当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Correlation of anti-HIV potency with lipophilicity in a series of cosalane analogs having normal alkenyl and phosphodiester chains as cholestane replacements.

Correlation of anti-HIV potency with lipophilicity in a series of cosalane analogs having normal alkenyl and phosphodiester chains as cholestane replacements.

Abstract：

:In order to define the role of the cholestane moiety in the anti-HIV agent cosalane, a series of cosalane analogs was synthesized in which the cholestane ring system was replaced by normal alkenyl and phosphodiester substituents having varied chain lengths and lipophilicities. The compounds containing simple alkenyl substituents were found to be more potent as inhibitors of the cytopathic effect of HIV-1 in cell culture than the phosphodiesters. In addition, the potencies of the alkene congeners correlated positively with chain length and lipophilicity of the alkene. The results indicate that the cholestane moiety of cosalane functions as a lipophilic accessory appendage to escort the dichlorodisalicylmethane pharmacophore to a lipid environment.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Keyes RF,Golebiewski WM,Cushman M

doi

10.1021/jm950666h

subject

Has Abstract

pub_date

1996-01-19 00:00:00

pages

508-14

issue

2

eissn

0022-2623

issn

1520-4804

pii

jm950666h

journal_volume

39

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Designing allosteric inhibitors of factor XIa. Lessons from the interactions of sulfated pentagalloylglucopyranosides.

    abstract：:We recently introduced sulfated pentagalloylglucopyranoside (SPGG) as an allosteric inhibitor of factor XIa (FXIa) (Al-Horani et al., J. Med Chem. 2013, 56, 867-878). To better understand the SPGG-FXIa interaction, we utilized eight SPGG variants and a range of biochemical techniques. The results reveal that SPGG's su...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500311e

    authors： Al-Horani RA,Desai UR

    更新日期：2014-06-12 00:00:00

  • Evaluation of the effects of the enantiomers of reduced haloperidol, azaperol, and related 4-amino-1-arylbutanols on dopamine and sigma receptors.

    abstract：:The enantiomers of reduced haloperidol (3a), azaperol (3b), and the related compound BMY-14802 (3c) were prepared in high optical purity. The affinity of these compounds for dopamine D2 and D3 receptors, and sigma S1 and S2 sites was determined in vitro. Both enantiomers of 3a display greatly decreased affinity for D2...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00076a022

    authors： Jaen JC,Caprathe BW,Pugsley TA,Wise LD,Akunne H

    更新日期：1993-11-26 00:00:00

  • Structure-guided design of selective inhibitors of neuronal nitric oxide synthase.

    abstract：:Nitric oxide synthases (NOSs) comprise three closely related isoforms that catalyze the oxidation of L-arginine to L-citrulline and the important second messenger nitric oxide (NO). Pharmacological selective inhibition of neuronal NOS (nNOS) has the potential to be therapeutically beneficial in various neurodegenerati...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm4000984

    authors： Huang H,Li H,Martásek P,Roman LJ,Poulos TL,Silverman RB

    更新日期：2013-04-11 00:00:00

  • cycloSal-Pronucleotides of 2'-fluoro-ara- and 2'-fluoro-ribo-2',3'- dideoxyadenosine as a strategy to bypass a metabolic blockade.

    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

    authors： Meier C,Knispel T,Marquez VE,Siddiqui MA,De Clercq E,Balzarini J

    更新日期：1999-05-06 00:00:00

  • N-Benzyl/Aryl Substituted Tryptanthrin as Dual Inhibitors of Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase.

    abstract：:Indoleamine 2,3-dioxygenase 1 (IDO1), which catalyzes the initial and rate-limiting step of the kynurenine pathway of tryptophan catabolism, has emerged as a key target in cancer immunotherapy because of its role in enabling cancers to evade the immune system. Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxy...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01079

    authors： Yang D,Zhang S,Fang X,Guo L,Hu N,Guo Z,Li X,Yang S,He JC,Kuang C,Yang Q

    更新日期：2019-10-24 00:00:00

  • Search for new purine- and ribose-modified adenosine analogues as selective agonists and antagonists at adenosine receptors.

