2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 3: Synthesis and activity of isosteric analogs.


:Structure-activity relationships and efforts to optimize the pharmacokinetic profile of isosteric analogs of 2-arylimino-5,6-dihydro-4H-1,3-thiazines as cannabinoid receptor agonists are described. Among those examined, compound 25 showed potent affinity for cannabinoid receptor 1 (CB1) and receptor 2 (CB2). This compound displayed oral bioavailability and analgesic activity.


Bioorg Med Chem Lett


Kai H,Morioka Y,Koriyama Y,Okamoto K,Hasegawa Y,Hattori M,Koike K,Chiba H,Shinohara S,Iwamoto Y,Takahashi K,Tanimoto N




Has Abstract


2008-12-15 00:00:00














  • Fluorescence detection of serum albumin with a turnover-based sensor utilizing Kemp elimination reaction.

    abstract::The Kemp elimination reaction is a well-known chemical reaction that is facilitated on a protein surface microenvironment, and in particular is highly accelerated in a unique binding pocket of serum albumin. We have designed and synthesized a fluorescently activatable coumarin derivative with a benzisoxazole scaffold ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sakamoto S,Komatsu T,Ueno T,Hanaoka K,Urano Y

    更新日期:2017-08-01 00:00:00

  • Novel HIV-1 protease inhibitors active against multiple PI-resistant viral strains: coadministration with indinavir.

    abstract::HIV-1 protease inhibitors (PI) with an N-arylpyrrole moiety in the P(3) position afforded excellent antiviral potency and substantially improved aqueous solubility over previously reported variants. The rapid in vitro clearance of these compounds in human liver microsomes prompted oral coadministration with indinavir ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kevin NJ,Duffy JL,Kirk BA,Chapman KT,Schleif WA,Olsen DB,Stahlhut M,Rutkowski CA,Kuo LC,Jin L,Lin JH,Emini EA,Tata JR

    更新日期:2003-11-17 00:00:00

  • Synthesis and anticancer evaluation of certain gamma-aryloxymethyl-alpha-methylene-gamma-phenyl-gamma-butyrolactones.

    abstract::Certain gamma-aryloxymethyl-alpha-methylene-gamma-phenyl- gamma-butyrolactones were synthesized and evaluated for their anticancer activity. These compounds demonstrated a strong growth inhibitory activity against leukemia cell lines but are relatively inactive against non-small cell lung cancers and CNS cancers. The ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Wang TC,Lee KH,Chen YL,Liou SS,Tzeng CC

    更新日期:1998-10-06 00:00:00

  • Synthesis and antiplatelet effects of an isoxazole series of glycoprotein IIb/IIIa antagonists.

    abstract::Despite the excellent in vitro potency of a series of benzamide glycoprotein IIb/IIIa antagonists, which have been reported previously, poor in vivo potency in the inhibition of platelet aggregation was observed when the most potent inhibitor XU057 was dosed intravenously to dogs. In this communication, we report that...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Xue CB,Roderick J,Mousa S,Olson RE,DeGrado WF

    更新日期:1998-12-15 00:00:00

  • Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors.

    abstract::Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions we...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Glunz PW,Zhang X,Zou Y,Delucca I,Nirschl AH,Cheng X,Weigelt CA,Cheney DL,Wei A,Anumula R,Luettgen JM,Rendina AR,Harpel M,Luo G,Knabb R,Wong PC,Wexler RR,Priestley ES

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  • Identification of 2-(4-pyridyl)thienopyridinones as GSK-3β inhibitors.

    abstract::The discovery of a novel series of 2-(4-pyridyl)thienopyridinone GSK-3β inhibitors is reported. X-ray crystallography reveals its binding mode and enables rationalization of the SAR. The initial optimization of the template for improved cellular activity and predicted CNS penetration is also presented. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Gentile G,Bernasconi G,Pozzan A,Merlo G,Marzorati P,Bamborough P,Bax B,Bridges A,Brough C,Carter P,Cutler G,Neu M,Takada M

    更新日期:2011-08-15 00:00:00

  • SAR studies of 1,5-diarylpyrazole-based CCK1 receptor antagonists.

    abstract::A high throughput screening campaign revealed compound 1 as a potent antagonist of the human CCK(1) receptor. Here, we report the syntheses and SAR studies of 1,5-diarylpyrazole analogs with various structural modifications of the alkane side chain of the molecule. The difference in affinity between the two enantiomer...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Gomez L,Hack MD,McClure K,Sehon C,Huang L,Morton M,Li L,Barrett TD,Shankley N,Breitenbucher JG

