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 of the double bond, switching the position of the nitrogen atom, shortening, and elongation resulted in decreased potencies with one exception: Compounds with the CH2NMeCH2CH2 group between the 1-naphthalene and the optionally substituted tert-butyl-acetylene function demonstrated high antifungal activity in vitro. The new homopropargylamine derivatives are more potent than terbinafine against Aspergillus fumigatus. The results support the hypothesis that two lipophilic domains linked by a spacer of appropriate length and a polar center at a defined position in the spacer are the general requirements for high activity of allylamine antimycotics.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Nussbaumer P,Leitner I,Stütz Adoi
10.1021/jm00031a010subject
Has Abstractpub_date
1994-03-04 00:00:00pages
610-5issue
5eissn
0022-2623issn
1520-4804journal_volume
37pub_type
杂志文章abstract：:Activators of nuclear factor-erythroid 2-related factor 2 (NRF2) could lead to promising therapeutics for prevention and treatment of oxidative stress and inflammatory disorders. Ubiquitination and subsequent degradation of the transcription factor NRF2 is mediated by Kelch-like ECH-associated protein-1 (KEAP1). Inhib...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01133
更新日期：2018-09-13 00:00:00
abstract：:To provide practical means for rapidly scanning the extensive experimental combinatorial chemistry libraries now available for high-throughput screening (HTS), it is essential to establish computational virtual ligand screening (VLS) techniques to rapidly identify out of a large library all active compounds against a ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030271v
更新日期：2004-01-01 00:00:00
abstract：:We have recently proposed a macromolecular prodrug strategy for improved cancer chemotherapy based on two features (Kratz, F.; et al. J. Med. Chem 2000, 43, 1253-1256.): (a) rapid and selective binding of thiol-reactive prodrugs to the cysteine-34 position of endogenous albumin after intravenous administration and (b)...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020276c
更新日期：2002-12-05 00:00:00
abstract：:A range of cis- and trans-3-substituted 1-aminocyclobutane-1-carboxylic acids has been synthesized and evaluated for antagonism at excitatory amino acid receptor sites and for anticonvulsant activity. Potent and selective antagonist activity at N-methyl-D-aspartate (NMDA) receptor sites in neonatal rat motoneurones wa...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00051a005
更新日期：1994-12-09 00:00:00
abstract：:Oligonucleotide-based therapeutics have made rapid progress in the clinic for treatment of a variety of disease indications. Unmodified oligonucleotides are polyanionic macromolecules with poor drug-like properties. Over the past two decades, medicinal chemists have identified a number of chemical modification and con...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.6b00551
更新日期：2016-11-10 00:00:00
abstract：:In an effort to develop selective inhibitors of vesicular acetylcholine storage, we have synthesized a series of semirigid vesamicol receptor ligands based on the structure of 2-(4-phenylpiperidino)-cyclohexanol (vesamicol, AH5183, 1). In these compounds, the planes of the phenyl and piperidyl moieties of the parent l...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00042a010
更新日期：1994-08-05 00:00:00
abstract：:Recent studies have indicated several therapeutic applications for delta opioid agonists and antagonists. To exploit the therapeutic potential of delta opioids developing a structural basis for the activity of ligands at the delta opioid receptor is essential. The conformationally sampled pharmacophore (CSP) method (B...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0612463
更新日期：2007-04-19 00:00:00
abstract：:A method for preparing a variety of 7-alkyl-6,7- didehydromorphinans from the corresponding 6- morphinanones is described. The key intermediates in this sequence are the 7-formyl derivatives. The two epimeric B/C-trans-7-(1- hydroxypentyl ) morphinans ( 16a ,b) are stereochemically similar to the endo- ethanotetrahydr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00371a013
更新日期：1984-05-01 00:00:00
abstract：:A variety of 8-substituted guanosine and 2'-deoxyguanosine derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells in culture. The most active agents in the guanosine series were 8-substituted-N(CH3)2, -NHCH3, -NH2, -OH, and -SO2CH3, which caused 68, 42, 34, 33...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00147a012
更新日期：1985-09-01 00:00:00
abstract：:2,4-Diaminoquinazoline antifolates with a lipophilic side chain at the 5-position, and in one case with a classical (p-aminobenzoyl)-L-glutamate side chain, were synthesized as potentially selective inhibitors of a site-directed mutant of human dihydrofolate reductase (DHFR) containing phenylalanine instead of leucine...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00005a002
更新日期：1995-03-03 00:00:00
abstract：:Nalfurafine, a κ-selective opioid receptor agonist, unexpectedly showed a selective antagonist activity toward the orexin 1 receptor (OX1R) (Ki = 250 nM). Modification of the 17-amino side chain of the opioid ligand to an arylsulfonyl group and the 6-furan acrylamide chain to 2-pyridyl acrylamide led to compound 71 wi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01418
更新日期：2017-02-09 00:00:00
abstract：:A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compound 1a [(E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00123a012
更新日期：1989-03-01 00:00:00
abstract：:Molecular docking studies of carbohydrate derivatives in protein binding sites are often challenging because of water-mediated interactions and the inherent flexibility of the many terminal hydroxyl groups. Using the recognition process between heat-labile enterotoxin from Escherichia coli and ganglioside GM1 as a par...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980472c
更新日期：1999-05-20 00:00:00
