Solution and solid phase combinatorial synthesis of peptidomimetic library containing diversified alpha-methylated amino acids.

abstract：:A series of structurally novel aryl ureas was derived from optimization of the HTS lead as selective histamine H3 receptor (H3R) antagonists. The SAR was explored and the data obtained set up the starting point and foundation for further optimization. The most potent tool compounds, as exemplified by compounds 2l, 5b,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao Z,Hurst WJ,Guillot E,Czechtizky W,Lukasczyk U,Nagorny R,Pruniaux MP,Schwink L,Sanchez JA,Stengelin S,Tang L,Winkler I,Hendrix JA,George PG

更新日期：2013-06-01 00:00:00

abstract：:Here we present first dinucleotide affinity resins for purification of proteins that specifically recognize the 5' end of mRNA. Constructed resins possess either a naturally occurring mono- or trimethylated cap or their analogues resistant towards enzymatic degradation, bearing a CH(2) bridge between β and γ position ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jankowska-Anyszka M,Piecyk K

更新日期：2011-10-15 00:00:00

abstract：:Glycogen synthase kinase-3 beta (GSK3β) kinase serves as a promising therapeutic target for the treatment of various human diseases, such as diabetes, obesity, and Alzheimer's disease. In this study, we report lead GSK3β inhibitors identified using a fragment-linking strategy. Through the systematic exploration, a six...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim J,Moon Y,Hong S

更新日期：2016-12-01 00:00:00

abstract：:A series of substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles has been prepared as Src kinase inhibitors. Optimal activity is observed with compounds that have basic amines attached via the para position of the 7-phenyl ring, and a hydrogen atom at the C-6 position. The best compounds are low nanomolar inhibitor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Berger D,Dutia M,Powell D,Wissner A,DeMorin F,Raifeld Y,Weber J,Boschelli F

更新日期：2002-10-21 00:00:00

abstract：:GSK2126458 is a highly potent inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with low picomolar to subnanomolar activity. [(11)C]GSK2126458 and [(18)F]GSK2126458, new potential PET agents for imaging of PI3K and mTOR in cancer, were first designed and synthesized in 40-50% and 2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Gao M,Miller KD,Sledge GW,Zheng QH

更新日期：2012-02-15 00:00:00

abstract：:The identification of a novel hit compound inhibitor of the protein-protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kessler U,Castagnolo D,Pagano M,Deodato D,Bernardini M,Pilger B,Ranadheera C,Botta M

更新日期：2013-10-15 00:00:00

abstract：:A series of diaryl ureas with an amide substitution at the 4-position was prepared and found to be potent and selective FLT3 inhibitors with good oral bioavailability and efficacy in a tumor xenograft model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patel HK,Grotzfeld RM,Lai AG,Mehta SA,Milanov ZV,Chao Q,Sprankle KG,Carter TA,Velasco AM,Fabian MA,James J,Treiber DK,Lockhart DJ,Zarrinkar PP,Bhagwat SS

更新日期：2009-09-01 00:00:00

abstract：:A series of imidazolopyrazinones 3, substituted at C-2, and C-2/C-6, has been prepared. The compounds behaved as quenchers of superoxide anion. The more active compounds are structurally related to coelenterazine, a natural substrate of marine bioluminescence. Theoretical parameters based on Hartree-Fock instabilities...

journal_title：Bioorganic & medicinal chemistry letters

authors： Devillers I,Dive G,De Tollenaere C,Falmagne B,de Wergifosse B,Rees JF,Marchand-Brynaert J

更新日期：2001-09-03 00:00:00

abstract：:Dihydroquinolines have been synthesized and have been shown to be potent n-NOS inhibitors. Selectivity versus e-NOS was increased to approximately 100-fold through appropriate substitution at the benzene ring. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jaroch S,Hölscher P,Rehwinkel H,Sülzle D,Burton G,Hillmann M,McDonald FM

更新日期：2002-09-16 00:00:00

abstract：:The enzyme ATP citrate lyase (ACL) catalyzes the formation of cytosolic acetyl CoA, the starting material for de novo lipid and cholesterol biosynthesis. The dysfunction and upregulation of ACL in numerous cancers makes it an attractive target for developing anticancer therapies. ACL inhibition by shRNA knockdown limi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jernigan FE,Hanai JI,Sukhatme VP,Sun L

