Abstract：
:Glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2) are proglucagon derived peptides that are released from gut endocrine cells in response to nutrient intake. These molecules are rapidly inactivated by the action of dipeptidyl peptidase IV (DPP-4) which limits their use as therapeutic agents. The recent emergence of three-dimensional structures of GPCRs such as GLP-1R and glucagon receptor has helped to drive the rational design of innovative peptide molecules that hold promise as novel peptide therapeutics. One emerging area is the discovery of multifunctional molecules that act at two or more pharmacological systems to enhance therapeutic efficacy. In addition, drug discovery efforts are also focusing on strategies to improve patient convenience through alternative routes of peptide delivery. These novel strategies highlight the broad utility of peptide-based therapeutics in human disease settings where unmet needs still exist.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Suzuki R,Brown GA,Christopher JA,Scully CCG,Congreve Mdoi
10.1021/acs.jmedchem.9b00835subject
Has Abstractpub_date
2020-02-13 00:00:00pages
905-927issue
3eissn
0022-2623issn
1520-4804journal_volume
63pub_type
杂志文章,评审abstract：:Reformatski condensation of benzyl 2-bromopropionate with 4-carbomethoxybenzaldehyde, followed by dehydration afforded benzyl 2-methyl-p-carbomethoxycinnamate (4a). Hydrogenation over a Pd catalyst gave the hydrocinnamic acid 5a. Conversion to the chloromethyl (6a) and azidomethyl ketone (7a) was followed by hydrogena...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00163a035
更新日期：1990-01-01 00:00:00
abstract：:Deregulation of CK1 (casein kinase 1) activity can be involved in the development of several pathological disorders and diseases such as cancer. Therefore, research interest in identifying potent CK1-specific inhibitors is still increasing. A previously published potent and selective benzimidazole-derived CK1δ/ε-speci...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500600b
更新日期：2014-10-09 00:00:00
abstract：:Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor (Ki = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9704098
更新日期：1997-11-21 00:00:00
abstract：:A new technique for using receptor surface models in quantitative structure-activity relationship (QSAR) analysis is described. Receptor surface models provide compact, quantitative descriptors which capture three-dimensional information about putative receptor/ligand interactions. Receptor surface models can be const...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00012a008
更新日期：1995-06-09 00:00:00
abstract：:As a part of our program aimed at exploring the biological activity of symmetrical substitution of side chains into the anthracene-9,10-dione chromophore, we have synthesized a series of 1,5-bisthioanthraquinones 2 and 1,5-bisacyloxyanthraquinones 3 that are related to the antitumor agent mitoxantrone. Since the telom...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020492l
更新日期：2003-07-17 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：:Lysosomotropic detergents, which kill mammalian cells by disrupting lysosomal membranes, have now been found to be antifungals also. All strains in our assay are susceptible. The mode of action is as yet undetermined, but intracellular vacuoles may be the primary targets. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00391a043
更新日期：1987-08-01 00:00:00
abstract：:New ruthenium(II) and iron(II) organometallic compounds of general formula [(η(5)-C5H5)M(PP)Lc][PF6], bearing carbohydrate derivative ligands (Lc), were prepared and fully characterized and the crystal structures of five of those compounds were determined by X-ray diffraction studies. Cell viability of colon cancer HC...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00403
更新日期：2015-05-28 00:00:00
abstract：:Prostate-specific membrane antigen (PSMA) is an excellent biomarker for the early diagnosis of prostate cancer progression and metastasis. The most promising PSMA-targeted agents in the clinical phase are based on the Lys-urea-Glu motif, in which Lys and Glu are α-(l)-amino acids. In this study, we aimed to determine ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b02022
更新日期：2020-03-26 00:00:00
abstract：:We have recently reported the phosphodiesterase 10A (PDE10A) inhibitor 2-[4-[1-(2-[(18)F]fluoroethyl)-4-pyridin-4-yl-1H-pyrazol-3-yl]-phenoxymethyl]-quinoline ([(18)F]1a) as a promising candidate for in vivo imaging using positron emission tomography (PET). We now describe the synthesis and biological evaluation of a ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200536d
更新日期：2011-08-25 00:00:00
abstract：:Previously reported 2-(hydroxymethyl)indoloquinones, prepared as their acetates or carbamates, were less active than 2-methyl analogues in bacterial cultures and they had no activity in mice, despite functionality appropriate for DNA cross-linking. On the basis of the hypothesis that these compounds might have been to...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00128a030
更新日期：1989-08-01 00:00:00
abstract：:A series of 1-R-5-alkoxy-3H-1,4-benzodiazepin-2(1H)-ones was prepared and evaluated for central nervous system depressant activity. Several of these compounds, in particular, 7-chloro-5-ethoxy-1-methyl-3H-1,4-benzodiazepin-2(1H)-one (2), gave a profile and activity level similar to diazepam when measured in mice. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00217a019
更新日期：1977-07-01 00:00:00
abstract：:To study the influence of substitution of CN for C identical to CH in the anti-herpes virus nucleoside 5-(propynyloxy)-2'-deoxyuridine (1), 5-[(cyanomethylene)oxy]-2'-deoxyuridine (2) was prepared. When the potassium salt of 5-hydroxy-2'-deoxyuridine was reacted with iodoacetonitrile in dry DMF, the bisalkylated produ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00136a007
更新日期：1981-04-01 00:00:00
abstract：:5-fluorouracil (5-FU) seco-nucleosdies having as the "sugar" moiety a two-carbon (C2) side chain carrying a N-(2-chloroethyl)-N-nitrosourea group were designed as molecular combinations of antimetabolite and alkylating agent, but hydrolytic release of free 5-FU was not fast enough for significant contribution to the h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9507237
更新日期：1996-03-29 00:00:00
abstract：:ACTIBIND and its human homologue RNASET2 are T2 ribonucleases (RNases). RNases are ubiquitous and efficient enzymes that hydrolyze RNA to 3' mononucleotides and also possess antitumorigenic and antiangiogenic activities. Previously, we have shown that ACTIBIND and RNASET2 bind actin and interfere with the cytoskeletal...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1015507
更新日期：2012-02-09 00:00:00
abstract：:Multiple recent studies have focused on unraveling the content of the medicinal chemist's toolbox. Here, we present an investigation of chemical reactions and molecules retrieved from U.S. patents over the past 40 years (1976-2015). We used a sophisticated text-mining pipeline to extract 1.15 million unique whole reac...
