共查询到20条相似文献,搜索用时 218 毫秒
1.
Bronk BS Letavic MA Bertsche CD George DM Hayashi SF Kamicker BJ Kolosko NL Norcia LJ Rushing MA Santoro SL Yang BV 《Bioorganic & medicinal chemistry letters》2003,13(12):1955-1958
Modification of the cladinose C-4" position via manipulation of the corresponding keto derivatives afforded two stereochemically pure series of compounds. The synthesis and structure determination of these compounds is described within. The in vitro and in vivo biological activity of this novel series of C-4" modified macrolides is also described. 相似文献
2.
Wrobleski ML Reichard GA Paliwal S Shah S Tsui HC Duffy RA Lachowicz JE Morgan CA Varty GB Shih NY 《Bioorganic & medicinal chemistry letters》2006,16(14):3859-3863
A series of novel cyclobutane derivatives as potent and selective NK1 receptor antagonists is described. Several compounds in this series exhibited high in vitro binding affinity (Ki 相似文献
3.
Mark J. Wall Nalin L. Subasinghe Michael P. Winters Mary Lou Lubin Michael F.A. Finley Ning Qin Michael R. Brandt Michael P. Neeper Craig R. Schneider Raymond W. Colburn Christopher M. Flores Zhihua Sui 《Bioorganic & medicinal chemistry letters》2018,28(23-24):3780-3783
A novel series of pyrazolyltetrahydropyran N-type calcium channel blockers are described. Structural modifications of the series led to potent compounds in both a cell-based fluorescent calcium influx assay and a patch clamp electrophysiology assay. Representative compounds from the series were bioavailable and showed efficacy in the rat CFA and CCI models of inflammatory and neuropathic pain. 相似文献
4.
Hanessian S Larsson A Fex T Knecht W Blomberg N 《Bioorganic & medicinal chemistry letters》2010,20(23):6925-6928
The synthesis of a series of novel macrocyclic compounds designed to target blood coagulation Factor XIa is described. The compounds were evaluated for their inhibition of a small set of serine proteases. Several compounds displayed modest activity and good selectivity for Factor XIa. Within the series, a promising lead structure for developing novel macrocyclic inhibitors of thrombin was identified. 相似文献
5.
Frazier K Jazan E McBride CM Pecchi S Renhowe PA Shafer CM Taylor C Bussiere D He MM Jansen JM Lapointe G Ma S Vora J Wiesmann M 《Bioorganic & medicinal chemistry letters》2006,16(8):2247-2251
Herein are described a series of novel heterocyclic analogs of the 4-amino-3-benzimidazol-2-ylhydroquinolin-2-one scaffold. These compounds are potent inhibitors of receptor tyrosine kinases and exhibit favorable pharmacokinetic profiles. The synthesis and SAR of these compounds are described. 相似文献
6.
Whitman DB Askew BC Duong le T Fernandez-Metzler C Halczenko W Hartman GD Hutchinson JH Leu CT Prueksaritanont T Rodan GA Rodan SB Duggan ME 《Bioorganic & medicinal chemistry letters》2004,14(17):4411-4415
A series of alphaVbeta3 receptor antagonists lacking the amide bond of previously-reported 'chain-shortened' compounds is described. Replacement of the lone amide bond with two methylene groups in this series yields more lipophilic compounds that have longer half-lives, lower clearance, and greater oral bioavailability when administered to dogs. 相似文献
7.
Zych AJ Lam SQ Jenkins DM Herr RJ Ting PC Lee JF Kuang R Wu H Kim DW Aslanian RG Wainhaus S Black TA Cacciapuoti A McNicholas PM Xu Y Walker SS 《Bioorganic & medicinal chemistry letters》2012,22(14):4896-4899
The structure-activity relationship studies of a novel sulfonylurea series of piperazine pyridazine-based small molecule glucan synthase inhibitors is described. The optimization of PK profiles within the series led to the discovery of several compounds with improved pharmacokinetic profiles which demonstrated in vitro potency against clinically relevant strains. However, the advancement of compounds from this series into a non-lethal systemic fungal infection model failed to show in vivo efficacy. 相似文献
8.
Gharbaoui T Skinner PJ Shin YJ Averbuj C Jung JK Johnson BR Duong T Decaire M Uy J Cherrier MC Webb PJ Tamura SY Zou N Rodriguez N Boatman PD Sage CR Lindstrom A Xu J Schrader TO Smith BM Chen R Richman JG Connolly DT Colletti SL Tata JR Semple G 《Bioorganic & medicinal chemistry letters》2007,17(17):4914-4919
A strategy for lead identification of new agonists of GPR109a, starting from known compounds shown to activate the receptor, is described. Early compound triage led to the formulation of a binding hypothesis and eventually to our focus on a series of pyrazole acid derivatives. Further elaboration of these compounds provided a series of 5,5-fused pyrazoles to be used as lead compounds for further optimization. 相似文献
9.
Gentile G Merlo G Pozzan A Bernasconi G Bax B Bamborough P Bridges A Carter P Neu M Yao G Brough C Cutler G Coffin A Belyanskaya S 《Bioorganic & medicinal chemistry letters》2012,22(5):1989-1994
5-Aryl-4-carboxamide-1,3-oxazoles are a novel, potent and selective series of GSK-3 inhibitors. The optimization of the series to yield compounds with cell activity and brain permeability is described. 相似文献
10.
Dymock B Barril X Beswick M Collier A Davies N Drysdale M Fink A Fromont C Hubbard RE Massey A Surgenor A Wright L 《Bioorganic & medicinal chemistry letters》2004,14(2):325-328
Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors. 相似文献
11.
