Discovery of novel thiourea derivatives as potent and selective beta3-adrenergic receptor agonists.


:In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, we prepared a novel series of phenoxypropanolamine derivatives containing the thiourea moiety and evaluated their biological activities at human beta3-, beta2-, and beta1-ARs. Among these compounds, 4-nitrophenylthiourea (18i) and 3-methoxyphenylthiourea (18k) derivatives were found to exhibit potent agonistic activity at the beta3-AR, with EC(50) values of 0.10 and 0.16 microM, respectively, and no agonistic activity for either the beta1- or beta2-AR. In addition, they showed significant hypoglycemic activity in a rodent diabetic model.


Bioorg Med Chem


Maruyama T,Seki N,Onda K,Suzuki T,Kawazoe S,Hayakawa M,Matsui T,Takasu T,Ohta M




Has Abstract


2009-08-01 00:00:00














  • Novel iron complexes bearing N6-substituted adenosine derivatives: synthesis, magnetic, 57Fe Mössbauer, DFT, and in vitro cytotoxicity studies.

    abstract::Iron complexes (1-7) involving N6-benzyladenosine derivatives of the predominant composition [Fe(L(n))Cl(3)].H(2)O {where L(1)=N6-(2-fluorobenzyl)adenosine (1), L(2)=N6-(4-fluorobenzyl)adenosine (2), L(3)=N6-(2-trifluoromethylbenzyl)adenosine (3), L(4)=N6-(3-trifluoromethylbenzyl)adenosine (4), L(5)=N6-(4-trifluoromet...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Trávnícek Z,Mikulík J,Cajan M,Zboril R,Popa I

    更新日期:2008-09-15 00:00:00

  • Synthesis and in vivo evaluation of ¹⁸F-fluoroethyl GF120918 and XR9576 as positron emission tomography probes for assessing the function of drug efflux transporters.

    abstract::The purpose of this study was to synthesize two new positron emission tomography (PET) probes, N-(4-(2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl)phenyl)-9,10-dihydro-5-[¹⁸F]fluoroethoxy-9-oxo-4-acridine carboxamide ([¹⁸F]3) and quinoline-3-carboxylic acid [2-(4-{2-[7-(2-[¹⁸F]fluoroethoxy)-6-methoxy-3,4-d...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kawamura K,Yamasaki T,Konno F,Yui J,Hatori A,Yanamoto K,Wakizaka H,Ogawa M,Yoshida Y,Nengaki N,Fukumura T,Zhang MR

    更新日期:2011-01-15 00:00:00

  • Drug design and synthesis of epsilon opioid receptor agonist: 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821) inducing antinociception mediated by putative epsilon opioid

    abstract::Here we report the new drug design and synthesis of a series of 6,14-endoethenomorphinan-7-carboxamide derivatives as a putative epsilon opioid receptor agonist. One of these compounds, 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821), ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fujii H,Narita M,Mizoguchi H,Murachi M,Tanaka T,Kawai K,Tseng LF,Nagase H

    更新日期:2004-08-01 00:00:00

  • Selective angiotensin II AT(2) receptor agonists devoid of the imidazole ring system.

    abstract::A versatile parallel synthetic method to obtain three series of non-cyclic analogues of the first drug-like selective angiotensin II AT(2) receptor agonist (1) has been developed. In analogy with the transformation of losartan to valsartan it was demonstrated that a non-cyclic moiety could be employed as an imidazole ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Murugaiah AM,Wallinder C,Mahalingam AK,Wu X,Wan Y,Plouffe B,Botros M,Karlén A,Hallberg M,Gallo-Payet N,Alterman M

    更新日期:2007-11-15 00:00:00

  • Use of cytokinins as agrochemicals.

    abstract::Plant hormones cytokinins regulate various aspects of plant growth and development. For their positive effects on branching, delaying of senescence, nutrient remobilisation, flower and seed set control they became interesting substances in search for potential agrochemicals. From the 1970' of the last century exogenou...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Koprna R,De Diego N,Dundálková L,Spíchal L

    更新日期:2016-02-01 00:00:00

  • High-throughput evaluation of relative cell permeability between peptoids and peptides.

    abstract::Peptides are limited in their use as drugs due to low cell permeability and vulnerability to proteases. In contrast, peptoids are immune to enzymatic degradation and some peptoids have been shown to be relatively cell permeable. In order to facilitate future design of peptoid libraries for screening experiments, it wo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tan NC,Yu P,Kwon YU,Kodadek T

    更新日期:2008-06-01 00:00:00

  • Design, synthesis and herbicidal activity of new iron chelating motifs for HPPD-inhibitors.

