Fancy bioisosteres: synthesis, SAR, and pharmacological investigations of novel nonaromatic dopamine D3 receptor ligands.

abstract：:The potency of a series of eight compounds structurally related with 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), a potent GABA(A) partial agonist exhibiting GABA(C) rho(1) antagonist effect (K(i)=25 microM), was determined electrophysiologically using homomeric human GABA(C) rho(1) receptors expressed in Xe...

journal_title：Bioorganic & medicinal chemistry

authors： Krehan D,Frølund B,Ebert B,Nielsen B,Krogsgaard-Larsen P,Johnston GA,Chebib M

更新日期：2003-11-17 00:00:00

abstract：:We report the kinetic properties and sulfonamide inhibition profile of an α-carbonic anhydrase (CA, EC 4.2.1.1), named CruCA4, identified in the red coral Corallium rubrum. This isoform is involved in the biomineralization process leading to the formation of a calcium carbonate skeleton. Experiments performed on the r...

journal_title：Bioorganic & medicinal chemistry

authors： Del Prete S,Vullo D,Zoccola D,Tambutté S,Capasso C,Supuran CT

更新日期：2017-07-01 00:00:00

abstract：:With the aim of developing small molecular non-peptide beta-secretase (BACE) inhibitors, Leu*Ala hydroxyethylene (HE) was investigated as a scaffold to design and synthesize a series of compounds. Taking advantage of efficient combinatorial synthesis approaches and molecular modeling, extensive structure-activity rela...

journal_title：Bioorganic & medicinal chemistry

authors： Xiao K,Li X,Li J,Ma L,Hu B,Yu H,Fu Y,Wang R,Ma Z,Qiu B,Li J,Hu D,Wang X,Shen J

更新日期：2006-07-01 00:00:00

abstract：:The activity-structure relationships (ASR) of phenolic compounds as hydroxyl-radical scavengers have mostly been studied and discussed with regard to their iron-chelating and hydrogen-donation properties in Fenton-type system, but extensive elucidation of multiple mechanisms underlying the hydroxyl radical scavenging ...

journal_title：Bioorganic & medicinal chemistry

authors： Cheng Z,Ren J,Li Y,Chang W,Chen Z

更新日期：2002-12-01 00:00:00

abstract：:Human CYP3A4 catalyzes the 10,11-epoxidation of carbamazepine (CBZ). However, the epoxide is less stable in terms of potential energy than hydroxides of the six-membered aromatic ring. To clarify the reason why CYP3A4 produces such an energetically unfavorable compound, the mechanism of epoxidation of CBZ by CYP3A4 wa...

journal_title：Bioorganic & medicinal chemistry

authors： Hata M,Tanaka Y,Kyoda N,Osakabe T,Yuki H,Ishii I,Kitada M,Neya S,Hoshino T

更新日期：2008-05-01 00:00:00

abstract：:Substituted diphenyl sulfones (10a-n) were synthesised, and the structures were confirmed by NMR, LC-MS and X-ray crystallography. Their antagonistic activities towards 5-HT₆ receptor were assessed in a cell-based functional assay. Diphenyl sulfone 10a, in spite of being the smallest and simplest known sulfonyl-contai...

journal_title：Bioorganic & medicinal chemistry

authors： Ivachtchenko A,Golovina E,Kadieva M,Mitkin O,Tkachenko S,Okun I

更新日期：2013-08-01 00:00:00

abstract：:Bovine plasma amine oxidase (BPAO) was previously shown to be irreversibly inhibited by propargylamine and 2-chloroallylamine. 1,4-Diamine versions of these two compounds are here shown to be highly potent inactivators, with IC50 values near 20 microM. Mono-N-alkylation or N,N-dialkylation greatly lowered the inactiva...