更新日期：2017-02-15 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：:KCNQ (Kv7) has emerged as a validated target for the development of novel anti-epileptic drugs. In this paper, a series of novel N-phenylbutanamide derivatives were designed, synthesized and evaluated as KCNQ openers for the treatment of epilepsy. These compounds were evaluated for their KCNQ opening activity in vitro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang S,Lu D,Ouyang P

更新日期：2018-09-15 00:00:00

abstract：:A newly designed curcumin mimic library (11a-11k) with 2-ethylamino groups in a chalcone structure and variously substituted triazole groups as side chains was synthesized using the Huisgen 1,3-cycloaddition reaction between various alkynes (a-k) and an intermediate (10), with CuSO4 and sodium ascorbate in a solution ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ahn Y,Oh S,Lee SJ,Park BG,Park YS,Shin WS,Jang HJ,Park JH,Kwon D,Lee S

更新日期：2014-08-01 00:00:00

abstract：:A new halicyclamine derivative, tetradehydrohalicyclamine B (1), was isolated from the marine sponge Acanthostrongylophora ingens, along with halicyclamine B (2) as proteasome inhibitors. Compound 1 is the second example found to have a pyridinium ring in the halicyclamine family. Although the relative configuration o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kato H,El-Desoky AH,Takeishi Y,Nehira T,Angkouw ED,Mangindaan REP,de Voogd NJ,Tsukamoto S

更新日期：2019-01-01 00:00:00

abstract：:Macrocarpins A (1), B (2), C (3) and D (4), four new nor-triterpenes, have been isolated from the roots of Maytenus macrocarpa. The structures were established by spectroscopic examinations. Natural compounds 1, 2, 4 and the acetyl derivative 1a are cytotoxic against four tumoral cell lines with IC50 values ranging be...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chávez H,Rodríguez G,Estévez-Braun A,Ravelo AG,Estévez-Reyes R,González AG,Fdez-Puente JL,García-Grávalos D

更新日期：2000-04-17 00:00:00

abstract：:Biphenylacetic acid (5) was identified through a library screen as an inhibitor of the prostaglandin D(2) receptor DP2 (CRTH2). Optimization for potency and pharmacokinetic properties led to a series of selective CRTH2 antagonists. Compounds demonstrated potency in a human DP2 binding assay and a human whole blood eos...

journal_title：Bioorganic & medicinal chemistry letters

authors： Scott JM,Baccei C,Bain G,Broadhead A,Evans JF,Fagan P,Hutchinson JH,King C,Lorrain DS,Lee C,Prasit P,Prodanovich P,Santini A,Stearns BA

更新日期：2011-11-01 00:00:00

abstract：:The targeted delivery of taxoids, in the form of taxane-antibody immunoconjugates, requires the preparation of taxoids containing moieties suitable for their conjugation to monoclonal antibodies. A series of taxoids incorporating a disulfide-containing linker at various positions of the taxoid framework have been prep...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miller ML,Roller EE,Wu X,Leece BA,Goldmacher VS,Chari RV,Ojima I

更新日期：2004-08-02 00:00:00

abstract：:New cis-fused tetrahydrochromeno[4,3-b]quinolines have been synthesized by intramolecular [4+2] imino-Diels-Alder reactions of 2-azadienes derived in situ from aromatic amines and 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones in the presence of 20mol% Yb(OTf)(3) in acetonitrile under reflux conditio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nagaiah K,Venkatesham A,Srinivasa Rao R,Saddanapu V,Yadav JS,Basha SJ,Sarma AV,Sridhar B,Addlagatta A

更新日期：2010-06-01 00:00:00

abstract：:New indole-porphyrin hybrid molecules were isolated from Escherichia coli harboring metagenomic DNA from the Japanese marine sponge Discodermia calyx. The indole was appended to the reactive vinyl substituent of the harderoporphyrin chromophore, encoded by the insert DNA. Thus, the chimeric pathway between the heterol...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang XL,Wakimoto T,Takeshige Y,He R,Egami Y,Awakawa T,Abe I

更新日期：2013-07-01 00:00:00

abstract：:Identification of a number of highly potent M2 receptor antagonists with >100-fold selectivity against the M1 and M3 receptor subtypes is described. In the rat microdialysis assay, this series of compounds showed pronounced enhancement of brain acetylcholine release after oral administration. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Y,Chackalamannil S,Hu Z,Clader JW,Greenlee W,Billard W,Binch H,Crosby G,Ruperto V,Duffy RA,McQuade R,Lachowicz JE