journal_title：Journal of medicinal chemistry
pub_type： 历史文章,杂志文章
doi：10.1021/acs.jmedchem.6b00153
更新日期：2016-05-12 00:00:00
abstract：:Pharmacophore, two-dimensional (2D), and three-dimensional (3D) quantitative structure-activity relationship (QSAR) modeling techniques were used to develop and test models capable of rationalizing and predicting human UDP-glucuronosyltransferase 1A4 (UGT1A4) substrate selectivity and binding affinity (as K(m,app)). T...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020397c
更新日期：2003-04-24 00:00:00
abstract：:If no structural information about a particular target protein is available, methods of rational drug design try to superimpose putative ligands with a given reference, e.g., an endogenous ligand. The goal of such structural alignments is, on the one hand, to approximate the binding geometry and, on the other hand, to...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm981037l
更新日期：1998-11-05 00:00:00
abstract：:A series of 1-amino- and 1-mercapto-7,8,9,10-tetrahydro-6H-dibenzo[b,d]pyrans was synthesized and subsequently evaluated in three rodent test systems for CNS activity. The structure-activity data generated indicate that, in general, a change of the 1-hydroxy group to an amine results in a retention of pharmacological ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00211a004
更新日期：1977-01-01 00:00:00
abstract：:N5-Acetyl-N5-hydroxy-L-ornithyl-N5-acetyl-N5-hydroxy-L-ornithyl-N5-acety l- N5-hydroxy-L-ornithine, the functionally instrumental component of the albomycins and ferrichromes, has been incorporated as a "carrier" substructure into both carbacephalosporin and oxamazin type beta-lactam antibiotics. The previously synthe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00107a014
更新日期：1991-03-01 00:00:00
abstract：:The effect of incorporation of an eleostearoyl group into molecules of aralkylhydrazines on their monoamine oxidase inhibitory potency was investigated in vitro and in vivo. The results showed that on a molar basis the hydrazides possessed an in vitro potency lower than and an in vivo potency and acute toxicity compar...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00235a004
更新日期：1975-01-01 00:00:00
abstract：:The preparation of stable complexes between the N7-[2-(2-pyridyl)ethyl] and N7-(2-piperazinylethyl) derivatives of mitomycin C and metal ions such as Cu(II), Zn(II), and Pt(II) was accomplished. Mitomycin C did not form stable complexes, but it rearranged to a mitosene capable of complex formation. Some of these compl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00151a023
更新日期：1986-01-01 00:00:00
abstract：:A variety of nonsteroidal systems can function as ligands for the estrogen receptor (ER), in some cases showing selectivity for one of the two ER subtypes, ER alpha or ER beta. We have prepared a series of heterocycle-based (furans, thiophenes, and pyrroles) ligands for the estrogen receptor and assessed their behavio...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010211u
更新日期：2001-11-08 00:00:00
abstract：:Inherently conducting polymers (ICPs) are a specific category of synthetic polymers with distinctive electro-optic properties, which involve conjugated chains with alternating single and double bonds. Polyaniline (PANI), as one of the most well-known ICPs, has outstanding potential applications in biomedicine because ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.9b00803
更新日期：2020-01-09 00:00:00
abstract：:A number of fatty acyl derivatives of (-)-2',3'-dideoxy-3'-thiacytidine (lamivudine, 3TC, 1) were synthesized and evaluated for their anti-HIV activity. The monosubstituted 5'-O-fatty acyl derivatives of 3TC (EC(50) = 0.2-2.3 μM) were more potent than the corresponding monosubstituted N(4)-fatty acyl (EC(50) = 0.4-29....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300492q
更新日期：2012-05-24 00:00:00
abstract：:The ionization and lipophilicity behavior of the antihistamine (H1-receptor antagonist) cetirizine was investigated, showing the drug to exist almost exclusively as a zwitterion in the pH region 3.5-7.5. In this pH range, its octanol/water lipophilicity is constant and low compared to cationic antihistamines (log D = ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9704311
更新日期：1998-03-12 00:00:00
abstract：:Because of the double-edged nature of NO, the development of isoform-selective NOS substrates is a highly desirable goal. Given the striking similarity in the heme active sites of the three NOS isoforms, it presents an challenging problem. Several N-aryl-N'-hydroxyguanidines have recently been shown as substrates that...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0340703
更新日期：2003-06-05 00:00:00
abstract：:Assembly of human immunodeficiency virus (HIV-1) represents an attractive target for antiretroviral therapy which is not exploited by currently available drugs. We established high-throughput screening for assembly inhibitors based on competition of small molecules for the binding of a known dodecapeptide assembly inh...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01089
更新日期：2016-01-28 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：: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
