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-dihydroxyacetophenone (27). In the 2,6 series activity against both microsomal systems varied only over a relatively narrow range, 6-allyloxy-2-hydroxyacetophenone (19) being the most potent inhibitor. In the 2,4 series, activity against aniline hydroxylase was poor or absent in most cases. tthe most potent inhibitor was 5-ethyl-2,4-dihydroxyacetophenone (31). In contrast, high activity against aminopyrine demethylase was frequently displayed in this series, 3,5-dibromo-2,4-dihydroxypropiophenone (36) showing greatest inhibitory potency. The effects of some compounds on hexobarbital sleeping times and zoxazolamine paralysis times in mice were also examined.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Bobik A,Holder GM,Ryan AJdoi
10.1021/jm00219a017subject
Has Abstractpub_date
1977-09-01 00:00:00pages
1194-9issue
9eissn
0022-2623issn
1520-4804journal_volume
20pub_type
杂志文章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：:The N-demethylation of 1-(N-methyl-N-trideuteriomethylamino)-3-phenylpropane (1) by rodent liver homogenates was studied. The ratio of 1-trideuteriomethylamino-3-phenylpropane (2)/1-methylamino-3-phenylpropane (3) was determined by gc-ms. The ratio of 2/3 in the product of N-demethylation of 1 by liver homogenate from...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00238a021
更新日期：1975-04-01 00:00:00
abstract：:Resistance to chemotherapy and endocrine therapy is a major cause of breast cancer treatment failure. We have synthesized six novel analogues using C8-ceramide as the lead analogue and studied their effect on hormone therapy resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. Pharmacologic inter...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9009668
更新日期：2009-09-24 00:00:00
abstract：:The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900461w
更新日期：2009-12-10 00:00:00
abstract：:A novel series of nonsteroidal heterocycles was discovered which display cell-type selective, high-affinity (nanomolar) binding to the progesterone receptors from TE85 osteosarcoma cells but > 1 microM binding affinity to the progesterone receptors from T47D and ZR75 human breast carcinoma cells. Structure-activity re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00025a004
更新日期：1995-12-08 00:00:00
abstract：:Based on the known biological activity of a variety of guanidine-containing agents, several N-substituted 3,4-dihydroquinazolines were synthesized. These compounds can be considered to be rigid analogues of phenylguanidines. In anesthetized rats the compounds decreased blood pressure and were antagonists of the presso...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00185a026
更新日期：1980-11-01 00:00:00
abstract：:2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00394a028
更新日期：1987-11-01 00:00:00
abstract：:Singlet oxygen can severely damage biological tissue, which is exploited in photodynamic therapy (PDT). In PDT, the effective range is limited by the distribution of the photosensitizer (PS) and the illuminated area. However, no distinction is made between healthy and pathological tissue, which can cause undesired dam...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01873
更新日期：2020-02-27 00:00:00
abstract：:Newly synthesized benzamide derivatives were evaluated for their inhibitory activity against histone deacetylase. The structure of these derivatives was unrelated to the known inhibitors, and IC(50) values of the active compounds were in the range of 2-50 microM. Structure-activity relationship on the benzanilide moie...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980565u
更新日期：1999-07-29 00:00:00
abstract：:As part of a continuing search for specific inhibitors of the enzymes involved in polyamine biosynthesis, we have designed and synthesized a multisubstrate adduct inhibitor, S-adenosyl-1,12-diamino-3-thio-9-azadodecane (AdoDATAD), in which critical portions of the nucleophilic aminopropyl acceptor are covalently linke...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00126a026
更新日期：1989-06-01 00:00:00
abstract：:9,10-Didehydro-6-methyl-8beta-arylergolines 2, in which the carboxyl group of lysergic acid and isolysergic acid is replaced by various aryl groups, were prepared in two steps by alkylation of aromatic substrates with the tetracyclic allylic alcohol 3, followed by aromatization with MnO2. The new ergolines 2 have mode...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00218a025
更新日期：1977-08-01 00:00:00
abstract：:The novel coronavirus disease COVID-19 that emerged in 2019 is caused by the virus SARS CoV-2 and named for its close genetic similarity to SARS CoV-1 that caused severe acute respiratory syndrome (SARS) in 2002. Both SARS coronavirus genomes encode two overlapping large polyproteins, which are cleaved at specific sit...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01063
更新日期：2020-11-12 00:00:00
abstract：:A study of the hydrolysis of 30 substituted-phenyl hippurates by the enzyme ficin has been made. From the results the following quantitative structure--activity relationship (QSAR) has been derived: log 1/Km = 0.79 pi'3 + 0.58 sigma + 0.28 MR4,5 + 3.70. In this expression Km is the Michaelis constant, pi'3 refers to t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00377a009
更新日期：1984-11-01 00:00:00
abstract：:The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Bart...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm001035c
