Abstract:
:A potent new class of inhibitors of phenylalanyl-tRNA synthetase from Escherichia coli B is described. N-Benzyl-2-phenylethylamine is a competitive inhibitor with respect to L-phenylalanine and appears to possess the structural features required for near-optimal binding. Hydrophobic substituents at the ortho position of either ring appear to be well tolerated, but substituents on both rings lead to large losses in binding. Poor noncompetitive inhibitors resllt from alkylation of the secondary nitrogen, further separation of the N-benzyl group from the nitrogen, or alkylation at the alpha position of the N-benzyl moiety. In contrast, placement of a methyl group at the 1 position of the 2-phenylethylamine moiety to give N-benzyl-D-amphetamine results in the most potent inhibitor yet described for this enzyme.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Anderson RT Jr,Santi DVdoi
10.1021/jm00233a002subject
Has Abstractpub_date
1976-11-01 00:00:00pages
1270-5issue
11eissn
0022-2623issn
1520-4804journal_volume
19pub_type
杂志文章abstract::Selective CCK-A agonist activity has been reported to induce satiety in a variety of animals, including man, and thereby suggests a therapeutic role for CCK in the management of obesity. To date, three general classes of CCK-A agonists have been reported, the full-length, sulfated hepta- and hexapeptides, a series of ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm990252e
更新日期:2000-06-15 00:00:00
abstract::New chemotherapeutics are urgently needed to combat malaria. We previously reported on a novel series of antimalarial, ethylenediamine-based inhibitors of protein farnesyltransferase (PFT). In the current study, we designed and synthesized a series of second generation inhibitors, wherein the core ethylenediamine scaf...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm800113p
更新日期:2008-09-11 00:00:00
abstract::The synthesis and the biological and pharmacological evaluation of several 14-phenylpropoxy analogues of 14-methoxymetopon are described. Most of the new compounds were nonselective and exhibited binding affinities in the subnanomolar or low nanomolar range at opioid receptors mu, kappa, delta), with 14-phenylpropoxym...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm030878b
更新日期:2003-09-11 00:00:00
abstract::The pyridine C-nucleosides 5-beta-D-ribofuranosylnicotinamide and its N-methylpyridinium derivative (1 and 2), which are isosteric and isoelectronic, respectively, to nicotinamide nucleoside were synthesized. Condensation of 3-bromo-5-lithiopyridine with 2,4:3,5-di-O-benzylidene-D-aldehydoribose (7) afforded an allo/a...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00388a030
更新日期:1987-05-01 00:00:00
abstract::Investigation of tricyclic heterocycles related to the 2-arylpyrazolo[4,3-c]quinolin-3(5H)-ones, structures with high affinity for the benzodiazepine (BZ) receptor, led to the synthesis of 2-phenyl-[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one, a compound with 4 nM binding affinity to the BZ receptor. Analogues were prep...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00105a044
更新日期:1991-01-01 00:00:00
abstract::Anthrax lethal factor (LF) is a critical virulence factor in the pathogenesis of anthrax. A structure-activity relationship (SAR) of potential lethal factor inhibitors (LFi) is presented in which the zinc-binding group (ZBG), linker, and backbone moieties for a series of hydroxypyrone-based compounds were systematical...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm8013212
更新日期:2009-02-26 00:00:00
abstract::A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC(50) of the most active compound (5da) was 15.7 nM. ABI analo...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm100884b
更新日期:2010-10-28 00:00:00
abstract::The synthesis of a series of substituted heterocyclic alkoxypropionic acids is described. They were evaluated for antiinflammatory effects in two animal models of chronic inflammation; adjuvant arthritis and type II collagen arthritis in the rat. The desired profile of biological activity was characterized by the redu...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00106a044
更新日期:1991-02-01 00:00:00
abstract::A set of 4-quinolone-3-carboxylic acids bearing different substituents on the condensed benzene ring was designed and synthesized as potential HIV-1 integrase inhibitors structurally related to elvitegravir. Some of the new compounds proved to be able to inhibit the strand transfer step of the virus integration proces...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm8003784
更新日期:2008-08-28 00:00:00
abstract::A series of 2- and 3-aminobenzanilides derived from ring-alkylated anilines were prepared and evaluated for anticonvulsant activity. These benzanilides were prepared in the course of studies designed to determine the relationship between the benzamide structure and anticonvulsant effects. The compounds were tested in ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00158a038
更新日期:1986-08-01 00:00:00
abstract::(E)-5-(2-Bromovinyl)isodideoxyuridine (BVisoDDU), synthesized on the basis of molecular modeling, is selectively active against HSV-1 (three different strains) but inactive against HSV-2. Unlike BVDU, BVisoDDU is completely resistant to cleavage by thymidine phosphorylase. BVisoDDU is also the first nucleoside analogu...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm025569k
更新日期:2002-12-05 00:00:00
abstract::Thymidylate synthase X (ThyX) represents an attractive target for tuberculosis drug discovery. Herein, we selected 16 compounds through a virtual screening approach. We solved the first X-ray crystal structure of Thermatoga maritima (Tm) ThyX in complex with a nonsubstrate analog inhibitor. Given the active site simil...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.6b00977
更新日期:2016-10-13 00:00:00
abstract::A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones were synthesized and evaluated for anticonvulsant activity in DBA/2 mice against sound-induced seizures and in rats against maximal electroshock-induced seizures. Most of the derivatives showed an anticonvulsant effect better than that of valproate, ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00121a019
更新日期:1989-01-01 00:00:00
