B Narasimhulu Naidu

Publications (14)39.54 Total impact

• Chapter: Simple and Accurate In Vitro Method for Predicting Serum Protein Binding of HIV Integrase Strand Transfer Inhibitors

  Ira B. Dicker, Michael A. Walker, Zeyu Lin, Brian Terry, Lori Pajor, Ming Zheng, B. Narasimhulu Naidu, Jacques Banville, Nicholas A. Meanwell, Mark Krystal
  09/2011: pages 275 - 286; , ISBN: 9781118015377
• Article: Solid phase synthesis of novel pyrrolidinedione analogs as potent HIV-1 integrase inhibitors.

  Annapurna Pendri, Timothy L Troyer, Michael J Sofia, Michael A Walker, B Narasimhulu Naidu, Jacques Banville, Nicholas A Meanwell, Ira Dicker, Zeyu Lin, Mark Krystal, Samuel W Gerritz
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  ABSTRACT: A novel series of HIV-1 integrase inhibitors were identified from a 100 member (4R(1) x 5R(2) x 5R(3)) library of pyrrolidinedione amides. A solid-phase route was developed which facilitates the simultaneous variation at R(1), R(2), and R(3) of the pyrrolidinedione scaffold. The resulting library samples were assayed for HIV-1 integrase activity and analyzed to determine the R(1), R(2), and R(3) reagent contributions towards the activity.
  Journal of Combinatorial Chemistry 11/2009; 12(1):84-90. · 3.41 Impact Factor
• Article: Benzyl amide-ketoacid inhibitors of HIV-integrase.

  Michael A Walker, Timothy Johnson, B Narasimhulu Naidu, Jacques Banville, Roger Remillard, Serge Plamondon, Alain Martel, Chen Li, Albert Torri, Himadri Samanta, Zeyu Lin, Ira Dicker, Mark Krystal, Nicholas A Meanwell
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  ABSTRACT: Integrase is one of three enzymes expressed by HIV and represents a validated target for therapy. Previous reports have demonstrated that the diketoacid-based chemotype is a useful starting point for the design of inhibitors of this enzyme. In this study, one of the ketone groups is replaced by a benzylamide resulting in a new potent chemotype. A preliminary SAR study is carried out to investigate the substitution requirements on the phenyl ring and methylene group of the benzylamide.
  Bioorganic & Medicinal Chemistry Letters 10/2007; 17(17):4886-90. · 2.55 Impact Factor
• Article: Synthesis and antibacterial activity of nocathiacin I analogues.

  B Narasimhulu Naidu, Margaret E Sorenson, John D Matiskella, Wenying Li, Justin B Sausker, Yunhui Zhang, Timothy P Connolly, Kin S Lam, Joanne J Bronson, Michael J Pucci, Hyekyung Yang, Yasutsugu Ueda
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  ABSTRACT: Stereoselective reduction of dehydroalanine double bond in nocathiacin I afforded the primary amide 2. Enzymatic hydrolysis of the amide 2 provided the carboxylic acid 3, which upon coupling with a variety of amines furnished amides 4-32. Some of these semi-synthetic derivatives have retained very good antibacterial activity and have improved aqueous solubility.
  Bioorganic & Medicinal Chemistry Letters 08/2006; 16(13):3545-9. · 2.55 Impact Factor
• Article: Developments in antiviral drug design, discovery and development in 2004.

  Nicholas A Meanwell, Makonen Belema, David J Carini, Stanley V D'Andrea, John F Kadow, Mark Krystal, B Narasimhulu Naidu, Alicia Regueiro-Ren, Paul M Scola, Sing-Yuen Sit, Michael A Walker, Tao Wang, Kap-Sun Yeung
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  ABSTRACT: This article summarizes key aspects of progress made during 2004 toward the design, discovery and development of antiviral agents for clinical use. Important developments in the identification, characterization and clinical utility of inhibitors of human immunodeficiency virus; the hepatitis viruses, hepatitis B, hepatitis C; the herpes family of viruses, herpes simplex viruses 1 and 2, varicella zoster virus, Epstein-Barr virus and human cytomegalovirus; the respiratory viruses, influenza, respiratory syncytial virus, human metapneumovirus, picornaviruses, measles and the severe acute respiratory syndrome coronavirus; human papilloma virus; rotavirus; Ebola virus and West Nile virus, are reviewed.
  Current Drug Targets - Infectious Disorders 01/2006; 5(4):307-400.
• Article: Synthesis, in vitro, and in vivo antibacterial activity of nocathiacin I thiol-Michael adducts.

