Design and synthesis of piperidinyl piperidine analogues as potent and selective M2 muscarinic receptor antagonists.

abstract：:A series of novel pyrimido and other fused quinoline derivatives like 4-methyl pyrimido [5,4-c]quinoline-2,5(1H,6H)-dione (4a), 4-methyl-2-thioxo-1,2-dihydropyrimido [5,4-c]quinoline-5(6H)-one (4b), 2-amino-4-methyl-1,2-dihydropyrimido [5,4-c]quinolin-5(6H)-one (4c), 3-methylisoxazolo [4,5-c]quinolin-4(5H)-one (4d), 3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sankaran M,Kumarasamy C,Chokkalingam U,Mohan PS

更新日期：2010-12-01 00:00:00

abstract：:The design and synthesis of a series of novel, reversible, small molecule inhibitors of caspase-3 are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Allen DA,Pham P,Choong IC,Fahr B,Burdett MT,Lew W,DeLano WL,Gordon EM,Lam JW,O'Brien T,Lee D

更新日期：2003-11-03 00:00:00

abstract：:A series of (E)-N-Aryl-2-oxo-2-(3,4,5-trimethoxyphenyl)acetohydrazonoyl cyanides have been synthesized and evaluated for their anticancer activity in human hepatocellular liver carcinoma HepG2 and breast adenocarcinoma MCF-7 cell lines. Among all the tested compounds, compound 3a, 3e and 3n displayed more activity tha...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang G,Peng Z,Peng S,Qiu J,Li Y,Lan Y

更新日期：2018-11-01 00:00:00

abstract：:Human isoprenylcysteine carboxyl methyltransferase (hIcmt) is a promising anticancer target as it is important for the post-translational modification of oncogenic Ras proteins. We herein report the synthesis and biochemical activity of 41 farnesyl-cysteine based analogs versus hIcmt. We have demonstrated that the ami...

journal_title：Bioorganic & medicinal chemistry letters

authors： Majmudar JD,Hahne K,Hrycyna CA,Gibbs RA

更新日期：2011-05-01 00:00:00

abstract：:Eight peptoids have been synthesized as peptidomimetics of the cytostatic Dolastatin 15, a depsipeptide isolated from the Indian sea hare Dolabella auricularia. The compounds have been tested against several human cancer cell lines and did not show any cytostatic properties. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schmitt J,Bernd M,Kutscher B,Kessler H

更新日期：1998-02-17 00:00:00

abstract：:Interleukin-2 inducible T-cell kinase (ITK) is a member of the Tec kinase family and is involved with T-cell activation and proliferation. Due to its critical role in acting as a modulator of T-cells, ITK inhibitors could provide a novel route to anti-inflammatory therapy. This work describes the discovery of ITK inhi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cook BN,Bentzien J,White A,Nemoto PA,Wang J,Man CC,Soleymanzadeh F,Khine HH,Kashem MA,Kugler SZ Jr,Wolak JP,Roth GP,De Lombaert S,Pullen SS,Takahashi H

更新日期：2009-02-01 00:00:00

abstract：:The isopolar nonisosteric phosphonate analogs of ApA differing in the position of extra methylene group introduced into the sugar-phosphate backbone, featuring both possible 2',5'- and 3',5'- pairs as well as their conformationally restricted congeners, were investigated for their ability to form complexes with polyU....

journal_title：Bioorganic & medicinal chemistry letters

authors： Pressová M,Endová M,Toĉík Z,Liboska R,Rosenberg I

更新日期：1998-05-19 00:00:00

abstract：:We synthesized prodrug-type phosphotriester (PTE) oligonucleotides containing the six-membered cyclic disulfide moiety by using phosphoramidite chemistry. Prodrug-type oligonucleotides named "Reducing-Environment-Dependent Uncatalyzed Chemical Transforming (REDUCT) PTE oligonucleotides" were converted into natural oli...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hayashi J,Samezawa Y,Ochi Y,Wada SI,Urata H

更新日期：2017-07-15 00:00:00

abstract：:In silico modelling was used to guide the positioning of the fluorescent dye NBD-F on the cannabinoid CB2 receptor agonist JWH-015. While the ultimate fluorescent conjugate lost extensive binding affinity to the cannabinoid CB2 receptor, affinity and efficacy studies on the naphthoyl 3-position modified precursor mole...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yates AS,Doughty SW,Kendall DA,Kellam B

更新日期：2005-08-15 00:00:00

abstract：:Pyrrole-imidazole polyamides can be synthesized to target predetermined sequences of DNA with nanomolar affinity and high specificity, and have been shown to modulate gene transcription both in vitro and in vivo. To make polyamides more readily available to biological laboratories, we have developed a rapid solid-phas...

