Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.

abstract：:Sulfonate analogues of combretastatin A-4 have been prepared. These compounds compete with colchicine and combretastatin A-4 for the colchicine binding site on tubulin and are potent inhibitors of tubulin polymerization and cell proliferation. Importantly, these compounds also inhibit the proliferation of P-glycoprote...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gwaltney SL 2nd,Imade HM,Barr KJ,Li Q,Gehrke L,Credo RB,Warner RB,Lee JY,Kovar P,Wang J,Nukkala MA,Zielinski NA,Frost D,Ng SC,Sham HL

更新日期：2001-04-09 00:00:00

abstract：:Novel indole-3-heterocycles were designed and synthesized and found to be potent CB1 receptor agonists. Starting from a microsomally unstable lead 1, a bioisostere approach replacing a piperazine amide was undertaken. This was found to be a good strategy for improving stability both in vitro and in vivo. This led to t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morrison AJ,Adam JM,Baker JA,Campbell RA,Clark JK,Cottney JE,Deehan M,Easson AM,Fields R,Francis S,Jeremiah F,Keddie N,Kiyoi T,McArthur DR,Meyer K,Ratcliffe PD,Schulz J,Wishart G,Yoshiizumi K

更新日期：2011-01-01 00:00:00

abstract：:Corticotropin-releasing factor (CRF), a 41 amino acid peptide neurohormone synthesised by specific hypothalamic nuclei in the brain, is implicated in stress-related function. Antagonism of CRF(1) receptors is an attractive therapeutic approach for the treatment of depression and anxiety. Unsaturated tetrahydrotriazaac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gentile G,Di Fabio R,Pavone F,Sabbatini FM,St-Denis Y,Zampori MG,Vitulli G,Worby A

更新日期：2007-09-15 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：:Cannabinoid CB(1) receptor antagonists reduce body weight in rodents and humans, but their clinical utility as anti-obesity agents is limited by centrally mediated side effects. Here, we describe the first mixed CB(1) antagonist/CB(2) agonist, URB447 ([4-amino-1-(4-chlorobenzyl)-2-methyl-5-phenyl-1H-pyrrol-3-yl](pheny...

journal_title：Bioorganic & medicinal chemistry letters

authors： LoVerme J,Duranti A,Tontini A,Spadoni G,Mor M,Rivara S,Stella N,Xu C,Tarzia G,Piomelli D

更新日期：2009-02-01 00:00:00

abstract：:The aryl hydrocarbon receptor (AHR) is one of the principal xenobiotic receptors in living organisms and is responsible for interacting with several drugs and environmental toxins, most notably tetrachlorodibenzodioxin (TCDD). Binding of diverse agonists to AHR initiates an extensive set of downstream gene expression ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jogalekar AS,Reiling S,Vaz RJ

更新日期：2010-11-15 00:00:00

abstract：:A Hit-to-Lead optimisation programme was carried out on the high throughput screening hit, the triazolethiol 1, resulting in the discovery of the potent, orally bioavailable triazolethiol CXCR2 receptor antagonist 45. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baxter A,Bennion C,Bent J,Boden K,Brough S,Cooper A,Kinchin E,Kindon N,McInally T,Mortimore M,Roberts B,Unitt J

更新日期：2003-08-18 00:00:00

abstract：:In general, serine protease chymase inhibitors readily decompose in plasma. We previously found that thiazolidine-2,4-dione and thiadiazole derivatives are also unstable. Using a pharmacophore-based database search, we identified a benzo[b]thiophen-2-sulfonamide derivative as a stable chymase inhibitor. Finding a lead...

journal_title：Bioorganic & medicinal chemistry letters

authors： Koide Y,Tatsui A,Hasegawa T,Murakami A,Satoh S,Yamada H,Kazayama S,Takahashi A

更新日期：2003-01-06 00:00:00

abstract：:A series of 9-aminoalkanamido-1-azabenzanthrones derviatives (3a-i Ar-NHCO(CH(2))(n)NR(1)R(2)) and their quaternary methiodide salts (4a-g Ar-NHCO(CH(2))(n)N(+)(CH(3))R(1)R(2)I(-)) were designed and synthesized as acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE) inhibitors. The synthetic compounds exhibite...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tang H,Ning FX,Wei YB,Huang SL,Huang ZS,Chan AS,Gu LQ

更新日期：2007-07-01 00:00:00

abstract：:The structure activity relationship on a series of ester and hydroxamate analogues of methionyl and isoleucyl adenylate has been investigated through introducing linkers between the 1'-position of ribose and adenine surrogates as methionyl-tRNA, and isoleucyl-tRNA synthetase inhibitors, respectively. The results indic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee J,Kang SU,Kim SY,Kim SE,Kang MK,Jo YJ,Kim S

