Abstract:
:5-Alkoxy-3-(N-substituted carbamoly)-1-phenylpyrazoles were prepared and tested for antiinflammatory and hypnotic activity. Four compounds showed antiinflammatory activity and three possessed hypnotic properties.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Sugiura S,Ohno S,Ohtani O,Izumi K,Kitamikado T,Asai H,Kato Kdoi
10.1021/jm00211a016subject
Has Abstractpub_date
1977-01-01 00:00:00pages
80-5issue
1eissn
0022-2623issn
1520-4804journal_volume
20pub_type
杂志文章abstract::With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm010080x
更新日期:2001-11-22 00:00:00
abstract::On the basis of our previous observation that N1-alkyl substituted chlorpropamide derivatives when administered to rats nonenzymatically eliminated n-propyl isocyanate, a known inhibitor of aldehyde dehydrogenase (AlDH), we have synthesized other latentiated n-propyl isocyanates as in vivo inhibitors of AlDH. N1-Allyl...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00050a018
更新日期:1994-11-25 00:00:00
abstract::A series of 8-phenylxanthine derivatives has been synthesized with oxyacetic acid on the para phenyl position to increase aqueous solubility and minimize nonspecific binding and iodinatable groups on the 1- or 3-position of the xanthine ring. The structure-activity relationship for binding of these compounds to A1 ade...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00399a010
更新日期:1988-04-01 00:00:00
abstract::The quinazoline class was exploited to search for a new translocator protein (TSPO) fluorescent probe endowed with improved affinity and residence time (RT). Computational studies on an "in-house" collection of quinazoline derivatives, featuring highly steric demanding groups at the amide nitrogen, suggested that, des...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.7b01031
更新日期:2017-09-28 00:00:00
abstract::WAY100635 (2), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide, is a silent serotonin 5-HT(1A) antagonist, which is now widely used to study the 5-HT(1A) receptor both in vivo and in vitro. In this paper, we describe the synthesis and in vitro (5-HT(1A) affinity and pA(2) values a...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm991088y
更新日期:2000-02-10 00:00:00
abstract::Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm049383s
更新日期:2005-04-21 00:00:00
abstract::Adenosine (ADO) is an endogenous homeostatic inhibitory neuromodulator that reduces cellular excitability at sites of tissue injury and inflammation. Inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO, selectively increases ADO concentrations at sites of tissue trauma and enhances the analgesic ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm000314x
更新日期:2001-06-21 00:00:00
abstract::Tumor suppressor protein, p53, is an intracellular protein that is critical within the biochemical cascade that leads to cell death via apoptosis. Recent studies identified the tetrahydrobenzothiazole analogue, pifithrin-alpha (2), as a p53 inhibitor that was effective in protecting neuronal cells against a variety of...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm020044d
更新日期:2002-11-07 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::Generation of a three-dimensional pharmacophore model (hypothesis) that correlates the biological activity of a series of farnesyl protein transferase (FPT) inhibitors, exemplified by the prototype 1-(4-pyridylacetyl)- 4-(8-chloro-5,6-dihydro-11H-benzo [5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine, Sch 44342, 1,...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm970291v
更新日期:1997-12-05 00:00:00
abstract::The synthesis and bioactivity of the retinoid X receptor (RXR) antagonist 4-[(3'-n-butyl-5',6',7',8'-tetrahydro-5',5',8',8'-tetramethyl-2'-naphthalenyl)(cyclopropylidene)methyl]benzoic acid and several heteroatom-substituted analogues are described. Ligand design was based on the scaffold of the 3'-methyl RXR-selectiv...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm030651g
更新日期:2004-08-26 00:00:00
abstract::N-Piperidinopropyl-galanthamine (2) and N-saccharinohexyl-galanthamine (3) were used to investigate interaction sites along the active site gorge of Torpedo californica actylcholinesterase (TcAChE). The crystal structure of TcAChE-2 solved at 2.3 A showed that the N-piperidinopropyl group in 2 is not stretched along t...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm901296p
更新日期:2010-01-28 00:00:00
abstract::The TOP2 poison etoposide has been implicated in the generation of secondary malignancies during cancer treatment. Structural similarities between TOP2 isoforms challenge the rational design of isoform-specific poisons to further delineate these processes. Herein, we describe the synthesis and biological evaluation of...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b00473
更新日期:2015-06-11 00:00:00
abstract::We investigated the pharmacological profile of a novel series of quinoxaline-based 5-HT(3) receptor ligands bearing an extra basic moiety on the piperazine N-4. High affinity and selectivity were dependent on the electronic properties of the substituents, and at cardiac level 3a and 3c modulated chronotropy but not in...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm901126m
更新日期:2009-11-12 00:00:00
abstract::New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cycl...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00093a009
更新日期:1992-07-24 00:00:00
abstract::We have previously reported that rhodacyanine dyes, such as 1 and 2, exhibited a potent inhibitory effect on the growth of several tumor cells and that 4-oxothiazolidine (rhodanine) was an essential moiety for antitumor activity. On the basis of our foregoing work, two types of rhodacyanine dyes, which categorized int...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm970590k
