3-(1-piperazinyl)-4,5-dihydro-1H-benzo[g]indazoles: high affinity ligands for the human dopamine D4 receptor with improved selectivity over ion channels.

abstract：:Our laboratory has identified several acrylamide derivatives with potent CCR3 inhibitory activity. In the present study, we evaluated the in vitro metabolic stability (CL(int); mL/min/kg) of these compounds in human liver microsomes (HLMs), and assessed the relationship between their structures and CL(int) values. Amo...

journal_title：Bioorganic & medicinal chemistry

authors： Sato I,Morihira K,Inami H,Kubota H,Morokata T,Suzuki K,Ohno K,Iura Y,Nitta A,Imaoka T,Takahashi T,Takeuchi M,Ohta M,Tsukamoto S

更新日期：2009-08-15 00:00:00

abstract：:Bromodomain-containing protein 4 (BRD4) is a key epigenetic regulator in cancer, and inhibitors targeting BRD4 exhibit great anticancer activity. By replacing the methyltriazole ring of the BRD4 inhibitor I-BET-762 with an N-methylthiazolidone heterocyclic ring, fifteen novel BRD4 inhibitors were designed and synthesi...

journal_title：Bioorganic & medicinal chemistry

authors： Li Q,Li J,Cai Y,Zou Y,Chen B,Zou F,Mo J,Han T,Guo W,Huang W,Qiu Q,Qian H

更新日期：2020-08-01 00:00:00

abstract：:Pin1 (Protein interacting with NIMA1) is a cis-trans isomerase and promotes the amide bond rotation of phosphoSer/Thr-Pro motifs in its substrates. Inhibition of Pin1 might be a novel strategy for developing anticancer agents. Herein, a series of pyrimidine derivatives were synthesized and their Pin1 inhibitory activi...

journal_title：Bioorganic & medicinal chemistry

authors： Cui G,Jin J,Chen H,Cao R,Chen X,Xu B

更新日期：2018-05-01 00:00:00

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

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

abstract：:Described here are the syntheses and preliminary biological evaluations of the first two enzymatically activated prodrugs of docetaxel (Taxotere) reported to date. These prodrugs were designed as potential candidates for selective chemotherapy in ADEPT or PMT. They are constituted of a glucuronic acid moiety, a double...

journal_title：Bioorganic & medicinal chemistry

authors： Bouvier E,Thirot S,Schmidt F,Monneret C

更新日期：2004-03-01 00:00:00

abstract：:Hypoxia is a common characteristic of many types of solid tumors and is associated with tumor propagation, malignant progression, and resistance to anti-cancer therapy. HIF-1 pathway is one of the survival pathways activated in tumor in response to hypoxia. In hypoxic condition, hypoxia-inducible factor-1α (HIF-1α) is...

journal_title：Bioorganic & medicinal chemistry

authors： Li J,Xi W,Li X,Sun H,Li Y

更新日期：2019-04-01 00:00:00

abstract：:Two new daphne diterpene esters Yuanhuajine (2) and Yuanhuagine (4), together with three known daphne diterpene esters yuanhuacine (1), yuanhuadine (3), and yuanhuapine (5), were isolated and identified from Daphne genkwa, a traditional Chinese medicine. Their structures were elucidated by a combination of UV, IR, MS ...

journal_title：Bioorganic & medicinal chemistry

authors： Zhang S,Li X,Zhang F,Yang P,Gao X,Song Q

更新日期：2006-06-01 00:00:00

abstract：:The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicrobial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N'-aryl-bishydrazones for their antibacterial and antifungal activities against panels of...

journal_title：Bioorganic & medicinal chemistry

authors： Shrestha SK,Kril LM,Green KD,Kwiatkowski S,Sviripa VM,Nickell JR,Dwoskin LP,Watt DS,Garneau-Tsodikova S

更新日期：2017-01-01 00:00:00

abstract：:The design and synthesis of novel 14- to 16-membered 11-azalides starting from 16-membered macrolides are reported. A linear 9-formylcarboxylic acid was isolated via a mobile dialdehyde previously reported. Sequential macrocyclization of the formylcarboxylic acid with amino alcohol followed by deprotection afforded co...

journal_title：Bioorganic & medicinal chemistry

authors： Miura T,Kanemoto K,Natsume S,Atsumi K,Fushimi H,Yoshida T,Ajito K

更新日期：2008-12-01 00:00:00

abstract：:The biochemistry of all living organisms uses complex, enzyme-catalyzed metabolic reaction networks. Yet, at life's origins, enzymes had not yet evolved. Therefore, it has been postulated that non-enzymatic metabolic pathways predated their enzymatic counterparts. In this account article, we describe our recent work t...

journal_title：Bioorganic & medicinal chemistry

authors： Muchowska KB,Chevallot-Beroux E,Moran J

更新日期：2019-06-15 00:00:00

abstract：:The preparation of novel 5-aryl-2-thio-1,3,4-oxadiazoles 4a-41 and the computer-aided study of their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) are reported. The average accuracy of the electronic-topological method and neural network methods applied to the activity predict...

