Abstract：
:A group of oligopeptides has been synthesized that are structurally related to the natural antiviral antitumor agents netropsin and distamycin but which bear alkylating functions. Cytostatic activity against both human and murine tumor cell lines as well as their in vitro activity against a range of viruses is reported. The biological activity of these agents is discussed both in terms of their alkylating reactivity and of their structural differences. The incorporation of alkylating moieties into these minor groove DNA binders results in up to 45-fold increase in cytostatic activity compared with netropsin and up to 18 times the activity of distamycin.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Krowicki K,Balzarini J,De Clercq E,Newman RA,Lown JWdoi
10.1021/jm00397a012subject
Has Abstractpub_date
1988-02-01 00:00:00pages
341-5issue
2eissn
0022-2623issn
1520-4804journal_volume
31pub_type
杂志文章abstract：:The discovery of selective endothelin (ET) receptor antagonists will facilitate identification of the physiological and pathological roles for ET and its isopeptides. Structure-activity studies of the C-terminal hexapeptide of ET have been carried out to elucidate those amino acids important for receptor binding and a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00070a001
更新日期：1993-09-03 00:00:00
abstract：:Three new dimeric analogues of ethidium cation in which the monomeric moieties are linked at the 3' positions by alpha,omega-diethers of varying length and composition have been synthesized. The circular dichroism spectra of all three compounds indicate that they double intercalate, and their effects on the thermal he...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00143a014
更新日期：1981-11-01 00:00:00
abstract：:A unique tetrahydrofuran ether class of highly potent α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiators has been identified using rational and structure-based drug design. An acyclic lead compound, containing an ether-linked isopropylsulfonamide and biphenyl group, was pharmacologically augmen...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00300
更新日期：2015-05-28 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：:2,4-Diaminoquinazoline antifolates with a lipophilic side chain at the 5-position, and in one case with a classical (p-aminobenzoyl)-L-glutamate side chain, were synthesized as potentially selective inhibitors of a site-directed mutant of human dihydrofolate reductase (DHFR) containing phenylalanine instead of leucine...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00005a002
更新日期：1995-03-03 00:00:00
abstract：:Several derivatives of erythro-beta-hydroxy-DL-aspartic acid (1) were prepared as a potential inhibitors of L-asparagine synthetase (ASase) from rat Novikoff hepatoma. Benzylation of 1 gave the dibenzyl ester 2 which upon coupling with carbobenzoxyglycine afforded the blocked dipeptide 3. Deblocking of 3 gave glycl-er...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00238a006
更新日期：1975-04-01 00:00:00
abstract：:Dicarba analogues of the cyclic opioid peptides H-Tyr-c[d-Cys-Gly-Phe-d(or l)-Cys]NH2 were synthesized on solid phase by substituting allylglycines for the cysteines and cyclization by ring-closing metathesis between the side chains of the allylglycine residues. Mixtures of cis and trans isomers of the resulting olefi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061294n
更新日期：2007-03-22 00:00:00
abstract：:The antineoplastic constituents of Combretum caffrum (Eckl. and Zeyh) Kuntze (Combretaceae family), a species indigenous to South Africa, have been investigated. Subsequently we isolated a series of closely related bibenzyls, stilbenes, and phenanthrenes from C. caffrum. Some of the stilbenes proved to be potent antim...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00010a011
更新日期：1995-05-12 00:00:00
abstract：:The phenolic "A-ring" of natural and synthetic estrogen receptor (ER) ligands was effectively replaced by a planar six-member ring formed through an intramolecular hydrogen bond within a salicylaldoxime. Thus, oxime 1, a structural analogue of a triarylethylene estrogen, showed a significant binding affinity for the E...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010948j
更新日期：2001-11-22 00:00:00
abstract：:Orally bioavailable SERDs may offer greater systemic drug exposure, improved clinical efficacy, and more durable treatment outcome for patients with ER-positive endocrine-resistant breast cancer. We report the design and synthesis of a boronic acid modified fulvestrant (5, ZB716), which binds to ERα competitively (IC5...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00753
更新日期：2016-09-08 00:00:00
abstract：:The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC(50) = 0.15 μM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antid...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2015952
更新日期：2012-04-12 00:00:00
abstract：:Factors influencing dose potency of 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) analogues in L1210 assays have been investigated by multiple regression analysis. The dependent variable was D40, the dose to provide 40% life extension in L1210 tests. Independent variables examined were chromatographic Rm val...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00137a009
更新日期：1981-05-01 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
abstract：:The bromodomain and extra-terminal (BET) family proteins have recently emerged as promising drug targets for cancer therapy. In this study, identification of an 8-methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one fragment (47) as a new binder to the BET bromodomains and the subsequent incorporation of fragment 47 to the scaffold...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01784
更新日期：2020-04-23 00:00:00
abstract：:Multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. P-glycoprotein (P-gp), a promiscuous drug efflux pump, has been extensively studied for its association with MDR due to overexpression in cancer cells. Several P-gp inhibitors or modulators have been investigated in clinical trials in hope ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.7b01457
