Abstract：
:Major urinary metabolites of carbidopa have been identified. Estimates were made based on the recovery or radio activity or by glc analysis of pooled urine of the amounts of the urinary metabolites II (2-methyl-3'-methoxy-4'-hydroxyphenylpropionic acid), III (2-methyl-3,4-dihydroxyphenylpropionic acid), IV (3,4-dihydroxyphenylacetone), V [2-methyl-3-(3'-methoxy-4'-hydroxyphenyl)lactic acid], VI [2-methyl-3-(3',4-dihydroxyphenyl)lactic acid], and VII (3-hydroxy-alpha-methylphenylpropionic acid). Metabolite II represented similar to 10% of the urinary radioactivity in both man and monkey and 16% in the dog. Metabolite III represented 10, 17, and 19% of the urinary radioactivity in man, monkey, and dog. Metabolite IV represented smaller than 5% of the urinary radioactivity in human and dog. Metabolite VII represented similar to 10% of the urinary radioactivity in man and monkey. The corresponding figure for the rat was similar to 20%. In the dog, compounds V and VI represented smaller than 5% of the urinary radioactivity. It was concluded that the loss of the hydrazine functional group(probably as molecular nitrogen) represents the major metabolic pathway for carbidopa.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Vickers S,Stuart EK,Hucker HBdoi
10.1021/jm00236a004subject
Has Abstractpub_date
1975-02-01 00:00:00pages
134-8issue
2eissn
0022-2623issn
1520-4804journal_volume
18pub_type
杂志文章abstract：:The observed structure-activity relationship of three distinct ATP noncompetitive With-No-Lysine (WNK) kinase inhibitor series, together with a crystal structure of a previously disclosed allosteric inhibitor bound to WNK1, led to an overlay hypothesis defining core and side-chain relationships across the different se...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00708
更新日期：2017-08-24 00:00:00
abstract：:The protein kinase MKK7 is linked to neuronal development and the onset of cancer. The field, however, lacks high-quality functional probes that would allow for the dissection of its detailed functions. Against this background, we describe an effective covalent inhibitor of MKK7 based on the pyrazolopyrimidine scaffol...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00102
更新日期：2019-03-14 00:00:00
abstract：:Eye diseases characterized by excessive angiogenesis such as wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity are major causes of blindness. Cremastranone is an antiangiogenic, naturally occurring homoisoflavanone with efficacy in retinal and choroidal neovascula...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00449
更新日期：2015-06-25 00:00:00
abstract：:A series of 4-anilinoquinoline-linked aniline mustards of widely varying mustard reactivity were prepared and evaluated for their antitumor activity. The compounds were designed as minor grove binding agents, where the aniline mustard ring is itself part of the DNA-binding ligand. While there was a general trend for c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00109a005
更新日期：1991-05-01 00:00:00
abstract：:We have derivatized Momordica saponins (MS) I and II through their coupling at C3 glucuronic acid site with dodecylamine. The derivatives show significantly different immunostimulant activity profiles from their respective natural parent saponins. In particular, adjuvant VSA-1 (5), the derivative of MS I, potentiates ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01511
更新日期：2019-11-14 00:00:00
abstract：:Pleuromutilin is an antibiotic that binds to bacterial ribosomes and thereby inhibit protein synthesis. A new series of semisynthetic pleuromutilin derivatives were synthesized by a click chemistry strategy. Pleuromutilin was conjugated by different linkers to a nucleobase, nucleoside, or phenyl group, as a side-chain...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm201266b
更新日期：2012-03-08 00:00:00
abstract：:During the course of our investigations in the oxazolidinone antibacterial agent area, we have identified a subclass with especially potent in vitro activity against mycobacteria. The salient structural feature of these oxazolidinone analogues, 6 (U-100480), 7 (U-101603), and 8 (U-101244), is their appended thiomorpho...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950956y
更新日期：1996-02-02 00:00:00
abstract：:A series of structurally related mono- and bis-1,3-disubstituted 2-[(hydroxyimino)methyl]imidazolium halides were evaluated in vitro for their ability to reactivate electric eel, bovine, and human erythrocyte (RBC) acetylcholinesterases (AChE) inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP) and 3,3-dimethyl-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00122a034
更新日期：1989-02-01 00:00:00
abstract：:Novel 19-norvitamin D analogues (ADYW1-4, 5a-d) in which an adamantyl diyne side chain is attached directly to the 17-position of the D ring are designed and stereoselectively synthesized. The adamantane ring of these analogues was expected to interfere with helix 12 (H12, activation function 2) of the vitamin D recep...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00792
更新日期：2015-12-24 00:00:00
abstract：:Polyamine transport is elevated in many tumor types, suggesting that toxic polyamine-drug conjugates could be targeted to cancer cells via the polyamine transporter (PAT). We have previously reported the use of Chinese hamster ovary (CHO) cells and its PAT-deficient mutant cell line, CHO-MG, to screen anthracene-polya...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701198s
更新日期：2008-01-24 00:00:00
abstract：:Drug-resistant bacterial infections and lack of available antibacterial agents in clinical practice are becoming serious risks to public health. We synthesized a new class of haloemodins by modifying a traditional Chinese medicine component, emodin. The novel haloemodin exerts strong inhibitory activity on bacterial t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401685f
更新日期：2014-05-08 00:00:00
abstract：:A series of 2,6- and 2,4-dihydroxyphenyl alkyl ketones has been investigated as inhibitors of hepatic microsomal aniline hydroxylase and aminopyrine demethylase activities. Structural alterations in both series did little to enhance the inhibitory activity of the parent compounds 2,6-dihydroxyacetophenone (3) and 2,4-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00219a017
