当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Retinobenzoic acids. 4. Conformation of aromatic amides with retinoidal activity. Importance of trans-amide structure for the activity.

Retinobenzoic acids. 4. Conformation of aromatic amides with retinoidal activity. Importance of trans-amide structure for the activity.

Abstract：

:N-Methylation of two retinoidal amide compounds, 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benz oic acid (3, Am80) and 4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)carbonyl]amino]benzoic acid (5, Am580), resulted in the disappearance of their potent differentiation-inducing activity on human promyelocytic leukemia cell line HL-60. Studies with 1H NMR and UV spectroscopy indicated that large conformational differences exist between the active secondary amides and the inactive N-methyl amides. From a comparison of the spectroscopic results of these amides with those of stilbene derivatives, the conformations of the active amides are expected to resemble that of (E)-stilbene, whereas the inactive amides resemble the Z isomer: 3 (Am80) and 5 (Am580) have a trans-amide bond and their whole structures are elongated, while the N-methylated compounds [4 (Am90) and 6 (Am590)] have a cis-amide bond, resulting in the folding of the two benzene rings. These structures in the crystals were related to those in solution by 13C NMR spectroscopic comparison between the two phases (solid and solution).

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Kagechika H,Himi T,Kawachi E,Shudo K

doi

10.1021/jm00130a011

subject

Has Abstract

pub_date

1989-10-01 00:00:00

pages

2292-6

issue

10

eissn

0022-2623

issn

1520-4804

journal_volume

32

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Studies in antifertility agents. 11. Secosteroids. 5. Synthesis of 9,11-secoestradiol.

    abstract：:9,11-Secoestradiol (9) and 11-hydroxy-9,11-secoestradiol (12) have been synthesized starting from 17-acetoxyestradiol 3-methyl ether (1) and found to possess significant antifertility activity in rats. 3-Methoxy-9,11-seco-9-oxo-17beta-acetoxyestra-1,3,5(10)-trien-11-oic acid (2), prepared by CrO3 oxidation of 1, on h...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00241a026

    authors： Kole P,Ray S,Kamboj VP,Anand N

    更新日期：1975-07-01 00:00:00

  • N-Substituted Quinolinonyl Diketo Acid Derivatives as HIV Integrase Strand Transfer Inhibitors and Their Activity against RNase H Function of Reverse Transcriptase.

    abstract：:Bifunctional quinolinonyl DKA derivatives were first described as nonselective inhibitors of 3'-processing (3'-P) and strand transfer (ST) functions of HIV-1 integrase (IN), while 7-aminosubstituted quinolinonyl derivatives were proven IN strand transfer inhibitors (INSTIs) that also displayed activity against ribonuc...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b00159

    authors： Pescatori L,Métifiot M,Chung S,Masoaka T,Cuzzucoli Crucitti G,Messore A,Pupo G,Madia VN,Saccoliti F,Scipione L,Tortorella S,Di Leva FS,Cosconati S,Marinelli L,Novellino E,Le Grice SF,Pommier Y,Marchand C,Costi R,Di

    更新日期：2015-06-11 00:00:00

  • Rational Design, Synthesis, and Biological Evaluation of 7-Azaindole Derivatives as Potent Focused Multi-Targeted Kinase Inhibitors.

    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

    authors： Daydé-Cazals B,Fauvel B,Singer M,Feneyrolles C,Bestgen B,Gassiot F,Spenlinhauer A,Warnault P,Van Hijfte N,Borjini N,Chevé G,Yasri A

    更新日期：2016-04-28 00:00:00

  • Conformation-function relationship of vitamin D: conformational analysis predicts potential side-chain structure.

    abstract：:In previous studies, we have grouped regions in space occupied by the vitamin D side chain into four: A, G, EA, and EG. We showed that the receptor (VDR) affinity of 1alpha,25-dihydroxyvitamin D3 derivatives increases, in terms of side-chain region, in the order EG, G, A, and EA. We called this the active space group ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm970761l

    authors： Yamada S,Yamamoto K,Masuno H,Ohta M

    更新日期：1998-04-23 00:00:00

  • Synthesis and evaluation of oxodioxolenylmethyl carbamate prodrugs of pseudomycins.

