Ravikumar Kapavarapu

Publications (11)35.4 Total impact

• Article: Vinylic amino group activation: a new and general strategy leading to functionalized fused heteroaromatics.

  Rajnikanth Sunke, Raju Adepu, Ravikumar Kapavarapu, Swetha Chintala, Chandana Lakshmi Teja Meda, Kishore V L Parsa, Manojit Pal
  [show abstract] [hide abstract]
  ABSTRACT: A conceptually new and general strategy has been developed for the construction of a benzimidazole or a benzoxazole ring fused with isoquinolinone affording a diverse and unique class of small molecules as potential and novel inhibitors of PDE4.
  Chemical Communications 03/2013; · 6.17 Impact Factor
• Article: AlCl3 induced (hetero)arylation of 2,3-dichloroquinoxaline: a one-pot synthesis of mono/disubstituted quinoxalines as potential antitubercular agents.

  K Shiva Kumar, D Rambabu, Sandhya Sandra, Ravikumar Kapavarapu, G Rama Krishna, M V Basaveswara Rao, Kiranam Chatti, C Malla Reddy, Parimal Misra, Manojit Pal
  [show abstract] [hide abstract]
  ABSTRACT: A direct and single-step method has been developed for the synthesis of mono and 2,3-disubstituted quinoxalines by using a AlCl(3) induced (hetero)arylation of 2,3-dichloroquinoxaline. Both symmetrical and unsymmetrical 2,3-disubstituted quinoxalines can be prepared conveniently by using this method under appropriate reaction conditions. The reaction proceeds via C-C bond formation and can be utilized for the preparation of a variety of quinoxaline derivatives from readily available starting materials and reagents. The molecular structure of a representative compound was confirmed by single crystal X-ray diffraction study. Some of the compounds synthesized were tested for chorismate mutase inhibitory properties in vitro and one compound showed promising activity representing one of the few examples of chorismate mutase inhibition by a heteroarene based small molecule.
  Bioorganic & medicinal chemistry 03/2012; 20(5):1711-22. · 2.82 Impact Factor
• Article: C-C bond formation at C-2 of a quinoline ring: synthesis of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors.

  K Shiva Kumar, S Kiran Kumar, B Yogi Sreenivas, Dhilli Rao Gorja, Ravikumar Kapavarapu, D Rambabu, G Rama Krishna, C Malla Reddy, M V Basaveswara Rao, Kishore V L Parsa, Manojit Pal
  [show abstract] [hide abstract]
  ABSTRACT: A number of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives were synthesized via AlCl(3)-mediated C-C bond forming reaction between 2-chloroquinoline-3-carbonitrile and various indoles. The methodology does not require any N-protection of the indoles employed and provided the corresponding products in good yields. The molecular structure of a representative compound was established unambiguously by single crystal X-ray diffraction and structural elaboration of a compound synthesized has been demonstrated. Many of these compounds synthesized showed PDE4 inhibitory properties in vitro. A brief structure-activity relationship studies within the series along with docking results of a representative compound (EC(50) ∼0.89 μM) is presented.
  Bioorganic & medicinal chemistry 02/2012; 20(7):2199-207. · 2.82 Impact Factor
• Source

  Available from: Shiva Kumar

  Article: Author's personal copy AlCl 3 induced C-arylation/cyclization in a single pot: a new route to benzofuran fused N-heterocycles of pharmacological interest

  K Shiva Kumar, Raju Adepu, Ravikumar Kapavarapu, D Rambabu, G Rama Krishna, C Malla Reddy, K Krishna Priya, Kishore V L Parsa, Manojit Pal
  [show abstract] [hide abstract]
  ABSTRACT: a b s t r a c t A new and one-pot synthesis of benzofuran fused N-heterocycles has been accomplished via AlCl 3 -mediated C–C followed by C–O bond formation between 2,3-dichloropyrazine or its derivatives and phenols. The methodology provided novel compounds as potential inhibitors of PDE4B. The single crystal X-ray data of a synthesized benzofuran derivative are presented. Scope of the methodology, in vitro phar-macological data of some of the synthesized compounds, along with docking study of an active compound are described. Conformational restriction of bioactive molecules offers the possibility of generating attractive structures that may provide valuable insights regarding the interaction of the precursory flexi-ble molecule with the putative receptor or enzyme. A series of polycyclic derivatives B therefore were generated by introducing restrictions in the parent compounds A (Fig. 1). 1a Since this strategy has been viewed as a potential opportunity for the identification of compounds possessing increased potency, we became interested in the synthesis and pharmacological evalu-ation of a series of nitrogen containing heterocycles C possessing benzofuran moiety as a central ring (Fig. 2). We were further encouraged by the pharmacological properties of similar class of compounds, for example, D (Elbfluorene—ALX-270-389) as selec-tive inhibitor of cyclin-dependent kinase 1 (CDK1/cyclin B; IC 50 = 4.2 lM) 1b or a benzofuro[3,2-d]pyrimidine derivative
  Tetrahedron Letters 01/2012; · 2.68 Impact Factor
• Source

  Available from: T Ram Reddy

  Article: Montmorillonite K-10 mediated green synthesis of cyano pyridines: Their evaluation as potential inhibitors of PDE4.

