Structural requirement of phenylthiourea analogs for their inhibitory activity of melanogenesis and tyrosinase.

abstract：:A series of new triazole fused imidazo[2,1-b]thiazole hybrids (9a-u) were designed, synthesized and evaluated as antimicrobial agents. Compounds 9c, 9d, 9e, 9j and 9l showed promising broad spectrum antimicrobial activity. Further, compound 9c exhibited significant anti-biofilm activity with single and mixed biofilm d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shareef MA,Sirisha K,Sayeed IB,Khan I,Ganapathi T,Akbar S,Ganesh Kumar C,Kamal A,Nagendra Babu B

更新日期：2019-10-01 00:00:00

abstract：:The importance of protein binding cavity volume (PCV) and ligand volume (LV) in rigid and flexible docking has been studied in 48 protein-ligand complexes belonging to eight protein families. In continuation of our earlier study on protein flexibility in relationship to PCV and LV, this study analyzes the importance o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Saranya N,Jeyakanthan J,Selvaraj S

更新日期：2012-12-15 00:00:00

abstract：:A series of pyrimidine benzamide-based thrombopoietin receptor agonists is described. The lead molecule contains a 2-amino-5-unsubstituted thiazole, a group that has been associated with idiosyncratic toxicity. The potential for metabolic oxidation at C-5 of the thiazole, the likely source of toxic metabolites, was re...

journal_title：Bioorganic & medicinal chemistry letters

authors： Reiter LA,Subramanyam C,Mangual EJ,Jones CS,Smeets MI,Brissette WH,McCurdy SP,Lira PD,Linde RG,Li Q,Zhang F,Antipas AS,Blumberg LC,Doty JL,Driscoll JP,Munchhof MJ,Ripp SL,Shavnya A,Shepard RM,Sperger D,Thomasco LM

更新日期：2007-10-01 00:00:00

abstract：:Cu (II) complex with 1,4,7,10-tetrakis(2-cyanoethyl-)-1,4,7,10-tetraazacyclododecane was prepared and characterized by X-ray diffraction. Four nitrogen atoms of macrocyclic ligand and oxygen atom of water molecule defined a tetragonal pyramidal polyhedron surrounding the central copper atom. Preliminary pharmacologica...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kong D,Qin C,Meng L,Xie Y

更新日期：1999-04-19 00:00:00

abstract：:We have designed, synthesized, and evaluated the factor Xa inhibitory activities of p-amidinophenyl-sulfones, amines, and alcohols intended to take advantage of the polarity and hydrogen-bonding potential of the oxyanion hole region of the S1 specificity pocket. We demonstrate that placement of an anionic group within...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rumthao S,Lee O,Sheng Q,Fu W,Mulhearn DC,Crich D,Mesecar AD,Johnson ME

更新日期：2004-10-18 00:00:00

abstract：:To improve the pharmacokinetics of a previously reported series of dipeptidyl nitrile cathepsin B inhibitors, the P(2)-P(3) amide group was replaced with an arylamine. Further optimization of this template resulted in highly potent and selective inhibitors with excellent oral availability. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Greenspan PD,Clark KL,Cowen SD,McQuire LW,Tommasi RA,Farley DL,Quadros E,Coppa DE,Du Z,Fang Z,Zhou H,Doughty J,Toscano KT,Wigg AM,Zhou S

更新日期：2003-11-17 00:00:00

abstract：:The structure-based design, synthesis, and anticancer activity of novel inhibitors of protein kinase CK2 are described. Using pyrazolo[1,5-a][1,3,5]triazine as the core scaffold, a structure-guided series of modifications provided pM inhibitors with microM-level cytotoxic activity in cell-based assays with prostate an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nie Z,Perretta C,Erickson P,Margosiak S,Almassy R,Lu J,Averill A,Yager KM,Chu S

更新日期：2007-08-01 00:00:00

abstract：:Based on the recently resolved crystal structure of complex (-)-huperzine A-AChE, we simulated the interaction between (-)-huperzine A analogues and AChE using molecular dynamics method. It was revealed that the methyl group at the three carbon bridge of (-)-huperzine A can form a weak hydrogen bond with the phenol hy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu DX,Jiang H,Wang QM,Chen KX,Ji RY

更新日期：1998-03-03 00:00:00

abstract：:A simple and versatile method for preparation of (D)-Phe-Pro peptidomimetic bicyclic thiazolidine lactams is presented. These bicyclic lactams have chemical diversity alpha to the lactam carbonyl and, when linked to electrophilic arginines, provide potent thrombin inhibitors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bachand B,DiMaio J,Siddiqui MA