    abstract：:The binding affinities at rat A1, A2a, and A3 adenosine receptors of a wide range of derivatives of adenosine have been determined. Sites of modification include the purine moiety (1-, 3-, and 7-deaza; halo, alkyne, and amino substitutions at the 2- and 8-positions; and N6-CH2-ring, -hydrazino, and -hydroxylamino) and...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00007a014

    authors： Siddiqi SM,Jacobson KA,Esker JL,Olah ME,Ji XD,Melman N,Tiwari KN,Secrist JA 3rd,Schneller SW,Cristalli G

    更新日期：1995-03-31 00:00:00

  • Investigations of neurotrophic inhibitors of FK506 binding protein via Monte Carlo simulations.

    abstract：:The binding and solution-phase properties of six inhibitors of FK506 binding protein (FKBP12) were investigated using free energy perturbation techniques in Monte Carlo statistical mechanics simulations. These nonimmunosuppressive molecules are of current interest for their neurotrophic activity when bound to FKBP12 a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm980062o

    authors： Lamb ML,Jorgensen WL

    更新日期：1998-10-08 00:00:00

  • Vaccine Adjuvants Derivatized from Momordica Saponins I and II.

    abstract：:We have derivatized Momordica saponins (MS) I and II through their coupling at C3 glucuronic acid site with dodecylamine. The derivatives show significantly different immunostimulant activity profiles from their respective natural parent saponins. In particular, adjuvant VSA-1 (5), the derivative of MS I, potentiates ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01511

    authors： Wang P,Ding X,Kim H,Škalamera Đ,Michalek SM,Zhang P

    更新日期：2019-11-14 00:00:00

  • Discovery of corticotropin releasing factor 2 receptor selective sauvagine analogues for treatment of skeletal muscle atrophy.

    abstract：:The corticotropin release factor 2 receptor (CRF2R) has many biological activities including modulation of the stress response. Recently, we have demonstrated that CRF2R activation functions to prevent skeletal muscle wasting resulting from a variety of physiological stimuli. Thus we are interested in identifying CRF2...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049490m

    authors： Isfort RJ,Wang F,Tscheiner M,Donnelly E,Bauer MB,Lefever F,Hinkle RT,Mazur AW

    更新日期：2005-01-13 00:00:00

  • Determinants of retinoid X receptor transcriptional antagonism.

    abstract：:The synthesis and bioactivity of the retinoid X receptor (RXR) antagonist 4-[(3'-n-butyl-5',6',7',8'-tetrahydro-5',5',8',8'-tetramethyl-2'-naphthalenyl)(cyclopropylidene)methyl]benzoic acid and several heteroatom-substituted analogues are described. Ligand design was based on the scaffold of the 3'-methyl RXR-selectiv...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030651g

    authors： Cavasotto CN,Liu G,James SY,Hobbs PD,Peterson VJ,Bhattacharya AA,Kolluri SK,Zhang XK,Leid M,Abagyan R,Liddington RC,Dawson MI

    更新日期：2004-08-26 00:00:00

  • beta-Carbolines as benzodiazepine receptor ligands. 1. Synthesis and benzodiazepine receptor interaction of esters of beta-carboline-3-carboxylic acid.

    abstract：:Several esters of beta-carboline-3-carboxylic acid were synthesized and tested in respect to their affinity for the benzodiazepine receptor in bovine cortex membranes. Out of these derivatives, the methyl, ethyl, and n-propyl ester were clearly the most potent, while the n-butyl, benzyl, and 3-pyridylmethyl ester were...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00358a008

    authors： Lippke KP,Schunack WG,Wenning W,Müller WE

    更新日期：1983-04-01 00:00:00

  • Conformationally restricted congeners of hypotensive and platelet aggregation inhibitors: 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones derived from 5H-indeno[1,2-c]pyridazine.

