Abstract：
:Proton magnetic spectra have been recorded for muscarine and two biologically active cyclopentane analogues. In order to observe homonuclear intramolecular nuclear Overhauser effects, the -N+(CH3)3 signal was irradiated and increases in integrated intensities for other key signals in the molecule were observed. The results indicate that the quaternary side chain in these compounds is in an extended conformation in aqueous solution.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
de Fontaine DL,Ternai B,Zupan JA,Givens RS,Wiley RAdoi
10.1021/jm00205a028subject
Has Abstractpub_date
1978-07-01 00:00:00pages
715-7issue
7eissn
0022-2623issn
1520-4804journal_volume
21pub_type
杂志文章abstract：:The preparation and antitubercular properties of a series of 2,8-bis(alkylaminomethyl)phenazines are described. These compounds all inhibited the growth of Mycobacterium smegmatis ATCC 607 in vitro. 2,8-Bis(dibutylaminomethyl)phenazine (5c) was also active against a lethal Mycobacterium tuberculosis H37Rv infection in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00202a020
更新日期：1978-04-01 00:00:00
abstract：:Basic derivatives of 6,7-dihydroindolo[1,7-ab][1]benzazepine and 6H-indolo[7,1-cd][1,5]benzoxazepine incorporating the imipramine basic side chain were synthesized and screened for antidepressant activity in mice. With few exceptions, the compounds unsubstituted at C-2 antagonized reserpine-induced ptosis and hypother...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00224a003
更新日期：1976-02-01 00:00:00
abstract：:An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to unders...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020113o
更新日期：2002-08-01 00:00:00
abstract：:In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401329s
更新日期：2014-03-13 00:00:00
abstract：:A series of 4'-substituted phenyl-4-piperidinylmethanol and benzoyl-4-piperidine derivatives was synthesized as potential novel serotonin 5-HT2A receptor ligands that can be radiolabeled for in vivo brain imaging. Compounds were prepared by alkylation of 4-substituted benzoyl-4-piperidine with an iodo- or fluoro-subst...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0200411
更新日期：2002-05-23 00:00:00
abstract：:The synthesis of water-soluble, unsymmetrical, trisulfonated zinc phthalocyanines (ZnPcS3) as single products of the ring expansion of boron tri(4-sulfo)subphthalocyanine (SubPc) is reported. The novel, water-soluble trisulfo-SubPcB(OH) was prepared via hydrolysis of the tris(4-chlorosulfonyl)SubPcB(Br) which in turn ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9702488
更新日期：1997-11-21 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：: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 novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A' ') for sequestering radiometals (86Y or 111In) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070657w
更新日期：2007-09-20 00:00:00
abstract：:The binding and solution-phase properties of six inhibitors of FK506 binding protein (FKBP12) were investigated using free energy perturbation techniques in Monte Carlo statistical mechanics simulations. These nonimmunosuppressive molecules are of current interest for their neurotrophic activity when bound to FKBP12 a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980062o
更新日期：1998-10-08 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 practices and tactics employed in successful optimizations are examined, judged from the trajectories of ligand efficiency and property evolution. A wide range of targets is analyzed, encompassing a variety of hit finding methods (HTS, fragments, encoded library technology) and types of molecules, including those ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.8b00180
更新日期：2018-08-09 00:00:00
abstract：:The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions. An alternative mechanistic proposal involving the ionic scission of the peroxide group and consequent generation of a c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060673d
更新日期：2006-10-05 00:00:00
abstract：:The synthesis of a series of 2-, 3-, and 4-substituted benzylamine derivatives is described. These compounds were studied for their effect on experimental cardiac arrhythmias. Many of the derivatives, but in particular 2-(p-methoxyphenylethynyl)benzylamine (3d), alpha,alpha-dimethyl-4y(phenylethynyl)benzylamine (7a), ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00236a006
更新日期：1975-02-01 00:00:00
abstract：:Structural simplification of an antimitotic natural product podophyllotoxin with mimetic heterocyclic scaffolds constructed using multicomponent reactions led to the identification of compounds exhibiting low nanomolar antiproliferative and apoptosis-inducing properties. The most potent compounds were found in the dih...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200410r
更新日期：2011-06-23 00:00:00
abstract：:In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401992e
更新日期：2014-04-24 00:00:00