    abstract::HPPD (p-hydroxyphenylpyruvate dioxygenase) is a herbicidal target that all major companies active in plant protection research have worked on intensely in the last decade. Several modern herbicides with this mode of action have been introduced recently, or are currently in development. The activity of all commercializ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Witschel M

    更新日期:2009-06-15 00:00:00

  • Synthesis and evaluation of novel modified γ-lactam prostanoids as EP4 subtype-selective agonists.

    abstract::To identify chemically and metabolically stable subtype-selective EP4 agonists, design and synthesis of a series of modified γ-lactam prostanoids has been continued. Prostanoids bearing 2-oxo-1,3-oxazolidine, 2-oxo-1,3-thiazolidine and 5-thioxopyrrolidine as a surrogate for the γ-hydroxycyclopentanone without a troubl...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kambe T,Maruyama T,Nagase T,Ogawa S,Minamoto C,Sakata K,Maruyama T,Nakai H,Toda M

    更新日期:2012-01-15 00:00:00

  • SAR studies of acidic dual γ-secretase/PPARγ modulators.

    abstract::A novel set of dual γ-secretase/PPARγ modulators characterized by a 2-benzyl hexanoic acid scaffold is presented. Synthetic efforts were focused on the variation of the substitution pattern of the central benzene. Finally, we obtained a new class of 2,5-disubstituted 2-benzylidene hexanoic acid derivatives, which act ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Hieke M,Ness J,Steri R,Greiner C,Werz O,Schubert-Zsilavecz M,Weggen S,Zettl H

    更新日期:2011-09-15 00:00:00

  • Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation.

    abstract::Protein phosphatase magnesium-dependent 1δ (PPM1D, Wip1) is a p53 inducible serine/threonine phosphatase. PPM1D is a promising target protein in cancer therapy since overexpression, missense mutations, truncating mutations, and gene amplification of PPM1D are reported in many tumors, including breast cancer and neurob...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ogasawara S,Kiyota Y,Chuman Y,Kowata A,Yoshimura F,Tanino K,Kamada R,Sakaguchi K

    更新日期:2015-10-01 00:00:00

  • Promising anti-growth effects of palladium(II) saccharinate complex of terpyridine by inducing apoptosis on transformed fibroblasts in vitro.

    abstract::Fibrosarcoma is one of the fatal cancer types and there is still not satisfactory success in its treatment despite new drugs. Therefore, the search for a new compound has been going on. It is currently known that some palladium-based anti-cancer compounds seem to have powerful apoptosis-inducing effects in cancer cell...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Coskun MD,Ari F,Oral AY,Sarimahmut M,Kutlu HM,Yilmaz VT,Ulukaya E

    更新日期:2013-08-01 00:00:00

  • Synthesis and evaluation of 18F labeled crizotinib derivative [18F]FPC as a novel PET probe for imaging c-MET-positive NSCLC tumor.

    abstract::c-MET-positive NSCLC is an important subtype accounting for about 5%~22% of lung cancer. NSCLC patients with activating c-MET are intensively sensitive to c-MET selective receptor tyrosine kinase (RTK) inhibitors, so we aimed to develop a specific PET probe targeting to c-MET-positive NSCLC for potential patients scre...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Lin Q,Zhang Y,Fu Z,Hu B,Si Z,Zhao Y,Shi H,Cheng D

    更新日期:2020-08-01 00:00:00

  • Investigation of novel pyrazole carboxamides as new apoptosis inducers on neuronal cells in Helicoverpa zea.

    abstract::Novel pyrazole carboxamides with a diarylamine-modified scaffold were modified based on the bixafen (Bayer) fungicide, which has excellent activity against Rhizoctonia solani, Rhizoctonia cerealis and Sclerotinia sclerotiorum. To discover the potential insecticidal activity of these novel pyrazole carboxamides, the pr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ren Y,Yang N,Yue Y,Jin H,Tao K,Hou T

    更新日期:2018-05-15 00:00:00

  • Design and synthesis of spirotryprostatin-inspired diketopiperazine systems from prolyl spirooxoindolethiazolidine derivatives.

    abstract::Based on the spirotryprostatin-A structure, we designed, synthesized, and evaluated different series of compounds belonging to the diketopiperazine structural class as potential cell cycle modulators and cytotoxic agents. Starting from the spirooxoindolthiazolidine scaffold, amide coupling with Pro derivatives and int...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bertamino A,Aquino C,Sala M,Simone Nd,Mattia CA,Erra L,Musella S,Iannelli P,Carotenuto A,Grieco P,Novellino E,Campiglia P,Gomez-Monterrey I