    abstract：:A number of 7-amino and 7-acylamino substituted 4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3-ones have been synthesized as rigid congeners of hypotensive 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones and tested as antihypertensive, antithrombotic, antiulcer, and antiinflammatory agents. Unlike the previously described 7...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00161a010

    authors： Cignarella G,Barlocco D,Pinna GA,Loriga M,Tofanetti O,Germini M,Sala F

    更新日期：1986-11-01 00:00:00

  • Structure-activity relationship and multidrug resistance study of new S-trityl-L-cysteine derivatives as inhibitors of Eg5.

    abstract：:The mitotic spindle is a validated target for cancer chemotherapy. Drugs such as taxanes and vinca alkaloids specifically target microtubules and cause the mitotic spindle to collapse. However, toxicity and resistance are problems associated with these drugs. Thus, alternative approaches to inhibiting the mitotic spin...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100991m

    authors： Kaan HY,Weiss J,Menger D,Ulaganathan V,Tkocz K,Laggner C,Popowycz F,Joseph B,Kozielski F

    更新日期：2011-03-24 00:00:00

  • pH-Activatable Singlet Oxygen-Generating Boron-dipyrromethenes (BODIPYs) for Photodynamic Therapy and Bioimaging.

    abstract：:Singlet oxygen can severely damage biological tissue, which is exploited in photodynamic therapy (PDT). In PDT, the effective range is limited by the distribution of the photosensitizer (PS) and the illuminated area. However, no distinction is made between healthy and pathological tissue, which can cause undesired dam...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01873

    authors： Radunz S,Wedepohl S,Röhr M,Calderón M,Tschiche HR,Resch-Genger U

    更新日期：2020-02-27 00:00:00

  • 4-[(Alkylamino)methyl]furo[3,2-c]pyridines: a new series of selective kappa-receptor agonists.

    abstract：:The synthesis of 5-(arylacetyl)-4-[(alkylamino)methyl]furo[3,2-c] pyridines (16-23, 26, 27) and their activities as kappa-opioid receptor agonists are described. kappa-Agonist potency was particularly sensitive to the nature of the basic moiety. In particular, in the rabbit vas deferens (kappa-specific tissue), the 3-...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00040a004

    authors： Naylor A,Judd DB,Scopes DI,Hayes AG,Birch PJ

    更新日期：1994-07-08 00:00:00

  • Isothiazolopyridones: synthesis, structure, and biological activity of a new class of antibacterial agents.

    abstract：:We report the syntheses of first-generation derivatives of isothiazolopyridones and their in vitro evaluation as antibacterial agents. These compounds, containing a novel heterocyclic nucleus composed of an isothiazolone fused to a quinolizin-4-one (at C-2 and C-3 of the quinolizin-4-one), were prepared using a sequen...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm051066d

    authors： Wiles JA,Hashimoto A,Thanassi JA,Cheng J,Incarvito CD,Deshpande M,Pucci MJ,Bradbury BJ

    更新日期：2006-01-12 00:00:00

  • Synthesis of 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans as selective ligands for antiestrogen-binding sites. Effects on cell proliferation and cholesterol synthesis.

    abstract：:A series of nonsteroidal compounds, 2-(p-chlorobenzyl)-3-aryl-6- methoxybenzofurans derived from the 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones has been synthesized. The key steps in the synthesis were reactions of 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones with the arylorganometallic reagents followed b...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00086a002

    authors： Teo CC,Kon OL,Sim KY,Ng SC

    更新日期：1992-04-17 00:00:00

  • Synthesis and antitussive activity of aminotetra- (and -hexa-) hydrodibenzofurans.