更新日期：1977-09-01 00:00:00
abstract：:Human topoisomerase I (TopoI) is recognized as a valuable target for the development of effective antitumor agents. Structure-based virtual screening was applied to the discovery of structurally diverse TopoI inhibitors. From 23 compounds selected by virtual screening, a total of 14 compounds were found to be TopoI in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100387d
更新日期：2010-11-11 00:00:00
abstract：:Edelfosine (ET-18-OCH3), a synthetic antitumor ether lipid, is taken up by malignant but not by normal cells, triggering apoptosis in a large variety of human tumor cells. The synthesis of the first fluorescent edelfosine analogue (6), with apoptotic activity comparable to that of the parent drug, is described. Fluore...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049808a
更新日期：2004-10-21 00:00:00
abstract：:A series of conformationally restricted congeners of pentamidine in which the flexible pentyl bridge of pentamidine was replaced by trans-1,2-bismethylenecyclopropyl, phenyl, pyridinyl, piperazinyl, homopiperazinyl, and piperidinyl groups were synthesized. The compounds were evaluated for trypanocidal activity in vitr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020375q
更新日期：2003-03-13 00:00:00
abstract：:A series of 4- and 5-[2,3-dihydro-6,7-bis[[(N-alkylcarbamoyl)oxy]methyl]-1H-pyrrol izin-5- yl]-2-halopyridinium iodides were synthesized. The rates of hydrolysis of the alpha-halopyridinium salts to the corresponding pyridones, and the reactivities of the carbamate moieties were studied as a function of pH, buffer com...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00168a021
更新日期：1990-06-01 00:00:00
abstract：:A novel series of nonsteroidal progestins, 5-benzylidene-1, 2-dihydrochromeno[3,4-f]quinolines (2), was discovered, and a preliminary structure-activity relationship study around the 5-benzylidene ring generated several potent human progesterone receptor agonists (compounds 8, 16). These new progestins showed biologic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980366a
更新日期：1998-10-22 00:00:00
abstract：:The gold(I) complexes of the general formula [Au(L(n))(PPh(3))]·xH(2)O (1-8; n = 1-8 and x = 0-1.5), where L(n) stands for a deprotonated form of the benzyl-substituted derivatives of 6-benzylaminopurine, were prepared, thoroughly characterized (elemental analyses, FT-IR, Raman and multinuclear NMR spectroscopy, ESI+ ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm201416p
更新日期：2012-05-24 00:00:00
abstract：:Network theory provides one of the most potent analysis tools for the study of complex systems. In this paper, we illustrate the network-based perspective in drug research and how it is coherent with the new paradigm of drug discovery. We first present data sources from which networks are built, then show some example...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01989
更新日期：2020-08-27 00:00:00
abstract：:Analogues of the antimycotic allylamine terbinafine were prepared in which the naphthalene and the tert-butyl-acetylene moieties were preserved, but the spacer between these two groups was varied, and the antifungal activity of the new compounds was evaluated. All modifications of the original spacer such as reduction...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00031a010
更新日期：1994-03-04 00:00:00
abstract：:Building on the previously and successfully applied hypothesis that stereochemical complication in the proximity of the critical cationic head of a cholinergic agonist would result in subtype selective compounds, we synthesized a series of chiral derivatives of furmethide and 5-methylfurmethide, with the aim of obtain...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800145d
更新日期：2008-07-10 00:00:00
abstract：:Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030091l
更新日期：2003-06-19 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：:A series of aryl bicyclic analogs of succinimide and glutarimide was prepared and evaluated for CNS depressant activity. The 8a-aryl-3,4,6,7,8,8a-hexahydro-2H-pyrrolo[2,1-beta][1,3]oxazin-6-ones possessed the best overall spectrum of activity relative to the standard agents glutethimide and phenobarbital. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00225a023
更新日期：1976-03-01 00:00:00
abstract：:Changes in expression and dysfunctional signaling of TrkA/B/C receptors and oncogenic Trk fusion proteins are found in neurological diseases and cancers. Here, we describe the development of a first 18F-labeled optimized lead suitable for in vivo imaging of Trk, [18F]TRACK, which is radiosynthesized with ease from a n...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01607
更新日期：2018-02-22 00:00:00
abstract：:Brr2 is an RNA helicase belonging to the Ski2-like subfamily and an essential component of spliceosome. Brr2 catalyzes an ATP-dependent unwinding of the U4/U6 RNA duplex, which is a critical step for spliceosomal activation. An HTS campaign using an RNA-dependent ATPase assay and initial SAR study identified two diffe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00461
更新日期：2017-07-13 00:00:00
abstract：:The pharmaceutical industry has recognized that many drug-like molecules can self-aggregate in aqueous media and have physicochemical properties that skew experimental results and decisions. Herein, we introduce the use of a simple NMR strategy for detecting the formation of aggregates using dilution experiments that ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400535b
更新日期：2013-06-27 00:00:00
abstract：:Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701049p
更新日期：2008-01-10 00:00:00
abstract：:The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0407761
更新日期：2004-12-02 00:00:00
abstract：:(R)-(-)- and (S)-(+)-alpha-methyl-beta-4-(fluorophenyl)-N-methyl-N- propynylethylamine [R)-(-)- and (S)-(+)-4-fluorodeprenyl) were synthesized via the reaction of 4-fluorobenzaldehyde with nitroethane followed by reduction with lithium aluminum hydride to produce racemic 4-fluoroamphetamine, which was resolved by recr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00169a034
更新日期：1990-07-01 00:00:00