abstract：:A series of N(6)-alkyl-2-alkynyl derivatives of adenosine (Ado) have been synthesized and evaluated for their affinity at human A(1), A(2A), and A(3) receptors and for their potency at A(2B) adenosine receptor subtypes. The corresponding 2-(1-alkynyl) derivatives of 5'-N-ethylcarboxamidoadenosine (NECA) and Ado are us...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0109762
更新日期：2002-07-18 00:00:00
abstract：:Target identification is a high-priority, albeit challenging, aspect of drug discovery. Diazirine-based photoaffinity probes (PAPs) can facilitate the process by covalently capturing transient molecular interactions. This can help identify target proteins and map the ligand's interactome. Diazirine probes have even be...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.7b01561
更新日期：2018-08-23 00:00:00
abstract：:H(3) receptor antagonists based on a 2-aminoethylbenzofuran skeleton have been discovered, which are potent in vitro at human and rat H(3) receptors, with K(i) values of 0.1-5.8 nM. Analogues were discovered with potent (0.01-1 mg/kg) cognition and attention enhancing properties in animal models. One compound in parti...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040118g
更新日期：2005-01-13 00:00:00
abstract：:The delta-selective opioid peptide deltorphin C(H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) (DEL C) was modified by para-substitution of Phe3 with halogens (F, Cl, Br, I), amino, or nitro groups. The bioactive potencies in peripheral tissues and brain receptor selectivities of these analogues depended upon the particular sub...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00103a001
更新日期：1992-12-11 00:00:00
abstract：:In previous studies we demonstrated that lipophilic (99m)Tc-labeled LTB4 antagonist 1 (RP517) accumulated in infectious foci in rabbits, but hepatobiliary clearance hampered imaging of abdominal lesions. We now report the use of cysteic acid as a pharmacokinetic modifier to improve the water solubility and renal clear...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050383h
更新日期：2005-10-06 00:00:00
abstract：:A molecular model of the alpha(IIb)beta(3) integrin has been developed utilizing (i). the crystal structure of alpha(v)beta(3), (ii). homology model of the alpha(IIb) subdomain, and (iii). the docking of alpha(IIb)beta(3)/alpha(v)beta(3) dual and selective inhibitors into the putative binding sites of alpha(IIb)beta(3...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030146j
更新日期：2003-12-04 00:00:00
abstract：:A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0109964
更新日期：2002-01-31 00:00:00
abstract：:A series of 3-acylbenzamidine (amidino)hydrazones 7a-h, the corresponding (hetero)aromatic congeners 7i-p, and 3,3'-bis-amidino-biaryls 25a-e were synthesized. The hydrazones 7a-p were prepared by conversion of the corresponding acyl nitriles 1a,c-d,i,n-p to the imido esters 3a,c-d,i and the amidines 5a,c-d,h-i, follo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00053a007
更新日期：1993-01-08 00:00:00
abstract：:Exposure of dopamine to an excess of linoleic acid 13-hydroperoxide (13-hydroperoxyoctadecadienoic acid) in the presence of ferrous ions in Tris buffer, pH 7.4, resulted in a relatively fast, oxygen-independent reaction exhibiting first-order kinetics with respect to both catecholamine and metal concentrations. Produc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970099t
更新日期：1997-07-04 00:00:00
abstract：:As a continuation of our project aimed at the search for new and safe chemotherapeutic and chemoprophylactic agents against American trypanosomiasis (Chagas' disease), several drugs structurally related to 4-phenoxyphenoxyethyl thiocyanate (4) were designed, synthesized, and evaluated as antiproliferative agents again...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0201518
更新日期：2002-08-29 00:00:00
abstract：:As FDA-approved chemotherapeutic agents, cisplatin, oxaliplatin, and 5-fluorouracil are widely used in clinic but limited by severe side-effects. To ameliorate their respective defects, a series of "dual-prodrug" by linking oxoplatin and 5-FU were designed and synthesized. The assembled compounds 10-17, named Fuplatin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00128
更新日期：2019-05-09 00:00:00
abstract：:Several pairs of cannabinoid isomers were synthesized and tested for psychotropic activity in rhesus monkeys. Two regularities were observed: (a) In the absence of the other substituents, the equatorial stereochemistry of the substituent at C-1 determines activity. (b) Two groups of THC-type cannabinoids which differ ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00184a002
更新日期：1980-10-01 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：:In an effort to improve the activities and bioavailabilities of stromal cell-derived factor-1 (SDF-1, CXCL12) sdf-(1-67)-OH (1), we have prepared a linear peptide analogue [sdf-(1-31)-NH(2) (2)] and two lactam analogues [cyclo(Lys(20)-Glu(24))-sdf-(1-31)-NH(2) (3) and cyclo(Glu(24)-Lys(28))-sdf-(1-31)-NH(2) (4)], cons...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0104015
更新日期：2002-05-09 00:00:00
abstract：:The need for drugs that lack the obtrusive and limiting side effects of the tricyclic antidepressants has prompted the search for agents with greatly enhanced selectivity for specific mechanisms believed to be essential for antidepressant efficacy. The potential role of derangements of 5-HT pathways in the etiology of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00377a021
更新日期：1984-11-01 00:00:00
abstract：:Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. The roles of four residues of the cyclin-dependent kinase active site in inhibitor selectivity were investigated by producing cyclin-dependent kinase 2 mutants bearing equivalent...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060216x
更新日期：2006-09-07 00:00:00
abstract：:In previous reports illustrating the effects of conformational restriction of the N-terminal region of human pancreatic growth hormone releasing factor, we demonstrated that D-amino acid substitutions in either of positions 1, 2, or 3 resulted in greatly increased growth hormone releasing activity both in vivo and in ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00380a006
更新日期：1985-02-01 00:00:00