journal_title：Bioorganic & medicinal chemistry

authors： Macaev F,Rusu G,Pogrebnoi S,Gudima A,Stingaci E,Vlad L,Shvets N,Kandemirli F,Dimoglo A,Reynolds R

更新日期：2005-08-15 00:00:00

abstract：:The hepatitis C virus (HCV) NS3/4A protease that plays an important role in the viral life cycle has been proven to be an excellent target for the discovery of anti-HCV drugs. Enlightened by some P2-triazole and amide compounds, which had been found as HCV NS3 protease inhibitors, we designed and synthesized a series ...

journal_title：Bioorganic & medicinal chemistry

authors： Shi F,Zhang Y,Xu W

更新日期：2015-09-01 00:00:00

abstract：:The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compo...

journal_title：Bioorganic & medicinal chemistry

authors： Fortuna CG,Berardozzi R,Bonaccorso C,Caltabiano G,Di Bari L,Goracci L,Guarcello A,Pace A,Palumbo Piccionello A,Pescitelli G,Pierro P,Lonati E,Bulbarelli A,Cocuzza CE,Musumarra G,Musumeci R

更新日期：2014-12-15 00:00:00

abstract：:Luteolin, 5,7-dihydroxy-2-(3,4-dihydroxyphenyl)-4H-chromen-4-one, has been proposed and proved to be a novel dopamine transporter (DAT) activator. In order to develop this potential of luteolin, a series of novel luteolin derivatives were designed, synthesized, and evaluated for their DAT agonistic activities, utilizi...

journal_title：Bioorganic & medicinal chemistry

authors： Zhang J,Liu X,Lei X,Wang L,Guo L,Zhao G,Lin G

更新日期：2010-11-15 00:00:00

abstract：:A quantitative structure-activity relationship (QSAR) study has been made on two different series of tetrahydropyrimidinones acting as HIV-1 protease inhibitors. A structural parameter, the first order valence molecular connectivity index ((1)chi(v)), has been used to account for the variation in the activity. The pro...

journal_title：Bioorganic & medicinal chemistry

authors： Gayathri P,Pande V,Sivakumar R,Gupta SP

更新日期：2001-11-01 00:00:00

abstract：:Several analogues of cirazoline (2), a selective alpha1-adrenoreceptor agonist, were prepared and their pharmacological profiles studied. Although at the alpha1-adrenoreceptor all the compounds displayed a significant agonist activity, at the alpha2-adrenoreceptor they showed either agonist or antagonist activity depe...

journal_title：Bioorganic & medicinal chemistry

authors： Pigini M,Quaglia W,Gentili F,Marucci G,Cantalamessa F,Franchini S,Sorbi C,Brasili L

更新日期：2000-05-01 00:00:00

abstract：:Colorectal cancer is the third and fourth leading cause of cancer in males and females, respectively. Flavonoids, including chalcones, are secondary metabolites in plants that exhibit diverse biological activities, including antibacterial, antimalarial, and antitumor activities. In order to find potent and novel chemo...

journal_title：Bioorganic & medicinal chemistry

authors： Shin SY,Yoon H,Hwang D,Ahn S,Kim DW,Koh D,Lee YH,Lim Y

更新日期：2013-11-15 00:00:00

abstract：:The bacterial strain Rhodococcus butanica (ATCC 21197), which exhibits nitrilase and nitrile hydratase/amidase activities, catalyses the enantioselective hydrolysis of racemic naproxen nitrile (R/S)-1 to furnish a moderate enantiomeric excess of (S)-naproxen (S)-3. Racemic naproxen amide (R/S)-2 is not a good substrat...

journal_title：Bioorganic & medicinal chemistry

authors： Effenberger F,Böhme J

更新日期：1994-07-01 00:00:00

abstract：NAD(P)H:quinone oxidoreductase 1 (NQO1) is an obligate two-electron reductase and is highly expressed in many human solid cancers. Because NQO1 can be induced immediately after exposure to ionizing radiation, we aimed to develop an NQO1-targeted radiolabeled agent to establish a novel internal radiation therapy that am...

journal_title：Bioorganic & medicinal chemistry

authors： Sasaki J,Sano K,Hagimori M,Yoshikawa M,Maeda M,Mukai T

更新日期：2014-11-01 00:00:00

abstract：:Several rationally designed analogs of 3-fluoro-2-oxo-3-phenylpropionic acid were chemically synthesized, and the reactions of the hydrate form of these compounds with 4-hydroxyphenylpyruvate dioxygenase from pig liver as inhibitors were examined. Compounds 14a and 14b were found to be potent competitive inhibitors of...

journal_title：Bioorganic & medicinal chemistry

authors： Ling TS,Shiu S,Yang DY

更新日期：1999-07-01 00:00:00

abstract：:MGAT2 (monoacylglycerol acyltransferase 2) is expected to be an attractive target for the drug treatment of obesity, diabetes, and other disease. We describe our exploration and structure-activity relationship (SAR) study of 2,3-dihydro-1H-isoindole-5-sulfonamide derivatives. In this study, we identified 29 as an oral...

