Modeling directed design and biological evaluation of quinazolinones as non-peptidic growth hormone secretagogues.

abstract：:We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sagar SR,Agarwal JK,Pandya DH,Dash RP,Nivsarkar M,Vasu KK

更新日期：2015-10-15 00:00:00

abstract：:The compound 1-(1-(2-(2-(2-fluoroethoxy)-4-(piperidin-4-yloxy)phenyl)acetyl)piperidin-4-yl)-3,4-dihydroquinolin-2(1H)-one (1) was synthesized and positively evaluated in vitro for high potency and selectivity with human oxytocin receptors. The positron emitting analogue, [F-18]1, was synthesized and investigated in vi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Smith AL,Freeman SM,Voll RJ,Young LJ,Goodman MM

更新日期：2013-10-01 00:00:00

abstract：:A novel series of monoamine reuptake inhibitors, the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols, have been discovered by combining virtual and focused screening efforts with design techniques. Synthesis of the two diastereomeric isomers of the molecule followed by chiral resolution of each enantiomer revealed the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim CY,Mahaney PE,McConnell O,Zhang Y,Manas E,Ho DM,Deecher DC,Trybulski EJ

更新日期：2009-09-01 00:00:00

abstract：:Two reactive metabolites were identified in vivo for the dual A(2A)/A(1) receptor antagonist 1. Two strategies were implemented to successfully mitigate the metabolic liabilities associated with 1. Optimization of the arylindenopyrimidines led to a number of amide, ether, and amino analogs having comparable in vitro a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shook BC,Rassnick S,Chakravarty D,Wallace N,Ault M,Crooke J,Barbay JK,Wang A,Leonard K,Powell MT,Alford V,Hall D,Rupert KC,Heintzelman GR,Hansen K,Bullington JL,Scannevin RH,Carroll K,Lampron L,Westover L,Russell

更新日期：2010-05-01 00:00:00

abstract：:Novel ligands, NBEA, NBPA, NETA, NE3TA, and NE3TA-Bn, were synthesized and evaluated as potential chelators of copper radioisotopes for use in targeted positron emission tomography (PET) imaging or radiation therapy. The new ligands were radiolabeled with (64)Cu, and in vitro stability of the radiolabeled complexes wa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chong HS,Mhaske S,Lin M,Bhuniya S,Song HA,Brechbiel MW,Sun X

更新日期：2007-11-15 00:00:00

abstract：:In the past few years a significant effort has been devoted by Pharmacia toward the discovery of novel antibiotics. We have recently described the identification of an anthranilic acid lead 1 and the optimization resulting in the advanced lead 2. In this report, we describe the preparation of several selected analogs ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thorarensen A,Li J,Wakefield BD,Romero DL,Marotti KR,Sweeney MT,Zurenko GE,Sarver RW

更新日期：2007-06-01 00:00:00

abstract：:A series of novel pyrazole peptidomimetics was synthesized from 3-aryl-1-arylmethyl-1H-pyrazole-5-carboxylic acid and amino acid ester. Structures of the compounds were characterized by means of IR, (1)H NMR and mass spectroscopy. Compounds 5e and 5k suppress effectively the growth of A549 lung cancer cells. Prelimina...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu YR,Luo JZ,Duan PP,Shao J,Zhao BX,Miao JY

更新日期：2012-11-15 00:00:00

abstract：:Single enantiomer (SS) and (RR) 2-[(phenoxy)(phenyl)methyl]morpholine derivatives 5, 8-23 are inhibitors of monoamine reuptake. Target compounds were prepared using an enantioselective synthesis employing a highly specific enzyme-catalysed resolution of racemic n-butyl 4-benzylmorpholine-2-carboxylate (26) as the key ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fish PV,Deur C,Gan X,Greene K,Hoople D,Mackenny M,Para KS,Reeves K,Ryckmans T,Stiff C,Stobie A,Wakenhut F,Whitlock GA

更新日期：2008-04-15 00:00:00

abstract：:A new method for the synthesis of 2'-O-methyl-2-thiouridine (s2Um) found in thermophilic bacterial tRNA was developed. Structural properties of s2Um and s2Um(p)U were studied by using 1H NMR spectroscopy. A modified nonaribonucleotide (RNA*: 5'-CGUUs2UmUUGC-3') was synthesized to study the base-recognition ability of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shohda K,Okamoto I,Wada T,Seio K,Sekine M

更新日期：2000-08-21 00:00:00

abstract：:A new class of non-ionic amphiphilic molecules suitable for biological purposes, especially extraction of membrane proteins, is reported. Such surfactants were prepared in two steps: addition of alkyl or fluoroalkyl mercaptan on Tris(hydroxymethyl)acrylamidomethane (THAM) derivatives, followed by the oxydation of sulf...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barthélémy P,Maurizis JC,Lacombe JM,Pucci B