    更新日期:2007-12-01 00:00:00

  • Lead optimization of a pyridine-carboxamide series as DGAT-1 inhibitors.

    abstract::The structure-activity relationship studies of a novel series of carboxylic acid derivatives of pyridine-carboxamides as DGAT-1 inhibitors is described. The optimization of the initial lead compound 6 based on in vitro and in vivo activity led to the discovery of key compounds 10j and 17h. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ting PC,Lee JF,Zorn N,Kim HM,Aslanian RG,Lin M,Smith M,Walker SS,Cook J,Van Heek M,Lachowicz J

    更新日期:2013-02-15 00:00:00

  • Antibody-mediated delivery of chimeric protein degraders which target estrogen receptor alpha (ERα).

    abstract::Chimeric molecules which effect intracellular degradation of target proteins via E3 ligase-mediated ubiquitination (e.g., PROTACs) are currently of high interest in medicinal chemistry. However, these entities are relatively large compounds that often possess molecular characteristics which may compromise oral bioavai...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Dragovich PS,Adhikari P,Blake RA,Blaquiere N,Chen J,Cheng YX,den Besten W,Han J,Hartman SJ,He J,He M,Rei Ingalla E,Kamath AV,Kleinheinz T,Lai T,Leipold DD,Li CS,Liu Q,Lu J,Lu Y,Meng F,Meng L,Ng C,Peng K,Le

    更新日期:2020-02-15 00:00:00

  • In vitro evolution of an HIV integrase binding protein from a library of C-terminal domain γS-crystallin variants.

    abstract::A protein without natural binding functions was engineered to bind HIV-1 integrase. Phage display selections applied a library of variants based on the C-terminal domain of the eye lens protein human γS-crystallin. Multiple loop regions were altered to encode libraries with ≈3.6 × 10(11) different variants. A crystall...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Moody IS,Verde SC,Overstreet CM,Edward Robinson W Jr,Weiss GA

    更新日期:2012-09-01 00:00:00

  • Syntheses of dendritic linkers containing chlorambucil residues for the preparation of antibody-multidrug immunoconjugates.

    abstract::A novel dendritic molecule with nine chlorambucil (CBL) residues on the surface and a maleimide moiety at the core terminus was synthesized using a convergent synthetic methodology. This molecule is ready for attachment to single-chain Fv antibodies (scFvs) to form antibody-multidrug immunoconjugates in an effort to s...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sun C,Wirsching P,Janda KD

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  • Synthesis of 2-methyl-1,4-naphthoquinones with higher gamma-glutamyl carboxylase activity than MK-4 both in vitro and in vivo.

    abstract::Vitamin K is the collective term for compounds that share a 2-methyl-1,4-naphthoquinone ring, but differ in the side-chain at the 3-position. We synthesized novel 2-methyl-1,4-naphthoquinone derivatives with different side chain length at the 3-position. Derivatives with C-14 and C-16 tails showed the highest in vitro...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Vermeer C,van 't Hoofd C,Knapen MHJ,Xanthoulea S

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  • Antimitotic activity of structurally simplified biaryl analogs of the anticancer agents colchicine and combretastatin A4.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: McNulty J,van den Berg S,Ma D,Tarade D,Joshi S,Church J

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kurosaki H,Yoshida H,Ito M,Koike H,Higuchi E,Goto M

    更新日期:2001-03-26 00:00:00

  • CVT-4325: a potent fatty acid oxidation inhibitor with favorable oral bioavailability.

    abstract::New inhibitors of palmitoyl-CoA oxidation are based on the introduction of nitrogen heterocycles in the 'Western Portion' of the molecule. SAR studies led to the discovery of CVT-4325 (shown), a potent FOXi (IC50=380 nM rat mitochondria) with favorable PK properties (F=93%, t(1/2)=13.6h, dog). ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Elzein E,Ibrahim P,Koltun DO,Rehder K,Shenk KD,Marquart TA,Jiang B,Li X,Natero R,Li Y,Nguyen M,Kerwar S,Chu N,Soohoo D,Hao J,Maydanik VY,Lustig DA,Zeng D,Leung K,Zablocki JA

    更新日期:2004-12-20 00:00:00

  • Recent advances in peptidomimetics antagonists targeting estrogen receptor α-coactivator interaction in cancer therapy.

