Abstract：
:In this work, a series of water-soluble propofol prodrugs were synthesized, and their propofol release rate and pharmacodynamic characteristics were measured. We found that inserting glycolic acid as a linker between propofol and the cyclic amino acid accelerated the release of propofol from prodrugs into the plasma while preserving its safety. In animal experiments, prodrugs (3e, 3g, and 3j) were significantly better than fospropofol (the only water-soluble propofol prodrug that has been used clinically) in terms of safety, onset, and duration time of anesthesia. Their molar dose, onset time, and anesthesia duration time were comparable to those of propofol, helping to maintain the clinical benefits of propofol. The experimental results showed the potential of such compounds as water-soluble prodrugs of propofol.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Liu LQ,Hong PX,Song XH,Zhou CC,Ling R,Kang Y,Qi QR,Yang Jdoi
10.1021/acs.jmedchem.0c00698subject
Has Abstractpub_date
2020-07-23 00:00:00pages
7857-7866issue
14eissn
0022-2623issn
1520-4804journal_volume
63pub_type
杂志文章abstract：:The corticotropin release factor 2 receptor (CRF2R) has many biological activities including modulation of the stress response. Recently, we have demonstrated that CRF2R activation functions to prevent skeletal muscle wasting resulting from a variety of physiological stimuli. Thus we are interested in identifying CRF2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049490m
更新日期：2005-01-13 00:00:00
abstract：:An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, and MLM melanoma. Several cis-stilbenes, structurally similar to ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00112a036
更新日期：1991-08-01 00:00:00
abstract：:Extensive quantum chemical calculations have been made of the electronic distribution and conformational behavior of meperidine and desmethyl-, (+)-alpha, and (+)-beta-prodine using PCILO, a semiempirical molecular orbital method. For this series of opiates, a phenyl equatorial conformation was preferred over a phenyl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00245a001
更新日期：1975-11-01 00:00:00
abstract：:A group of nitro and amino derivatives of lucanthone was prepared and tested for antitumor activity. Reaction of 1-chloro-4-methyl-7-nitrothioxanthenone and N,N-diethylethylenediamine gave the 7-amino analogue (11) directly, accompanied by 7-amino-1-chloro-4-methylthioxanthenone. The antitumor activity of 11 was infer...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00345a020
更新日期：1982-03-01 00:00:00
abstract：:Bis (1-aziridinyl)(hexahydro-1H-azepin-1-yl)phosphine sulfide, an active anticancer agent with low hematopoietic toxicity in animals and man, was recommended several years ago for breast cancer adjuvant chemotherapy as an alternate drug to thiotepa. This hope had led to the syntheses of aziridinylallylaminophosphine o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00228a014
更新日期：1976-06-01 00:00:00
abstract：:A variety of derivatives of 2-pyridinecarboxaldehyde 1-oxide benzenesulfonylhydrazone, containing substituents on the benzene or pyridine rings as well as on the nitrogen atom which is bonded directly to the sulfonyl group, have been synthesized. The antineoplastic activity of these compounds has been assessed in mice...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00180a010
更新日期：1980-06-01 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：:The synthesis of cis and trans isomers of N,N-N-trimethyl-2-phenoxycyclohexylammonium bromide, cis-N,N,-N-trimethyl-2(2',6'-xylyloxy)cyclohexylammonium bromide, and N,N-dimethyl-3-phenoxypiperidinium bromide is described. Their structures and conformations were determined by NMR and uv absorption spectroscopy, the min...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00227a022
更新日期：1976-05-01 00:00:00
abstract：:Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. We previously reported that analogs of 1 with thiophene groups at C-7 retained the Src activity of the parent compound. The corresponding C-7 furan analogs were pre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061031t
更新日期：2006-12-28 00:00:00
abstract：:Several 1,3-disubstituted and 1-substituted derivatives of 5-propionoxy-5-(1-phenylethyl)barbituric acid were synthesized and evaluated for analgesic activity. Three of these compounds, 1,3-bis(methoxymethyl)-5-propionoxy-5-(1-phenylethyl)barbituric acid (2), 1,3-dimethyl-5-propionoxy-5-(1-phenylethyl)barbituric acid...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00241a010
更新日期：1975-07-01 00:00:00
abstract：:Macrophage elastase [matrix metalloproteinase (MMP)-12] is the most upregulated MMP in abdominal aortic aneurysm (AAA) and, hence, MMP-12-targeted imaging may predict AAA progression and rupture risk. Here, we report the design, synthesis, and evaluation of three novel hydroxamate-based selective MMP-12 inhibitors (CG...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01514
更新日期：2020-12-10 00:00:00
abstract：:A new series of zinc(II) phthalocyanine derivatives have been synthesized and characterized. These macrocycles exhibited a sharp absorption band in the red visible region in DMF, which indicated that they were dissolved well and almost did not aggregate in this solvent. Compared with the unsubstituted zinc(II) phthalo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400722d
更新日期：2013-07-25 00:00:00
abstract：:In order to define the role of the cholestane moiety in the anti-HIV agent cosalane, a series of cosalane analogs was synthesized in which the cholestane ring system was replaced by normal alkenyl and phosphodiester substituents having varied chain lengths and lipophilicities. The compounds containing simple alkenyl s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950666h
更新日期：1996-01-19 00:00:00
abstract：:5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00174a008
更新日期：1990-12-01 00:00:00
abstract：:4,4-Ditritio-(-)-nicotine (5) of high specific activity (4.7 Ci/mmol) has been synthesized from (-)-nicotine via the readily prepared 4,4-dibromocotinine (3). Scatchard analysis of the binding of 5 to the crude mitochondrial fraction of whole rat brain revealed a Ka of 4.7 X 10(6) M-1 and 13 fmol of binding sites/mg o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00182a028
