Abstract：
:A series of 2,2'-disubstituted 5,5'-dibenzimidazolyl ketones and related compounds have been synthesized of which 2,2'-bis(carbomethoxyamino)-5,5'-dibenzimidazolyl ketone exhibited a broad spectrum of anthelmintic activity in experimental animals. At doses of 10-50 mg/kg given intraperitoneally, 5 killed 100% of the adult worms of Litomosoides carinii, Dipetalonema viteae, and Brugia malayi. By the oral route the macrofilaricidal efficacy of 5 was 97-100% at 100-200 mg/kg X 5 days. The treated animals showed gradual disappearance of microfilariae and before autopsy they became amicrofilariaemic. Some of the compounds also showed 100% efficacy against the human hookworms and tapeworm, Ancylostoma ceylanicum in hamsters, and Hymenolepis nana in rats at a single oral dose of 50-250 mg/kg. Compound 5 was also effective against Syphacia obvelata in mice at a single oral dose of 100 mg/kg and was found to be well tolerated by mice up to an oral dose of 2500 mg/kg.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Abuzar S,Sharma S,Fatma N,Gupta S,Murthy PK,Katiyar JC,Chatterjee RK,Sen ABdoi
10.1021/jm00157a032subject
Has Abstractpub_date
1986-07-01 00:00:00pages
1296-9issue
7eissn
0022-2623issn
1520-4804journal_volume
29pub_type
杂志文章abstract：:1,2-Dihydro-1-(chloromethyl)-5-hydroxy-8-methyl-3H-furano[3,2-e]in dole (CFI) as a novel replacement of the cyclopropylpyrroloindoline (CPI) alkylation subunit of CC-1065, U-71184, and U-73975 (adozelesin) has been synthesized and incorporated into a series of efficacious antineoplastic agents. A partial solution to a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00028a005
更新日期：1994-01-21 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：:A series of 1-[1-(3,4-dimethoxy-1H-2-benzopyran-1-yl)alkyl]-4-arylpiperazines that shows hypotensive activity in the conscious rat has been investigated. Structure-activity relationships are described. A typical example that was investigated in greater detail is 1-[2-(3,4-dihydro-6,7-dimethoxy-1H-2-benzopyran-1-yl)eth...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00343a015
更新日期：1982-01-01 00:00:00
abstract：:A pharmacophore-based search led to the identification of thiazolopyridine ureas as a novel scaffold with antitubercular activity acting through inhibition of DNA Gyrase B (GyrB) ATPase. Evaluation of the binding mode of thiazolopyridines in a Mycobacterium tuberculosis (Mtb) GyrB homology model prompted exploration o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401268f
更新日期：2013-11-14 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
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abstract：:As part of an ongoing effort to discover novel small-molecule antifolates combining the enzyme-binding species selectivity of trimethoprim (TMP) with the potency of piritrexim (PTX), 10 previously unreported 2,4-diamino-5-(2'-methoxy-5'-substituted)benzylpyrimidines (2-11) containing a carboxyl group at the distal end...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020466n
更新日期：2003-04-24 00:00:00
abstract：:Novel lavendamycins including two water soluble derivatives were synthesized via short and efficient methods. Pictet-Spengler condensation of 7-N-acylamino-2-formylquinoline-5,8-diones with tryptophans produced lavendamycin esters or amides 11-17. Lavendamycins 18-21 were obtained, respectively, by further transformat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304414
更新日期：2003-12-18 00:00:00
abstract：:The cancer research community has begun to address the in silico modeling approaches, such as quantitative structure-activity relationships (QSAR), as an important alternative tool for screening potential anticancer drugs. With the compilation of a large dataset of nucleosides synthesized in our laboratories, or elsew...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061445m
更新日期：2007-04-05 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.7b01457
更新日期：2018-06-28 00:00:00
abstract：:Peptidyl alpha-keto amides have been synthesized and tested as inhibitors of the cysteine protease calpain. A stereospecific synthesis was devised in which Cbz-dipeptidyl-alpha-hydroxy amides were oxidized with TEMPO/hypochlorite to the corresponding alpha-keto amides. This oxidation was accomplished in good yields an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00044a013
更新日期：1994-09-02 00:00:00
abstract：:A computational chemistry study has been performed on a series of tetrahydropyrimidine-2-ones (THPs) as HIV-1 protease (HIV-1 PR) inhibitors. The present investigation focuses on the correlation of inhibitor-enzyme complexation energies (E(compl)), inhibitor solvation energies E(solv)[I], and both polar and nonpolar b...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010417v
更新日期：2002-02-14 00:00:00
abstract：:Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain "diazaindole" moieties and display different transcriptional regulatory profiles in vitro and are considered "dissociated" between gene transrepression and transa...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4019178
更新日期：2014-02-27 00:00:00
abstract：:Here we describe the design, synthesis, and pharmacological profile of 5-HT(1A) receptor ligands related to 1 (WAY-100635). The cyclohexyl moiety in 1 and its O-desmethylated analogue 3 were replaced by the bridgehead iodinated bridge-fused rings: adamantyl, cubyl, bicyclo[2.2.2]octyl, or bicyclo[2.2.1]heptyl. All ana...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1009956
更新日期：2011-05-26 00:00:00