journal_title：Bioorganic & medicinal chemistry

authors： Jeon HB,Lee Y,Qiao C,Huang H,Sayre LM

更新日期：2003-10-15 00:00:00

abstract：:4-Oxalocrotonate tautomerase (4-OT) catalyzes the isomerization of 4-oxalocrotonate, 1, to 2-oxo-3E-hexenedioate, 3, using a general acid/base mechanism that involves a conserved N-terminal proline residue. The P1A and P1G mutants have been shown to catalyze this isomerization but at reduced rates. Analysis of these m...

journal_title：Bioorganic & medicinal chemistry

authors： Brik A,Dawson PE,Keinan E

更新日期：2002-12-01 00:00:00

abstract：:Two types of nonspacer- and spacer-N-linked tetravalent glycosides bearing N-acetylglucosamine (GlcNAc), N,N'-diacetylchitobiose [(GlcNAc)(2)] and N-acetyllactosamine (LacNAc) were designed and prepared as glycomimetics. The interactions of wheat germ (Triticum vulgaris) agglutinin (WGA) and coral tree (Erythrina cris...

journal_title：Bioorganic & medicinal chemistry

authors： Masaka R,Ogata M,Misawa Y,Yano M,Hashimoto C,Murata T,Kawagishi H,Usui T

更新日期：2010-01-15 00:00:00

abstract：:The synthesis of a range of 2-amido-3-hydroxypyridin-4-ones as bidentate iron(III) chelators with potential for oral administration is described. The pKa values of the ligands together with the stability constants of their iron(III) complexes have been determined. Results indicate that the introduction of an amido sub...

journal_title：Bioorganic & medicinal chemistry

authors： Liu ZD,Piyamongkol S,Liu DY,Khodr HH,Lu SL,Hider RC

更新日期：2001-03-01 00:00:00

abstract：:Bioactive compounds present in grapefruit juice are known to increase the bioavailability of certain medications by acting as potent CYP 3A4 inhibitors. An efficient technique has been developed for isolation and purification of three furocoumarins. The isolated compounds have been tested for the inhibition of human C...

journal_title：Bioorganic & medicinal chemistry

authors： Girennavar B,Poulose SM,Jayaprakasha GK,Bhat NG,Patil BS

更新日期：2006-04-15 00:00:00

abstract：:Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. A series of flavonols and their 3-methyl ether derivatives were synthesized and assessed for cytotoxicity. It was found that 3'-hydroxy-3,4'-dimethoxyflavone (flavonoid 7a) displayed strong cytotoxicity agains...

journal_title：Bioorganic & medicinal chemistry

authors： Estévez-Sarmiento F,Said M,Brouard I,León F,García C,Quintana J,Estévez F

更新日期：2017-11-01 00:00:00

abstract：:Antagonists of type 1 cannabinoid receptors (CB1) may be useful in treating diabetes, hepatic disorders, and fibrosis. Otenabant (1) is a potent and selective CB1 inverse agonist that was under investigation as an anti-obesity agent, but its development was halted once adverse effects associated with another marketed ...

journal_title：Bioorganic & medicinal chemistry

authors： Amato G,Wiethe R,Manke A,Vasukuttan V,Snyder R,Runyon S,Maitra R

更新日期：2019-08-15 00:00:00

abstract：:The acyclic chiral nucleic acid analogue, Glycol Nucleic Acid (GNA), displayed exceptional structural simplicity and atom economy while forming self-paired duplexes, using canonical Watson-Crick base pairing. We disclose here that the replacement of phosphodiester linker in GNA with somewhat rigid and shorter carbamat...

journal_title：Bioorganic & medicinal chemistry

authors： Bose T,Kumar VA

更新日期：2014-11-01 00:00:00

abstract：:The 1,2,4-triazolo[1,5-a]quinoxaline (TQX) scaffold was extensively investigated in our previously reported studies and recently, our attention was focused at position 5 of the tricyclic nucleus where different acyl and carboxylate moieties were introduced (compounds 2-15). This study produced some interesting compoun...