    abstract：:With the aim of increasing therapeutic indexes of novel cyclic depsinonapeptide pseudomycins, we synthesized and evaluated a series of mono-, di-, and trioxodioxolenylmethyl carbamate prodrugs (2 and 4) of pseudomycin B 1 and pseudomycin C' 3. It is rather encouraging to note that several members of the newly synthesi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm000425w

    authors： Sun X,Rodriguez M,Zeckner D,Sachs B,Current W,Boyer R,Paschal J,McMillian C,Chen SH

    更新日期：2001-08-02 00:00:00

  • Synthesis and biological evaluation of 3-biphenyl-4-yl-4-phenyl-4H-1,2,4-triazoles as novel glycine transporter 1 inhibitors.

    abstract：:We describe the preparation and evaluation of a novel series of glycine transporter 1 (GlyT1) inhibitors derived from a high-throughput screening hit. The SAR studies resulted in the discovery of 3-biphenyl-4-yl-4-(2-fluorophenyl)-5-isopropyl-4H-1,2,4-triazole (6p). A pharmacokinetic study was also conducted and revea...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm101031u

    authors： Sugane T,Tobe T,Hamaguchi W,Shimada I,Maeno K,Miyata J,Suzuki T,Kimizuka T,Kohara A,Morita T,Doihara H,Saita K,Aota M,Furutani M,Shimada Y,Hamada N,Sakamoto S,Tsukamoto S

    更新日期：2011-01-13 00:00:00

  • Piperazinylquinoxalines with central serotoninmimetic activity.

    abstract：:Regioselective syntheses of substituted 2-chloroquinoxalines and derived 2-(1-piperazinyl)quinoxalines are described. Selectivity in regards to serotonin reuptake blocking and serotoninmimetic activities of the piperazinylquinoxalines is reported. In general, introduction of a 6-substituent into the piperazinylquinoxa...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00133a019

    authors： Lumma WC Jr,Hartman RD,Saari WS,Engelhardt EL,Lotti VJ,Stone CA

    更新日期：1981-01-01 00:00:00

  • Discovery and structure-activity relationships of sulfonamide ETA-selective antagonists.

    abstract：:Random screening of compounds in an ETA receptor binding assay led to the discovery of a class of benzenesulfonamide ligands. Optimization led to the development of 5-amino-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamides which were functional antagonists. Structural features which were important to activity in...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00008a013

    authors： Stein PD,Floyd DM,Bisaha S,Dickey J,Girotra RN,Gougoutas JZ,Kozlowski M,Lee VG,Liu EC,Malley MF

    更新日期：1995-04-14 00:00:00

  • Tailoring the Physicochemical Properties of Antimicrobial Peptides onto a Thiazole-Based γ-Peptide Foldamer.

    abstract：:Antimicrobial peptides (AMPs) are amphipathic molecules displaying broad-spectrum bactericidal activity, providing opportunities to develop a new generation of antibiotics. However, their use is limited either by poor metabolic stability or by high hemolytic activity. We herein addressed the potential of thiazole-base...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c00077

    authors： Bonnel C,Legrand B,Simon M,Clavié M,Masnou A,Jumas-Bilak E,Kang YK,Licznar-Fajardo P,Maillard LT,Masurier N

    更新日期：2020-09-10 00:00:00

  • Hydrophilic pyrazine dyes as exogenous fluorescent tracer agents for real-time point-of-care measurement of glomerular filtration rate.

    abstract：:Various hydrophilic pyrazine-bis(carboxamides) derived from 3,5-diamino-pyrazine-2,5-dicarboxylic acid bearing neutral and anionic groups were prepared and evaluated for use as fluorescent glomerular filtration rate (GFR) tracer agents. Among these, the dianionic d-serine pyrazine derivatives 2d and 2j, and the neutra...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200257k

    authors： Rajagopalan R,Neumann WL,Poreddy AR,Fitch RM,Freskos JN,Asmelash B,Gaston KR,Galen KP,Shieh JJ,Dorshow RB