更新日期：2001-04-23 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：:Several chemical modifications in the N(1)-benzenesulfonamide ring of celecoxib are presented. The series with a hydroxymethyl group adjacent to the sulfonamide was found to be the most potent modification that yielded many compounds selectively active against COX-2 enzyme in vitro. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh SK,Reddy PG,Rao KS,Lohray BB,Misra P,Rajjak SA,Rao YK,Venkateswarlu A

更新日期：2004-01-19 00:00:00

abstract：:This Letter describes the chemical optimization of a novel series of M4 positive allosteric modulators (PAMs) based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3-d]pyrimidine core, identified from an MLPCN functional high-throughput screen. The HTS hit was potent and selective, but not CNS penetrant. Potency was main...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wood MR,Noetzel MJ,Engers JL,Bollinger KA,Melancon BJ,Tarr JC,Han C,West M,Gregro AR,Lamsal A,Chang S,Ajmera S,Smith E,Chase P,Hodder PS,Bubser M,Jones CK,Hopkins CR,Emmitte KA,Niswender CM,Wood MW,Duggan ME,C

更新日期：2016-07-01 00:00:00

abstract：:New Lp-PLA(2) inhibitors were synthesized by the bioisosteric replacement of the amide group of Darapladib with an imidazole or a triazole. Unfortunately, the inhibitory activities of these derivatives were lower than that of Darapladib. But interestingly, a series of quaternary ammonium salts that were isolated as by...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang K,Xu W,Liu Y,Zhang W,Wang W,Shen J,Wang Y

更新日期：2013-03-01 00:00:00

abstract：:An Mg2+ and ATP dependent beta-lactam synthetase (BLS) catalyses formation of a beta-lactam ring during the biosynthesis of clavulanic acid, an important beta-lactamase inhibitor. An epimeric mixture of a 2-methylated derivative of the natural BLS substrate N2-(2-carboxyethyl)-L-arginine was synthesised and found to b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sleeman MC,MacKinnon CH,Hewitson KS,Schofield CJ

更新日期：2002-02-25 00:00:00

abstract：:A series of N-phenylnicotinamides (1-40) were designed and evaluated in vitro for their COX inhibitory activities. Most of the synthesized compounds were proved to be potent and selective inhibitors of COX-1. Compound 28 showed the most potent COX-1 inhibitory activity (COX-1 IC(50) = 0.68 ± 0.07 μM) and good selectiv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi L,Li ZL,Yang Y,Zhu ZW,Zhu HL

更新日期：2011-01-01 00:00:00

abstract：:2,3-Dihydro-3,8-diphenylbenzo[1,4]oxazines were identified as a new class of potent cholesteryl ester transfer protein inhibitors. The most potent compound 6a (IC50=26 nM) possessed a favorable pharmacokinetic profile with good oral bioavailability in rat (F=53%) and long human liver microsome stability (t(1/2)=62 min...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang A,Prouty CP,Pelton PD,Yong M,Demarest KT,Murray WV,Kuo GH

更新日期：2010-02-15 00:00:00

abstract：:We have discovered a new class of colchicine-derived therapeutic agents for immune diseases including rejection of organ-transplantation and autoimmune disease. Compound 2, which had been developed to overcome poor pharmacokinetic properties of compound 1, a first-generation colchicine analog, turned out to show toxic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chang DJ,Kim WJ

更新日期：2014-07-15 00:00:00

abstract：:Early studies led to the identification of 11β-aryl-4',5'-dihydrospiro[estra-4,9-diene-17β,4'-oxazole] analogs with potent and more selective antiprogestational activity compared to antiglucocorticoid activity than mifepristone. In the present study, we replaced the 4'-dimethylaminophenyl group of mifepristone with th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin C,Fix SE,Kepler JA,Cook CE

更新日期：2012-02-15 00:00:00

abstract：:New A-ring modified betulinic acid derivatives having small steric hindrance were prepared and tested for cytotoxic activity on 3 cancer cell lines: 10 compounds showed stronger cytotoxic activity than betulinic acid. Especially, the compounds bearing 1-ene-3-oxo with electron-withdrawing groups at C2 showed strong cy...

journal_title：Bioorganic & medicinal chemistry letters

authors： You YJ,Kim Y,Nam NH,Ahn BZ

更新日期：2003-10-06 00:00:00

abstract：:A series of aryl amines was found to induce cleavage of DNA. Subsequent refinement led to an efficient family of dimeric derivatives capable of cleavage at low concentration. Initial investigations suggest this is an unprecedented mode of DNA cleavage, which may be ultimately applied to the development of sequence-spe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Warner PM,Qi J,Meng B,Li G,Xie L,El-Shafey A,Jones GB