    abstract::Estrogen receptor α (ERα) is a crucial target for ERα positive breast cancer treatment. Previous drug discovery efforts were focused on developing inhibitors that targeted the canonical ligand binding pockets of the ligand binding domain (LBD) of ERα. However, significant percentage of patients developed cancer relaps...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章,评审


    authors: Qin W,Xie M,Qin X,Fang Q,Yin F,Li Z

    更新日期:2018-09-15 00:00:00

  • Chroman-3-amides as potent Rho kinase inhibitors.

    abstract::Inhibition of Rho kinase (ROCK) is an attractive strategy for the treatment of diseases such as hypertension, glaucoma, and cancer. Here we report chroman-3-amides as highly potent ROCK inhibitors with sufficient kinase selectivity, excellent cell activity, good microsomal stability, and desirable pharmacokinetic prop...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Chen YT,Bannister TD,Weiser A,Griffin E,Lin L,Ruiz C,Cameron MD,Schürer S,Duckett D,Schröter T,LoGrasso P,Feng Y

    更新日期:2008-12-15 00:00:00

  • Inhibition of NaV1.6 sodium channel currents by a novel series of 1,4-disubstituted-triazole derivatives obtained via copper-catalyzed click chemistry.

    abstract::We have synthesized and evaluated a series of 1,4-disubstituted-triazole derivatives for inhibition of the rat Na(V)1.6 sodium channel isoform, an isoform thought to play an important role in controlling neuronal firing. Starting from a series of 2,4(1H)-diarylimidazoles previously published, we decided to extend the ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Rivara M,Patel MK,Amori L,Zuliani V

    更新日期:2012-10-15 00:00:00

  • Protein ligand-tethered synthetic calcium indicator for localization control and spatiotemporal calcium imaging in plant cells.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Takaoka Y,Shigenaga M,Imai M,Nukadzuka Y,Ishimaru Y,Saito K,Yokoyama R,Nishitani K,Ueda M

    更新日期:2016-01-01 00:00:00

  • Orally active esters of dihydroartemisinin: Synthesis and antimalarial activity against multidrug-resistant Plasmodium yoelii in mice.

    abstract::A series of artemisinin derived esters 7a-j, incorporating pharmacologically privileged substructure, such as biphenyl, adamantane and fluorene, have been prepared and evaluated for antimalarial activity against multidrug-resistant (MDR) Plasmodium yoelii nigeriensis by oral route. Several of these compounds were foun...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Singh C,Chaudhary S,Puri SK

    更新日期:2008-02-15 00:00:00

  • Synthesis and anti-inflammatory activity of some [4,6-(4-substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid derivatives.

    abstract::A series of [4,6-(substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid (4a-r) has been synthesized by the base catalyzed condensation of beta-aroylpropionic acid, thiourea with aldehyde in ethanol. Structures of the new compound were established on the basis of (1)H NMR and IR spectral data. Anti-...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Bahekar SS,Shinde DB

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  • Structure-activity relationship and improved hydrolytic stability of pyrazole derivatives that are allosteric inhibitors of West Nile Virus NS2B-NS3 proteinase.

    abstract::West Nile Virus (WNV) is a potentially deadly mosquito-borne flavivirus which has spread rapidly throughout the world. Currently there is no effective vaccine against flaviviral infections. We previously reported the identification of pyrazole ester derivatives as allosteric inhibitors of WNV NS2B-NS3 proteinase. Thes...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sidique S,Shiryaev SA,Ratnikov BI,Herath A,Su Y,Strongin AY,Cosford ND

    更新日期:2009-10-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Liu W,Dong W,Liao X,Yan Z,Guan B,Wang N,Liu Z

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ting PC,Lee JF,Anthes JC,Shih NY,Piwinski JJ

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Smaine FZ,Winum JY,Montero JL,Regainia Z,Vullo D,Scozzafava A,Supuran CT

    更新日期:2007-09-15 00:00:00

  • Muscarinic acetylcholine receptor binding affinities of pethidine analogs.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Lee NR,Zhang X,Darna M,Dwoskin LP,Zheng G

    更新日期:2015-11-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Swamy N,Addo JK,Ray R

    更新日期:2000-02-21 00:00:00

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ishiba H,Noguchi T,Shu K,Ohno H,Honda K,Kondoh Y,Osada H,Fujii N,Oishi S

    更新日期:2017-06-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Yamamoto M,Ikeda S,Kondo H,Inoue S

    更新日期:2002-02-11 00:00:00

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Brown A,Ellis D,Favor DA,Kirkup T,Klute W,MacKenny M,McMurray G,Stennett A

    更新日期:2013-11-15 00:00:00