journal_title：Bioorganic & medicinal chemistry

authors： Catarzi D,Varano F,Poli D,Squarcialupi L,Betti M,Trincavelli L,Martini C,Dal Ben D,Thomas A,Volpini R,Colotta V

更新日期：2015-01-01 00:00:00

abstract：:Alpha7 agonists were identified via GOLD (CCDC) docking in the putative agonist binding site of an alpha7 homology model and a series of aminoalkyl benzoimidazoles was synthesised to obtain potentially brain penetrant drugs. The array was prepared starting from the reaction of ortho-fluoronitrobenzenes with a selectio...

journal_title：Bioorganic & medicinal chemistry

authors： Micco I,Nencini A,Quinn J,Bothmann H,Ghiron C,Padova A,Papini S

更新日期：2008-03-01 00:00:00

abstract：:It was determined, with a systematic mode, the carbonyl group frequency in the region of the infrared of N-[(dimethylamine)methyl] benzamides 4-substituted (set A) and their hydrochlorides (set B), that had its local anesthetical activity evaluated. The application of the Hammett equation considering the values of the...

journal_title：Bioorganic & medicinal chemistry

authors： Tavares LC,do Amaral AT

更新日期：2004-03-15 00:00:00

abstract：:The total synthesis of (+)-crocacin D has been achieved in 15 steps (9 isolated intermediates) and 14% overall yield from commercially available starting materials and using (+)-crocacin C as a key intermediate. A number of simplified analogues and their biological activities are also reported. ...

journal_title：Bioorganic & medicinal chemistry

authors： Pasqua AE,Ferrari FD,Crawford JJ,Whittingham WG,Marquez R

更新日期：2015-03-01 00:00:00

abstract：:Cancer cells reprogram their metabolism due to genetic alteration to compensate for increased energy demand and enhanced anabolism, cell proliferation, and protection from oxidative damage. Here, we assessed the cytotoxicity of three dimeric naphthoquinones against the glycolytic MCF-7 versus the oxidative MDA-453 bre...

journal_title：Bioorganic & medicinal chemistry

authors： Emadi A,Le A,Harwood CJ,Stagliano KW,Kamangar F,Ross AE,Cooper CR,Dang CV,Karp JE,Vuica-Ross M

更新日期：2011-12-01 00:00:00

abstract：:We synthesized the biotinylated chondroitin sulfate tetrasaccharides CS-CC [-3)βGalNAc6S(1-4)βGlcA(1-]2 and CS-DD [-3)βGalNAc6S(1-4)βGlcA2S(1-]2 which possess sulfate groups at O-6 of GalNAc and an additional sulfate group at O-2 of GlcA, respectively. We also analyzed interactions among CS-CC and CS-DD and the antibo...

journal_title：Bioorganic & medicinal chemistry

authors： Matsushita K,Nakata T,Takeda-Okuda N,Nadanaka S,Kitagawa H,Tamura JI

更新日期：2018-03-01 00:00:00

abstract：:The structure-activity relationship of a number of synthetic green tea polyphenol analogs involving modifications of A ring and B ring of epi-gallocatechin gallate (EGCG) as proteasome inhibitors has been examined. It was found that in B ring, a decrease in the number of OH groups led to decreased potency. Introductio...

journal_title：Bioorganic & medicinal chemistry

authors： Wan SB,Landis-Piwowar KR,Kuhn DJ,Chen D,Dou QP,Chan TH

更新日期：2005-03-15 00:00:00

abstract：:In this work, we report the solution structure, thermodynamic studies, and the pharmacological properties of a new modified thrombin binding aptamer (TBA) containing a G-LNA residue, namely d(5'-GGTTGGTGTGGTTGg-3'), where upper case and lower case letters represent DNA and LNA residues, respectively. NMR and CD spectr...

