Synthesis and biological evaluation of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R).

abstract：:A new cyclic heptapeptide, cyclonatsudamine A (1), cyclo (-Gly-Tyr-Leu-Leu-Pro-Pro-Ser-), has been isolated from the peels of Citrus natsudaidai and the structure was elucidated by 2D NMR analysis and chemical degradation. Cyclonatsudamine A (1) relaxed norepinephrine-induced contractions of rat aorta, which may be me...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morita H,Enomoto M,Hirasawa Y,Iizuka T,Ogawa K,Kawahara N,Goda Y,Matsumoto T,Takeya K

更新日期：2007-10-01 00:00:00

abstract：:Chelerythrine, an isoquinoline alkaloid isolated from the herbaceous perennial Chelidonium majus, was found to potently and selectively inhibit an isoform of recombinant human monoamine oxidase-A (MAO-A) with an IC50 value of 0.55 µM. Chelerythrine was a reversible competitive MAO-A inhibitor (Ki = 0.22 µM) with a pot...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baek SC,Ryu HW,Kang MG,Lee H,Park D,Cho ML,Oh SR,Kim H

更新日期：2018-08-01 00:00:00

abstract：:A number of new amine scaffolds with good inhibitory activity in the ADP-induced platelet aggregation assay have been found to be potent antagonists of the P2Y1 receptor. SAR optimization led to the identification of isoindoline 3c and piperidine 4a which showed good in vitro binding and functional activities, as well...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ruel R,L'Heureux A,Thibeault C,Lapointe P,Martel A,Qiao JX,Hua J,Price LA,Wu Q,Chang M,Zheng J,Huang CS,Wexler RR,Rehfuss R,Lam PY

更新日期：2013-12-15 00:00:00

abstract：:Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miller LM,Mayer SC,Berger DM,Boschelli DH,Boschelli F,Di L,Du X,Dutia M,Floyd MB,Johnson M,Kenny CH,Krishnamurthy G,Moy F,Petusky S,Tkach D,Torres N,Wu B,Xu W

更新日期：2009-01-01 00:00:00

abstract：:Steroidal glucocorticoids (GR agonists) have been widely used for the topical treatment of skin disorders, including atopic dermatitis. They are a very effective therapy, but they are associated with both unwanted local effects in the skin (skin thinning/atrophy) and systemic side effects. These effects can limit the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dack KN,Johnson PS,Henriksson K,Eirefelt S,Carnerup MA,Stahlhut M,Ollerstam AK

更新日期：2020-09-01 00:00:00

abstract：:The fruits of Cudrania tricuspidata (Carr.) Bur. (Moraceae) significantly inhibited pancreatic lipase, which plays a key role in fat absorption. Optimization of extraction conditions with minimum pancreatic lipase activity and maximum yield was determined using response surface methodology with three-level-three-facto...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jeong JY,Jo YH,Lee KY,Do SG,Hwang BY,Lee MK

更新日期：2014-05-15 00:00:00

abstract：:The synthesis and immunogenicity of a tetanus toxoid (TT)-conjugate of the hexasaccharide portion of the cell-wall polysaccharide (CWPS) of the Group A Streptococcus (GAS) is described. The synthesis relies on the reaction of an allyl glycoside of the hexasaccharide with cysteamine, followed by the reaction of the res...

journal_title：Bioorganic & medicinal chemistry letters

authors： Auzanneau FI,Borrelli S,Pinto BM

更新日期：2013-11-15 00:00:00

abstract：:In this paper, we present the results of a ligand- and structure-based virtual screen targeting LRRK2, a kinase that has been implicated in Parkinson's disease. For the ligand-based virtual screen, the structures of 12 competitor compounds were used as queries for a variety of 2D and 3D searches. The structure-based v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gancia E,De Groot M,Burton B,Clark DE

更新日期：2017-06-01 00:00:00

abstract：:TGR5 is a member of G protein-coupled receptor (GPCR) superfamily, a promising molecular target for metabolic diseases. Activation of TGR5 promotes secretion of glucagon-like peptide-1 (GLP-1), which activates insulin secretion. A series of 2-thio-imidazole derivatives have been identified as novel, potent and orally ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Agarwal S,Sasane S,Kumar J,Deshmukh P,Bhayani H,Giri P,Giri S,Soman S,Kulkarni N,Jain M

更新日期：2018-06-01 00:00:00

abstract：:To explore the hydrophobic groove subsite within the CB1 cannabinoid receptor we have designed and synthesized a group of tail-substituted anandamide analogs. Our design involves the introduction of aryl or heterocyclic ring as terminal substituents that are connected to the last cis-arachidonyl double bond through al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yao F,Li C,Vadivel SK,Bowman AL,Makriyannis A