更新日期：2002-01-07 00:00:00

abstract：:We demonstrate the synthesis and selective binding of two novel furan based tricyclic homo-oligopeptides to G-quadruplex and using Real Time PCR show its repressive effect on c-MYC transcription. CD spectroscopy and FRET melting studies show that these ligands can induce G-quadruplex structures in the G rich 22 mer c-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Agarwal T,Roy S,Chakraborty TK,Maiti S

更新日期：2010-08-01 00:00:00

abstract：:Novel phenethylpyridone derivatives were identified as potent human melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. A search for surrogates for the 4-(2-aminoethoxy)phenyl moiety of 1 resulted in discovery of 2-[4-(aminomethyl)phenyl]ethyl substructure as in 6a. Successive optimization of the right-hand...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ando M,Sekino E,Haga Y,Moriya M,Ito M,Ito J,Iwaasa H,Ishihara A,Kanatani A,Ohtake N

更新日期：2009-09-01 00:00:00

abstract：:New inhibitors of palmitoyl-CoA oxidation are based on the introduction of nitrogen heterocycles in the 'Western Portion' of the molecule. SAR studies led to the discovery of CVT-4325 (shown), a potent FOXi (IC50=380 nM rat mitochondria) with favorable PK properties (F=93%, t(1/2)=13.6h, dog). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Elzein E,Ibrahim P,Koltun DO,Rehder K,Shenk KD,Marquart TA,Jiang B,Li X,Natero R,Li Y,Nguyen M,Kerwar S,Chu N,Soohoo D,Hao J,Maydanik VY,Lustig DA,Zeng D,Leung K,Zablocki JA

更新日期：2004-12-20 00:00:00

abstract：:In a continuing effort to discover novel PDE5 inhibitors, we have successfully found quinazolines with 4-benzylamino substitution as potent and selective PDE5 inhibitors. Initial lead compound (1) was found to be easily metabolized when incubated with human liver microsomes mainly through C6 amide hydrolysis. Blocking...

journal_title：Bioorganic & medicinal chemistry letters

authors： Choi H,Lee J,Kim YH,Im DS,Hwang IC,Kim SJ,Moon SK,Lee HW,Lee SS,Ahn SK,Kim SW,Choi NS,Lee KJ

更新日期：2010-01-01 00:00:00

abstract：:We report the discovery of piperazine urea based compound 1, a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist. Compound 1 shows anti-obesity efficacy without potentiating erectile activity in the rodent models. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hong Q,Bakshi RK,Palucki BL,Park MK,Ye Z,He S,Pollard PG,Sebhat IK,Liu J,Guo L,Cashen DE,Martin WJ,Weinberg DH,MacNeil T,Tang R,Tamvakopoulos C,Peng Q,Miller RR,Stearns RA,Chen HY,Chen AS,Strack AM,Fong TM,M

更新日期：2011-04-15 00:00:00

abstract：:The synthesis of novel C6-aryl substituted derivatives of 3-(dimethylamino)chroman is described. The novel derivatives display 5-HT(7) receptor affinities that varies from nM to muM, indicating that this small set of derivatives constitute a novel and interesting starting point for further structure-serotonin 5-HT(7) ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Holmberg P,Tedenborg L,Rosqvist S,Johansson AM

更新日期：2005-02-01 00:00:00

abstract：:A series of substituted biphenyl ethylene ether compounds has been designed to target the gp41N-trimer in order to inhibit formation of the six-helical bundle that represents the end state of gp41-mediated viral fusion. A size exclusion HPLC based helical bundle formation (HBF) assay was developed to evaluate in vitro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu B,Joseph RW,Dorsey BD,Schiksnis RA,Northrop K,Bukhtiyarova M,Springman EB

更新日期：2009-10-01 00:00:00

abstract：:Perfluorination of phthalimides leads to dramatically increased potency as inhibitors of TNF-alpha production. We examined the enantiodependence for several tetrafluorophthalimides and alpha-methylthalidomide, 3. Only 3 exhibited strikingly enantiodependent activity. The key structural determinant for the enhanced act...

journal_title：Bioorganic & medicinal chemistry letters

authors： Niwayama S,Loh C,Turk BE,Liu JO,Miyachi H,Hashimoto Y

更新日期：1998-05-05 00:00:00

abstract：:The chiral analogues of gemfibrozil 5-(2,5-dimethylphenoxy)-2-methylpentanoic acid and 5-(2,5-dimethylphenoxy)-2-ethylpentanoic acid were synthesized in optically active form using (S)-4-(1-methylethyl)-2-oxazolidinone as chiral auxiliary. All compounds inhibit human platelet aggregation. From these data, one can surm...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ammazzalorso A,Amoroso R,Baraldi M,Bettoni G,Braghiroli D,De Filippis B,Duranti A,Moretti M,Tortorella P,Tricca ML,Vezzalini F

更新日期：2002-03-11 00:00:00