    更新日期：2011-07-28 00:00:00

  • Stereochemical requirements for cannabinoid activity.

    abstract：:Several pairs of cannabinoid isomers were synthesized and tested for psychotropic activity in rhesus monkeys. Two regularities were observed: (a) In the absence of the other substituents, the equatorial stereochemistry of the substituent at C-1 determines activity. (b) Two groups of THC-type cannabinoids which differ ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00184a002

    authors： Mechoulam R,Lander N,Varkony TH,Kimmel I,Becker O,Ben-Zvi Z,Edery H,Porath G

    更新日期：1980-10-01 00:00:00

  • Fluorinated retinoic acids and their analogues. 1. Synthesis and Biological activity of (4-methoxy-2,3,6-trimethylphenyl)nonatetraenoic acid analogues.

    abstract：:(4-Methoyx-2,3,6-trimethylphenyl)nonatetraenoic acids, esters, and amides (analogues of retinoic acid) bearing a fluorine atom(s) or a trifluoromethyl group on the polyene side chain were synthesized. The biological activities of these compounds and of 10-, 12-, and 14-fluororetinoic acid esters were evaluated in vivo...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00195a010

    authors： Pawson BA,Chan KK,DeNoble J,Han RJ,Piermattie V,Specian AC,Srisethnil S,Trown PW,Bohoslawec O,Machlin LJ,Gabriel E

    更新日期：1979-09-01 00:00:00

  • Bispyridinium cyclophanes: novel templates for human choline kinase inhibitors.

    abstract：:The synthesis and biological activities of four novel bispyridinium cyclophanes as choline kinase (ChoK) inhibitors are presented. Their synthetic methodology has been optimized according to dilution, temperature, and reaction time and provides pure bispyridinium cyclophanes in high yields very easily. One of these cy...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030792i

    authors： Conejo-García A,Campos JM,Sánchez-Martín RM,Gallo MA,Espinosa A

    更新日期：2003-08-14 00:00:00

  • Detailed analysis of scoring functions for virtual screening.

    abstract：:We present a comprehensive study of the performance of fast scoring functions for library docking using the program FlexX as the docking engine. Four scoring functions, among them two recently developed knowledge-based potentials, are evaluated on seven target proteins whose binding sites represent a wide range of siz...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0003992

    authors： Stahl M,Rarey M

    更新日期：2001-03-29 00:00:00

  • Inhibitors of human renin with C-termini derived from amides and esters of alpha-mercaptoalkanoic acids.

    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

    authors： Ashton WT,Cantone CL,Tolman RL,Greenlee WJ,Lynch RJ,Schorn TW,Strouse JF,Siegl PK

    更新日期：1992-07-24 00:00:00

  • Predicting binding modes from free energy calculations.

    abstract：:To produce reliable predictions of bioactive conformations is a major challenge in the field of structure-based inhibitor design and is a requirement for accurate binding free energy predictions with structure-based methods. A series of HIV-1 reverse transcriptase inhibitors was cross-docked using a non-native crystal...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm701218j

    authors： Nervall M,Hanspers P,Carlsson J,Boukharta L,Aqvist J

    更新日期：2008-05-08 00:00:00

  • Structure-based design, synthesis, and antimicrobial activity of indazole-derived SAH/MTA nucleosidase inhibitors.

    abstract：:The structure-based design, synthesis, and biological activity of a novel indazole-containing inhibitor series for S-adenosyl homocysteine/methylthioadenosine (SAH/MTA) nucleosidase are described. Use of 5-aminoindazole as the core scaffold provided a structure-guided series of low nanomolar inhibitors with broad-spec...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0302039

    authors： Li X,Chu S,Feher VA,Khalili M,Nie Z,Margosiak S,Nikulin V,Levin J,Sprankle KG,Tedder ME,Almassy R,Appelt K,Yager KM

    更新日期：2003-12-18 00:00:00

  • Proteolytically stable cancer targeting peptides with high affinity for breast cancer cells.