更新日期：2008-11-15 00:00:00

abstract：:Fatty acylated dipeptides homologous to Gi alpha N-termini affect ligand binding to muscarinic acetylcholine receptors. Myristylglycine-serine containing dipeptides decrease antagonist binding at both M1 and M2 muscarinic receptors. Palmitate on the serine analogous to native palmitoylated cysteine affords dipeptide w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Krishnan V,Pham WN,Messer WS Jr,Peseckis SM

更新日期：1999-12-06 00:00:00

abstract：:Herein we report the discovery and SAR of an indole-based protease activated receptor-4 (PAR-4) antagonist scaffold derived from a similarity search of the Vanderbilt HTS collection, leading to MLPCN probe ML354 (VU0099704). Using a novel PAC-1 fluorescent αIIbβ3 activation assay this probe molecule antagonist was fou...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wen W,Young SE,Duvernay MT,Schulte ML,Nance KD,Melancon BJ,Engers J,Locuson CW 2nd,Wood MR,Daniels JS,Wu W,Lindsley CW,Hamm HE,Stauffer SR

更新日期：2014-10-01 00:00:00

abstract：:We synthesized pyrrolomorphinan derivatives 6, 7, and 9 to examine whether the pyrrole ring would be an accessory site in the kappa opioid receptor selective antagonist, nor-binaltorphimine. Derivative 6 had an alpha,beta-unsaturated ketone substituent that strongly bound to the kappa receptor. The compound with the h...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujii H,Ida Y,Hanamura S,Osa Y,Nemoto T,Nakajima M,Hasebe K,Nakao K,Mochizuki H,Nagase H

更新日期：2010-09-01 00:00:00

abstract：:A serendipitous discovery that the metalloprotease binding profile of a novel class of 2-carboxamide-3-hydroxamic acid piperidines could be significantly attenuated by the modification of the unexplored P1 substituent enabled the design and synthesis of a novel 2-carboxamide-1-hydroxamic acid cyclohexyl scaffold core ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Burns DM,Li YL,Shi E,He C,Xu M,Zhuo J,Zhang C,Qian DQ,Li Y,Wynn R,Covington MB,Katiyar K,Marando CA,Fridman JS,Scherle P,Friedman S,Metcalf B,Yao W

更新日期：2009-07-01 00:00:00

abstract：:Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of the S1P signaling pathway has attracted significant attention because alteration of S1P levels is linked to several disease states including cancer, fibrosis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Congdon MD,Childress ES,Patwardhan NN,Gumkowski J,Morris EA,Kharel Y,Lynch KR,Santos WL

更新日期：2015-11-01 00:00:00

abstract：:Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiong H,Brugel TA,Balestra M,Brown DG,Brush KA,Hightower C,Hinkley L,Hoesch V,Kang J,Koether GM,McCauley JP Jr,McLaren FM,Panko LM,Simpson TR,Smith RW,Woods JM,Brockel B,Chhajlani V,Gadient RA,Spear N,Sygowski LA

更新日期：2010-12-15 00:00:00

abstract：:Based on the findings that cholest-4-en-3-one, an intestinal metabolite of cholesterol, has an anti-obesity effect on animals, the structure-effect relationship of its 3-oxo derivatives and related compounds were investigated. Cholesten-3-ones, which possesses an enone structure with a carbonyl group at C3, markedly i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suzuki K,Shimizu T,Nakata T

更新日期：1998-08-18 00:00:00

abstract：:Pyrido pyrimidinones are selective agonists of the human high affinity niacin receptor GPR109A (HM74A). They show no activity on the highly homologous low affinity receptor GPR109B (HM74). Starting from a high throughput screening hit the in vitro activity of the pyrido pyrimidinones was significantly improved providi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peters JU,Kühne H,Dehmlow H,Grether U,Conte A,Hainzl D,Hertel C,Kratochwil NA,Otteneder M,Narquizian R,Panousis CG,Ricklin F,Röver S

更新日期：2010-09-15 00:00:00

abstract：:Cyclophilins (Cyps) are ubiquitous proteins that effect the cis-trans isomerization of Pro amide bonds, and are thus crucial to protein folding. CypA is the most prevalent of the ~19 human Cyps, and plays a crucial role in viral infectivity, most notably for HIV-1 and HCV. Cyclophilins have been shown to play key role...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peel M,Scribner A

更新日期：2013-08-15 00:00:00

abstract：:A potent and novel class of product-like inhibitors of the HCV NS3 protease was discovered by employing a phosphinic acid as a carboxylate isostere. The replicon activity and pharmacokinetic profile of this series of compounds was optimized by exploring the substitution of the phosphinic acid, as well as conformationa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clarke MO,Chen X,Cho A,Delaney WE 4th,Doerffler E,Fardis M,Ji M,Mertzman M,Pakdaman R,Pyun HJ,Rowe T,Yang CY,Sheng XC,Kim CU

