Abstract：
:A series of novel 3-quinolinecarboxylic acid derivatives have been prepared and their antibacterial activity evaluated. These derivatives are characterized by fluorine attached to the 6-position and substituted amino groups appended to the 1- and 7-positions. Structure-activity relationship studies indicate that antibacterial potency is greatest when the 1-substituent is methylamino and the 7-substituent is either 4-methyl-1-piperazinyl, 16, or 1-piperazinyl, 21. Derivatives 16 and 21, the 1-methylamino analogues of pefloxacin and norfloxacin, respectively, show comparable in vitro and in vivo antibacterial potency to these two known agents. The activity (vs. Escherichia coli Vogel) of 16 (amifloxacin) is the following: in vitro MIC (microgram/mL) = 0.25; in vivo (mice) PD50 (mg/kg) = 1.0 (po), 0.6 (sc).
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Wentland MP,Bailey DM,Cornett JB,Dobson RA,Powles RG,Wagner RBdoi
10.1021/jm00375a003subject
Has Abstractpub_date
1984-09-01 00:00:00pages
1103-8issue
9eissn
0022-2623issn
1520-4804journal_volume
27pub_type
杂志文章abstract：:New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cycl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00093a009
更新日期：1992-07-24 00:00:00
abstract：:Conjugates of curcumin to two differently sized poly(ethylene glycol) molecules were synthesized in an attempt to overcome the low aqueous solubility of this natural product with cytotoxic activity against some human cancer cell lines. The soluble conjugates exhibited enhanced cytotoxicity as compared to that of the p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm700988f
更新日期：2007-11-29 00:00:00
abstract：:Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-targeted kinase inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tum...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00087
更新日期：2016-04-28 00:00:00
abstract：:Combretastatin A-4 (CA-4) in phosphate and serine pro-drug forms is under phase II clinical trials. With our interest of discovering CA-4 inspired new chemical entities, a novel series of 4,5-diaryl-2-aminoimidazole analogues of the compound was designed and synthesized by an efficient and diversity feasible route inv...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00101
更新日期：2016-04-14 00:00:00
abstract：:Nonpeptidic chiral macrocycles were designed on the basis of an analogue of suberoylanilide hydroxamic acid (2) (SAHA, vorinostat) and evaluated against 11 histone deacetylase (HDAC) isoforms. The identification of critical amino acid residues highly conserved in the cap region of HDACs guided the design of the subero...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm101092u
更新日期：2010-12-09 00:00:00
abstract：:The immunoproteasome (iP), an inducible proteasome variant harboring three immunosubunits, low molecular mass polypeptide-2 (LMP2), multicatalytic endopeptidase complex subunit-1, and low molecular mass polypeptide-7 (LMP7), is involved in multiple facets of inflammatory responses. We recently reported that YU102, a d...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00416
更新日期：2020-04-09 00:00:00
abstract：:A number of 6-sulfenamide, 6-sulfinamide, and 6-sulfonamide derivatives of 2-aminopurine and certain related purine ribonucleosides have been synthesized and evaluated for antileukemic activity in mice. Amination of 6-mercaptopurine ribonucleoside (7a) and 6-thioguanosine (7b) with chloramine solution gave 9-beta-D-ri...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00163a020
更新日期：1990-01-01 00:00:00
abstract：:Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While promising efficacy was observed in vivo, this compound showed effects on depolarization of Purkinje fibers in an in vitro assay and CV hypotension in vivo. Guided by an X...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0701019
更新日期：2007-06-28 00:00:00
abstract：:In this paper we report the systematic search for new, potent, and selective DPP II inhibitors. A study of the structure-activity relationship was conducted starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of the P(1) and P(2) building blocks led to the discovery of some very potent DPP II ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0308803
更新日期：2003-11-06 00:00:00
abstract：:The synthesis and in vitro and in vivo antibreast and antiprostate cancers activities of novel C-4 heteroaryl 13-cis-retinamides that modulate Mnk-eIF4E and AR signaling are discussed. Modifications of the C-4 heteroaryl substituents reveal that the 1H-imidazole is essential for high anticancer activity. The most pote...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501792c
更新日期：2015-02-26 00:00:00
abstract：:3-Phenylpiperidines (PPEs) have been thoroughly investigated in view of their interesting dopaminergic activity, and the N-n-propyl substitution has been suggested as the most effective among several PPEs differently substituted on the phenyl ring. In previous studies, we found that the dimethyl substitution on the ph...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9708700
更新日期：1998-12-03 00:00:00
abstract：:A series of 10-ketomorphinan analogues were synthesized, and their binding affinity at all three opioid receptors was investigated. In most cases, high affinity at micro and kappa receptors, and lower affinity at delta receptor was observed, resulting in good selectivity for micro and kappa receptors. A wide range of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304156
更新日期：2004-01-01 00:00:00
abstract：:The synthesis, stability, and antitumor activity of a series of water-soluble third generation platinum(II) complexes have been described. Among these complexes, [2,2-bis(aminomethyl)-1,3- propanediol-N,N'] [1,1-cyclobutanedicarboxylato(2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylate(2-)-O,O'](tetrahydro-4H-py...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00128a052
更新日期：1989-08-01 00:00:00