更新日期:1998-01-01 00:00:00
abstract::A number of bis(diazeniumdiolates) that we designed to release up to 4 mol of nitric oxide (NO) and that are structural analogues of the NO prodrug and anticancer lead compound O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2- diolate (PABA/NO) were synthesized and studied...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm800831y
更新日期:2008-12-25 00:00:00
abstract::Identification of a selective inhibitor for a particular protein kinase without inhibition of other kinases is critical for use as a biological tool or drug. However, this is very difficult because there are hundreds of homologous kinases and their kinase domains including the ATP binding pocket have a common folding ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm010326y
更新日期:2001-12-20 00:00:00
abstract::Several imidazolylphenyl sulfamate and (imidazolylphenoxy)alkyl sulfamate derivatives were synthesized and evaluated as topically active carbonic anhydrase inhibitors. Water solubility, pKa, carbonic anhydrase inhibition, and partition coefficient for the compounds were measured. Sulfamic acid 2-[4-(1H-imidazol-1-yl)p...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00104a003
更新日期:1992-12-25 00:00:00
abstract::In tissue engineering, survival of larger constructs remains challenging due to limited supply of oxygen caused by a lack of early vascularization. Controlled release of oxygen from small organic molecules represents a possible strategy to prevent cell death under anoxic conditions. A comprehensive study of methylated...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm4016137
更新日期:2013-12-27 00:00:00
abstract::The synthesis, structure-activity relationship (SAR), and evolution of a novel series of oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent FLAP binding potency (IC50 < 10 nM) and pot...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm501185j
更新日期:2015-02-26 00:00:00
abstract::Antagonism of mercaptopropionic acid (MPA) induced convulsions, reflecting a GABAergic mechanism, was observed in a series of 1-aryl-3-(aminoalkylidene)oxindoles. Optimal MPA antagonism was associated with 3-halo, 3-alkyl, and/or 4-alkoxy substituents in the pendant aryl ring and with (dimethylamino)methylene, 1-(dime...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00122a025
更新日期:1989-02-01 00:00:00
abstract::Fifteen 7-substituted 4-hydroxyquinoline-3-carboxylic acids have been designed to minimize covariance between the physicochemical substituent parameters: pi, MR, and sigmap. The molecules have been synthesized and evaluated for their ability to inhibit the respiration of Ehrlich ascites cells as a whole cell model and...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00218a003
更新日期:1977-08-01 00:00:00
abstract::A series of tetrahydrobenzofuranyl and tetrahydrobenzothienyl propenoic acids that showed potent agonist activity against RXRalpha were synthesized via a structure-based design approach. Among the compounds studied, 46a,b showed not only very good potency against RXRalpha (K(i) = 6 nM) but was also found to be greater...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm030565g
更新日期:2004-04-08 00:00:00
abstract::On the basis of the fact that apio dideoxynucleosides, in which the furanose oxygen and the C2 of the 2,3-dideoxyribose are transposed, exhibited potent anti-HIV activity and 2',3'-dideoxy-2',3'-didehydronucleosides also showed potent anti-HIV activity, we synthesized apio dideoxydidehydronucleosides in which the oxyg...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm000342f
更新日期:2001-03-01 00:00:00
abstract::The oxazolidinone antibacterials target the 50S subunit of prokaryotic ribosomes. To gain insight into their mechanism of action, the crystal structure of the canonical oxazolidinone, linezolid, has been determined bound to the Haloarcula marismortui 50S subunit. Linezolid binds the 50S A-site, near the catalytic cent...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm800379d
更新日期:2008-06-26 00:00:00
abstract::A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2-(alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7-12 and the related 6-(2,6-difluorobenzyl) counterparts 13-15 in HIV-1 infected cells and in the HIV-1 reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs showed up to picomola...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm500284x
更新日期:2014-06-26 00:00:00
abstract::Four new 2-(2-piperidinoethyl)benzocycloalkanone derivatives, 20-23, were prepared and evaluated as potential antipsychotic agents in receptor binding assays for dopamine (DA) and 5-HT2A receptors and in functional and behavioral screens. Their affinities for D2 receptors (Ki's in the nanomolar range: 46.7-70.7) and D...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00042a009
更新日期:1994-08-05 00:00:00
abstract::New 5'-O-carbonate prodrugs of zidovudine (AZT) have been synthesized in order to enhance its uptake by HIV-1 infected cells, to improve its anti-HIV potency, and to optimize the intramolecular cyclic rearrangement process related to the 5'-O-(4-hydroxybutyl) carbonate moiety. Evidence of this prodrug rearrangement wa...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm010863i
更新日期:2001-08-30 00:00:00
abstract::Thymidylate kinase (TMK), an essential enzyme in bacterial DNA biosynthesis, is an attractive therapeutic target for the development of novel antibacterial agents, and we continue to explore TMK inhibitors with improved potency, protein binding, and pharmacokinetic potential. A structure-guided design approach was emp...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm500463c
更新日期:2014-06-12 00:00:00