    abstract：:Cancer cell targeting peptides have emerged as a highly efficient approach for selective delivery of chemotherapeutics and diagnostics to different cancer cells. However, the use of α-peptides in pharmaceutical applications is hindered by their enzymatic degradation and low bioavailability. Starting with a 10-mer α-pe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200750x

    authors： Soudy R,Gill A,Sprules T,Lavasanifar A,Kaur K

    更新日期：2011-11-10 00:00:00

  • New drug-like hydroxyphenylnaphthol steroidomimetics as potent and selective 17β-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of estrogen-dependent diseases.

    abstract：:Inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a novel and attractive approach to reduce the local levels of the active estrogen 17β-estradiol in patients with estrogen-dependent diseases like breast cancer or endometriosis. With the aim of optimizing the biological profile of 17β-HSD1 inhibitors ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm1009082

    authors： Marchais-Oberwinkler S,Wetzel M,Ziegler E,Kruchten P,Werth R,Henn C,Hartmann RW,Frotscher M

    更新日期：2011-01-27 00:00:00

  • MutT Homolog 1 (MTH1): The Silencing of a Target.

    abstract：:MTH1 is a member of the nudix phosphohydrolase superfamily of enzymes, and it is involved in nucleotide pool homeostasis. The protein exerts its scavenging action by hydrolyzing oxidized nucleotides, thus avoiding their misincorporation into replicating DNA. Recent reports have validated its inhibition as a potential ...

    journal_title：Journal of medicinal chemistry

    pub_type： 评论,杂志文章

    doi：10.1021/acs.jmedchem.6b00283

    authors： Papeo G

    更新日期：2016-03-24 00:00:00

  • Selective thromboxane synthetase inhibitors. 4. 2-(1H-imidazol-1-ylmethyl) carboxylic acids of benzo[b]furan, benzo[b]thiophene, indole, and naphthalene.

    abstract：:The preparation of a series of 2-(1H-imidazol-1-ylmethyl)-substituted carboxylic acids of benzo[b]furan, benzo-[b]thiophene, indole, and naphthalene is described. All compounds showed a similar level of activity as TxA2 synthetase inhibitors in vitro, having IC50 values between 1 and 7 X 10(-8) M. In the cases examine...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00159a013

    authors： Cross PE,Dickinson RP,Parry MJ,Randall MJ

    更新日期：1986-09-01 00:00:00

  • PABA/NO as an anticancer lead: analogue synthesis, structure revision, solution chemistry, reactivity toward glutathione, and in vitro activity.

    abstract：:PABA/NO is a diazeniumdiolate of structure Me(2)NN(O)=NOAr (where Ar is a 5-substituted-2,4-dinitrophenyl ring whose 5-substituent is N-methyl-p-aminobenzoic acid). It has shown activity against human ovarian cancer xenografts in mice rivaling that of cisplatin, but it is poorly soluble and relatively unstable in wate...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm050700k

    authors： Saavedra JE,Srinivasan A,Buzard GS,Davies KM,Waterhouse DJ,Inami K,Wilde TC,Citro ML,Cuellar M,Deschamps JR,Parrish D,Shami PJ,Findlay VJ,Townsend DM,Tew KD,Singh S,Jia L,Ji X,Keefer LK

    更新日期：2006-02-09 00:00:00

  • Potential latentiation forms of biologically active compounds based on action of leucine aminopeptidase. Dipeptide derivatives of the tricycloaliphatic alpha-amino acid, adamantanine.

    abstract：:Some glycine, leucine and phenylalanine dipeptide derivatives of the transport inhibitory, tricycloaliphatic alpha-amino acid, adamantanine (1), have been synthesized using classical methods of peptide synthesis with the aim of improving the latter's bioavailability. Although test doses of glycyladamantanine and L-leu...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00242a013

    authors： Nagasawa HT,Elberling JA,Shirota FN

    更新日期：1975-08-01 00:00:00

  • 8-Azatetracyclines: synthesis and evaluation of a novel class of tetracycline antibacterial agents.