更新日期：2018-06-28 00:00:00
abstract：:[4-Phenylalanine]oxytocin was prepared from Z-Cys(Bzl)-Tyr(Bzl)-Ile-Phe-Asn-Cys(Bzl)-Pro-Leu-Gly-NG2 (4) by deprotection with Na in NH3 followed by cyclization of the resulting disulfhydryl compound with ICH2CH2I. The protected peptide 4 was prepared from Boc-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 by the stepwise solution metho...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00244a014
更新日期：1975-10-01 00:00:00
abstract：:The kinome-wide virtual profiling of small molecules with high-dimensional structure-activity data is a challenging task in drug discovery. Here, we present a virtual profiling model against a panel of 391 kinases based on large-scale bioactivity data and the multitask deep neural network algorithm. The obtained model...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00855
更新日期：2020-08-27 00:00:00
abstract：:Various semicarbazones derived from aryl aldehydes, phenylalkyl aldehydes, and phenylalkyl ketones as well as some related compounds were evaluated for anticonvulsant activity. Most of the compounds displayed anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00068a001
更新日期：1993-08-06 00:00:00
abstract：:Acyclic nucleosides 1-[[2-hydroxy-1-(hydroxymethyl)ethoxy] methyl]-5-benzyluracil (DHPBU) (1) and 1-[[2-hydroxy-1-(aminomethyl)ethoxy]methyl]-5-benzyluracil (AHPBU) (2) have been synthesized by direct coupling of bis(trimethylsilyl)-5-benzyluracil with the corresponding chloromethyl ether, followed by removal of the b...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00145a023
更新日期：1985-07-01 00:00:00
abstract：:Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) have been used for the first time to study the interaction of human alpha-thrombin with methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carbox ylate (LY806303; 1), a potent and selective inhibitor whose mechanism of ac...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00068a012
更新日期：1993-08-06 00:00:00
abstract：:The F9/Yde/Fml pilus, tipped with the FmlH adhesin, has been shown to provide uropathogenic Escherichia coli (UPEC) a fitness advantage in urinary tract infections (UTIs). Here, we used X-ray structure guided design to optimize our previously described ortho-biphenyl Gal and GalNAc FmlH antagonists such as compound 1 ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01561
更新日期：2019-01-24 00:00:00
abstract：:Novel, lipophilic cycloSal triesters 4a-c and 5a-c were synthesized, respectively, from the ara- and ribo-configurated 2'-fluorinated-2', 3'-dideoxyadenosines 2 and 3. The cycloSal phosphotriesters were used as tools to study the effects of the two different sugar pucker conformations induced by two opposite configura...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm981097r
更新日期：1999-05-06 00:00:00
abstract：:The synthesis, antiarrhythmic activity, and blood hydrolysis properties of a series of mono- and bis(aminomethyl)phenylacetic acid esters related to a previously reported class Ic antiarrhythmic agent (ACC-9358) are described. Of the various oxa-, aza-, thia-, and carbacyclic esters initially prepared in the bis(pyrro...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00069a007
更新日期：1993-08-20 00:00:00
abstract：:Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest in less planar bioactive compounds has given rise to the development of synthetic methodologies for the preparation of spirocyclic scaffolds. In this Perspective, we summarize the diverse synthetic routes to o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01473
更新日期：2021-01-14 00:00:00
abstract：:Substituted 6-anilinouracils were found to be potent inhibitors of the replication-specific enzyme, DNA polymerase III, from Bacillus subtilis. Inhibition potency was maximized by inclusion of small alkyl groups or halogens in the meta and para positions of the phenyl ring; polar substituents decreased activity consi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00175a007
更新日期：1980-01-01 00:00:00
abstract：:A series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines were synthesized and tested for their ability to inhibit the binding of [3H]diazepam to rat brain receptors in vitro. Compounds bearing a phenyl, 4-methoxyphenyl, or methyl group at position 3 and a dialkylamino group at position 6 showed the highest affinit...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00147a034
更新日期：1985-09-01 00:00:00
abstract：:The N-arginyl derivative of methionine-enkephalin (fragment 60-65 of beta-lipotropin) has been shown to be equiactive with the parent pentapeptide, despite the fact that the tyrosine amino group in this compound has been neutralized by the formation of an amide linkage. A series of N-(amino acid) derivatives of (-)-5,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00143a007
更新日期：1981-11-01 00:00:00
abstract：:Compstatin peptides are complement inhibitors that bind and inhibit cleavage of complement C3. Peptide binding is enhanced by hydrophobic interactions; however, poor solubility promotes aggregation in aqueous environments. We have designed new compstatin peptides derived from the W4A9 sequence (Ac-ICVWQDWGAHRCT-NH2, c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501345y
更新日期：2015-01-22 00:00:00
abstract：:Conformational analysis using molecular mechanics calculations (MM2(87)) has been performed for four different types of benzamides which display high affinity for the dopamine D-2 receptor. In order to elucidate the conformation of the receptor-bound molecules, a previously described dopamine D-2 receptor-interaction ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00091a002
更新日期：1992-06-26 00:00:00
abstract：:We disclose the design of a novel series of cyanoguanidines that are potent (IC(50) approximately 10-100 nM) and selective (> or = 100-fold) P2X(7) receptor antagonists against the other P2 receptor subtypes such as the P2Y(2), P2X(4), and P2X(3). We also found that these P2X(7) antagonists effectively reduced nocicep...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8015848
更新日期：2009-05-28 00:00:00
