Abstract：
:Two natural occurring melanotropins, camel betaC2-MSH and bovine beta-MSH, have been synthesized by improved solid-phase procedures. The coupling reaction of tert-butyloxycarbonylamino acids was achieved by using their preformed symmetrical anhydrides. The synthetic hormones were purified by gel filtration on Sephadex G-10 and G-25, chromatography on carboxymehtylcellulose, and partition chromatography on Sephadex G-25 with final yields of 56 and 35% for betac2-MSH and betab-MSH, respectively. They were then shown to be identical with their natural hormones in amino acid analysis, paper electrophoresis, disc electrophoresis, thin-layer chromatography, enzymic digests, and bioassays. Bioassay data of these two synthetic melanotropins indicate that the replacement of Ser by Gly in betab-MSH does not change its melanocyte-stimulating activity.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Lemaire S,Yamashiro D,Li CHdoi
10.1021/jm00225a006keywords:
subject
Has Abstractpub_date
1976-03-01 00:00:00pages
373-6issue
3eissn
0022-2623issn
1520-4804journal_volume
19pub_type
杂志文章abstract：:This series of reports describe the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. The compounds reported in this paper contain an additional phenyl ring, which has significantly improved the receptor affinity. The effect of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00166a017
更新日期：1990-04-01 00:00:00
abstract：:Continuing studies on the chemical modification of the previously reported novel tripeptide SP antagonist, N alpha-[N alpha-[N alpha- (tert-butyloxycarbonyl)glutaminyl]-N1-formyl-D-tryptophyl]phenylalanine benzyl ester [Boc-Gln-D-Trp-(CHO)-Phe-OBzl (1)], are described herein. We initially investigated the stability of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00095a013
更新日期：1992-08-21 00:00:00
abstract：:A series of 2-substituted methyl 2,3-dihydroimidazo[1, 2-c]quinazolin-5(6H)-ones (4), 3-substituted methyl 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-ones (5), 3-substituted methyl 2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-ones (15a,b), 3-substituted methyl 2,3-dihydroimidazo[2,1-b]quinazolin-5(1H)-ones (16a,b), 3-su...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970159v
更新日期：1998-08-13 00:00:00
abstract：:The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4'-phenyl-6,7:2',3'-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent deltaopioid receptor (DOR) antagonists while ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040817t
更新日期：2004-12-16 00:00:00
abstract：:Dimethylallylguanidine, also known as galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8011933
更新日期：2009-06-11 00:00:00
abstract：:The chemokine receptor CXCR4 is a critical regulator of inflammation and immune surveillance, and it is specifically implicated in cancer metastasis and HIV-1 infection. On the basis of the observation that several of the known antagonists remarkably share a C(2) symmetry element, we constructed symmetric dimers with ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2009716
更新日期：2011-11-10 00:00:00
abstract：:New series of pyrrolidine mercaptosulfide, 2-mercaptocyclopentane arylsulfonamide, and 3-mercapto-4-arylsulfonamidopyrrolidine matrix metalloproteinase inhibitors (MMPIs) were designed, synthesized, and evaluated. Exhibiting unique properties over other MMPIs (e.g., hydroxamates), these newly reported compounds are ca...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400529f
更新日期：2013-06-13 00:00:00
abstract：:A series of novel 3-quinolinecarboxamides that are structurally similar to the quinolone class of antibacterial agents possess excellent antiherpetic properties. By modifying the quinoline ring at the 1-, 2-, 3-, and 7-positions, analogues were identified that have up to 5-fold increased HSV-2 plaque-reduction potency...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00063a008
更新日期：1993-05-28 00:00:00
abstract：:A series of next in class small-molecule hepatitis C virus (HCV) NS5A inhibitors with picomolar potency containing 2-pyrrolidin-2-yl-5-{4-[4-(2-pyrrolidin-2-yl-1H-imidazol-5-yl)buta-1,3-diynyl]phenyl}-1H-imidazole cores was designed based on the SAR studies available for the reported NS5A inhibitors. Compound 13a (AV4...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500951r
更新日期：2014-09-25 00:00:00
abstract：:Here, we report the synthesis of a designed multi-pharmacophore ligand derived from the linkage of a delta selective peptide antagonist (Dmt-Tic) and a mu/kappa morphinan agonist butorphan (MCL 101) through a two methylene spacer. The new compound MCL 450 maintains the same characteristics as those the two reference c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0605785
更新日期：2006-09-07 00:00:00
abstract：:In this work, we describe the synthesis and in vitro evaluation of a novel series of multitarget-directed ligands (MTDL) displaying both nanomolar dual-binding site (DBS) acetylcholinesterase inhibitory effects and partial 5-HT4R agonist activity, among which donecopride was selected for further in vivo evaluations in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00115
更新日期：2015-04-09 00:00:00
abstract：:The endocannabinoid system consists of two cannabinoid receptors (CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes involved in the metabolism of the endocannabinoids, including fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL). In the present study, virtual screening of MGL inhibitor...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060394q
更新日期：2006-07-27 00:00:00