journal_title：Bioorganic & medicinal chemistry

authors： Busujima T,Tanaka H,Shirasaki Y,Munetomo E,Saito M,Kitano K,Minagawa T,Yoshida K,Osaki N,Sato N

更新日期：2015-09-01 00:00:00

abstract：:In order to improve the immunotherapeutical potential of H-Cys-Leu-Gly-Gly-Leu-Leu-Thr-Met-Val-OH (CLG) peptide, an Epstein-Barr virus (EBV) subdominant epitope derived from the membrane protein LMP2, we have synthesized and tested CLG analogues containing cis- and/or trans-4-aminocyclohexanecarboxylic acid (ACCA) rep...

journal_title：Bioorganic & medicinal chemistry

authors： Marastoni M,Bazzaro M,Micheletti F,Gavioli R,Tomatis R

更新日期：2002-09-01 00:00:00

abstract：:V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing...

journal_title：Bioorganic & medicinal chemistry

authors： Niculescu-Duvaz D,Niculescu-Duvaz I,Suijkerbuijk BM,Ménard D,Zambon A,Nourry A,Davies L,Manne HA,Friedlos F,Ogilvie L,Hedley D,Takle AK,Wilson DM,Pons JF,Coulter T,Kirk R,Cantarino N,Whittaker S,Marais R,Springer CJ

更新日期：2010-09-15 00:00:00

abstract：:This study describes the synthesis and radiosynthesis of eight new [18F]fluoro-inositol-based radiotracers in myo- and scyllo-inositol configuration. These radiotracers are equipped with a propyl linker bearing fluorine-18. This fluorinated arm is either on a hydroxyl group, i.e. O-alkylated inositols, or on the cyclo...

journal_title：Bioorganic & medicinal chemistry

authors： Collet C,Schmitt S,Maskali F,Clément A,Chrétien F,Karcher G,Marie PY,Poussier S,Lamandé-Langle S

更新日期：2017-10-15 00:00:00

abstract：:In order to develop structure-activity relationships and to provide access to antibacterial agents for dual action studies, a variety of aryl group-substituted 2-aryl-5-nitro-1H-indoles were synthesized and the activity of the compounds assessed as inhibitors of the NorA multidrug resistance pump in the bacterium Stap...

journal_title：Bioorganic & medicinal chemistry

authors： Samosorn S,Bremner JB,Ball A,Lewis K

更新日期：2006-02-01 00:00:00

abstract：:Local excess of nitric oxide (NO) has been implicated in beta-cell damage, thus, a possible approach to the treatment of autoimmune IDDM is the selective inhibition of inducible nitric oxide synthase (iNOS). A series of variously substituted hexahydropyridazine-1-carbothioamides, -carbothioimidic acid esters and -carb...

journal_title：Bioorganic & medicinal chemistry

authors： Morgenstern O,Wanka H,Röser I,Steveling A,Kuttler B

更新日期：2004-03-01 00:00:00

abstract：:Inhibition of receptor tyrosine kinases (RTKs) continued to be a successful approach for the treatment of many types of human cancers and many potent small molecules kinase inhibitors have been discovered the last decade. In the present study, we describe the synthesis of thienopyrimidine derivatives and their pharmac...

journal_title：Bioorganic & medicinal chemistry

authors： Ravez S,Arsenlis S,Barczyk A,Dupont A,Frédérick R,Hesse S,Kirsch G,Depreux P,Goossens L

更新日期：2015-11-15 00:00:00

abstract：:Several N-substituted quindolines were made to further evaluate the role of N-alkylation on the activity of indoloquinolines as antifungal agents. While N-5 substitution is required for these activities, N-10 alkylation alone leads to inactive products but is tolerated in the presence of N-5 alkyl groups. It was also ...

journal_title：Bioorganic & medicinal chemistry

authors： Mardenborough LG,Zhu XY,Fan P,Jacob MR,Khan SI,Walker LA,Ablordeppey SY

更新日期：2005-06-02 00:00:00

abstract：:A series of twenty-two BODIPY compounds were synthesized, containing various meso-phenyl and meso-thienyl groups, and their spectroscopic and structural properties were investigated using both experimental and computational methods. Further functionalization of the BODIPY framework via iodination at the 2,6-pyrrolic p...

journal_title：Bioorganic & medicinal chemistry

authors： Gibbs JH,Robins LT,Zhou Z,Bobadova-Parvanova P,Cottam M,McCandless GT,Fronczek FR,Vicente MG

更新日期：2013-09-15 00:00:00

abstract：:1,11-Didechloro-6-methyl-4'-O-demethyl rebeccamycin (JDC-108), a rebeccamycin analog possessing potent anti-tumor activities, was prepared via a concise one-pot strategy in good yield. The interaction between JDC-108 and human serum albumin (HSA) was studied by spectroscopic methods including fluorescence spectroscopy...

journal_title：Bioorganic & medicinal chemistry

authors： Cui F,Qin L,Zhang G,Liu X,Yao X,Lei B

更新日期：2008-08-15 00:00:00