Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Bandarpalle B. Shankar is active.

Publication


Featured researches published by Bandarpalle B. Shankar.


Bioorganic & Medicinal Chemistry Letters | 2010

Discovery and SAR of hydantoin TACE inhibitors.

Wensheng Yu; Zhuyan Guo; Peter Orth; Madison; Liya Chen; Chaoyang Dai; Robert J. Feltz; Viyyoor Moopil Girijavallabhan; Seongkon Kim; Joseph A. Kozlowski; Brian J. Lavey; Dansu Li; Daniel Lundell; Xiaoda Niu; John J. Piwinski; Janeta Popovici-Muller; Razia Rizvi; Kristin E. Rosner; Bandarpalle B. Shankar; Neng-Yang Shih; M.A Siddiqui; Jing Sun; Ling Tong; Shelby Umland; Michael K.C. Wong; De-Yi Yang; Guowei Zhou

We disclose inhibitors of TNF-alpha converting enzyme (TACE) designed around a hydantoin zinc binding moiety. Crystal structures of inhibitors bound to TACE revealed monodentate coordination of the hydantoin to the zinc. SAR, X-ray, and modeling designs are described. To our knowledge, these are the first reported X-ray structures of TACE with a hydantoin zinc ligand.


Bioorganic & Medicinal Chemistry Letters | 2010

Biaryl substituted hydantoin compounds as TACE inhibitors

Wensheng Yu; Ling Tong; Seong Heon Kim; Michael K.C. Wong; Lei Chen; De-Yi Yang; Bandarpalle B. Shankar; Brian J. Lavey; Guowei Zhou; Aneta Kosinski; Razia Rizvi; Dansu Li; Robert J. Feltz; John J. Piwinski; Kristin E. Rosner; Neng-Yang Shih; M. Arshad Siddiqui; Zhuyan Guo; Peter Orth; Himanshu Shah; Jing Sun; Shelby Umland; Daniel Lundell; Xiaoda Niu; Joseph A. Kozlowski

We disclose further optimization of hydantoin TNF-alpha convertase enzyme (TACE) inhibitors. SAR with respect to the non-prime region of TACE active site was explored. A series of biaryl substituted hydantoin compounds was shown to have sub-nanomolar K(i), good rat PK, and good selectivity versus MMP-1, -2, -3, -7, -9, and -13.


Bioorganic & Medicinal Chemistry Letters | 2011

III. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl-piperazinyl-piperidine scaffold.

Seong Heon Kim; Gopinadhan N. Anilkumar; Lisa Guise Zawacki; Qingbei Zeng; De-Yi Yang; Yuefei Shao; Guizhen Dong; Xiaolian Xu; Wensheng Yu; Yueheng Jiang; Chung-Her Jenh; James W. Hall; Carolyn DiIanni Carroll; Doug W. Hobbs; John J. Baldwin; Brian F. Mcguinness; Stuart B. Rosenblum; Joseph A. Kozlowski; Bandarpalle B. Shankar; Neng-Yang Shih

The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. Compound 16e with single-digit CXCR3 affinity, good rat PK and hERG profiles has been identified as a lead for further study.


Bioorganic & Medicinal Chemistry Letters | 2016

Discovery of silyl proline containing HCV NS5A inhibitors with pan-genotype activity: SAR development

Anilkumar G. Nair; Qingbei Zeng; Oleg Selyutin; Stuart B. Rosenblum; Yueheng Jiang; De-Yi Yang; Kerry Keertikar; Guowei Zhou; Michael P. Dwyer; Seong Heon Kim; Bandarpalle B. Shankar; Wensheng Yu; Ling Tong; Lei Chen; Robert Mazzola; John P. Caldwell; Haiqun Tang; Melissa L. Allard; Ronald N. Buckle; Polivina Jolicia F Gauuan; Christian L. Holst; Gregory Scott Martin; Kannan P. Naicker; Samuel Vellekoop; Sony Agrawal; Rong Liu; Rong Kong; Paul Ingravallo; Ellen Xia; Ying Zhai

HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays thus making them attractive components for inclusion in an all oral fixed dose combination treatment regimen. Herein we describe the research efforts that led to the discovery of silyl proline containing HCV NS5A inhibitors such as 7e and 8a with pan-genotype activity profile and acceptable pharmacokinetic properties.


Bioorganic & Medicinal Chemistry Letters | 2011

2-(2-Aminothiazol-4-yl)pyrrolidine-based tartrate diamides as potent, selective and orally bioavailable TACE inhibitors.

Chaoyang Dai; Dansu Li; Janeta Popovici-Muller; Lianyun Zhao; Vinay Girijavallabhan; Kristin E. Rosner; Brian J. Lavey; Razia Rizvi; Bandarpalle B. Shankar; Michael K.C. Wong; Zhuyan Guo; Peter Orth; Corey O. Strickland; Jing Sun; Xiaoda Niu; Shiying Chen; Joseph A. Kozlowski; Daniel Lundell; John J. Piwinski; Neng-Yang Shih; M. Arshad Siddiqui

TNF-α converting enzyme (TACE) inhibitors are promising agents to treat inflammatory disorders and cancer. We have investigated novel tartrate diamide TACE inhibitors where the tartrate core binds to zinc in a unique tridentate fashion. Incorporating (R)-2-(2-N-alkylaminothiazol-4-yl)pyrrolidines into the left hand side amide of the tartrate scaffold led to the discovery of potent and selective TACE inhibitors, some of which exhibited good rat oral bioavailability.