Andrews MJ Clase JA Bar G Tricarico G Edwards PJ Brys R Chambers M Schmidt W MacLeod A Hirst K Allen V Birault V Le J Harris J Self A Nash K Dixon G 《Bioorganic & medicinal chemistry letters》2012,22(6):2266-2270
MAPKAPK5 has been proposed to play a role in regulation of matrix metalloprotease expression and so to be a potential target for intervention in rheumatoid arthritis. We present here the identification of a series of compounds against this target which are effective in both biochemical and cell assays. The expansion of the series is described, along with early SAR and pharmacokinetics for some representative compounds. 相似文献
12.
Carreon JR Stewart KM Mahon KP Shin S Kelley SO 《Bioorganic & medicinal chemistry letters》2007,17(18):5182-5185
A series of fluorescent compounds suitable for live cell imaging is described. Functionalized forms of four different asymmetric cyanine dyes are reported that are amenable to peptide conjugation. The photophysical properties of the modified dyes and conjugates and the use of the compounds as cellular imaging agents are described. The results obtained indicate that these spectrally versatile compounds, which have absorption and emission profiles spanning the visible spectrum, are useful probes for cellular imaging. 相似文献
13.
The synthesis and biological activity of a series of azatricyclodecane analogues of cocaine are described. All compounds studied in this series exhibit nanomolar potency and good selectivity for the serotonin transporter versus the dopamine transporter. 相似文献
14.
Bruncko M McClellan WJ Wendt MD Sauer DR Geyer A Dalton CR Kaminski MA Weitzberg M Gong J Dellaria JF Mantei R Zhao X Nienaber VL Stewart K Klinghofer V Bouska J Rockway TW Giranda VL 《Bioorganic & medicinal chemistry letters》2005,15(1):93-98
A series of non-amide-linked 6-substituted-2-naphthamidine urokinase plasminogen activator (uPA) inhibitors are described. These compounds possess excellent binding activities and selectivities with significantly improved pharmacokinetic profiles versus previously described amide-linked inhibitors. 相似文献
15.
Xianfeng Li Yong-Kang Zhang Yang Liu Charles Z. Ding Qun Li Yasheen Zhou Jacob J. Plattner Stephen J. Baker Xuelei Qian Dazhong Fan Liang Liao Zhi-Jie Ni Gemma V. White Jackie E. Mordaunt Linos X. Lazarides Martin J. Slater Richard L. Jarvest Pia Thommes Malcolm Ellis Colin M. Edge Lewis E. Pennicott 《Bioorganic & medicinal chemistry letters》2010,20(12):3550-3556
We have designed and synthesized a novel series of α-amino cyclic boronates and incorporated them successfully in several acyclic templates at the P1 position. These compounds are inhibitors of the HCV NS3 serine protease, and structural studies show that they inhibit the NS3 protease by trapping the Ser-139 hydroxyl group in the active site. Synthetic methodologies and SARs of this series of compounds are described. 相似文献
16.
Lagu B Gerchak C Pan M Hou C Singer M Malaviya R Matheis M Olini G Cavender D Wachter M 《Bioorganic & medicinal chemistry letters》2007,17(15):4382-4386
A number of compounds bearing a quaternary ammonium moiety were found to be antagonists with nanomolar binding affinity for the chemokine receptor-2. The structure-activity relationships in the series are described herein along with some detailed characterization of the interesting compounds. 相似文献
17.
Noel R Song X Shin Y Banerjee S Kojetin D Lin L Ruiz CH Cameron MD Burris TP Kamenecka TM 《Bioorganic & medicinal chemistry letters》2012,22(11):3739-3742
The design and synthesis of a novel series of Rev-erbα agonists is described. The development and optimization of the tetrahydroisoquinoline series was carried out from an earlier acyclic series of Rev-erbα agonists. Through the optimization of the scaffold 1, several potent compounds with good in vivo profiles were discovered. 相似文献
18.
Hennessy EJ Saeh JC Sha L MacIntyre T Wang H Larsen NA Aquila BM Ferguson AD Laing NM Omer CA 《Bioorganic & medicinal chemistry letters》2012,22(4):1690-1694
A series of structurally unique Smac mimetics that act as antagonists of inhibitor of apoptosis proteins (IAPs) has been discovered. While most previously described Smac mimetics contain the proline ring (or a similar cyclic motif) found in Smac, a key feature of the compounds described herein is that this ring has been removed. Despite this, compounds in this series potently bind to cIAP1 and elicit the expected phenotype of cIAP1 inhibition in cancer cells. Marked selectivity for cIAP1 over XIAP is observed for these compounds, which is attributed to a slight difference in the binding groove between the two proteins and the resulting steric interactions with the inhibitors. XIAP binding can be improved by constraining the inhibitor so that these unfavorable steric interactions are minimized. 相似文献
19.
Denonne F Binet S Burton M Collart P Defays S Dipesa A Eckert M Giannaras A Kumar S Levine B Nicolas JM Pasau P Pégurier C Preda D Van houtvin N Volosov A Zou D 《Bioorganic & medicinal chemistry letters》2007,17(12):3262-3265
The synthesis and structure-activity relationships against the C3a receptor of a series of substituted aminopiperidine derivatives are reported. DMPK properties and functional activities of selected compounds are described. The compounds obtained are the first non-arginine ligands of C3aR. 相似文献
20.
Roy V Zerrouki R Krausz P Laumond G Aubertin AM 《Nucleosides, nucleotides & nucleic acids》2007,26(5):413-421
This article describes the synthesis of a series of AZT analogues bearing an acyclic chain between the sugar and the base moieties is described. These new compounds were readily obtained using microwave irradiation. The compounds were characterized by (1)H NMR and IR spectroscopy. Antiviral (HIV-1) properties of these compounds were examined. 相似文献