    更新日期:2010-06-15 00:00:00

  • Hippuryl-alpha-methylphenylalanine and hippuryl-alpha-methylphenyllactic acid as substrates for carboxypeptidase A. Syntheses, kinetic evaluation and mechanistic implication.

    abstract::(R)- and (S)-Hippuryl-alpha-methylphenylalanine [(R)- and (S)-Hipp-alpha-MePhe] and (S)-hippuryl-alpha-methylphenyllactic acid [(S)-Hipp-alpha-MeOPhe] were synthesized and evaluated as substrates for carboxypeptidase A (CPA) in an effort to shed further light on the catalytic mechanism of the enzyme. The rate of CPA-c...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Lee M,Kim DH

    更新日期:2000-04-01 00:00:00

  • Synthesis and in vivo evaluation of a new PET radioligand for studying sigma-2 receptors.

    abstract::The cyclohexyl piperazine 1 (1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-propyl]-piperazine) has been shown to be a potent and selective sigma-2 receptor ligand. In the present study, we prepared [(11)C]1 by O-alkylation of the phenolic precursor 2 with [(11)C]CH(3)I. [(11)C]1 was obtained in a 29...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kassiou M,Dannals RF,Liu X,Wong DF,Ravert HT,Scheffel UA

    更新日期:2005-06-01 00:00:00

  • Design, synthesis, radiolabeling and in vivo evaluation of potential positron emission tomography (PET) radioligands for brain imaging of the 5-HT₇ receptor.

    abstract::Here we describe the design, synthesis, and pharmacological evaluation of a set of compounds structurally related to the high affinity serotonin 5-HT7 receptor agonist N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (6, LP-211). Specific structural modifications were performed in order to maintain affini...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Lacivita E,Niso M,Hansen HD,Di Pilato P,Herth MM,Lehel S,Ettrup A,Montenegro L,Perrone R,Berardi F,Colabufo NA,Leopoldo M,Knudsen GM

    更新日期:2014-03-01 00:00:00

  • Synthesis and preliminary biological evaluation of radiolabeled 5-BDBD analogs as new candidate PET radioligands for P2X4 receptor.

    abstract::P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer's disease. This study reports the first design, synthesis, radiolabeling and biological evaluation of new candidate PET P2X4 receptor radioligands using 5-BDBD, a ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wang M,Gao M,Meyer JA,Peters JS,Zarrinmayeh H,Territo PR,Hutchins GD,Zheng QH

    更新日期:2017-07-15 00:00:00

  • Phenylhydrazides as inhibitors of Leishmania amazonensis arginase and antileishmanial activity.

    abstract::Searching for new substances with antileishmanial activity, we synthesized and evaluated a series of α,α-difluorohydrazide and α,α-difluoramides against Leishmania amazonensis arginase (LaArg). Four α,α-difluorohydrazide derivatives showed activity against LaArg with Ki in the range of 1.3-26 μM. The study of the kine...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Crizanto de Lima E,Castelo-Branco FS,Maquiaveli CC,Farias AB,Rennó MN,Boechat N,Silva ER

    更新日期:2019-09-01 00:00:00

  • Synthesis, state-of-the-art NMR-binding and molecular modeling study of new benzimidazole core derivatives as Pin1 inhibitors: Targeting breast cancer.

    abstract::New series of benzimidazole ring core conjugated with either dithiocarbamate or thiopropyl linkers, hybridized with different secondary amines were synthesized; 5-15 and 22-31; respectively. The new compounds were characterized by different spectroscopic techniques (1H, 13C 1D & 2D NMR, ESI-MS and IR). They were scree...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Nashaat S,Henen MA,El-Messery SM,Eisa H

    更新日期:2020-06-01 00:00:00

  • On the nature of the irreversible inhibition of histidine ammonia lyase by cysteine and dioxygen.

    abstract::The irreversible inhibition of histidine ammonia lyase by L-cysteine and dioxygen has been reexamined. After denaturation and consecutive digestion of the inhibited enzyme by trypsin and endoproteinase Glu-C, the generated chromophoric system (lambda max = 340 nm) remained intact and was isolated in an octapeptide con...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Weber K,Rétey J

    更新日期:1996-07-01 00:00:00

  • Bis-pyrene-labeled molecular beacon: a monomer-excimer switching probe for the detection of DNA base alteration.

    abstract::A new bis-pyrene-labeled oligonucleotide probe (BP-probe) has been designed for the detection of a single base mismatch in single strand (ss) DNA as a target. The sequence of BP-probe was chosen to form stem-loop structure similar to a molecular beacon (MB-probe), yielding bis-pyrene-labeled molecular beacon (BP-MB-pr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yamana K,Ohshita Y,Fukunaga Y,Nakamura M,Maruyama A