  B Narasimhulu Naidu, Margaret E Sorenson, Joanne J Bronson, Michael J Pucci, Junius M Clark, Yasutsugu Ueda
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  ABSTRACT: The synthesis and antibacterial activity of a series of nocathiacin I derivatives (4-20) containing polar water solubilizing groups is described. Thiol-Michael adducts containing acidic polar groups have reduced antibacterial activity whereas those with basic polar groups have retained very good antibacterial activity.
  Bioorganic & Medicinal Chemistry Letters 05/2005; 15(8):2069-72. · 2.55 Impact Factor
• Article: Discovery of a fluoroindolo[2,3-a]carbazole clinical candidate with broad spectrum antitumor activity in preclinical tumor models superior to the marketed oncology drug, CPT-11.

  Mark G Saulnier, Balu N Balasubramanian, Byron H Long, David B Frennesson, Edward Ruediger, Kurt Zimmermann, Jeffrey T Eummer, Denis R St Laurent, Karen M Stoffan, B Narasimhulu Naidu, [......], Craig R Fairchild, Linda K Stadnick, William C Rose, Carola Solomon, Henry Wong, Alain Martel, John J Wright, Robert Kramer, David R Langley, Dolatrai M Vyas
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  ABSTRACT: A series of fluoroglycosylated fluoroindolocarbazoles was examined with respect to their topoisomerase I activity, cytotoxicity, and selectivity. The lead clinical candidate from this series, BMS-250749, displays broad spectrum antitumor activity superior to CPT-11 against some preclinical xenograft models, including curative antitumor activity against Lewis lung carcinoma.
  Journal of Medicinal Chemistry 05/2005; 48(7):2258-61. · 5.25 Impact Factor
• Article: Facile one-pot synthesis of 2,3,5-substituted 1,2,4-oxadiazolines from nitriles in aqueous solution.

  B Narasimhulu Naidu, Margaret E Sorenson
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  ABSTRACT: [reaction: see text] Alkyl/aryl amidoximes, prepared from the corresponding nitriles and N-alkylhydroxylamines, have readily undergone consecutive Michael additions to electron-deficient alkynes and provided highly substituted 1,2,4-oxadiazolines in good yields in homogeneous aqueous solution.
  Organic Letters 04/2005; 7(7):1391-3. · 5.86 Impact Factor
• Article: Nocathiacin I analogues: synthesis, in vitro and in vivo biological activity of novel semi-synthetic thiazolyl peptide antibiotics.

  B Narasimhulu Naidu, Margaret E Sorenson, Yunhui Zhang, Oak K Kim, John D Matiskella, John A Wichtowski, Timothy P Connolly, Wenying Li, Kin S Lam, Joanne J Bronson, Michael J Pucci, Junius M Clark, Yasutsugu Ueda
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  ABSTRACT: Several nocathiacin I analogues (4-35) were synthesized and evaluated for their antibacterial activity. Most of these semi-synthetic analogues retained very good in vitro and in vivo antibacterial activity of 1.
  Bioorganic & Medicinal Chemistry Letters 12/2004; 14(22):5573-7. · 2.55 Impact Factor
• Article: Synthesis and antibacterial activity of O-substituted nocathiacin I derivatives.

  B Narasimhulu Naidu, Margaret E Sorenson, Thomas Hudyma, Xiaofan Zheng, Yunhui Zhang, Joanne J Bronson, Michael J Pucci, Junius M Clark, Yasutsugu Ueda
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  ABSTRACT: The synthesis and antibacterial activity of a series of new nocathiacin I derivatives (1-12) containing polar water solubilizing groups is described. Most of these compounds exhibited potent antibacterial activity and have improved water solubility. In addition, compounds 5, 7-9 also exhibited potent in vivo activity.
  Bioorganic & Medicinal Chemistry Letters 08/2004; 14(14):3743-6. · 2.55 Impact Factor
• Article: Design and synthesis of a fluoroindolocarbazole series as selective topoisomerase I active agents. Discovery of water-soluble 3,9-difluoro-12,13-dihydro-13-[6-amino-beta-D-glucopyranosyl]-5H,13H-benzo[b]- thienyl[2,3-a]pyrrolo[3,4-c]carbazole- 5,7(6H)-dione (BMS-251873) with curative antitumor activity against prostate carcinoma xenograft tumor model.