更新日期：1999-04-05 00:00:00

abstract：:New bis-pyridinium oxime reactivators connected with CH2O(CH2)n OCH2 linkers between two pyridinium rings were designed and synthesized, and their reactivation potency was evaluated for AChE inhibited by organophosphorus VX agent. Among the prepared compounds, 1,2-dimethoxy-ethylene-bis-N,N'-4-pyridiumaldoxime dichlor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Oh KA,Yang GY,Jun D,Kuca K,Jung YS

更新日期：2006-09-15 00:00:00

abstract：:SAR studies on the extension of P3 unit of Boceprevir (1, SCH 503034) with amides and lactams and their synthesis is described. Extensive SAR studies resulted in the identification of 36 bearing 4, 4-dimethyl lactam as the new P4 cap unit with improved potency (K(i)( *)=15nM, EC 90=70nM) and pharmacokinetic properties...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nair LG,Sannigrahi M,Bogen S,Pinto P,Chen KX,Prongay A,Tong X,Cheng KC,Girijavallabhan V,George Njoroge F

更新日期：2010-01-15 00:00:00

abstract：:A series of novel 9-O-arylalkyloxime analogs based on three different 16-membered macrolide scaffolds-5-O-mycaminosyltylonolide (OMT), tilmicosin, and 20-deoxy-20-(3,5-dimethyl-1-piperidin-1-yl)-OMT-was synthesized. In vitro antibiotic activities were assayed against Gram-positive Streptococcus pneumoniae and Staphylo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fu H,Marquez S,Gu X,Katz L,Myles DC

更新日期：2006-03-01 00:00:00

abstract：:A series of 7-alkyl ether derivatives related to zanamivir were synthesized using direct alkylation of the C-7 alcohol of sialic acid. Alkyl ether moiety of less than 12 carbons in length showed low nanomolar inhibitory activity against influenza A virus sialidase. Furthermore, their moiety improved influenza A virus ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Honda T,Masuda T,Yoshida S,Arai M,Kaneko S,Yamashita M

更新日期：2002-08-05 00:00:00

abstract：:The inhibition of ribonuclease Bi by 3'-N-hydroxyurea-3'-deoxythymidine 5'-phosphate is enhanced by 30-fold in the presence of Zn(2+). Thus, an N-hydroxyurea nucleotide can recruit Zn(2+) to inhibit the enzymatic activity of a ribonuclease. This result engenders a general strategy for the inhibition of non-metalloenzy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Higgin JJ,Yakovlev GI,Mitkevich VA,Makarov AA,Raines RT

更新日期：2003-02-10 00:00:00

abstract：:Phenylpiperazine derivatives were synthesized as dual cytokine regulators with TNF-alpha suppressing and IL-10 augmenting activity. Lead optimization led to compound 5k having the potent regulatory activity and demonstrating remarkable protective effects against the lethal challenge of LPS in mice. suggesting that 5k ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanano T,Adachi K,Aoki Y,Morimoto H,Naka Y,Hisadome M,Fukuda T,Sumichika H

更新日期：2000-05-01 00:00:00

abstract：:A series of novel cyclic analogues of curcumin were synthesized and analyzed for in vitro cytostatic activity. Condensation of 2-acetylcycloalkanones with a variety of aromatic aldehydes resulted in the formation of 2-arylidene-6-(3-arylacryoyl)-cycloalkanone derivatives. A number of these analogues were found to have...

journal_title：Bioorganic & medicinal chemistry letters

authors： Youssef D,Nichols CE,Cameron TS,Balzarini J,De Clercq E,Jha A

更新日期：2007-10-15 00:00:00

abstract：:The reaction between methanethiosulfonate reagents and cysteine mutants of subtilisin is quantitative and can be used to prepare chemically modified mutant enzymes (CMMs) with novel properties. The virtually unrestricted structural variations possible for CMMs presents a preparative and screening challenge. To address...

journal_title：Bioorganic & medicinal chemistry letters

authors： Plettner E,Khumtaveeporn K,Shang X,Jones JB

更新日期：1998-09-08 00:00:00

abstract：:A novel neurokinin-1 receptor antagonist, (+/-)-(1R( *),3S( *),4S( *),5S( *))-4-[(N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-3-phenyl-2-aza-7-oxabicyclo[3.3.0]octane (1), was synthesized stereoselectively using Padwa's intramolecular 1,3-dipolar cycloaddition methodology as the key step. Compound (+/-)-1 showed high...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shishido Y,Ito F,Morita H,Ikunaka M

更新日期：2007-12-15 00:00:00

abstract：:Novel benzo[b]thiophene diamine thrombin inhibitors were investigated, focusing on a contracted C4'-side chain series. SAR studies identified compounds with either a pyrrolidino or morpholino group as potent, active site directed thrombin inhibitors when the amino group was connected to the C3-phenyl ring with a methy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takeuchi K,Kohn TJ,Harper RW,Lin HS,Gifford-Moore DS,Richett ME,Sall DJ,Smith GF,Zhang M