    更新日期:2008-01-01 00:00:00

  • QSAR of 1,4-benzoxazin-3-one antimicrobials and their drug design perspectives.

    abstract::Synthetic derivatives of 1,4-benzoxazin-3-ones have been shown to possess promising antimicrobial activity, whereas their natural counterparts were found lacking in this respect. In this work, quantitative structure-activity relationships (QSAR) of natural and synthetic 1,4-benzoxazin-3-ones as antimicrobials were est...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: de Bruijn WJC,Hageman JA,Araya-Cloutier C,Gruppen H,Vincken JP

    更新日期:2018-12-15 00:00:00

  • Design, synthesis and biological evaluation of inhibitors of cathepsin K on dedifferentiated chondrocytes.

    abstract::Selective proteinase inhibitors have demonstrated utility in the investigation of cartilage degeneration mechanisms and may have clinical use in the management of osteoarthritis. The cysteine protease cathepsin K (CatK) is an attractive target for arthritis therapy. Here we report the synthesis of two cathepsin K inhi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yuan XY,Ren Z,Wu Y,Bougault C,Brizuela L,Magne D,Buchet R,Mebarek S

    更新日期:2019-03-15 00:00:00

  • Structure-activity relationship of human GLO I inhibitory natural flavonoids and their growth inhibitory effects.

    abstract::Glyoxalase I (GLO I) is the rate-limiting enzyme for detoxification of methylglyoxal (MG), a side product of glycolysis, which is able to induce apoptosis. Since GLO I is known to be highly expressed in the most tumor cells and little in normal cells, specific inhibitors of this enzyme have been expected as effective ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Takasawa R,Takahashi S,Saeki K,Sunaga S,Yoshimori A,Tanuma S

    更新日期:2008-04-01 00:00:00

  • Design, synthesis and biological evaluation of cycloalkyl arylpyrimidines (CAPYs) as HIV-1 NNRTIs.

    abstract::A series of 18 cycloalkyl arylpyrimidines (CAPYs) were designed from lead compounds diarylpyrimidines (DAPYs), synthesized and evaluated for in vitro anti-HIV activity. Among them, the compound 1p displayed potent anti-HIV-1 activity against WT HIV-1 with an EC(50) value of 0.055 μM and a selectivity index (SI) >7290....

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Gu SX,Yang SQ,He QQ,Ma XD,Chen FE,Dai HF,Clercq ED,Balzarini J,Pannecouque C

    更新日期:2011-12-01 00:00:00

  • Immunostimulatory activity of CpG oligonucleotides containing non-ionic methylphosphonate linkages.

    abstract::Bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CpG-motifs in a particular sequence context activate vertebrate immune cells. We examined the significance of negatively charged internucleoside linkages in the flanking sequences 5' and 3' to the CpG-motif on immunostimulatory activity. Cell pr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yu D,Kandimalla ER,Zhao Q,Cong Y,Agrawal S

    更新日期:2001-11-01 00:00:00

  • Alkyne derivatives of isocoumarins as clickable activity-based probes for serine proteases.

    abstract::Activity-based probes (ABPs) have found increasing use in functional proteomics studies. Recently, ABPs that can be employed in combination with click chemistry gained particular attention due to their flexible application in vitro and in vivo. Moreover, there is a continuous need for new ABPs that target small subset...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Haedke U,Götz M,Baer P,Verhelst SH

    更新日期:2012-01-15 00:00:00

  • Comparison of the dark and light-induced toxicity of thio and seleno analogues of the thiopyrylium dye AA1.

    abstract::2,6-Bis(4-anilino)-4-(4-N,N-dimethylanilino)thiopyrylium chloride (AA1) and -selenopyrylium chloride (AA1-Se) and 2,6-bis(4-anilino)-4-(4-N-morpholinophenyl)thiopyrylium chloride (1) and -selenopyrylium chloride (2) were prepared via the addition of 4-N,N-dimethylanilino magnesium bromide and 4-N-morpholinophenyl magn...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Detty MR,Gibson SL,Hilf R

    更新日期:2004-05-15 00:00:00

  • Synthesis and activity evaluation of the cyclic dipeptides arylidene N-alkoxydiketopiperazines.

    abstract::A series of arylidene N-alkoxydiketopiperazines was designed and stereoselectively synthesized via oxime-ether formation and intramolecular acylation. Possible cyclization and acid-catalyzed rearrangement-fragmentation mechanisms were discussed. The crystal structure of the novel diketopiperazine further confirmed the...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tian X,Feng J,Fan SM,Zhen XL,Han JR,Liu SX

    更新日期:2016-11-01 00:00:00