abstract：:Syntheses of several tripeptide analogues of leupeptin containing C-terminal argininal, lysinal, or ornithinal units are presented. The synthetic analogues were tested as inhibitors of trypsin, plasmin, and kallikrein. (Benzyloxycarbonyl)-L-leucyl-L-leucyl-L-argininal (2a) was significantly less effective as an inhibi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00163a014
更新日期：1990-01-01 00:00:00
abstract：:We have developed a fast and robust computational method for prediction of antiviral activity in automated de novo design of HIV-1 reverse transcriptase inhibitors. This is a structure-based approach that uses a linear relation between activity and interaction energy with discrete orientation sampling and with localiz...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049534r
更新日期：2005-03-24 00:00:00
abstract：:The synthesis of 2-amino-2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene is reported. This compound did not produce vasodilation in the dog renal artery and was inactive as a DA1-type dopamine agonist. This is in contrast to the 2-nonmethylated homologue 6,7-ADTN, which is a potent DA1 agonist. High-field 1H NMR ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00378a029
更新日期：1984-12-01 00:00:00
abstract：:In this Perspective, recent advances and challenges in the development of GPR119 agonists as new oral antidiabetic drugs will be discussed. Such agonists are expected to exhibit a low risk to induce hypoglycemia as well as to have a beneficial impact on body weight. Many pharmaceutical companies have been active in th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.5b01198
更新日期：2016-04-28 00:00:00
abstract：:A series of 3-(1,2-disubstituted-1H-benzimidazol-5-yl)-N-hydroxyacrylamides (1) were designed and synthesized as HDAC inhibitors. Extensive SARs have been established for in vitro potency (HDAC1 enzyme and COLO 205 cellular IC(50)), liver microsomal stability (t(1/2)), cytochrome P450 inhibitory (3A4 IC(50)), and clog...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2003552
更新日期：2011-07-14 00:00:00
abstract：:Podophyllotoxin has been extensively used as a lead agent in the development of new anticancer drugs. On the basis of the previously reported simplified 4-aza-2,3-didehydro podophyllotoxin analogues, we implemented a bioisosteric replacement of the methylenedioxybenzene subunit with a pyrazole moiety to afford tetracy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070528f
更新日期：2007-10-18 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049940a
更新日期：2004-11-04 00:00:00
abstract：:The selective inhibition of the lipid signaling enzyme PI3Kγ constitutes an opportunity to mediate immunosuppression and inflammation within the tumor microenvironment but is difficult to achieve due to the high sequence homology across the class I PI3K isoforms. Here, we describe the design of a novel series of poten...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01203
更新日期：2020-10-08 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00421
更新日期：2018-06-14 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01280
更新日期：2021-01-14 00:00:00
abstract：:Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity ( 7, 18- 20) ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8000949
更新日期：2008-06-26 00:00:00
abstract：:A series of pyridine-2-carboxaldehyde N-oxide and pyridine-2-carboxaldehyde (thio)phosphoric hydrazones and two cupric chelates was synthesized. The hydrazones, chelates, and combinations of hydrazones and cupric chloride were tested against mice bearing P388 lymphocytic leukemia, Sarcoma 180, or Ehrlich carcinoma asc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00209a011
更新日期：1978-11-01 00:00:00
abstract：:Protein-protein interfaces provide an important class of drug targets currently receiving increased attention. The typical design strategy to inhibit protein-protein interactions usually involves large molecules such as peptides and macrocycles. One exception is tranexamic acid (TXA), which, as a lysine mimetic, inhib...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301818g
更新日期：2013-04-25 00:00:00
abstract：:The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conf...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00972
更新日期：2019-09-26 00:00:00
abstract：:Seven pyranoses and three furanoses with a nitrogen in the ring were prepared by chemical synthesis, microbial conversion, and isolation from plants to investigate the contribution of epimerization, deoxygenation, and conformation to the potency of inhibition and specificity of mammalian glycosidases. The seven pyrano...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00048a006
更新日期：1994-10-28 00:00:00
abstract：:In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00207a023
更新日期：1978-09-01 00:00:00
abstract：:Epigenetic regulators that exhibit aberrant enzymatic activities or expression profiles are potential therapeutic targets for cancers. Specifically, enzymes responsible for methylation at histone-3 lysine-9 (like G9a) and aberrant DNA hypermethylation (DNMTs) have been implicated in a number of cancers. Recently, mole...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01925
更新日期：2018-08-09 00:00:00
abstract：:An enzymatically activated liposome-based drug-delivery concept involving masked antitumor ether lipids (AELs) has been investigated. This concept takes advantage of the cytotoxic properties of AEL drugs as well as the membrane permeability enhancing properties of these molecules, which can lead to enhanced drug diffu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm031029r
更新日期：2004-03-25 00:00:00