abstract：:Nineteen derivatives of adenosine 5'-phosphate (AMP) bearing acylaminomethyl, acetoxy, or alkylaminomethyl substituents on the phosphate-ribose bridge (5' and O-5' positions) of AMP together with 2',3'-O-ethylidene, 2',3',-O-isopropylidene, and 2',3'-di-O-acetyl derivatives of AMP have been synthesized. Their substrat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00234a004
更新日期：1976-12-01 00:00:00
abstract：:A structure-activity relationship (SAR) study of the South African willow tree (Combretum caffrum) antineoplastic constituent combretastatin A-4 (3b) led to the discovery of a potent cancer cell growth inhibitor designated phenstatin (5a). This benzophenone derivative of combretastatin A-4 showed remarkable antineopla...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000045a
更新日期：2000-07-13 00:00:00
abstract：:Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. They are key agents in inflammation and apoptosis and are attractive targets for therapy against inflammation, neurodegeneration, ischemia, and cancer. Many caspase structures are known, but most involve either peptide or protein inhibitors, unatt...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0305523
更新日期：2004-05-06 00:00:00
abstract：:The syntheses of 2-amino-N-(2-benzoyl)-4-chlorophenyl)acetamides are reported. The pharmacological properties of these compounds were compared with data obtained from the corresponding cyclized products [5-(2,6-dichlorophenyl)-1,4-benzodiazepin-2-ones]. Evidence is presented which suggests that the central nervous sys...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00351a009
更新日期：1982-09-01 00:00:00
abstract：:The pyridine C-nucleosides 5-beta-D-ribofuranosylnicotinamide and its N-methylpyridinium derivative (1 and 2), which are isosteric and isoelectronic, respectively, to nicotinamide nucleoside were synthesized. Condensation of 3-bromo-5-lithiopyridine with 2,4:3,5-di-O-benzylidene-D-aldehydoribose (7) afforded an allo/a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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abstract：:A series of indolequinones bearing various functional groups has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (NQO1) were studied. Indolequinones were selected for study on the basis of the X-ray crystal structure of the human e...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010884c
更新日期：2001-09-27 00:00:00
abstract：:Inhibition of histone deacetylase (HDAC) results in growth arrest, differentiation, and apoptosis in nearly all tumor cell lines, promoting HDACs as promising targets for antitumor therapy. In our previous study we developed a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDAC inhibit...
journal_title：Journal of medicinal chemistry
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doi：10.1021/jm101605z
更新日期：2011-04-28 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2006-02-09 00:00:00
abstract：:We have reported that [methyl- (11)C] (3 R,5 R)-5-(3-methoxyphenyl)-3-[(R)-1-phenylethylamino]-1-(4-trifluoromethylphenyl)pyrrolidin-2-one ([(11)C] 8, [(11)C]MePPEP) binds with high selectivity to cannabinoid type-1 (CB 1) receptors in monkey brain in vivo. We now describe the synthesis of 8 and four analogues, namely...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2008-09-25 00:00:00
abstract：:Multivalent ligands are promising pharmacological tools that may be more efficacious for several diseases than highly selective single-target drugs. A combined therapy using dopaminergic agonists and adenosinergic antagonists is currently being evaluated for the treatment of Parkinson's disease. [(a) Kanda, T.; et al....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2007-06-28 00:00:00
abstract：:Nitrosourea derivatives of ergolines have been synthesized for the purpose of obtaining agents with both prolactin-and tumor-inhibitory activity. Two derivatives of 8-amino-6-methylergoline (3), 8-[3-(2-chloroethyl)-3-nitrosoureido]-1-nitroso-6-methylergoline (5c) and 8-[3-2-chloroethyl)-3-nitrosoureido]-6-methylergol...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00187a008
更新日期：1979-01-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2004-01-15 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00105a046
更新日期：1991-01-01 00:00:00
abstract：:PABA/NO is a diazeniumdiolate of structure Me(2)NN(O)=NOAr (where Ar is a 5-substituted-2,4-dinitrophenyl ring whose 5-substituent is N-methyl-p-aminobenzoic acid). It has shown activity against human ovarian cancer xenografts in mice rivaling that of cisplatin, but it is poorly soluble and relatively unstable in wate...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050700k
更新日期：2006-02-09 00:00:00
abstract：:A series of methanoprolinenitrile-containing dipeptide mimetics were synthesized and assayed as inhibitors of the N-terminal sequence-specific serine protease dipeptidyl peptidase IV (DPP-IV). The catalytic action of DPP-IV is the principle means of degradation of glucagon-like peptide-1, a key mediator of glucose-sti...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2004-05-06 00:00:00
abstract：:Structure-based design led to the discovery of novel (S)-isothiazolidinone ((S)-IZD) heterocyclic phosphotyrosine (pTyr) mimetics that when incorporated into dipeptides are exceptionally potent, competitive, and reversible inhibitors of protein tyrosine phosphatase 1B (PTP1B). The crystal structure of PTP1B in complex...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2005-10-20 00:00:00
abstract：:Human coagulation factor XIa (FXIa), a serine protease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation cascade. To investigate the potential of FXIa inhibitors as safe anticoagulants, a series of potent, selectiv...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060978s
更新日期：2006-12-28 00:00:00