journal_title：Bioorganic & medicinal chemistry letters

authors： Krutzik PO,Chamberlin AR

更新日期：2002-08-19 00:00:00

abstract：:Beginning with carbazole 1a, the amide and alkyl substituents were optimized to maintain potency while adding solubilizing groups. Efforts to replace the 3-amino-9-ethylcarbazole core, a known carcinogen, used the SAR generated in the carbazole series for guidance and led to the synthesis of a number of core-modified ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hammond M,Elliott RL,Gillaspy ML,Hager DC,Hank RF,LaFlamme JA,Oliver RM,DaSilva-Jardine PA,Stevenson RW,Mack CM,Cassella JV

更新日期：2003-06-16 00:00:00

abstract：:Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new drugs acting at the dopamine receptors (DR) as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous stud...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moreno L,Cabedo N,Ivorra MD,Sanz MJ,Castel AL,Carmen Álvarez M,Cortes D

更新日期：2013-09-01 00:00:00

abstract：:The design and synthesis of a novel series of non-nucleoside HIV reverse transcriptase inhibitors (NNRTIs) based on a pyrazole template is described. These compounds are active against wild type reverse transcriptase (RT) and retain activity against clinically important mutants. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mowbray CE,Burt C,Corbau R,Perros M,Tran I,Stupple PA,Webster R,Wood A

更新日期：2009-10-01 00:00:00

abstract：:A series of 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues were synthesized and evaluated for cytotoxic activity against eight human cancer cell lines. Compounds 18, 21, 28, 29, 30 and 31 showed cytotoxic activity with GI(50) values in the range of 2.1-8.1 microM concentration. Among these, compounds 21...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharma VM,Adi Seshu KV,Vamsee Krishna C,Prasanna P,Chandra Sekhar V,Venkateswarlu A,Rajagopal S,Ajaykumar R,Deevi DS,Rao Mamidi NV,Rajagopalan R

更新日期：2003-05-19 00:00:00

abstract：:This communication describes the high-throughput screen of a diverse library of 50,000 small molecules against Escherichia coli dihydrofolate reductase to detect inhibitors. Sixty-two compounds were identified as having significant inhibitory activity against the enzyme. Secondary screening of these revealed twelve mo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zolli-Juran M,Cechetto JD,Hartlen R,Daigle DM,Brown ED

更新日期：2003-08-04 00:00:00

abstract：:The general strategy and rationale underlying the design of COPD therapeutics that possess protease inhibitory activity and are also capable of releasing a species that attenuates inflammation by inhibiting caspase-1, are described. The synthesis and in vitro biochemical evaluation of a dual function molecule that seq...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dou D,He G,Alliston KR,Groutas WC

更新日期：2011-05-15 00:00:00

abstract：:SAR studies for the exploration a novel class of anti-human immunodeficiency virus type 1 (HIV-1) agents based on the hematoxylin structure (1) are described. The systematic deoxygenations of 1 including asymmetric synthesis were conducted to obtain a compound showing high potencies for inhibiting the nuclear import a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishii H,Koyama H,Hagiwara K,Miura T,Xue G,Hashimoto Y,Kitahara G,Aida Y,Suzuki M

更新日期：2012-02-01 00:00:00

abstract：:All the stereoisomers of 2-(2-carboxy-3,3-difluorocyclopropyl)glycines (F2CCGs) were synthesized in enantiomerically pure forms using (R)-2,3-O-isopropyl-ideneglyceraldehyde as a chiral precursor. L-F2CCG-I, one of the stereoisomers corresponding to an extended form of L-glutamate was found to be a potent agonist for ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shibuya A,Sato A,Taguchi T

更新日期：1998-08-04 00:00:00

abstract：:A high throughput screen allowed the identification of N-hydroxyimide inhibitors of ERCC1-XPF endonuclease activity with micromolar potency, but they showed undesirable selectivity profiles against FEN-1. A scaffold hop to a hydroxypyrimidinone template gave compounds with similar potency but allowed selectivity to be...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chapman TM,Wallace C,Gillen KJ,Bakrania P,Khurana P,Coombs PJ,Fox S,Bureau EA,Brownlees J,Melton DW,Saxty B

更新日期：2015-10-01 00:00:00

abstract：:Constraining the catechol aryl ether moiety of bastadins by incorporation into a macrocyle is not necessary in order to mimic the effects of these marine natural products on neuronal calcium homeostasis. Simple, acyclic analogs that embody the 'western' or 'eastern' parts of bastadins were found to evoke comparable re...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zieminska E,Lazarewicz JW,Couladouros EA,Moutsos VI,Pitsinos EN