abstract：:The mitotic kinesin Eg5 is critical for the assembly of the mitotic spindle and is a promising chemotherapy target. Previously, we identified S-trityl-L-cysteine as a selective inhibitor of Eg5 and developed triphenylbutanamine analogues with improved potency, favorable drug-like properties, but moderate in vivo activ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm3014597
更新日期：2013-03-14 00:00:00
abstract：:Three novel C-4 aziridine-bearing paclitaxel analogs, 3-5, have been synthesized during the course of our continuing effort at C-4 modification. The key step in the synthesis is the aziridine ring formation at the C-4 position via an intramolecular Mitsunobu reaction. The syntheses and the biological evaluation of the...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00012a029
更新日期：1995-06-09 00:00:00
abstract：:Bivalent molecules containing two beta-turn mimics with side chains that correspond to hot-spots on the neurotrophin NT-3 were prepared. Binding assays showed the mimetics to be selective TrkC ligands, and biological assays showed one mimetic to be an antagonist of the TrkC receptor. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100148d
更新日期：2010-07-08 00:00:00
abstract：:A series of novel compounds having a benzothiazoline skeleton was studied for their structure-activity relationship (SAR) with respect to Ca2+ antagonistic activity. As test compounds, analogues of 3-acyl-2-arylbenzothiazolines (3) were synthesized. Benzothiazoline derivatives (3) exerted higher Ca2+ antagonistic acti...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00400a006
更新日期：1988-05-01 00:00:00
abstract：:Prodrug-mediated utilization of the cytochrome P450 (CYP) 1A1 to obtain the selective release of potent anticancer products within cancer tissues is a promising approach in chemotherapy. We herein report the rationale, preparation, biological evaluation, and mechanism of action of phenyl 4-(2-oxo-3-alkylimidazolidin-1...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00343
更新日期：2017-06-22 00:00:00
abstract：:A series of novel monoacylated vitamin C derivatives were chemically synthesized with a stable ascorbate derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), and acid anhydrides in pyridine. Their solubility in organic phase, thermal stability, radical scavenging activity, and in vitro skin permeability was...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010379f
更新日期：2002-01-17 00:00:00
abstract：:In an attempt to rationalize the inability of phenolic benzocycloheptenylamines to activate dopamine (DA) D2 receptors, we have studied the conformational preferences and topography of 6,7,8,9-tetrahydro-1-hydroxy-N,N-dipropyl-5H-benzocyclohepten-6-++ +ylamine (1). Preferred conformations of 1 have been defined by use...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00124a007
更新日期：1989-04-01 00:00:00
abstract：:We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm058167w
更新日期：2005-11-03 00:00:00
abstract：:2,5-Dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4' - yl]methyl]-3H-1,2,4-triazol-3-one, SC-51316, was synthesized as a potent and orally active angiotensin II (AII) receptor antagonist with a long duration of action. To explore the lipophilic pocket in the AII receptor interacting with the substituent ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00067a015
更新日期：1993-07-23 00:00:00
abstract：:A new family of chelating agents based on 4-(substituted-carbamoyl)-3-hydroxy-2-pyridinones is reported. These have optional terminal substituents on the nitrogens, and the hydroxypyridonate (HOPO) rings are attached to molecular backbones through amide linkages. A very important feature of the methyl-substituted liga...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00014a013
更新日期：1995-07-07 00:00:00
abstract：:(3-Phenyl-7-flavonoxy)propanolamines have been shown to exhibit antihypertensive activity in spontaneously hypertensive rats. Although they are structurally similar to classical beta-adrenergic blocking compounds, their activity is not due to inhibition of beta-adrenoceptors. In the present study, a series of simple f...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00121a034
更新日期：1989-01-01 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 synthesis and some biological activities of [4-beta-(2-thienyl)-L-alanine]oxytocin are reported. This analogue has been studied in an ongoing exploration of the biological effects of introducing amino acid residues with bulky hydrophobic side chains into the second corner position of the beta turn present in the c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00199a022
更新日期：1978-01-01 00:00:00
abstract：:A series of α-ketooxazoles containing conformational constraints in the C2 acyl side chain of 2 (OL-135) were examined as inhibitors of fatty acid amide hydrolase (FAAH). Only one of the two possible enantiomers displayed potent FAAH inhibition (S vs R enantiomer), and their potency is comparable or improved relative ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm101597x
更新日期：2011-04-28 00:00:00