  T Ram Reddy, G Rajeshwar Reddy, L Srinivasula Reddy, Subbarao Jammula, Y Lingappa, Ravikumar Kapavarapu, Chandana Lakshmi T Meda, Kishore V L Parsa, Manojit Pal
  [show abstract] [hide abstract]
  ABSTRACT: An efficient and green synthesis of functionalized cyano pyridines has been achieved via montmorillonite K-10 mediated multi-component reaction in a chemo- and regioselective manner. The four-component reaction of β-keto ester, arylaldehyde, malononitrile and an alcohol provided a variety of pyridine derivatives and montmorillonite K-10 was found to be a reusable catalyst. The potential of this operationally simple methodology has been demonstrated in further structure elaboration of a compound synthesized via C-C bond forming reactions under Suzuki, Sonogashira and Heck conditions. Some of the cyano pyridines synthesized showed PDE4B inhibitory properties in vitro and good interactions with PDE4B protein in silico suggesting cyano pyridine scaffold as a potential template for the discovery of novel PDE4 inhibitors.
  European journal of medicinal chemistry 12/2011; 48:265-74. · 3.27 Impact Factor
• Article: A Pd-mediated new strategy to functionalized 2-aminochromenes: their in vitro evaluation as potential anti tuberculosis agents.

  T Ram Reddy, L Srinivasula Reddy, G Rajeshwar Reddy, Venkata Subbaiah Nuthalapati, Y Lingappa, Sandhya Sandra, Ravikumar Kapavarapu, Parimal Misra, Manojit Pal
  [show abstract] [hide abstract]
  ABSTRACT: A multi component based synthesis involving palladium catalyzed C-C bond forming reaction has been developed as a new strategy to access systematically modified functionalized 2-aminochromenes. This MCR involves the use of bromobenzaldehyde as a key component and is highlighted by generating a new compound library. Many of these compounds showed Mycobacterium tuberculosis H37Rv chorismate mutase inhibiting properties in vitro representing the lead example of chorismate mutase inhibition by heteroarene based compounds.
  Bioorganic & medicinal chemistry letters 08/2011; 21(21):6433-9. · 2.65 Impact Factor
• Article: Novel 1-alkynyl substituted 1,2-dihydroquinoline derivatives from nimesulide (and their 2-oxo analogues): a new strategy to identify inhibitors of PDE4B.

  Sarbani Pal, Shylaprasad Durgadas, Suresh Babu Nallapati, Khagga Mukkanti, Ravikumar Kapavarapu, Chandana Lakshmi T Meda, Kishore V L Parsa, Manojit Pal
  [show abstract] [hide abstract]
  ABSTRACT: A number of novel 1-(3-arylprop-2-ynyl) substituted 1,2-dihydroquinoline derivatives related to nimesulide and their 2-oxo analogues have been designed as potential inhibitors of PDE4. All these compounds were synthesized by using Sonogashira coupling as a key step. In vitro PDE4B inhibitory properties and molecular modeling studies of some of the compounds synthesized are presented.
  Bioorganic & medicinal chemistry letters 08/2011; 21(21):6573-6. · 2.65 Impact Factor
• Article: Pd-mediated new synthesis of pyrroles: their evaluation as potential inhibitors of phosphodiesterase 4.

  G Rajeshwar Reddy, T Ram Reddy, Suju C Joseph, K Sateesh Reddy, L Srinivasula Reddy, P Mahesh Kumar, G Rama Krishna, C Malla Reddy, D Rambabu, Ravikumar Kapavarapu, Chandana Lakshmi, Teja Meda, K Krishna Priya, Kishore V L Parsa, Manojit Pal
  [show abstract] [hide abstract]
  ABSTRACT: A sequential Pd-mediated multi-component reaction followed by Suzuki or Heck or Sonogashira coupling in a single pot has been developed for the synthesis of functionalized pyrroles as potential inhibitors of PDE4.
  Chemical Communications 07/2011; 47(27):7779-81. · 6.17 Impact Factor
• Source

  Available from: Prasad Bagineni

  Article: A new route to indoles via in situ desilylation–Sonogashira strategy: identification of novel small molecules as potential anti-tuberculosis agents

