Abstract：
:The vinyl ethers of choline and of its alpha- and beta-methyl homologues were prepared to determine their cholinergic effects and to determine whether a separation of the dual physiologic activity (nicotinic and muscarinic) reported for the vinyl ether of choline could be achieved by this modification. A literature method of vinyl transetherification of amino alcohols has been studied and modified. The ethyl ethers of choline and of alpha- and beta-methylcholine were prepared for comparison with the vinyl ethers. Two independent, unequivocal syntheses of the ethyl ether of beta-methylcholine have been accomplished. This study showed that the two literature methods for synthesis of this compound are equivocal, and, hence, the biological data reported for this compound in the older literature may not be valid. Certain of the ethers showed marked nicotinic or muscarinic activities.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Cannon JG,Gangjee Adoi
10.1021/jm00229a015subject
Has Abstractpub_date
1976-07-01 00:00:00pages
934-7issue
7eissn
0022-2623issn
1520-4804journal_volume
19pub_type
杂志文章abstract：:The enantiomers of the leukotriene D4 antagonist 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid (L-660,711)(MK-571) have been prepared, their absolute stereochemistry has been assigned as S for (+)-1 and R for (-)-1 by X-ray analysis of a synthetic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00172a025
更新日期：1990-10-01 00:00:00
abstract：:Sulfur mustard (SM) is a highly toxic chemical warfare agent. A satisfactory treatment regimen is not yet available for this toxicant. In a search for an effective antidote against SM, a series of novel S-2(omega-aminoalkylamino)ethyl alkyl/aryl thioethers [H(2)N(CH(2))(n)()NHCH(2)CH(2)SR], where R = alky, alicyclic, ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030099v
更新日期：2004-07-15 00:00:00
abstract：:The four stereoisomers of the muscarinic agonist 7 have been synthesized from enantiomerically pure exo-azanorbornane esters (13a,b). The esters were obtained in optically active form by separation of the carboxamide diastereomers 12a,b, formed from the borane complex of exo-azanorbornane-3-carboxylate 10 and a chiral...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00083a016
更新日期：1992-03-06 00:00:00
abstract：:A series of 80 7-(het)aryl- and 7-ethynyl-7-deazapurine ribonucleosides bearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl, or oxo group at position 6, or 2,6-disubstituted derivatives bearing a methyl or amino group at position 2, were prepared, and the biological activity of the compounds was stud...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4018948
更新日期：2014-02-13 00:00:00
abstract：:Three rationally designed pyrrolobenzodiazepine (PBD) drug-linkers have been synthesized via intermediate 19 for use in antibody-drug conjugates (ADCs). They lack a cleavable trigger in the linker and consist of a maleimide for cysteine antibody conjugation, a hydrophilic spacer, and either an alkyne (6), triazole (7)...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00736
更新日期：2017-12-14 00:00:00
abstract：:A series of eight C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (+-)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaborati...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00165a029
更新日期：1990-03-01 00:00:00
abstract：:Aliphatic amino acids glycine, alanine, valine, and leucine were conjugated to the antitumor drug N2-methyl-9-hydroxyellipticinium (NMHE) through a peroxidase-catalyzed oxidation reaction. NMR studies of the adducts so obtained have indicated (i) that the amino acids were linked to NMHE between the nitrogen of their p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00375a013
更新日期：1984-09-01 00:00:00
abstract：:A series of 1-thia analogues of the pyrrolizine bis(carbamate) 9 (NSC-278214), namely 5-aryl-2,3-dihydropyrrolo-[2,1-b]thiazole-6,7-dimethanol 6,7-bis(isopropylcarbamates) (7a-d), were prepared by multistep syntheses from the proline analogue thiazolidine-2-carboxylic acid. The compounds were tested for growth inhibit...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00402a030
更新日期：1988-07-01 00:00:00
abstract：:A number of new 4(1H)-quinazolinones were synthesized and evaluated in the carrageenin-induced paw edema test. Most of the compounds were obtained by the cyclization of the appropriately substituted anthranilamides with acid chlorides, followed by further chemical transformation. Structure-activity data suggest that 2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm50001a006
更新日期：1985-05-01 00:00:00
abstract：:In this study, a new series of more than 60 quinoline derivatives has been synthesized and evaluated against Mycobacterium tuberculosis (H37Rv). Apart from the SAR exploration around the initial hits, the optimization process focused on the improvement of the physicochemical properties, cytotoxicity, and metabolic sta...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00245
更新日期：2016-07-28 00:00:00
abstract：:A total of 53 N-benzoylated phenoxazines and phenothiazines, including their S-oxidized analogues, were synthesized and evaluated for antiproliferative activity, interaction with tubulin, and cell cycle effects. Potent inhibitors of multiple cancer cell lines emerged with the 10-(4-methoxybenzoyl)-10H-phenoxazine-3-ca...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200436t
更新日期：2011-06-23 00:00:00
abstract：:Continuing our search for vitamin D analogues, we explored the modification of the steroidal side chain and inserted a methylene moiety in position C-22 together with either lengthening the side chain or introducing a ring at the terminal end. Our conformational studies confirmed that the presence of a methylene group...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00580
更新日期：2020-07-09 00:00:00
abstract：:We have focused on optimization of the inadequate pharmacokinetic profile of trans-4-substituted cyclohexanecarboxylic acid 5, which is commonly observed in many small molecule very late antigen-4 (VLA-4) antagonists. We modified the lipophilic moiety in 5 and found that reducing the polar surface area of this moiety ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901154c