    abstract：:The synthesis of a novel series of antitussive agents is described. Two series of amino-substituted tetra- and hexahydrodibenzofurans were prepared and examined for antitussive activity in the guinea pig after cough elicited by electrical stimulation of the vagus nerve. A significant level of activity, comparable with...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00212a003

    authors： Matharu SS,Rowlands DA,Taylor JB,Westwood R

    更新日期：1977-02-01 00:00:00

  • Synthesis and central nervous system depressant activity of some bicyclic amides.

    abstract：:A series of aryl bicyclic analogs of succinimide and glutarimide was prepared and evaluated for CNS depressant activity. The 8a-aryl-3,4,6,7,8,8a-hexahydro-2H-pyrrolo[2,1-beta][1,3]oxazin-6-ones possessed the best overall spectrum of activity relative to the standard agents glutethimide and phenobarbital. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00225a023

    authors： Aeberli P,Gogerty JH,Houlihan WJ,Iorio LC

    更新日期：1976-03-01 00:00:00

  • Zwitterionic 3'-O-acyl derivatives of thymidine 5'-phosphate as potential sources of intracellular thymidine 5'-phosphate in cells in culture.

    abstract：:A convenient route is described for attachment of acyl groups CO(CH2)nN(Et)2(CH2)mNH(Et)2 (n = 3, m = 2; n = 4, m = 2-4), CO(CH2)nN(Et)2(CH2)mNEt3 (n = 4, m = 2-4), or CO(CH2)4N(CH2CH2)3N(CH2)nCH3 (n = 1 or 9) to O-3' of thymidine 5'-phosphate (TMP). The compounds are prototypes of 5'-nucleotide derivatives in which t...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00155a033

    authors： Chawla RR,Freed JJ,Kappler F,Hampton A

    更新日期：1986-05-01 00:00:00

  • DNA-directed alkylating agents. 4. 4-anilinoquinoline-based minor groove directed aniline mustards.

    abstract：:A series of 4-anilinoquinoline-linked aniline mustards of widely varying mustard reactivity were prepared and evaluated for their antitumor activity. The compounds were designed as minor grove binding agents, where the aniline mustard ring is itself part of the DNA-binding ligand. While there was a general trend for c...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00109a005

    authors： Gravatt GL,Baguley BC,Wilson WR,Denny WA

    更新日期：1991-05-01 00:00:00

  • Polyacrylamides bearing pendant alpha-sialoside groups strongly inhibit agglutination of erythrocytes by influenza A virus: multivalency and steric stabilization of particulate biological systems.

    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

    authors： Lees WJ,Spaltenstein A,Kingery-Wood JE,Whitesides GM

    更新日期：1994-09-30 00:00:00

  • Development of potent glucagon-like peptide-1 agonists with high enzyme stability via introduction of multiple lactam bridges.

    abstract：:Glucagon-like peptide-1 (GLP-1) has the ability to lower the blood glucose level, and its regulatory functions make it an attractive therapeutic agent for the treatment of type 2 diabetes. However, its rapid degradation by enzymes like dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11 severely com...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100602m

    authors： Murage EN,Gao G,Bisello A,Ahn JM

    更新日期：2010-09-09 00:00:00

  • Structural Basis of Wee Kinases Functionality and Inactivation by Diverse Small Molecule Inhibitors.

    abstract：:Members of the Wee family of kinases negatively regulate the cell cycle via phosphorylation of CDK1 and are considered potential drug targets. Herein, we investigated the structure-function relationship of human Wee1, Wee2, and Myt1 (PKMYT1). Purified recombinant full-length proteins and kinase domain constructs diffe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b00996

    authors： Zhu JY,Cuellar RA,Berndt N,Lee HE,Olesen SH,Martin MP,Jensen JT,Georg GI,Schönbrunn E

    更新日期：2017-09-28 00:00:00

  • (1,3-Dialkyl-5-amino-1H-pyrazol-4-yl)arylmethanones. A series of novel central nervous system depressants.