更新日期：1998-06-16 00:00:00

abstract：:3-Hydroxyethyl- and 3-hydroxypropyl-7-substituted-tetrahydroisoquinolines (9, 10, 16, and 17) were synthesized and evaluated for their phenylethanolamine N-methyltransferase (PNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. Although alpha(2)-adrenoceptor affinity decreased for these compounds, sele...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grunewald GL,Romero FA,Seim MR,Criscione KR,Deupree JD,Spackman CC,Bylund DB

更新日期：2005-02-15 00:00:00

abstract：:A series of 2-phenylbenzofuran derivatives with a diphenylmethylcarbamoyl group at the 5 or 6 position of the benzofuran ring were synthesized and evaluated for rat and human testosterone 5 alpha-reductase inhibitory activities in vitro. They had inhibitory activities against both enzymes and the 6-carbamoyl derivativ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishibashi K,Nakajima K,Sugioka Y,Sugiyama M,Hamada T,Horikoshi H,Nishi T

更新日期：1998-03-17 00:00:00

abstract：:COPD is a major cause of mortality in the western world. A(2A) agonists are postulated to reduce the lung inflammation that causes COPD. The cardiovascular effects of A(2A) agonists dictate that a compound needs to be delivered by inhalation to be therapeutically useful. The pharmacological and pharmacokinetic SAR of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mantell SJ,Stephenson PT,Monaghan SM,Maw GN,Trevethick MA,Yeadon M,Walker DK,Selby MD,Batchelor DV,Rozze S,Chavaroche H,Lemaitre A,Wright KN,Whitlock L,Stuart EF,Wright PA,Macintyre F

更新日期：2009-08-01 00:00:00

abstract：:Four new peptidyl aldehydes bearing proline mimetics at the P(2)-position were synthesized and studied as inhibitors of calpain I, cathepsin B, and selected serine proteases. The ring size of the P(2)-constraining residue influenced the inhibitory potency and selectivity of the compounds for calpain I compared to the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donkor IO,Korukonda R,Huang TL,LeCour L Jr

更新日期：2003-03-10 00:00:00

abstract：:The discovery of a series of novel and orally efficacious type II calcimimetics, developed from the lead compound 1, is described herein. Compound 22 suppressed plasma PTH levels relative to vehicle when dosed orally in a rat pharmacodynamic model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Harrington PE,St Jean DJ Jr,Clarine J,Coulter TS,Croghan M,Davenport A,Davis J,Ghiron C,Hutchinson J,Kelly MG,Lott F,Lu JY,Martin D,Morony S,Poon SF,Portero-Larragueta E,Reagan JD,Regal KA,Tasker A,Wang M,Yang Y,

更新日期：2010-09-15 00:00:00

abstract：:A series of 2-phenoxy-indan-1-one derivatives have been designed, synthesized, and tested as acetylcholinesterase inhibitors. The most potent compound exhibited high AChE inhibitory activity (IC50 = 50 nM), and the molecular docking study indicated that it was nicely accommodated by AChE. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sheng R,Lin X,Li J,Jiang Y,Shang Z,Hu Y

更新日期：2005-09-01 00:00:00

abstract：:Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus associated with mangrove forests. It contains an oxygen-bridged cyclooctadiene core and an α,β-unsaturated δ-lactone moiety. MED induced the reorganization of cytoskeleton in actively growing HeLa cells by promoting formation of actin stress fiber and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang J,Zhao B,Zhang W,Wu X,Wang R,Huang Y,Chen D,Park K,Weimer BC,Shen Y

更新日期：2010-12-01 00:00:00

abstract：:Based on the information from molecular modeling and X-ray crystal structures, the kinase specificity pocket of ITK could be occupied upon extension of the right-hand-side of the 2-benzimidazole core of the inhibitors. 2-Aminobenzimidazoles with a trans-stilbene-like extension were designed and synthesized as novel IT...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lo HY,Bentzien J,Fleck RW,Pullen SS,Khine HH,Woska JR Jr,Kugler SZ,Kashem MA,Takahashi H

更新日期：2008-12-01 00:00:00

abstract：:A small library combining two different benzoquinone cores with seven (L) amino acid methyl esters (alanine, Nomega-nitro-arginine, Nepsilon-BOC-lysine, isoleucine, methionine, phenylalanine and tryptophan) was prepared and tested for prion replication inhibition in ScGT1 cells. The most potent hit, 6a, displayed an E...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tran HN,Bongarzone S,Carloni P,Legname G,Bolognesi ML