  Balu N Balasubramanian, Denis R St Laurent, Mark G Saulnier, Byron H Long, Carol Bachand, Francis Beaulieu, Wendy Clarke, Milind Deshpande, Jeffrey Eummer, Craig R Fairchild, [......], B Narasimhulu Naidu, William C Rose, John Russell, Edward Ruediger, Carola Solomon, Karen M Stoffan, Henry Wong, John J Wright, Kurt Zimmermann, Dolatrai M Vyas
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  ABSTRACT: A series of fluoroindolocarbazoles were studied with respect to their topoisomerase I activity, cytotoxicity, selectivity, and in vivo antitumor activity. Emerging from this series was BMS-251873, a potential clinical candidate possessing a robust pharmacological profile including curative antitumor activity against prostate carcinoma.
  Journal of Medicinal Chemistry 04/2004; 47(7):1609-12. · 5.25 Impact Factor
• Article: Design and Synthesis of a Fluoroindolocarbazole Series as Selective Topoisomerase I Active Agents. Discovery of Water-Soluble 3,9-Difluoro-12,13-dihydro-13-[6-amino-β- d-glucopyranosyl]-5H,13H-benzo[b]- thienyl[2,3-a]pyrrolo[3,4-c]carbazole- 5,7(6H)-dione (BMS-251873) with Curative Antitumor Activity against Prostate Carcinoma Xenograft Tumor Model§

  Balu N. Balasubramanian, Denis R. St. Laurent, Mark G. Saulnier, Byron H. Long, Carol Bachand, Francis Beaulieu, Wendy Clarke, Milind Deshpande, Jeffrey Eummer, Craig R. Fairchild, [......], Alain Martel, B. Narasimhulu Naidu, William C. Rose, John Russell, Edward Ruediger, Carola Solomon, Karen M. Stoffan, Henry Wong, Kurt Zimmermann, Dolatrai M. Vyas
  [show abstract] [hide abstract]
  ABSTRACT: A series of fluoroindolocarbazoles were studied with respect to their topoisomerase I activity, cytotoxicity, selectivity, and in vivo antitumor activity. Emerging from this series was BMS-251873, a potential clinical candidate possessing a robust pharmacological profile including curative antitumor activity against prostate carcinoma.
  02/2004;
• Article: Novel semi-synthetic nocathiacin antibiotics: synthesis and antibacterial activity of bis- and mono-O-alkylated derivatives.

  Alicia Regueiro-Ren, B Narasimhulu Naidu, Xiaofan Zheng, Thomas W Hudyma, Timothy P Connolly, John D Matiskella, Yunhui Zhang, Oak K Kim, Margaret E Sorenson, Michael Pucci, Junius Clark, Joanne J Bronson, Yasutsugu Ueda
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  ABSTRACT: Several semi-synthetic bis- and mono-O-alkyl nocathiacin derivatives were synthesized and evaluated for antibacterial activity. Mono-O-alkyl N-hydroxyindole analogues 3a-l were prepared by regioselective alkylation. Bis-O-alkyl nocathiacins 4a-f were obtained by treatment with base and excess electrophile. A one-pot protection-alkylation-deprotection strategy was developed for the preparation of mono-O-alkyl hydroxypyridine analogues 5a,b. Most of the bis- and mono-O-alkyl nocathiacins maintained good in vitro activity but showed reduced in vivo efficacy when compared with the natural product. The excellent in vivo activity and improved water solubility of phosphate analogues 3m and 4g suggest their use as potential pro-drugs.
  Bioorganic & Medicinal Chemistry Letters 02/2004; 14(1):171-5. · 2.55 Impact Factor
• Article: Michael addition of amines and thiols to dehydroalanine amides: a remarkable rate acceleration in water.

  B Narasimhulu Naidu, Margaret E Sorenson, Timothy P Connolly, Yasutsugu Ueda
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  ABSTRACT: In water, the rate of Michael addition of amines and thiols to dehydroalanine amides was greatly accelerated, leading to shorter reaction times and higher yields. The scope of the new conditions was tested with a range of amines, thiols, and dehydroalanine amides. The ease and efficiency of this method provides an attractive route to the synthesis of natural and unnatural amino acid derivatives.
  The Journal of Organic Chemistry 01/2004; 68(26):10098-102. · 4.45 Impact Factor