Bioorganic & Medicinal Chemistry Letters | 2010

Expansion of SAR studies on triaryl bis sulfone cannabinoid CB2 receptor ligands

Ling Tong; Bandarpalle B. Shankar; Lei Chen; Razia Rizvi; Joseph Kelly; Eric J. Gilbert; Chunli Huang; De-Yi Yang; Joseph A. Kozlowski; Neng-Yang Shih; W. Gonsiorek; R. William Hipkin; Asra Malikzay; Charles A. Lunn; Daniel Lundell

We report further expansion of the structure activity relationship (SAR) on the triaryl bis sulfone class of compounds (I), which are potent CB(2) receptor ligands with excellent selectivity over the CB(1) receptor. This study was extended to B ring changes, followed by simultaneous optimization of the A-, B-, and C-rings. Compound 42 has excellent CB(2) potency, selectivity and rat exposure.


Bioorganic & Medicinal Chemistry Letters | 2010

Structure and activity relationships of tartrate-based TACE inhibitors.

Dansu Li; Janeta Popovici-Muller; David B. Belanger; John P. Caldwell; Chaoyang Dai; Maria David; Vinay Girijavallabhan; Brian J. Lavey; Joe F. Lee; Zhidan Liu; Rob Mazzola; Razia Rizvi; Kristin E. Rosner; Bandarpalle B. Shankar; Jim Spitler; Pauline C. Ting; Henry M. Vaccaro; Wensheng Yu; Guowei Zhou; Zhaoning Zhu; Xiaoda Niu; Jing Sun; Zhuyan Guo; Peter Orth; Shiying Chen; Joseph A. Kozlowski; Daniel Lundell; Vincent Madison; Brian A. McKittrick; John J. Piwinski

The syntheses and structure-activity relationships of the tartrate-based TACE inhibitors are discussed. The optimization of both the prime and non-prime sites led to compounds with picomolar activity. Several analogs demonstrated good rat pharmacokinetics.


Bioorganic & Medicinal Chemistry Letters | 2012

5-Benzothiazole substituted pyrimidine derivatives as HCV replication (replicase) inhibitors

Ashok Arasappan; Frank Bennett; Vinay Girijavallabhan; Yuhua Huang; Regina Huelgas; Carmen Alvarez; Lei Chen; Stephen Gavalas; Seong-Heon Kim; Aneta Kosinski; Patrick Pinto; Razia Rizvi; Randall R. Rossman; Bandarpalle B. Shankar; Ling Tong; Francisco Velazquez; Srikanth Venkatraman; Vishal Verma; Joseph A. Kozlowski; Neng-Yang Shih; John J. Piwinski; Malcolm Maccoss; Cecil D. Kwong; Jeremy L. Clark; Anita T. Fowler; Feng Geng; Hollis S. Kezar; Abhijit Roychowdhury; Robert C. Reynolds; Joseph A. Maddry

Based on a previously identified HCV replication (replicase) inhibitor 1, SAR efforts were conducted around the pyrimidine core to improve the potency and pharmacokinetic profile of the inhibitors. A benzothiazole moiety was found to be the optimal substituent at the pyrimidine 5-position. Due to potential reactivity concern, the 4-chloro residue was replaced by a methyl group with some loss in potency and enhanced rat in vivo profile. Extensive investigations at the C-2 position resulted in identification of compound 16 that demonstrated very good replicon potency, selectivity and rodent plasma/target organ concentration. Inhibitor 16 also demonstrated good plasma levels and oral bioavailability in dogs, while monkey exposure was rather low. Chemistry optimization towards a practical route to install the benzothiazole moiety resulted in an efficient direct C-H arylation protocol.


Bioorganic & Medicinal Chemistry Letters | 2016

Matched and mixed cap derivatives in the tetracyclic indole class of HCV NS5A inhibitors.

Michael P. Dwyer; Kerry Keertikar; Lei Chen; Ling Tong; Oleg Selyutin; Anilkumar G. Nair; Wensheng Yu; Guowei Zhou; Brian J. Lavey; De-Yi Yang; Michael Wong; Seong Heon Kim; Craig A. Coburn; Stuart B. Rosenblum; Qingbei Zeng; Yueheng Jiang; Bandarpalle B. Shankar; Razia Rizvi; Amin Nomeir; Rong Liu; Sony Agrawal; Ellen Xia; Rong Kong; Ying Zhai; Paul Ingravallo; Ernest Asante-Appiah; Joseph A. Kozlowski

A matched and mixed capping SAR study was conducted on the tetracyclic indole class of HCV NS5A inhibitors to examine the influence of modifications of this region on the overall HCV virologic resistance profiles.


Bioorganic & Medicinal Chemistry Letters | 2010

Non-aromatic A-ring replacement in the triaryl bis-sulfone CB2 receptor inhibitors.

Eric J. Gilbert; Guowei Zhou; Michael K.C. Wong; Ling Tong; Bandarpalle B. Shankar; Chunli Huang; Joseph Kelly; Brian J. Lavey; Stuart W. McCombie; Lei Chen; Razia Rizvi; Youhao Dong; Youheng Shu; Joseph A. Kozlowski; Neng-Yang Shih; R. William Hipkin; Waldemar Gonsiorek; Asra Malikzay; Charles A. Lunn; Len Favreau; Daniel Lundell

The triaryl bis-sulfone 1 was modified by converting the aryl A-ring to a piperidine ring. The piperidine ring was further elaborated to a spirocyclopropyl piperidine moiety. The effect on CB2 binding potency, rat calcium channel affinity, and CYP 2C9 inhibition is described.

Collaboration


Dive into the Bandarpalle B. Shankar's collaboration.

Researchain Logo
Decentralizing Knowledge