更新日期：2000-06-05 00:00:00

abstract：:The structures of the uracil and thiouracils were examined using NMR spectroscopy and crystal structure data when available. The relationships between the extent of polarization and the C5-C6 bond length as well as the H5-H6 coupling constants were probed. It was found that the bond length and coupling constants corre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang S,Gronert S,Wu W

更新日期：2011-11-01 00:00:00

abstract：:Multiple asthma-relevant cytokines including IL-4, IL-5, IL-13, and TSLP depend upon JAKs for signaling. JAK inhibition may, therefore, offer a novel intervention strategy for patients with disease refractory to current standards of care. Multiple systemically delivered JAK inhibitors have been approved for human use ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zak M,Dengler HS,Rajapaksa NS

更新日期：2019-10-15 00:00:00

abstract：:Prodrug esters of the indolocarbazole CEP-751 (KT-6587) were prepared with the goal of identifying water soluble, stable but cleavable forms for intravenous dosing. A dipeptide proform Lys-beta-Ala (16, CEP-2563/KT-8391) was identified for advancement to clinical trials. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hudkins RL,Iqbal M,Park CH,Goldstein J,Herman JL,Shek E,Murakata C,Mallamo JP

更新日期：1998-07-21 00:00:00

abstract：:A series of regioisomeric bis-fulleropyrrolidines bearing two ammonium groups have been synthesized and their activities against HIV-1 and HIV-2 have been evaluated. Two trans isomers have been endowed with interesting antiviral properties, confirming the importance of the relative positions of the substituent on the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marchesan S,Da Ros T,Spalluto G,Balzarini J,Prato M

更新日期：2005-08-01 00:00:00

abstract：:A series of novel 1,3-benzodiazapine based D1 antagonists was designed according to the understanding of pharmacophore models derived from SCH 23390 (1b), a potent and selective D1 antagonist. The new design features an achiral cyclic-amidine that maintains desired basicity. Solid phase synthesis was developed for SAR...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhu Z,Sun ZY,Ye Y,McKittrick B,Greenlee W,Czarniecki M,Fawzi A,Zhang H,Lachowicz JE

更新日期：2009-09-01 00:00:00

abstract：:Scaffold hybridization of several natural and synthetic anticancer leads led to the consideration of indenoindolones as potential novel anticancer agents. A series of these compounds were prepared by a diversity-feasible synthetic method. They were found to possess anticancer activities with higher potency compared to...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kashyap M,Das D,Preet R,Mohapatra P,Satapathy SR,Siddharth S,Kundu CN,Guchhait SK

更新日期：2012-04-01 00:00:00

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

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

更新日期：1998-12-15 00:00:00

abstract：:An HTS campaign of our corporate compound library resulted in thieno[2,3-b]pyridines derivative hits with mGluR5 negative allosteric modulator effects. During the hit-to-lead development our objective was to improve affinity, and to keep the ligand efficiency values at an acceptable level. After different modification...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nógrádi K,Wágner G,Domány G,Bobok A,Magdó I,Kiss B,Kolok S,Fónagy K,Gyertyán I,Háda V,Kóti J,Gál K,Farkas S,Keserű GM,Greiner I,Szombathelyi Z

更新日期：2014-08-15 00:00:00

abstract：:Sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Starting from a screening hit 8 that had modest affinity for the cannabinoid CB(2) receptor, a parallel synthesis approach and initial SAR are described, leading to compound 27 with 120-fold functional selectivity for the CB(2) rec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Worm K,Zhou QJ,Saeui CT,Green RC,Cassel JA,Stabley GJ,DeHaven RN,Conway-James N,LaBuda CJ,Koblish M,Little PJ,Dolle RE

更新日期：2008-05-01 00:00:00

abstract：:Multiple regions of the 3-oxazolidinedione-6-naphthyl-pyridinone series identified via high throughput screening were explored. SAR studies of these regions including the left-hand side oxazolidinedione moiety, α-substituent on the oxazolidinedione ring, central pyridinone core, and substituents on the central pyridin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morales-Ramos ÁI,Li YH,Hilfiker M,Mecom JS,Eidam P,Shi D,Tseng PS,Brooks C,Zhang D,Wang N,Jaworski JP,Morrow D,Fries H,Edwards R,Jin J

更新日期：2011-05-15 00:00:00

abstract：:The 18-deoxy derivative (3) of a simplified analogue (1) of aplysiatoxin with antiproliferative activity was synthesized to examine the role of the phenolic hydroxyl group at position 18 in the biological activities of 1. Compound 3 as well as 1 showed significant affinity for protein kinase Cδ (PKCδ), and the antipro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yanagita RC,Kamachi H,Tanaka K,Murakami A,Nakagawa Y,Tokuda H,Nagai H,Irie K

更新日期：2010-10-15 00:00:00