Abstract:
:The inhibitory activity of 1058 inhibitors of the title enzymes has been formulated in 13 equations correlating chemical structure with inhibitory potency. Two types of regions in enzymes have been defined by means of pi and molar refractivity constants. The use of indicator variables has been extensively developed to suggest special enzyme-ligand interactions. Several examples are given of the use of correlation equations in comparing structural features of different systems.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Yoshimoto M,Hansch Cdoi
10.1021/jm00223a015keywords:
subject
Has Abstractpub_date
1976-01-01 00:00:00pages
71-98issue
1eissn
0022-2623issn
1520-4804journal_volume
19pub_type
杂志文章abstract::This work reports on the synthesis, characterization, and in vitro cytotoxic activity of some new platinum(II), palladium(II), and gold(III) derivatives of methylsarcosinedithiocarbamate and its S-methyl ester, to study their behavior as potential antitumor agents. The biological activity of these compounds, as determ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm049191x
更新日期:2005-03-10 00:00:00
abstract::8-β-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in the treatment of STZ-induced diabetic rats, producing normalization of fasting hyperglycemia and amelioration of excessive postprandial glucose excursions and and increasing β-cell ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm501069h
更新日期:2014-11-26 00:00:00
abstract::Two new peptides, tailored after Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (TRI), namely, Ac-Thr-D-Trp(CHO)-Phe-NMe alpha MeBzl (TRA) and Ac-Thr-D-Trp(CHO)-Oic-NMeBzl (TOI), in which Phe is replaced by (3aS, 7aS)-octahydroindole-2-carboxylic acid, proved more potent and selective NK1 antagonists. The conformational properties of a...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm960213s
更新日期:1997-02-14 00:00:00
abstract::A new class of substituted 1-phenyl-3-piperazinyl-2-propanones with antimuscarinic activity is reported. As part of a structure-activity relationship study of this class, various structural modifications, particularly ones involving substitution of position 1 and the terminal piperazine nitrogen, were investigated. Th...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00057a010
更新日期:1993-03-05 00:00:00
abstract::Mercapto derivatives of palmitic acid are capable of binding 99mTc. Based on the hypothesis that 99mTc-labeled palmitic acid derivatives would behave biologically like palmitic acid and thus could be used as myocardial imaging agents, three mercaptopalmitic acid derivatives have been prepared. The synthesis of 2-merca...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00191a024
更新日期:1979-05-01 00:00:00
abstract::Twenty N- and/or C-modified Dmt-Tic analogues yielded similar K(i) values with either [(3)H]DPDPE (delta(1) agonist) or [(3)H]N, N(Me)(2)-Dmt-Tic-OH (delta antagonist). N-Methylation enhanced delta antagonism while N-piperidine-1-yl, N-pyrrolidine-1-yl, and N-pyrrole-1-yl were detrimental. Dmt-Tic-X (X = -NHNH(2), -NH...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm990165m
更新日期:1999-12-02 00:00:00
abstract::Treatment with HIV-1 protease inhibitors, a component of highly active antiretroviral therapy (HAART), often results in viral resistance. Structural and biochemical characterization of a 6X protease mutant arising from in vitro selection with compound 1, a C 2-symmetric diol protease inhibitor, has been previously des...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm800149m
更新日期:2008-10-23 00:00:00
abstract::The endogenous peptides somatostatin (SRIF) and substance P comprise very different structures. Although both bind G-protein-coupled receptors, the SRIF receptors (SSTR 1-5) recognize SRIF and related peptides which retain its beta-turn such as the potent cyclic hexapeptide SRIF agonist L-363,301 (6a), but not substan...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm960281e
更新日期:1996-06-21 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::Four 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepines were prepared and evaluated as central nervous system agents. All were active psychotropic agents as determined by animal screening tests. The most interesting compound, 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine, showed dual activity as an ant...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00178a020
更新日期:1980-04-01 00:00:00
abstract::Inhibitors of human methionine aminopeptidase type 2 (hMetAP2) are of interest as potential treatments for cancer. A new class of small molecule reversible inhibitors of hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound 24, a potent inhibitor of cobalt-activated hMetAP2, also inhibits human an...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm050408c
更新日期:2005-09-08 00:00:00
abstract::Our previous reports have highlighted the first-generation leukotriene B4 (LTB4) receptor antagonist SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]3,4- dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid) which has potent oral, topical, and intracolonic activity in various animal models of inflammation. Ex...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00006a002
更新日期:1995-03-17 00:00:00
abstract::A variety of N-(phenylsulfonyl)-N-phenylglycines 5, N-(phenylsulfonyl)-2-phenylglycines 6, and N-(phenylsulfonyl)anthranilic acids 7 were prepared as analogues of the N-(phenylsulfonyl)glycine 1 aldose reductase inhibitors. In the rat lens assay, several derivatives of 5 display greater inhibitory activity than the co...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00121a027
更新日期:1989-01-01 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::The enantiomers of the leukotriene D4 antagonist 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid (L-660,711)(MK-571) have been prepared, their absolute stereochemistry has been assigned as S for (+)-1 and R for (-)-1 by X-ray analysis of a synthetic...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00172a025