journal_title：Bioorganic & medicinal chemistry

authors： Virno A,Randazzo A,Giancola C,Bucci M,Cirino G,Mayol L

更新日期：2007-09-01 00:00:00

abstract：:An amine group was synthesized starting from an optically active bicyclo[2.2.1]heptane compound, which was then used to build the 5 atoms ring of a key 6-chloropurine intermediate. This was then reacted with ammonia and selected amines obtaining new adenine- and 6-substituted adenine conformationally constrained carbo...

journal_title：Bioorganic & medicinal chemistry

authors： Tănase CI,Drăghici C,Căproiu MT,Shova S,Mathe C,Cocu FG,Enache C,Maganu M

更新日期：2014-01-01 00:00:00

abstract：:The discovery of the first class of potent glucose-6-phosphatase catalytic site inhibitors, substituted 4,5,6,7-tetrahydrothieno[3,2-c]- and -[2,3-c]pyridines, is described. Optimisation of this series involved solution phase combinatorial synthesis and very potent compounds were prepared with IC50 values down to 140 ...

journal_title：Bioorganic & medicinal chemistry

authors： Madsen P,Lundbeck JM,Jakobsen P,Varming AR,Westergaard N

更新日期：2000-09-01 00:00:00

abstract：:The scaffold of 3,5-diaryl-1H-pyrazole was selected as a molecular template to synthesize novel growth-inhibitory agents in the present study. Our findings suggested that analogs bearing electron-withdrawing groups on one ring while electron-donating groups on another reveal significant activities. In particular, 26 b...

journal_title：Bioorganic & medicinal chemistry

authors： Shaw AY,Liau HH,Lu PJ,Yang CN,Lee CH,Chen JY,Xu Z,Flynn G

更新日期：2010-05-01 00:00:00

abstract：:The human skin is constantly exposed to external factors that affect its integrity, UV radiation being one of the main stress factors. The repeated exposure to this radiation leads to increased production of Reactive Oxygen Species (ROS) which activate a series of processes involved in photoaging. Excessive UV exposur...

journal_title：Bioorganic & medicinal chemistry

authors： Rosa GP,Palmeira A,Resende DISP,Almeida IF,Kane-Pagès A,Barreto MC,Sousa E,Pinto MMM

更新日期：2021-01-01 00:00:00

abstract：:The synthesis of a series of 2,4-disubstituted morpholines is described and their affinities at human dopamine receptors reported. The orally bioavailable 7-azaindole compound 11 has nanomolar affinity at the hD4 receptor with > 1000-fold selectivity over the hD2 receptor. ...

journal_title：Bioorganic & medicinal chemistry

authors： Showell GA,Emms F,Marwood R,O'Connor D,Patel S,Leeson PD

更新日期：1998-01-01 00:00:00

abstract：:Protein-protein interfaces are prominent in many therapeutically important targets. Using small organic molecules to disrupt protein-protein interactions is a current challenge in chemical biology. An important example of protein-protein interactions is provided by the Myc protein, which is frequently deregulated in h...

journal_title：Bioorganic & medicinal chemistry

authors： Xu Y,Shi J,Yamamoto N,Moss JA,Vogt PK,Janda KD

更新日期：2006-04-15 00:00:00

abstract：:A series of catechol diazo dyes were synthesized and tested as substrates for the enzyme catechol-O-methyltransferase (COMT) with the aim of developing a sensitive HPLC assay method using visible wavelength light detection. A method was developed which allowed for the determination of the two regioisomeric methylated ...

journal_title：Bioorganic & medicinal chemistry

authors： Bailey K,Cowling R,Tan EW,Webb D

更新日期：2004-02-01 00:00:00

abstract：:Endogenous opioid peptides consist of a conserved amino acid residue of Phe(3) and Phe(4), although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the mu opioid receptor, possesses two Phe residues at the consecutive positions 3 an...

journal_title：Bioorganic & medicinal chemistry

authors： Honda T,Shirasu N,Isozaki K,Kawano M,Shigehiro D,Chuman Y,Fujita T,Nose T,Shimohigashi Y

更新日期：2007-06-01 00:00:00