更新日期：2008-11-01 00:00:00

abstract：:A novel class of indomethacin analogs were synthesized wherein a N-difluoromethyl-1,2-dihydropyrid-2-one moiety (5-LOX pharmacophore) was attached at its C-4 or C-5 position via either a CO (14a-b) or CH(2) (19a-b) linker to the indole N(1)-position. In this regard, replacement of the 4-chlorobenzoyl group present in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chowdhury MA,Huang Z,Abdellatif KR,Dong Y,Yu G,Velázquez CA,Knaus EE

更新日期：2010-10-01 00:00:00

abstract：:Extensive SAR studies and optimization of ADME properties of benzimidazol-2-one derivatives led to the identification of BMS-433771 (3) as an orally active RSV fusion inhibitor. In order to extend the structure-activity relationships for this compound series, substitution of the benzimidazole ring was examined with a ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang XA,Cianci CW,Yu KL,Combrink KD,Thuring JW,Zhang Y,Civiello RL,Kadow KF,Roach J,Li Z,Langley DR,Krystal M,Meanwell NA

更新日期：2007-08-15 00:00:00

abstract：:We report a sensitive and efficient magnetic bead-based assay for viral DNA identification using isothermal amplification of a reporting probe. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schopf E,Fischer NO,Chen Y,Tok JB

更新日期：2008-11-15 00:00:00

abstract：:The synthesis of N-(O,O-diisopropylphosphoryl)-benzyltetrahydroisoquinoline (3) has been achieved in a 'one pot' procedure from imine (2) and diisopropyl-phosphorochloridate (1) generated in situ (POCl3 + iPrOH). Compound 3 is the first benzyltetrahydroisoquinoline derivative found to be a potent inhibitor of mitochon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Andreu I,Cabedo N,Tormo JR,Bermejo A,Mello R,Cortes D

更新日期：2000-07-03 00:00:00

abstract：:A regiochemical and stereochemical mixture of flexible linkers bearing terminal azide functionality was synthesized in two steps from squalene and was used to connect two high affinity NDP-alpha-MSH ligands or two low affinity MSH(4) ligands. The ligands were N-terminally acylated using N-hydroxysuccinimidoyl 5-hexyno...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jagadish B,Sankaranarayanan R,Xu L,Richards R,Vagner J,Hruby VJ,Gillies RJ,Mash EA

更新日期：2007-06-15 00:00:00

abstract：:Hydroxy urea moieties are introduced as a new class of bradykinin B(1) receptor antagonists. First, the SAR of the lead compound was systematically explored. Subsequent optimization resulted in the identification of several biaryl-based hydroxyurea bradykinin B(1) receptor antagonists with low-nanomolar activity and v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schnatbaum K,Schaudt M,Stragies R,Pfeifer JR,Gibson C,Locardi E,Scharn D,Richter U,Kalkhof H,Dinkel K,Zischinsky G

更新日期：2010-02-01 00:00:00

abstract：:In order to obtain rigidity within the sugar moiety of nucleosides, the bicyclic pyrimidine derivatives of N,O-isoxazolidines were designed and synthesized by using 1,3-dipolar cycloaddition of Delta(1)-pyrrolidine-1-oxide and the appropriate vinyl-nucleobases. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Procopio A,Alcaro S,De Nino A,Maiuolo L,Ortuso F,Sindona G

更新日期：2005-02-01 00:00:00

abstract：:We identified and tested bisphosphonates as inhibitors of a protozoan molecular target. Computational modeling studies demonstrated that these compounds are mimics of the natural substrate of the enzyme. The most potent bisphosphonates in vitro are pamidronate and risedronate, which inhibit the purine transferase from...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fernández D,Wenck MA,Craig SP 3rd,Delfino JM

更新日期：2004-09-06 00:00:00

abstract：:Fatty acid biosynthesis is essential for bacterial survival. FabH, beta-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and -negative bacteria. Fifty-six 1-acetyl-3,5-diph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lv PC,Sun J,Luo Y,Yang Y,Zhu HL

更新日期：2010-08-01 00:00:00

abstract：:Myelin associated glycoprotein (Siglec-4) is a myelin adhesion receptor, that is, well established for its role as an inhibitor of axonal outgrowth in nerve injury, mediated by binding to sialic acid containing ligands on the axonal membrane. Because disruption of myelin-ligand interactions promotes axon outgrowth, we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zeng Y,Rademacher C,Nycholat CM,Futakawa S,Lemme K,Ernst B,Paulson JC

更新日期：2011-09-01 00:00:00