  Ali Nakhi, Bagineni Prasad, Uppender Reddy, Raja Mohan Rao, Sandhya Sandra, Ravikumar Kapavarapu, D Rambabu, G Rama, C Malla Reddy, Kishore Ravada, Parimal Misra, Javed Iqbal, Manojit Pal
  [show abstract] [hide abstract]
  ABSTRACT: A new Pd/C-mediated tandem reaction has been developed for the one pot synthesis of indoles containing an o-(RSO 2 NH)C 6 H 4 group at the C-2 position. The methodology provided novel indoles as inhibitors of Mycobacterium tuberculosis H37Rv chorismate mutase in vitro representing the first example of chorismate mutase inhibition by a heteroarene based small molecule. The indole ring is considered as one of the privileged structures in the area of drug discovery. Indole derivatives display a range of valuable pharmacological properties. 1 For example, indole (2, Scheme 1) containing an o-(MeSO 2 NH)C 6 H 4 group at C-2 has been reported to be useful for the potential treatment of multiple disorders. 2 While a number of methods are available for the preparation of 2-aryl indoles, 3 a direct and general method for the construction of the key indole moiety of 2 has not been reported yet. The existing method for 2 requires a multi-step process. 2 Recently, because of their environmental and economic advantages, one-pot multi-step syntheses which do not require the typical purification and isolation of products in each step have gained considerable interest. Thus, a one-pot, four-step synthesis of 2-substituted indoles has been reported. 4,5 More recently, we have observed that coupling of o-iodoanilide with trimethylsilylacetylene (TMSA) directly provides the indole derivatives unexpectedly without the requirement of any addi-tional catalyst or reagent for the removal of a Me 3 Si– group or a cyclization step, respectively. This resulted in the development of the first Pd/C-mediated one-pot synthesis of bioactive indoles possessing an o-(RSO 2 NH)C 6 H 4 group at C-2 (2, Scheme 1) via in situ desilylation–Sonogashira strategy. While a similar type of strategy i.e. the Sila-Sonogashira reaction 6 found applications in the preparation of internal alkynes, its use as a key step in heterocyclic synthesis remained unexplored. Tuberculosis (TB), though curable, remains a deadly disease that kills more than two million people a year worldwide. The growing incidences of multi-drug-resistance TB and its synergism with HIV is an emerging threat which requires immediate attention. Thus characterization of new enzyme targets and the identification of new drugs are highly desirable. The shikimate pathway for the biosynthesis of aromatic amino acids such as phenylalanine and tyrosine involves the Claisen rearrangement of chorismate to prephenate in the presence of chorismate mutase or CM (EC 5.4.99.5). Due to the absence of this pathway in animals but not in bacteria CM is considered as a novel target for the identification of effective antibacterial agents. 7 However, to our knowledge only a few small molecules 8 have been reported to possess inhibitory activity against CM including a sulfon-amide derivative A (Fig. 1). 8a In this communication we wish to present our preliminary work on the discovery of novel small molecules as inhibitors of CM synthesis of which was carried out via a new tandem reaction. The key role played by the sulfon-amide moiety of A during its interaction with the active site 8a of CM prompted us to design the indole 2 containing the o-(RSO 2 NH)C 6 H 4 group at C-2 (C) via the structure B (Fig. 1). Based on the earlier report that the trimethylsilyl group participates in Pd-mediated C–C bond forming reaction, 6 we examined the reaction of TMSA with N-(4-chloro-2-iodophenyl) methanesulfonamide (1a) under Pd/C–Cu catalysis. While the formation of a 1,2-diarylethyne via a Sila-Sonogashira type reaction was expected, the isolated product however was
  med chem communications. 07/2011;
• Article: A new three-component reaction: green synthesis of novel isoindolo[2,1-a]quinazoline derivatives as potent inhibitors of TNF-α.

  K Siva Kumar, P Mahesh Kumar, K Anil Kumar, M Sreenivasulu, Ahamed A Jafar, D Rambabu, G Rama Krishna, C Malla Reddy, Ravikumar Kapavarapu, K Shivakumar, K Krishna Priya, Kishore V L Parsa, Manojit Pal
  [show abstract] [hide abstract]
  ABSTRACT: Concurrent construction of five and six membered fused N-heretocyclic ring was achieved via a conceptually new three-component reaction affording 6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-diones as novel inhibitors of TNF-αin vitro. This represents one of the few examples of direct TNF-α inhibition by small molecules.
  Chemical Communications 03/2011; 47(17):5010-2. · 6.17 Impact Factor
• Article: Novel 1-alkynyl substituted 1,2-dihydroquinoline derivatives from nimesulide (and their 2-oxo analogues): A new strategy to identify inhibitors of PDE4B

  Sarbani Pal, Shylaprasad Durgadas, Suresh Babu Nallapati, Khagga Mukkanti, Ravikumar Kapavarapu, Chandana Lakshmi T. Meda, Kishore V.L. Parsa, Manojit Pal
  Bioorganic & Medicinal Chemistry Letters. 21(21):6573-6576.