更新日期：2001-02-15 00:00:00
abstract：:(E)-5-(2-Bromovinyl)-2'-deoxy-5'-O-(3-methyl-2-oxo-5-formyl-1,3,2- oxazaphosphacyclopentan-2-yl)uridine has been synthesized and, under physiological conditions and without the necessity for enzyme activity, has been shown to yield the 5'-nucleotide in vitro. Unfortunately this compound is not sufficiently stable in s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00171a009
更新日期：1990-09-01 00:00:00
abstract：:Upon the basis of The Cancer Genome Atlas (TCGA) data set, we identified that several autophagy-related proteins such as AMP-activated protein kinase (AMPK) were remarkably downregulated in breast cancer. Combined with coimmunoprecipitation assay, we demonstrated that BRD4 might interact with AMPK. After analyses of t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00275
更新日期：2017-12-28 00:00:00
abstract：:The ecteinascidins (Ets), which are natural products derived from marine tunicates, exhibit potent antitumor activity. Of the numerous Ets isolated, Et 743 is presently being evaluated in phase II clinical trials. Et 743 binds in the minor groove of DNA and alkylates N2 of guanine. Although structurally similar to saf...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990241l
更新日期：1999-07-15 00:00:00
abstract：:The prevalence of multidrug resistance among clinically significant bacterial pathogens underscores a critical need for the development of new classes of antibiotics with novel mechanisms of action. Here we describe the synthesis and evaluation of a guanidinomethyl biaryl compound {1-((4'-(tert-butyl)-[1,1'-biphenyl]-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm3012728
更新日期：2012-11-26 00:00:00
abstract：:Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00930
更新日期：2018-10-11 00:00:00
abstract：:6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100846r
更新日期：2010-09-23 00:00:00
abstract：:A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00151a003
更新日期：1986-01-01 00:00:00
abstract：:We previously reported that (+/-)-6-(4-(benzylamino)-7-quinazolinyl)-4,5- dihydro-5-methyl-3(2H)-pyridazinone (+/-)-1, KF15232) showed potent cardiotonic activity with a strong myofibrillar Ca(2+)-sensitizing effect. As an extension of our work, we attempted to synthesize optically active 1. (+/-)-4-(4-(Benzylamino)-7...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950197j
更新日期：1996-01-05 00:00:00
abstract：:Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD) by genome-wide association studies (GWAS). The most common LRRK2 mutation, G2019S, which is relatively rare in the total population, gives rise to increased kinase activity. As such, LRRK2 kinase inhibitors are potentially use...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5014055
更新日期：2015-01-08 00:00:00
abstract：:In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D2 receptors, albeit somewha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9804533
更新日期：1999-03-11 00:00:00
abstract：:Tumor protein 53 (p53) is a critical regulator of cell cycle and apoptosis that is frequently disabled in human tumors. In many tumor types, p53 is deleted or mutated, but in others p53 is inactivated by overexpression or amplification of its negative regulator mouse double minute 2 (MDM2). A high-throughput screening...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900681h
更新日期：2009-11-26 00:00:00
abstract：:The endogenous peptides somatostatin (SRIF) and substance P comprise very different structures. Although both bind G-protein-coupled receptors, the SRIF receptors (SSTR 1-5) recognize SRIF and related peptides which retain its beta-turn such as the potent cyclic hexapeptide SRIF agonist L-363,301 (6a), but not substan...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960281e
更新日期：1996-06-21 00:00:00
abstract：:The synthesis of a series of 1-amino-substituted pyrido[4,3-b]carbazole derivatives, based on the substitution of corresponding 1-chloroellipticines, is reported. The cytotoxic properties on tumor cells grown in vitro, the in vivo acute toxicity of the most potent in vitro cytotoxic compounds, and the antitumor proper...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00185a012
更新日期：1980-11-01 00:00:00
abstract：:Partition properties, that is partition coefficients and enthalpies (delta Hp degree) and entropies (delta Sp degree) of partition, have been measured for 50 benzoic acids in the 1-octanol/water system, and their role in QSAR (quantitative structure-activity relationship) analysis examined. The novel hydrophobic param...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00096a014
更新日期：1992-09-04 00:00:00
abstract：:BRD4 has recently emerged as a promising drug target. Therefore, identifying novel inhibitors with distinct properties could enrich their use in anticancer treatment. Guided by the cocrystal structure of hit compound 4 harboring a five-membered-ring linker motif, we quickly identified lead compound 7, which exhibited ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01094
更新日期：2019-09-26 00:00:00
abstract：:Twelve 1,4-naphthoquinones have been tested against the ascitic form of sarcoma 180 in Swiss mice. Statistical analysis shows that the most important molecular parameter determining their effectiveness in prolonging the life of mice bearing this tumor is their redox potentials. Although the toxicities of the compounds...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00358a021
更新日期：1983-04-01 00:00:00
