排序方式: 共有56条查询结果,搜索用时 15 毫秒
1.
Njoroge FG Vibulbhan B Pinto P Strickland C Kirschmeier P Bishop WR Girijavallabhan V 《Bioorganic & medicinal chemistry letters》2004,14(23):5877-5880
Successful efforts to make farnesyl transferase (FT) inhibitors with appropriately tethered ligands designed to interact with a catalytic zinc that exist in the enzyme have been realized. Thus, by introducing either a pyridylmethylamino or propylaminolimidazole amide moieties off the 2-position of the piperidine ring, FT inhibitors with activities in the picomolar range have been achieved as exemplified by compounds 12a and 12b. An X-ray structure of 11b bound to FT shows the enhanced activity is a result of interacting with the active-site zinc. 相似文献
2.
Girijavallabhan VM Chen L Dai C Feltz RJ Firmansjah L Li D Kim SH Kozlowski JA Lavey BJ Kosinski A Piwinski JJ Popovici-Muller J Rizvi R Rosner KE Shankar BB Shih NY Siddiqui MA Tong L Wong MK Yang DY Yang L Yu W Zhou G Guo Z Orth P Madison V Bian H Lundell D Niu X Shah H Sun J Umland S 《Bioorganic & medicinal chemistry letters》2010,20(24):7283-7287
Our research on hydantoin based TNF-α converting enzyme (TACE) inhibitors has led to an acetylene containing series that demonstrates sub-nanomolar potency (K(i)) as well as excellent activity in human whole blood. These studies led to the discovery of highly potent TACE inhibitors with good DMPK profiles. 相似文献
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Srikanth Venkatraman Wanli Wu Andrew Prongay Viyyoor Girijavallabhan F. George Njoroge 《Bioorganic & medicinal chemistry letters》2009,19(1):180-183
Chronic hepatitis C infection is the leading causes for cirrhosis of the liver and hepatocellular carcinoma, leading to liver failure and liver transplantation. The etiological agent, HCV virus produces a single positive strand of RNA that is processed with the help of serine protease NS3 to produce mature virus. Inhibition of NS3 protease can be potentially used to develop effective drugs for HCV infections. Numerous efforts are now underway to develop potent inhibitors of HCV protease that contain ketoamides as serine traps. Herein we report the synthesis of a series of potent inhibitors that contain a boronic acid as a serine trap. The activity of these compounds were optimized to 200 pM. X-ray structure of compound 17 bound to NS3 protease is also discussed. 相似文献
5.
Pedro LC Pinheiro João CR Cardoso Ana S Gomes Juan Fuentes Deborah M Power Adelino VM Canário 《BMC evolutionary biology》2010,10(1):373
Background
Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) belong to a family of endocrine factors that share a highly conserved N-terminal region (amino acids 1-34) and play key roles in calcium homeostasis, bone formation and skeletal development. Recently, PTH-like peptide (PTH-L) was identified in teleost fish raising questions about the evolution of these proteins. Although PTH and PTHrP have been intensively studied in mammals their function in other vertebrates is poorly documented. Amphibians and birds occupy unique phylogenetic positions, the former at the transition of aquatic to terrestrial life and the latter at the transition to homeothermy. Moreover, both organisms have characteristics indicative of a complex system in calcium regulation. This study investigated PTH family evolution in vertebrates with special emphasis on Xenopus and chicken. 相似文献6.
Venkatraman S Njoroge FG Wu W Girijavallabhan V Prongay AJ Butkiewicz N Pichardo J 《Bioorganic & medicinal chemistry letters》2006,16(6):1628-1632
Prolonged hepatitis C infection is the leading cause for cirrhosis of the liver and hepatocellular carcinoma. The etiological agent HCV virus codes a single polyprotein of approximately 3000 amino acids that is processed with the help of a serine protease NS3A to produce structural and non-structural proteins required for viral replication. Inhibition of NS3 protease can potentially be used to develop drugs for treatment of HCV infections. Herein, we report the development of a series of novel NS3 serine protease inhibitors derived from 2-aza-bicyclo[2.2.1]-heptane carboxylic acid with potential therapeutic use for treatment of HCV infections. 相似文献
7.
Hydroxylated analogues of the orally active broad spectrum antifungal, Sch 51048 (1), and the discovery of posaconazole [Sch 56592; 2 or (S,S)-5 总被引:1,自引:0,他引:1
Bennett F Saksena AK Lovey RG Liu YT Patel NM Pinto P Pike R Jao E Girijavallabhan VM Ganguly AK Loebenberg D Wang H Cacciapuoti A Moss E Menzel F Hare RS Nomeir A 《Bioorganic & medicinal chemistry letters》2006,16(1):186-190
As part of a detailed study, the syntheses, biological activities, and pharmacokinetic properties of hydroxylated analogues of the previously described broad spectrum antifungal agents, Sch 51048 (1), Sch 50001 (3), and Sch 50002 (4), are described. Based on an overall superior profile, one of the alcohols, Sch 56592 (2), was selected for clinical studies. 相似文献
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Njoroge FG Vibulbhan B Pinto P Strickland CL Bishop WR Kirschmeir P Girijavallabhan V Ganguly AK 《Bioorganic & medicinal chemistry》2003,11(1):139-143
SCH 66336 is a trihalo tricyclic compound that is currently undergoing Phase II clinical trials for the treatment of solid tumors. Modifications of SCH 66336 by incorporating such groups as amides, acids, esters, ureas and lactams off the first or the distal piperidine (from the tricycle) provided potent FPT inhibitors some of which exhibited good cellular activity. A number of these compounds incorporate properties that might improve pharmacokinetic stability of these inhibitors by virtue of their increased solubility or by their change in log P. 相似文献
9.
VM Girijavallabhan C Alvarez F Bennett L Chen S Gavalas Y Huang SH Kim A Kosinski P Pinto R Rizvi R Rossman B Shankar L Tong F Velazquez S Venkatraman VA Verma J Kozlowski NY Shih JJ Piwinski M Maccoss CD Kwong N Bansal JL Clark AT Fowler HS Kezar J Valiyaveettil RC Reynolds JA Maddry S Ananthan JA Secrist C Li R Chase S Curry HC Huang X Tong FG Njoroge A Arasappan 《Bioorganic & medicinal chemistry letters》2012,22(17):5652-5657
Introduction of a nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzothiazole inhibitor 1, resulted in the discovery of the more potent pyridothiazole analogues 3. The potency and PK properties of the compounds were attenuated by the introductions of various functionalities at the R(1), R(2) or R(3) positions of the molecule (compound 3). Inhibitors 38 and 44 displayed excellent potency, selectivity (GAPDH/MTS CC(50)), PK parameters in all species studied, and cross genotype activity. 相似文献
10.
Hugh Y. Zhu Alan B. Cooper Jagdish Desai George Njoroge Paul Kirschmeier W. Robert Bishop Corey Strickland Alan Hruza Ronald J. Doll Viyyoor M. Girijavallabhan 《Bioorganic & medicinal chemistry letters》2010,20(3):1134-1136
The discovery of C-linked imidazole azaheptapyridine bridgehead FPT inhibitors is described. This novel class of compounds are sub nM FPT enzyme inhibitors with potent cellular inhibitory activities. This series also has reduced hERG activity versus previous N-linked imidazole series. X-ray of compound 10a bound to FTase revealed strong interaction between bridgehead imidazole 3N with catalytic zinc atom. 相似文献