更新日期：2011-06-15 00:00:00

abstract：:Novel, quinolone-fluoroquinolone conjugates 10a-f, 11a-f, 13a-f and 14a-f with amino acid linkers were synthesized in good yields utilizing benzotriazole chemistry. Antibacterial bioassay showed the synthesized bis-conjugates exhibit anti-bacterial properties comparable with the parent drugs. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Panda SS,Liaqat S,Girgis AS,Samir A,Hall CD,Katritzky AR

更新日期：2015-09-15 00:00:00

abstract：:The side chain benzylic methylene is a critical element for the vanilloid activity of resiniferatoxin (2a, RTX), and introduction of branching, oxygen functions, or isosteric substitution at this center proved detrimental, with a decrease of potency of 2-3 orders of magnitude compared to the natural product. Conversel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Appendino G,Ech-Chahad A,Minassi A,De Petrocellis L,Di Marzo V

更新日期：2010-01-01 00:00:00

abstract：:Bis(mu-hydroxo)diiron(III) complex, [Fe2III(mu-OH)2(NE)2](NO3)2 x 3H2O (3) (N-(4-nitro-2-hydroxy)phenylmethyl-N-(2-pyridylethyl)-N-(2-pyridylmethyl)amine = HNE, where H denotes a dissociable proton of the p-nitrophenol group), has been prepared and characterized by X-ray crystallography, electronic and magnetic spectr...

journal_title：Bioorganic & medicinal chemistry letters

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

更新日期：2001-03-26 00:00:00

abstract：:A series of 6-hydroxy-7-methoxy-4-chromanone- (2a-e) and chroman-2-carboxamides (3a-e) were synthesized and their antioxidant activities were evaluated. While compounds 2a-e were less active, compounds 3a-e exhibited more potent inhibition of lipid peroxidation initiated by Fe(2+) and ascorbic acid in rat brain homoge...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee H,Lee K,Jung JK,Cho J,Theodorakis EA

更新日期：2005-06-02 00:00:00

abstract：:The structural modification of the benzylic ether region of oxime 1 has resulted in the identification of several novel aryl amides as selective or dual NK(1)/NK(2) antagonists. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shih NY,Albanese M,Anthes JC,Carruthers NI,Grice CA,Lin L,Mangiaracina P,Reichard GA,Schwerdt J,Seidl V,Wong SC,Piwinski JJ

更新日期：2002-01-21 00:00:00

abstract：:In the search for new antibacterial agents, the enzyme FabI has been identified as an attractive target. Employing a structure guided approach, the previously reported ene-amide series of FabI inhibitors were expanded to include 2,3,4,5-tetrahydro-1H-pyrido[2,3-b and e][1,4]diazepines. These novel series incorporate a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ramnauth J,Surman MD,Sampson PB,Forrest B,Wilson J,Freeman E,Manning DD,Martin F,Toro A,Domagala M,Awrey DE,Bardouniotis E,Kaplan N,Berman J,Pauls HW

更新日期：2009-09-15 00:00:00

abstract：:Forty caffeate analogues were synthesized via a convenient method starting from vanillin with moderate to good yields. The testing of biological activity of these compounds against HIV-1 integrase indicates that four compounds: bornyl caffeate, bornyl 2-nitrocaffeate, 5-nitrocaffeic acid and 5-nitrocaffeic acid phenet...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xia CN,Li HB,Liu F,Hu WX

更新日期：2008-12-15 00:00:00

abstract：:2'-O-[N-(4-Aminobutylcarbamoyl)]uridine (U(abcm)) was synthesized and incorporated into oligonucleotides. The oligonucleotides incorporating U(abcm) formed more stable duplexes with their complementary and mismatched RNAs than those containing 2'-O-carbamoyluridine (U(cm)). The stability of duplex with a U(abcm)-rG ba...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seio K,Tokugawa M,Kanamori T,Tsunoda H,Ohkubo A,Sekine M

更新日期：2012-04-01 00:00:00

abstract：:4-(Substituted-benzylidine)-2-substituted-5,6-dihydrobenzo[h]quinazoline (5a-p) and 4-(substituted-benzylidine)-2-substituted-3, 4, 5, 6-tetrahydrobenzo[h]quinazoline (6a-p) have been synthesized from 2-(substituted-benzylidine)tetralone-1(3a-d) and several substituted guanidine sulfates(4a-d).These compounds were tes...

journal_title：Bioorganic & medicinal chemistry letters

authors： Agarwal KC,Sharma V,Shakya N,Gupta S

更新日期：2009-09-15 00:00:00

abstract：:Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Iserloh U,Wu Y,Cumming JN,Pan J,Wang LY,Stamford AW,Kennedy ME,Kuvelkar R,Chen X,Parker EM,Strickland C,Voigt J

更新日期：2008-01-01 00:00:00