and in vivo activity is strongly d...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300187x
更新日期：2012-05-10 00:00:00
abstract：:We have found that (R,S)-1-(phenylthio)-aminopropane (4a), a synthetic alternate substrate for the terminal enzyme of norepinephrine biosynthesis, dopamine beta-monooxygenase (DBM), is both an indirect sympathomimetic and a potent antihypertensive agent in spontaneously hypertensive rats. We demonstrate herein that th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00107a031
更新日期：1991-03-01 00:00:00
abstract：:Three rationally designed pyrrolobenzodiazepine (PBD) drug-linkers have been synthesized via intermediate 19 for use in antibody-drug conjugates (ADCs). They lack a cleavable trigger in the linker and consist of a maleimide for cysteine antibody conjugation, a hydrophilic spacer, and either an alkyne (6), triazole (7)...
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abstract：:Multidrug resistance-associated protein 1 (MRP1/ABCC1) is a very promiscuous transporter. Herein we used topological polar surface area (TPSA), a descriptor defined as the sum of surfaces of polar atoms in a molecule, to analyze drug transport by MRP1. We suggested that compounds with high TPSA are transported while t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2009-02-26 00:00:00
abstract：:Protein tyrosine phosphatases (PTPases) are involved in the control of tyrosine phosphorylation levels in the cell and are believed to be crucial for the regulation of a multitude of cellular functions. A detailed understanding of the role played by PTPases in various signaling pathways has not yet been achieved, and ...
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pub_type： 杂志文章
doi：10.1021/jm990329z
更新日期：2000-01-27 00:00:00
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journal_title：Journal of medicinal chemistry
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doi：10.1021/jm015522j
更新日期：2001-08-16 00:00:00
abstract：:The directional properties of hydrogen bonds play a major role in determining the specificity of intermolecular interactions. An energy function which takes explicit account of these properties has been developed for use in the determination of energetically favorable ligand binding sites on molecules of known structu...
journal_title：Journal of medicinal chemistry
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doi：10.1021/jm00053a018
更新日期：1993-01-08 00:00:00
abstract：:The pathology of chronic dermal ulcers is characterized by excessive proteolytic activity which degrades extracellular matrix (required for cell migration) and growth factors and their receptors. The overexpression of MMP-3 (stromelysin-1) and MMP-13 (collagenase-3) is associated with nonhealing wounds, whereas active...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0308038
更新日期：2003-07-31 00:00:00
abstract：:Replacing the 1alpha-OH group of the natural hormone 1alpha,25-dihydroxyvitamin D(3) (calcitriol) by a 1alpha-CHF(2) group and incorporating a potentiating side chain produced two new hybrid analogs 6 and 7. Both of these two hybrid analogs are as transcriptionally active as calcitriol and are strongly antiproliferati...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0609925
更新日期：2006-12-14 00:00:00
abstract：:A series of 10-ketomorphinan analogues were synthesized, and their binding affinity at all three opioid receptors was investigated. In most cases, high affinity at micro and kappa receptors, and lower affinity at delta receptor was observed, resulting in good selectivity for micro and kappa receptors. A wide range of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304156
更新日期：2004-01-01 00:00:00
abstract：:A series of phenylenebis(oxy)bis[2,2-dimethylpentanoic acid]s have been synthesized and evaluated as potential hypolipidemic agents. Compound 18 (CI-924) was found to be the most potent compound in this series. In rats, compound 18 not only reduced low-density lipoprotein cholesterol but also increased high-density li...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00361a015
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abstract：:The importance of inhibitors of glycosidases as therapeutic agents for viral, proliferative, and metabolic diseases is being increasingly recognised. Several years ago we reported that the activities of mannosidase inhibitors may be explained in terms of their similarity to the mannosyl cation intermediate postulated ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960237z
更新日期：1996-10-11 00:00:00
abstract：:Acyl-CoA:cholesterol acyltransferase (ACAT) is the primary enzyme involved in intracellular cholesterol esterification. Arterial wall infiltration by macrophages and subsequent uncontrolled esterification of cholesterol leading to foam cell formation is believed to be an important process which leads to the developmen...
journal_title：Journal of medicinal chemistry
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更新日期：1995-03-31 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400879w
更新日期：2014-03-27 00:00:00
abstract：:Extensive quantum chemical calculations have been made of the electronic distribution and conformational behavior of meperidine and desmethyl-, (+)-alpha, and (+)-beta-prodine using PCILO, a semiempirical molecular orbital method. For this series of opiates, a phenyl equatorial conformation was preferred over a phenyl...
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abstract：:Factors influencing dose potency of 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) analogues in L1210 assays have been investigated by multiple regression analysis. The dependent variable was D40, the dose to provide 40% life extension in L1210 tests. Independent variables examined were chromatographic Rm val...
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pub_type： 杂志文章
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更新日期：1981-05-01 00:00:00
abstract：:Protease activated receptors (PARs) or thrombin receptors constitute a class of G-protein-coupled receptors (GPCRs) implicated in the activation of many physiological mechanisms. Thus, thrombin activates many cell types such as vascular smooth muscle cells, leukocytes, endothelial cells, and platelets via activation o...
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00390a021
更新日期：1987-07-01 00:00:00
abstract：:As part of a program aimed at the discovery of antinociceptive therapy for inflammatory conditions, a screening hit was found to inhibit microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 17.4 μM. Structural information was used to improve enzyme potency by over 1000-fold. Addition of an appropriate subst...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01249
更新日期：2016-01-14 00:00:00
abstract：:The nature of the carbonyl and nitrogen substituents of hydroxamic acids has a major influence on the biological profile of these compounds. Hydroxamates with small groups such as methyl appended to the carbonyl and relatively large nitrogen substituents generally have longer duration in vivo, produce greater plasma c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00118a016
更新日期：1988-10-01 00:00:00
abstract：:Results from previous studies indicate that rabbit liver microsomal cytochrome P-450 catalyzes the C-5' two-electron oxidation of (S)-nicotine stereoselectivity with preferential loss of the pro-(E)-hydrogen atom trans to the pyridine ring. We now have examined the regio- and stereochemical features of the oxidation o...
journal_title：Journal of medicinal chemistry
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更新日期：1988-03-01 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：1999-08-12 00:00:00
abstract：:A new series of N'-(pyridinioacetyl)alkanoic and -benzoic acid hydrazides, as chloride salts, and some cyclic analogues produced ring closure have been synthesize and tested in a search for more effective germicides. Physicochemical parameters, such as surface tension, critical micelle concentration, and thermodynamic...
journal_title：Journal of medicinal chemistry
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journal_title：Journal of medicinal chemistry
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doi：10.1021/jm00066a011
更新日期：1993-07-09 00:00:00
abstract：:Protecting enkephalins, endogenous opioid peptides released in response to nociceptive stimuli, is an innovative approach for acute and neuropathic pain alleviation. This is achieved by inhibition of their enzymatic degradation by two membrane-bound Zn-metallopeptidases, neprilysin (NEP, EC 3.4.24.11) and aminopeptida...
journal_title：Journal of medicinal chemistry
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更新日期：2014-07-10 00:00:00
abstract：:The diester 2a obtained from 1,1'-ferrocenedicarboxylic acid and the highly and indiscriminately cytotoxic fungal metabolite illudin M (1) displayed antiproliferative activity at submicromolar IC(50) (72 h) values against a panel of eight cancer cell lines. Compound 2a was about 40 times less toxic than 1 to nonmalign...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2011-09-22 00:00:00
