Seetharamaiyer Padmanabhan

Bio: Seetharamaiyer Padmanabhan is an academic researcher from Scion. The author has contributed to research in topics: Prodrug & Hepatitis B virus. The author has an hindex of 15, co-authored 47 publications receiving 540 citations.

Asymmetric synthesis of a neuroprotective and orally active N-methyl-d-aspartate receptor ion-channel blocker, CNS 5788☆

Abstract: Asymmetric synthesis of N -(2-chloro-5-methylthiophenyl)- N′ -(3-methylsulfinylphenyl)- N′ -methylguanidine (CNS 5788) was achieved in high enantiomeric excess through condensation of the cyanamide derivative, 6 and the sulfinylaniline hydrochloride, 5 . The key step involved the asymmetric oxidation of N -methyl-3-methylthioaniline using a Davis reagent.

Pharmaceutically active compounds and methods of use

Abstract: The present invention relates to certain imine-substituted heterocyclic compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are particularly useful for the treatment or prophylaxis of neurological injury and neurodegenerative disorders.

Antiviral Efficacy and Host Innate Immunity Associated with SB 9200 Treatment in the Woodchuck Model of Chronic Hepatitis B

Abstract: SB 9200, an oral prodrug of the dinucleotide SB 9000, is being developed for the treatment of chronic hepatitis B virus (HBV) infection and represents a novel class of antivirals. SB 9200 is thought to activate the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) resulting in interferon (IFN) mediated antiviral immune responses in virus-infected cells. Additionally, the binding of SB 9200 to these sensor proteins could also sterically block the ability of the viral polymerase to access pre-genomic RNA for nucleic acid synthesis. The immune stimulating and direct antiviral properties of SB 9200 were evaluated in woodchucks chronically infected with woodchuck hepatitis virus (WHV) by daily, oral dosing at 15 and 30 mg/kg for 12 weeks. Prolonged treatment resulted in 2.2 and 3.7 log10 reductions in serum WHV DNA and in 0.5 and 1.6 log10 declines in serum WHV surface antigen from pretreatment level with the lower or higher dose of SB 9200, respectively. SB 9200 treatment also resulted in lower hepatic levels of WHV nucleic acids and antigen and reduced liver inflammation. Following treatment cessation, recrudescence of viral replication was observed but with dose-dependent delays in viral relapse. The antiviral effects were associated with dose-dependent and long-lasting induction of IFN-α, IFN-β and IFN-stimulated genes in blood and liver, which correlated with the prolonged activation of the RIG-I/NOD2 pathway and hepatic presence of elevated RIG-I protein levels. These results suggest that in addition to a direct antiviral activity, SB 9200 induces antiviral immunity during chronic hepadnaviral infection via activation of the viral sensor pathway.

Antiviral Efficacy and Host Immune Response Induction during Sequential Treatment with SB 9200 Followed by Entecavir in Woodchucks.

Abstract: SB 9200, an orally bioavailable dinucleotide, activates the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) causing the induction of the interferon (IFN) signaling cascade for antiviral defense. The present study evaluated the overall antiviral response in woodchucks upon induction of immune response, first with SB 9200 followed by Entecavir (ETV) versus reduction of viral burden with ETV followed by SB 9200 immunomodulation. Woodchucks chronically infected with woodchuck hepatitis virus (WHV) were treated orally with SB 9200 (30 mg/kg/day) and ETV (0.5 mg/kg/day). Group 1 received ETV for 4 weeks followed by SB 9200 for 12 weeks. Group 2 received SB 9200 for 12 weeks followed by ETV for 4 weeks. At the end of treatment in Group 2, average reductions of 6.4 log10 in serum WHV DNA and 3.3 log10 in WHV surface antigen were observed whereas in Group 1, average reductions of 4.2 log10 and 1.1 log10 in viremia and antigenemia were noted. Both groups demonstrated marked reductions in hepatic WHV nucleic acid levels which were more pronounced in Group 2. Following treatment cessation and the 8-week follow-up, recrudescence of viral replication was observed in Group 1 while viral relapse in Group 2 was significantly delayed. The antiviral effects observed in both groups were associated with temporally different induction of IFN-α, IFN-β, and IFN-stimulated genes in blood and liver. These results suggest that the induction of host immune responses by pretreatment with SB 9200 followed by ETV resulted in antiviral efficacy that was superior to that obtained using the strategy of viral reduction with ETV followed by immunomodulation.

Compositions and methods for treating viral infections

Abstract: The present invention provides compositions methods for treating susceptible viral infections, especially hepatitis C viral (HCV) infections as well as co infections of HCV with other viruses such as HBV and/or HIV In one embodiment, the present invention provides compositions having the formula (I) and their use in treating viral infections: or a pharmaceutically acceptable salt, ester, stereoisomer, tautomers, solvate, prodrug, or combination thereof

Expandable support device and method of use

Abstract: An expandable support device for tissue repair is disclosed. The device can be used to repair hard or soft tissue, such as bone or vertebral discs. A method of repairing tissue is also disclosed. The device and method can be used to treat compression fractures. The compression fractures can be in the spine. The device can be deployed by compressing the device longitudinally resulting in radial expansion.

Enantioselective synthesis of sulfoxides: 2000-2009.

Abstract: 1.2.2. Davis Oxaziridines 4305 1.2.3. Metal Complexes in Enantioselective Oxidation 4305 1.3. New Applications 4307 1.3.1. Chiral Sulfinate Method 4307 1.3.2. Oxidation with Chiral Oxaziridines 4309 1.3.3. Oxidation Using Metal Complexes 4310 1.4. New Systems 4313 1.4.1. C-S Bond Formation 4314 1.4.2. Organic Oxidants 4315 1.4.3. Oxidations Catalyzed by Metal Complexes 4316 1.5. Diastereoselective Oxidations 4330 1.6. Heterogenized Systems 4332 1.7. Summary 4335 2. Biological Oxidations 4336 2.