更新日期：2000-10-16 00:00:00

abstract：:An α-carbonic anhydrase (CA, EC 4.2.1.1) isolated from the living fossil sponge Astrosclera willeyana, Astrosclerin, was investigated for its inhibition profile with simple inorganic anions, complex anions and other small molecules known to interact with these zinc enzymes. Astrosclerin is a catalytically highly effic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohradanova A,Vullo D,Pastorekova S,Pastorek J,Jackson DJ,Wörheide G,Supuran CT

更新日期：2012-02-01 00:00:00

abstract：:Approaches to improve the efficiency of molecular optimizations have received great attention and numerous efficiency metrics have been introduced to assist in this effort. Optimization of properties is equally important to optimization of potency and therefore these metrics contain potency versus property calculation...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shultz MD

更新日期：2013-11-01 00:00:00

abstract：:A β-carbonic anhydrases (CAs, EC 4.2.1.1) was recently cloned, purified and characterized kinetically in the pathogen Clostridium perfringens. We report here the first inhibition study of this enzyme (CpeCA). CpeCA was poorly inhibited by iodide and bromide, and was inhibited with KIs in the range of 1-10mM by a range...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vullo D,Sai Kumar RS,Scozzafava A,Capasso C,Ferry JG,Supuran CT

更新日期：2013-12-15 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：:The use of chitosan as the wall of microcapsule designed for delivery of encapsulated celecoxib is reported. Microcapsules were characterised with respect to size and encapsulation efficiency of celecoxib. In vivo animals demonstrated that both free celecoxib administration and chitosan/celecoxib microcapsules adminis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheng SY,Yuen MC,Lam PL,Gambari R,Wong RS,Cheng GY,Lai PB,Tong SW,Chan KW,Lau FY,Kok SH,Lam KH,Chui CH

更新日期：2010-07-15 00:00:00

abstract：:A novel alpha7 nAChR agonist, N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (3a, PHA-709829), has been identified for the potential treatment of cognitive deficits in schizophrenia. The compound shows potent and selective alpha7 in vitro activity, excellent brain penetration, good rat oral b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Acker BA,Jacobsen EJ,Rogers BN,Wishka DG,Reitz SC,Piotrowski DW,Myers JK,Wolfe ML,Groppi VE,Thornburgh BA,Tinholt PM,Walters RR,Olson BA,Fitzgerald L,Staton BA,Raub TJ,Krause M,Li KS,Hoffmann WE,Hajos M,Hurst RS,

更新日期：2008-06-15 00:00:00

abstract：:Two types of P1-P3-linked macrocyclic renin inhibitors containing the hydroxyethylene isostere (HE) scaffold just outside the macrocyclic ring have been synthesized. An aromatic or aliphatic substituent (P3sp) was introduced in the macrocyclic ring aiming at the S3 subpocket (S3sp) in order to optimize the potency. A ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sund C,Belda O,Wiktelius D,Sahlberg C,Vrang L,Sedig S,Hamelink E,Henderson I,Agback T,Jansson K,Borkakoti N,Derbyshire D,Eneroth A,Samuelsson B

更新日期：2011-01-01 00:00:00

abstract：:Novel conformationally-restricted mTOR kinase inhibitors with cyclic sulfone scaffold were designed. Synthesis and structure-activity relationship (SAR) studies are described with emphasis on optimization of the mTOR potency and selectivity against class I PI3Kα kinase. PF-05139962 was identified with excellent mTOR b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu KK,Bailey S,Dinh DM,Lam H,Li C,Wells PA,Yin MJ,Zou A

更新日期：2012-08-01 00:00:00

abstract：:The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Z,Powell CE,Groendyke BJ,Gero TW,Feru F,Feutrill J,Chen B,Li B,Szabo H,Gray NS,Scott DA

更新日期：2020-10-01 00:00:00

abstract：:A set of 31 DNA minor groove binders (MGBs) with diverse structural features relating to both physical chemical properties and DNA binding sequence preference has been evaluated as potential drugs to treat Plasmodium falciparum infections using a chloroquine sensitive strain (3D7) and a chloroquine resistant strain (D...

journal_title：Bioorganic & medicinal chemistry letters

authors： Scott FJ,Khalaf AI,Duffy S,Avery VM,Suckling CJ

更新日期：2016-07-15 00:00:00