    abstract：:A series of novel (1,3-dialkyl-5-amino-1H-pyrazol-4-yl)arylmethanones was synthesized. Pharmacological evaluation of these compounds demonstrated central nervous system depressant activity, potential anticonvulsant properties, and a low order of acute toxicity. In addition, selected compounds showed potential antipsyc...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00377a003

    authors： Butler DE,Wise LD,DeWald HA

    更新日期：1984-11-01 00:00:00

  • Biphenyl-4-carboxylic acid [2-(1H-indol-3-yl)-ethyl]-methylamide (CA224), a nonplanar analogue of fascaplysin, inhibits Cdk4 and tubulin polymerization: evaluation of in vitro and in vivo anticancer activity.

    abstract：:Biphenyl-4-carboxylic acid-[2-(1H-indol-3-yl)-ethyl]-methylamide 1 (CA224) is a nonplanar analogue of fascaplysin (2) that specifically inhibits Cdk4-cyclin D1 in vitro. Compound 1 blocks the growth of cancer cells at G0/G1 phase of the cell cycle. It also blocks the cell cycle at G2/M phase, which is explained by the...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm5014743

    authors： Mahale S,Bharate SB,Manda S,Joshi P,Bharate SS,Jenkins PR,Vishwakarma RA,Chaudhuri B

    更新日期：2014-11-26 00:00:00

  • Exploration of novel aryl binding sites of farnesyltransferase using molecular modeling and benzophenone-based farnesyltransferase inhibitors.

    abstract：:Most non-thiol CAAX-peptidomimetic farnesyltransferase inhibitors bear nitrogen-containing heterocycles in place of the terminal cysteine which are supposed to coordinate the enzyme-bound zinc. However, it has been shown that those nitrogen-containing heterocycles can be replaced by carbocyclic aromatic moieties which...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm010873j

    authors： Böhm M,Mitsch A,Wissner P,Sattler I,Schlitzer M

    更新日期：2001-09-13 00:00:00

  • 1-Methyl-1H-pyrazole-5-carboxamide Derivatives Exhibit Unexpected Acute Mammalian Toxicity.

    abstract：:A series of 1-methyl-1H-pyrazole-5-carboxamides were synthesized as potent inhibitors of the parasitic nematode of sheep, Haemonchus contortus. These compounds did not show overt cytotoxicity to a range of mammalian cell lines under standard in vitro culture conditions, had high selectivity indices, and were progresse...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c01793

    authors： Preston S,Garcia-Bustos J,Hall LG,Martin SD,Le TG,Kundu A,Ghoshal A,Nguyen NH,Jiao Y,Ruan B,Xue L,Huang F,Chang BCH,McGee SL,Wells TNC,Palmer MJ,Jabbar A,Gasser RB,Baell JB

    更新日期：2021-01-14 00:00:00

  • Novel anaplastic lymphoma kinase inhibitors targeting clinically acquired resistance.

    abstract：:The study by Huang et al. is an excellent example of rational structure-based and lipophilic-efficiency optimization of crizotinib (Xalkori) aimed at novel ALK inhibitors capable of overcoming clinically acquired resistance against the current drug in NSCLC patients. One of the most promising new compounds, 8e, displa...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500178r

    authors： Lu X,Ding K

    更新日期：2014-02-27 00:00:00

  • Benzodiazepine receptor binding activity of 6,9-disubstituted purines.

    abstract：:A series of 6,9-disubstituted purines were tested for their ability to bind to the benzodiazepine receptor in rat brain tissue. One of the most active compounds was 9-(3-aminobenzyl)-6-(dimethylamino)-9H-purine (44) with an IC50 = 0.9 microM, which was only 4.5-fold higher than the IC50 for chlordiazepoxide. Substitut...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00125a015

    authors： Kelley JL,McLean EW,Ferris RM,Howard JL

    更新日期：1989-05-01 00:00:00