更新日期:1990-10-01 00:00:00
abstract::Multifunctional ligands with agonist bioactivities at μ/δ opioid receptors (MOR/DOR) and antagonist bioactivity at the neurokinin-1 receptor (NK1R) have been designed and synthesized. These peptide-based ligands are anticipated to produce better biological profiles (e.g., higher analgesic effect with significantly les...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b01170
更新日期:2015-11-12 00:00:00
abstract::Sansalvamide A, a cyclic depsipeptide isolated from a marine fungus of the genus Fusarium, is composed of four hydrophobic amino acids (Phe, two Leu, Val) and one hydroxy acid ((S)-2-hydroxy-4-methylpentanoic acid; O-Leu) with five stereogenic centers all having S-stereochemistry. We have recently synthesized the corr...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm048952t
更新日期:2005-05-19 00:00:00
abstract::Conformationally restricted 2'-spironucleosides and their prodrugs were synthesized as potential anti-HCV agents. Although the replicon activity of the new agents containing pyrimidine bases was modest, the triphosphate of a 2'-oxetane cytidine analogue demonstrated potent intrinsic biochemical activity against the NS...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm401224y
更新日期:2014-03-13 00:00:00
abstract::Omapatrilat was designed as a vasopeptidase inhibitor with dual activity against the zinc metallopeptidases angiotensin-1 converting enzyme (ACE) and neprilysin (NEP). ACE has two homologous catalytic domains (nACE and cACE), which exhibit different substrate specificities. Here, we report high-resolution crystal stru...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.8b01309
更新日期:2018-11-21 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
abstract::Androgens are well-known to stimulate prostate cancer (PC) growth. Thus, blockade of androgen production in testes and adrenals by CYP17 inhibition is a promising strategy for the treatment of PC. Moreover, many PC patients suffer from glucocorticoid overproduction, and importantly mutated androgen receptors can be st...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm100317b
更新日期:2010-08-12 00:00:00
abstract::Four novel steroidal alpha-methylene delta-lactones have been synthesized and shown to be active against human nasopharyngeal carcinoma (KB) cells in culture. The syntheses involved the use of known alpha-methylenation procedures. In addition, the lactone 6 was directly methylenated by reaction with CH2O/KOH or Et2NH/...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00175a019
更新日期:1980-01-01 00:00:00
abstract::Peptide mimetics of the RGDF sequence in which Arg-Gly has been replaced with 5-(4-amidinophenyl)pentanoyl mimetic has led to a 1000-fold increase in inhibitory potency over the natural RGDF ligand. The guanidine residue of the arginine may be involved in a reinforced ionic interaction with a carboxylate of the recept...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00065a003
更新日期:1993-06-25 00:00:00
abstract::A number of cycloalkyl substituents (from C-3 to C-8) have been introduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guano...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm9911231
更新日期:2000-01-27 00:00:00
abstract::The photo "Wolff" rearrangement of readily available 2-diazoceph-3-em oxides (1) directly affords carbapen-2-ems, allowing a facile entry into a ring system previously accessible only by total synthesis, lengthly semisynthesis or fermentation. The chirality of the cephalosporin is accurately translated into the corres...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00163a048
更新日期:1990-01-01 00:00:00
abstract::SAR exploration at P1' using an anti-succinate-based macrocyclic hydroxamic acid as a template led to the identification of several bulky biphenylmethyl P1' derivatives which confer potent porcine TACE and anti-TNF-alpha cellular activities with high selectivity versus most of the MMPs screened. Our studies demonstrat...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0155502
更新日期:2001-10-11 00:00:00
abstract::Human African trypanosomiasis is causing thousands of deaths every year in the rural areas of Africa. In this manuscript we describe the optimization of a family of phtalazinone derivatives. Phosphodiesterases have emerged as attractive molecular targets for a novel treatment for a variety of neglected parasitic disea...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.9b00985
更新日期:2020-04-09 00:00:00
abstract::Starting from the structure of the novel nonpeptidic angiotensin II antagonist DuP 753, a series of more rigid analogues was prepared by replacing the biphenyl part of DuP 753 with a naphthalene ring. Five different regioisomers (compounds 6a-e) were synthesized, and receptor binding in rat smooth muscle cell preparat...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00114a021
更新日期:1991-10-01 00:00:00
abstract::Photodynamic therapy (PDT) as a rising platform of the cancer treatment method is receiving increased attention. Through systematic evaluation of halogen substitution on aza-4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPY), we have found that monoiodo-derived aza-BODIPYs provided greater efficacy than other haloge...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c00882
更新日期:2020-09-10 00:00:00
abstract::Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing lipophilic electron-donating 1'-anilino substituents are active against both the promastigote and amastigote forms of the parasite Leishmania major. A series of analogues of the known 1'-NHhexyl lead compound were prepared and evaluated agai...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm970232h
更新日期:1997-08-01 00:00:00