更新日期：2009-12-24 00:00:00
abstract：:A series of 7-(3-amino- or 3-aminomethyl-1-pyrrolidinyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-o xo-3-quinolinecarboxylic acids was synthesized and tested for antibacterial activity. Unique to these quinolones was the presence of a methyl or phenyl group in the pyrrolidine ring. Although the in vitro activity of th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00164a060
更新日期：1990-02-01 00:00:00
abstract：:Hydroxy-2-phenylindoles carrying substituted benzyl groups and similar substituents at the nitrogen were synthesized and tested for their ability to displace estradiol from its receptor. All of the derivatives tested exhibited high binding affinities for the calf uterine estrogen receptor, with RBA values ranging from...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00384a022
更新日期：1987-01-01 00:00:00
abstract：:The N- and C-terminal domains of human somatic angiotensin I converting enzyme (sACE-1) demonstrate distinct physiological functions, with resulting interest in the development of domain-selective inhibitors for specific therapeutic applications. Herein, the activity of lisinopril-coupled transition metal chelates was...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4009345
更新日期：2013-12-27 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：:Inhibitor of apoptosis proteins (IAPs) are promising anticancer targets, given their roles in the evasion of apoptosis. Several peptidomimetic IAP antagonists, with inherent selectivity for cellular IAP (cIAP) over X-linked IAP (XIAP), have been tested in the clinic. A fragment screening approach followed by structure...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00900
更新日期：2018-08-23 00:00:00
abstract：:The discovery of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymatic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocul...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901226j
更新日期：2009-11-12 00:00:00
abstract：:A series of cyclic pseudopeptides of the formula cyclo(Leu psi[CH2NH]Xaa-Gln-Trp-Phe-beta Ala), where Xaa represents the residue of an alpha-amino acid, has been synthesized in order to establish the role of the Xaa side chain for tachykinin NK-2 receptor antagonist activity. Syntheses have been carried out in solid p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00047a020
更新日期：1994-10-14 00:00:00
abstract：:(+)-12-Fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2a) and (+)-15-epi-12-fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2b) were prepared from the readily available (-)-7-fluorospiro[bicyclo[2.2.1]hept-5-ene-2,2'-[1,3]dioxolane]-7-methanol (3). Fluoroprostaglandins 2a and 2b possess truly signific...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00139a014
更新日期：1981-07-01 00:00:00
abstract：:A series of substituted (E)-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acids was prepared and evaluated in the rat passive cutaneous anaphylaxis (PCA) test for antiallergic activity. Alkoxy, alkylthio, and isopropyl substituents at the 6- or 8-positions provided highly potent compounds. Conversion to the Z isomer, reduc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00357a018
更新日期：1983-03-01 00:00:00
abstract：:We report the discovery of chroman 28, a potent and selective antagonist of human, nonhuman primate, rat, and rabbit bradykinin B1 receptors (0.4-17 nM). At 90 mg/kg s.c., 28 decreased plasma extravasation in two rodent models of inflammation. A novel method to calculate entropy is introduced and ascribed approximatel...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061224g
更新日期：2007-02-22 00:00:00
abstract：:Antitumor activity in mice was observed for the oxime of the previously reported ethyl [6-amino-4-[(1-methyl-2-phenyl-2-oxoethyl)amino]-5-nitropyridin -2-yl] carbamate (8) and several related compounds. These compounds are precursors of the active ethyl pyrido[3,4-b]pyrazin-7-ylcarbamates (e.g., 4), which are potent a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00098a014
更新日期：1992-10-02 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：:Dysfunction of monoacylglycerol lipase (MAGL) is associated with several psychopathological disorders, including drug addiction and neurodegenerative diseases. Herein we design, synthesize, and evaluate several irreversible fluorine-containing MAGL inhibitors for positron emission tomography (PET) ligand development. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00936
更新日期：2019-10-10 00:00:00
abstract：:Oxadiazoles, like the benzoyl group in a series of imidazo[1,2-a]pyrimidines, have been found to be metabolically stable alternatives to ester groups in benzodiazepine-receptor ligands. This change has lead to a number of compounds which bind to the receptors and which exhibit potent agonist activity in a food-motivat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00111a021
更新日期：1991-07-01 00:00:00
abstract：:Neurofibrillary tangles (NFTs) made up of aggregated tau protein have been identified as the pathologic hallmark of several neurodegenerative diseases including Alzheimer's disease. In vivo detection of NFTs using PET imaging represents a unique opportunity to develop a pharmacodynamic tool to accelerate the discovery...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00166
更新日期：2016-05-26 00:00:00
abstract：:We have prepared azabicyclo[3.2.1] derivatives (C-3-substituted tropanes) that bind with high affinity to the dopamine transporter and inhibit dopamine reuptake. Within the series, 3-[2-[bis-(4-fluorophenyl)methoxy]ethylidene]-8-methyl-8-azabicyclo[3.2.1]octane (8) was found to have the highest affinity and selectivit...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0101592
更新日期：2001-11-08 00:00:00
abstract：:CC chemokine receptors 2 (CCR2) and 5 (CCR5) are involved in many inflammatory diseases; however, most CCR2 and CCR5 clinical candidates have been unsuccessful. (Pre)clinical evidence suggests that dual CCR2/CCR5 inhibition might be more effective in the treatment of such multifactorial diseases. In this regard, the h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00742
更新日期：2019-12-26 00:00:00