更新日期：1980-08-01 00:00:00
abstract：:The 5-fluoro and 8-fluoro analogues of trimetoquinol, TMQ, have been synthesized and evaluated for beta 2- and beta 1-adrenoceptor activity in guinea pig trachea and atria, respectively. The fluoro analogues of TMQ maintained potent beta 2-adrenoceptor agonist activity but had reduced beta 1-adrenoceptor agonist activ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00384a015
更新日期：1987-01-01 00:00:00
abstract：:Ligand-induced stabilization of G-quadruplex structures formed by the human telomeric DNA is an active area of research. The compounds which stabilize the G-quadruplexes often lead to telomerase inhibition. Herein we present the results of interaction of new monomeric and dimeric ligands having 1,3-phenylene-bis(piper...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200860b
更新日期：2012-04-12 00:00:00
abstract：:All three amino-substituted 3-beta-D-ribofuranosyl-1,2,4-triazolo[4,3-b]pyridazines (5, 19, and 20) structurally related to formycin A were prepared and tested for their antitumor and antiviral activity in cell culture. Dehydrative coupling of 4-amino-5-chloro-3-hydrazinopyridazine (7) with 3,4,6-tri-O-benzoyl-2,5-anh...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00127a024
更新日期：1989-07-01 00:00:00
abstract：:The effects of 3-position substitution of 9-aminomethyl-9,10-dihydroanthracene (AMDA) on 5-HT 2A receptor affinity were determined and compared to a parallel series of DOB-like 1-(2,5-dimethoxyphenyl)-2-aminopropanes substituted at the 4-position. The results were interpreted within the context of 5-HT 2A receptor mod...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800771x
更新日期：2008-11-13 00:00:00
abstract：:Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor with roles in glucose, lipid, and lipoprotein homeostasis, and PPARγ ligands are expected have therapeutic potential in these as well as other areas. We report here the design, synthesis, crystallographic analysis, and c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm101233f
更新日期：2011-01-13 00:00:00
abstract：:We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of highly potent, specific, orally active, small molecule kinase inhibitors directed aga...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020143r
更新日期：2002-08-15 00:00:00
abstract：:A series of 4- aminobenzamides of some simple primary and secondary amines were prepared and evaluated for anticonvulsant effects. The compounds were tested in mice against seizures induced by electroshock and pentylenetetrazole ( metrazole ) and in the rotorod assay for neurologic deficit. For those N-alkyl amides te...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00372a013
更新日期：1984-06-01 00:00:00
abstract：:We have identified a novel series of antidiabetic N-(2-benzoylphenyl)-L-tyrosine derivatives which are potent, selective PPARgamma agonists. Through the use of in vitro PPARgamma binding and functional assays (2S)-3-(4-(benzyloxy)phenyl)-2-((1-methyl-3-oxo-3-phenylpropenyl)+ ++amin o)propionic acid (2) was identified ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9804127
更新日期：1998-12-03 00:00:00
abstract：:Agents that target the two highly conserved Zn fingers of the human immunodeficiency virus (HIV) nucleocapsid p7 (NCp7) protein are under development as antivirals. These agents covalently modify Zn-coordinating cysteine thiolates of the fingers, causing Zn ejection, loss of native protein structure and nucleic acid b...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9708543
更新日期：1998-04-23 00:00:00
abstract：:We have previously shown that the oral administration of the small molecule hPTHR1 agonist PCO371 and its lead compound, 1 (CH5447240) results in PTH-like calcemic and hypophostemic activity in thyroparathyroidectomized rats. However, 1 was converted to a reactive metabolite in a human liver microsome assay. In this a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01743
更新日期：2020-05-28 00:00:00
abstract：:We report two crystal structures of the PARP domain of human tankyrase-2 (TNKS2). Tankyrases are involved in fundamental cellular processes such as telomere homeostasis and Wnt signaling. The complex of TNKS2 with the potent inhibitor XAV939 provides insights into the molecular basis of the strong interaction and sugg...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100249w
更新日期：2010-07-22 00:00:00
abstract：:The synthesis of 5-(arylacetyl)-4-[(alkylamino)methyl]furo[3,2-c] pyridines (16-23, 26, 27) and their activities as kappa-opioid receptor agonists are described. kappa-Agonist potency was particularly sensitive to the nature of the basic moiety. In particular, in the rabbit vas deferens (kappa-specific tissue), the 3-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00040a004
更新日期：1994-07-08 00:00:00
abstract：:In order to determine the influence of a 6alpha-methyl group activity, the 6alpha-methyl derivative of digitoxigenin 3-acetate 14 was prepared and pharmacologically tested in comparison with digitoxigenen 3-acetate. The synthesis of 6alpha-methyldigitoxigenin 3-acetate (14) was performed starting from 21-hydroxy-4-pre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00246a020
更新日期：1975-12-01 00:00:00
abstract：:Recent evidence suggests that intraneuronal metabolism of ethanol by catalase/H2O2 and an ethanol-inducible form of cytochrome P450 together generate acetaldehyde and oxygen radicals including the hydroxyl radical (HO.). Within the cytoplasm of serotonergic neurons, these metabolic processes would thus provide acetald...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9504870
更新日期：1996-03-29 00:00:00
abstract：:A series of 7(8 leads to 11 alpha)abeo steroids was synthesized by a modification of the previously described total synthesis of this class of compounds and evaluated for biological activity. In general, there was a marked reduction in the relative binding affinities of these compounds for the rabbit uterus estrogen a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00214a017
更新日期：1977-04-01 00:00:00