更新日期：2010-03-15 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：:Structure-activity relationships for a recently discovered thiazolyl phenyl ether series of acetyl-CoA carboxylase (ACC) inhibitors were investigated. Preliminary efforts to optimize the series through modification of the distal aryl ether moiety of the lead scaffold resulted in the identification of compounds exhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clark RF,Zhang T,Xin Z,Liu G,Wang Y,Hansen TM,Wang X,Wang R,Zhang X,Frevert EU,Camp HS,Beutel BA,Sham HL,Gu YG

更新日期：2006-12-01 00:00:00

abstract：:A series of alisol A derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and cytotoxicities in vitro. The preliminary investigation demonstrates that simple modifications of the parent structure of alisol A can produce a number of potentially important derivatives against HBV. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang Q,Jiang ZY,Luo J,Cheng P,Ma YB,Zhang XM,Zhang FX,Zhou J,Chen JJ

更新日期：2008-08-15 00:00:00

abstract：:A novel type of caspase inhibitor prodrug that improves systemic exposure after oral administration in rats has been designed. Such a prodrug, based on a 6,6a-dihydrofuro[3,2-d]oxazol-5(3aH)-one motif, has the advantage of rapidly liberating the active inhibitor without producing any cleavage by-product. Prodrugs 6-8,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Charrier JD,Durrant SJ,Studley J,Lawes L,Weber P

更新日期：2012-01-01 00:00:00

abstract：:Structure-activity relationships (SAR) were analyzed within a library of diverse yet simple compounds prepared as histamine H3 antagonists. The libraries were constructed with a variety of low molecular weight pyrrolidines, selected from (R)-2-methylpyrrolidine, (S)-2-methylpyrrolidine, and pyrrolidine. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nersesian DL,Black LA,Miller TR,Vortherms TA,Esbenshade TA,Hancock AA,Cowart MD

更新日期：2008-01-01 00:00:00

abstract：:In our search for a new agent, human neutrophil elastase (HNE) inhibitor, for the treatment of acute respiratory failure, we rationally designed and synthesized a series of peptide-based carboxylic acid-containing transition-state inhibitors. The presence of valyl moiety is found to be essential for potent in vitro in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sato F,Inoue Y,Omodani T,Imano K,Okazaki H,Takemura T,Komiya M

更新日期：2002-02-25 00:00:00

abstract：:Selective monofluorination of the alpha-glycosidase inhibitor and antidiabetic agent Miglitol at position C2 creates an competitive inhibitor of five times higher activity than the parent compound. Its screening against a panel of human cell lines showed a low cytotoxicity therefore making this compound an interesting...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prell E,Csuk R

更新日期：2009-10-01 00:00:00

abstract：:The synthesis and SAR of a novel series of non-nucleoside pyridopyrimidine inhibitors of the enzyme adenosine kinase (AK) are described. It was found that pyridopyrimidines with a broad range of medium and large non-polar substituents at the 5-position potently inhibited AK activity. A narrower range of analogues was ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cowart M,Lee CH,Gfesser GA,Bayburt EK,Bhagwat SS,Stewart AO,Yu H,Kohlhaas KL,McGaraughty S,Wismer CT,Mikusa J,Zhu C,Alexander KM,Jarvis MF,Kowaluk EA

更新日期：2001-01-08 00:00:00

abstract：:A series of compounds originally derived from thalidomide were synthesized and evaluated. The most potent compounds in this series, 5HPP-33 and compound 20, inhibited NF-kappaB activation in HeLa cells. Preliminary study indicated that the mechanism of inhibition of NF-kappaB activation is through inhibition of its tr...

journal_title：Bioorganic & medicinal chemistry letters

authors： de-Blanco EJ,Pandit B,Hu Z,Shi J,Lewis A,Li PK

更新日期：2007-11-01 00:00:00

abstract：:2-Propargylthiobenzimidazole 1, 4-bromomethyl coumarins/1-aza-coumarins 2/3 and sodium azide have been reacted in one pot under Click chemistry conditions to give exclusively 1,4-disubstituted triazoles 5a-n. Anti-tubercular assays against M. tuberculosis (H37Rv) coupled with in silico molecular docking studies indica...

journal_title：Bioorganic & medicinal chemistry letters

authors： Anand A,Kulkarni MV,Joshi SD,Dixit SR

更新日期：2016-10-01 00:00:00

abstract：:Neuropeptide Y is one of the most potent appetite stimulating hormones known. Novel thiophene and benzo[b]thiophene hydrazide derivatives were synthetized and evaluated biologically as NPY Y(1) and Y(5) receptor subtype antagonists. They were found to have nanomolar binding affinities for human NPY Y(5) receptor, obta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Galiano S,Erviti O,Pérez S,Moreno A,Juanenea L,Aldana I,Monge A

更新日期：2004-02-09 00:00:00