    abstract：:A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (tet(K)) and ribosomal protection (tet(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds w...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm1015389

    authors： Clark RB,He M,Fyfe C,Lofland D,O'Brien WJ,Plamondon L,Sutcliffe JA,Xiao XY

    更新日期：2011-03-10 00:00:00

  • Medicinal chemistry of catechol O-methyltransferase (COMT) inhibitors and their therapeutic utility.

    abstract：:Catechol O-methyltransferase (COMT) is the enzyme responsible for the O-methylation of endogenous neurotransmitters and of xenobiotic substances and hormones incorporating catecholic structures. COMT is a druggable biological target for the treatment of various central and peripheral nervous system disorders, includin...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500572b

    authors： Kiss LE,Soares-da-Silva P

    更新日期：2014-11-13 00:00:00

  • Synthesis and in vitro and in vivo functional studies of ortho-substituted phenylpiperazine and N-substituted 4-N-(o-methoxyphenyl)aminopiperidine analogues of WAY100635.

    abstract：:WAY100635 (2), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide, is a silent serotonin 5-HT(1A) antagonist, which is now widely used to study the 5-HT(1A) receptor both in vivo and in vitro. In this paper, we describe the synthesis and in vitro (5-HT(1A) affinity and pA(2) values a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm991088y

    authors： Mensonides-Harsema MM,Liao Y,Böttcher H,Bartoszyk GD,Greiner HE,Harting J,de Boer P,Wikström HV

    更新日期：2000-02-10 00:00:00

  • Selective Phenylimidazole-Based Inhibitors of the Mycobacterium tuberculosis Proteasome.

    abstract：:Proteasomes of pathogenic microbes have become attractive targets for anti-infectives. Coevolving with its human host, Mycobacterium tuberculosis (Mtb) has developed mechanisms to resist host-imposed nitrosative and oxidative stresses. Genetic deletion or pharmacological inhibition of the Mtb proteasome (Mtb20S) rende...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01187

    authors： Zhan W,Hsu HC,Morgan T,Ouellette T,Burns-Huang K,Hara R,Wright AG,Imaeda T,Okamoto R,Sato K,Michino M,Ramjee M,Aso K,Meinke PT,Foley M,Nathan CF,Li H,Lin G

    更新日期：2019-10-24 00:00:00

  • Synthesis and quantitative structure-activity relationship of imidazotetrazine prodrugs with activity independent of O6-methylguanine-DNA-methyltransferase, DNA mismatch repair, and p53.

    abstract：:The antitumor prodrug temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (E.C. 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilin...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm401121k

    authors： Pletsas D,Garelnabi EA,Li L,Phillips RM,Wheelhouse RT

    更新日期：2013-09-12 00:00:00

  • Orally effective acid prodrugs of the beta-lactamase inhibitor sulbactam.

    abstract：:Sulbactam (1) is a beta-lactamase inhibitor with limited oral bioavailability. Lipophilic double-ester prodrug sulbactam pivoxil (2) significantly improves the oral absorption of sulbactam, as does the mutual prodrug double ester sultamicillin (3). We have found that double-ester prodrugs of sulbactam terminating in a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00163a055

    authors： English AR,Girard D,Jasys VJ,Martingano RJ,Kellogg MS

    更新日期：1990-01-01 00:00:00

  • Structure-Based Scaffold Repurposing for G Protein-Coupled Receptors: Transformation of Adenosine Derivatives into 5HT2B/5HT2C Serotonin Receptor Antagonists.

    abstract：:Adenosine derivatives developed to activate adenosine receptors (ARs) revealed micromolar activity at serotonin 5HT2B and 5HT2C receptors (5HTRs). We explored the structure-activity relationship at 5HT2Rs and modeled receptor interactions in order to optimize affinity and simultaneously reduce AR affinity. Depending o...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01183

    authors： Tosh DK,Ciancetta A,Warnick E,Crane S,Gao ZG,Jacobson KA

    更新日期：2016-12-22 00:00:00