abstract：:Aiming to image NTS1 overexpressing tumors, the diarylpyrazole glycoconjugate 8, derived from the potent NTS1 antagonist SR142948A, was synthesized taking advantage of the palladium-catalyzed aminocarbonylation reaction. The glycoconjugate 8 displayed excellent affinity and selectivity toward NTS1. Radiosynthesis proc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401491e
更新日期：2013-11-27 00:00:00
abstract：:alpha-Fluoromethyl amino acids are enzyme-activated irreversible inhibitors of amino acid decarboxylases. Aromatic L-amino acid decarboxylase (AADC) is the enzyme responsible for the final step in the biosynthesis of both dopamine and serotonin via decarboxylation of L-dopa and 5-hydroxy-L-tryptophan, respectively. Ou...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00055a001
更新日期：1993-02-05 00:00:00
abstract：:The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants. However, evidence has emerged that MPO-derived oxidants contribute to propagation of inflammatory diseases. Because of the deleterious effects of circulating MPO, there is a great ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00285
更新日期：2017-08-10 00:00:00
abstract：:Reaction of 26 aromatic/heterocyclic sulfonamides containing amino, imino, hydrazino, or hydroxyl groups with Boc-Gly, Boc-Sar, TrS-Crt, or Boc-Gly-Gly (Sar = sarcosine, N-Me-Gly; Crt = creatine, N-amidinosarcosine; TrS = tritylsulfenyl; Boc = tert-butoxycarbonyl) in the presence of carbodiimide derivatives afforded a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9901879
更新日期：1999-09-09 00:00:00
abstract：:Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alph...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990200p
更新日期：1999-11-18 00:00:00
abstract：:HIV-1 maturation can be impaired by altering protease (PR) activity, the structure of the Gag-Pol substrate, or the molecular interactions of viral structural proteins. Here we report the synthesis and characterization of new cationic N,N-dimethyl[70]fulleropyrrolidinium iodide derivatives that inhibit more than 99% o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00994
更新日期：2016-12-22 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：:USP7 is a promising target for cancer therapy as its inhibition is expected to decrease function of oncogenes, increase tumor suppressor function, and enhance immune function. Using a structure-based drug design strategy, a new class of reversible USP7 inhibitors has been identified that is highly potent in biochemica...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00245
更新日期：2020-05-28 00:00:00
abstract：:In the past few years sirtuins have gained growing attention for their involvement in many biological processes such as cellular metabolism, apoptosis, aging and inflammation. In this contribution, we report the synthesis of a library of thioacetylated pseudopeptides that were screened against human sirtuins 1-3 to re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400438k
更新日期：2013-09-12 00:00:00
abstract：:A series of thymidylate synthetase inhibitors was synthesized, some of which were potential irreversible inhibitors. 5-Formyl-2'-deoxyuridine (9) and its dithiolane derivative 11 were prepared by condensation of the bis(trimethylsilyl) derivative of 5-formyluracil dimethyl acetal and the protected chloro sugar followe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00229a010
更新日期：1976-07-01 00:00:00
abstract：:A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00151a003
更新日期：1986-01-01 00:00:00
abstract：:2-Aminopyridine-3,5-dicarbonitrile compounds were previously identified as mimetics of dominant-negative prion protein mutants and inhibit prion replication in cultured cells. Here, we report findings from a comprehensive structure-activity relationship study of the 6-aminopyridine-3,5-dicarbonitrile scaffold. We iden...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061045z
更新日期：2007-01-11 00:00:00
abstract：:The synthesis and sigma 1 and sigma 2 binding properties of several (+)- and (-)-2-benzyl- and 2-dimethylallyl-2'-substituted-5,9 alpha-dimethyl-6,7-benzomorphans (3 and 4) are presented. In agreement with previously reported binding data for 2-substituted 5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphans (N-substituted...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00015a022
更新日期：1995-07-21 00:00:00
abstract：:The concept that polyamines may represent a universal template in the receptor recognition process is embodied in the design of new selective muscarinic ligands. Tetraamines 4-7 and 16-20 and diamine diamides 8-15 were synthesized, and their pharmacological profiles at muscarinic receptor subtypes were assessed by fun...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm981038d
更新日期：1998-10-08 00:00:00
abstract：:Many nonquaternary ammonium muscarinic agonists have been developed over the last few years, but most of the existing compounds (e.g., arecoline, RS-86, AF-30) behave as weak partial agonists at cholinergic receptors in tissues of limited receptor reserve. The current paper describes the synthesis and biochemical asse...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00397a039
更新日期：1988-02-01 00:00:00
abstract：:Alpha-galactoglycosphingolipids (alpha-GalGSLs) are unique immunostimulatory glycosphingolipids from marine sponges. Analysis of the glycosphingolipid composition of the marine sponge Axinella damicornis revealed the presence of a new alpha-GalGSL, damicoside (3a), which is the first alpha-GalGSL with a glycosylated g...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050506y
更新日期：2005-11-17 00:00:00
abstract：:An alpha-sialoside linked to acrylamide by a short connector (5-acetamido-2-O-(N-acryloyl-8-amino-5-oxaoctyl)-2,6-anhydro-3,5-d ideoxy-D-galacto-alpha-nonulopyranosonoic acid, 1) was prepared. Compound 1 formed high molecular weight copolymers with acrylamide, derivatives of acrylamide, and/or vinylpyrrolidone upon ph...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00046a027
更新日期：1994-09-30 00:00:00