abstract::The synthesis and structure-activity relationships of a new class of vinylcephalosporins substituted with a lactamyl residue are described. These compounds show excellent activity against enterococci and retain the broad spectrum activity of third-generation cephalosporins such as ceftriaxone. ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm950886v
更新日期:1996-04-26 00:00:00
abstract::The diphenylsulfonyl sulfonamide scaffold represented by 1 (WAY-316606) are small molecule inhibitors of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic agents for the treatment of osteoporosis or other bone-related di...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm801144h
更新日期:2009-01-08 00:00:00
abstract::HIV-1 replication has been inhibited by using a compound able to target the human cellular cofactor DEAD-box ATPase DDX3, essential for HIV-1 RNA nuclear export. This compound, identified by means of a computational protocol based on pharmacophoric modeling and molecular docking calculations, represents the first smal...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm8008844
更新日期:2008-11-13 00:00:00
abstract::Natural product rakicidin A induces cell death in TKI-resistant chronic myelogenous leukemia (CML) cells. Therefore, 14 rakicidin A analogues were synthesized via a highly efficient combinatorial strategy and were evaluated against CML cell lines. The conjugated diene moiety was found to be crucial for the anti-CML ac...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b01841
更新日期:2016-02-11 00:00:00
abstract::Several 1,2-dihydro-5-(substituted phenyl)-2(1H)-pyridinones were synthesized and evaluated for inotropic activity. 1,2-Dihydro-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2-oxo-3- pyridinecarbonitrile (5a) and the corresponding unsubstituted analogue 14a were the most potent positive inotropic agents in this series. Alth...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00389a011
更新日期:1987-06-01 00:00:00
abstract::A single pot dipolar cycloaddition reaction/Cope elimination sequence was developed to access novel 1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridine P2X7 antagonists that contain a synthetically challenging chiral center. The structure-activity relationships of the new compounds are described. Two of these compoun...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.7b01279
更新日期:2018-01-11 00:00:00
abstract::Molecular modeling methods have been used to design a novel series of conformationally constrained cyclic peptide inhibitors of human renin. Three goals were defined: enhanced inhibitory potency, high specificity for renin, and increased metabolic stability. Three cyclic compounds were synthesized with ring sizes 10, ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00397a003
更新日期:1988-02-01 00:00:00
abstract::A series of conformationally locked N-glycosides having a cis-1,2-fused pyranose-1,3-oxazoline-2-thione structure and bearing different substituents at the exocyclic sulfur has been prepared. The polyhydroxylated bicyclic system was built in only three steps by treatment of the corresponding readily available 1,2-anhy...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm3006178
更新日期:2012-08-09 00:00:00
abstract::A series of pepstatin analogues having structural variations in the P2', P1', and P2 positions have been synthesized and tested for inhibition of porcine pepsin. The standard peptide for this study was Iva-Sta-Val-Ala-Iaa. Structural variations in the P2' and P1' positions have relatively little effect on Ki; however,...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00360a022
更新日期:1983-06-01 00:00:00
abstract::1-(Tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU), which is named Ftorafur or FT-207 and is used clinically as an antitumor agent, was conveniently synthesized by condensation of the trimethylsilyl derivative of 5-fluorouracil with 2-acetoxytetrahydrofuran using NaI as a catalyst. This optically inactive Thf-FU was res...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00222a011
更新日期:1977-12-01 00:00:00
abstract::A series of N-aryl-N'-(2-chloroethyl)ureas (CEUs) and derivatives were synthesized and evaluated for antiproliferative activity against a wide panel of tumor cell lines. Systematic structure--activity relationship (SAR) studies indicated that: (i) a branched alkyl chain or a halogen at the 4-position of the phenyl rin...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0010264
更新日期:2001-03-01 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::Antivirulence strategies are now attracting interest for the inherent mechanism of action advantages. In our previous work, diapophytoene desaturase (CrtN) was identified to be an attractive and drugable target for fighting pigmented S. aureus infections. In this research, we developed a series of effective benzocyclo...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.6b00122
更新日期:2016-05-26 00:00:00
abstract::A series of substituted 4-anilinoquinazolines and related compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptor (Flt and KDR) tyrosine kinase activity. Enzyme screening indicated that a narrow structure-activity relationship (SAR) existed for the bicyclic ring system,...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm990345w
更新日期:1999-12-30 00:00:00
abstract::Development of orally available phosphodiesterase 4 (PDE4) inhibitors as anti-inflammatory drugs has been going on for decades. However, only roflumilast has received FDA approval. One key challenge has been the low therapeutic window observed in the clinic for PDE4 inhibitors, primarily due to PDE4 mediated side effe...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1021/jm500378a
更新日期:2014-07-24 00:00:00
abstract::Treatment of the sodium salt of 4-chloro-2-(methylthio)pyrrolo[2,3-d]pyrimidine (2) with (2-acetoxyethoxy)methyl bromide (3) has provided 4-chloro-2-(methylthio)-7[(2-acetoxyethoxy)methyl]pyrrolo[2,3- d]pyrimidine (4). Ammonolysis of 4 at room temperature gave 4-chloro-2-(methylthio)-7-[(2-hydroxyethoxy)methyl]pyrrolo...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00403a005
更新日期:1988-08-01 00:00:00
abstract::The cytotoxicity of oxysterols was systematically studied in tumor and normal cells. Synthetic strategies to prepare this library included oxidations at ring B and a new method to yield 6β-hemiphthalates directly from Δ(5)-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer cells, LAMA-84 cel...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm1007769
更新日期:2010-11-11 00:00:00