B. Yogi Sreenivas

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

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.

Catalysis by Amberlyst-15 under ultrasound in water: a green synthesis of 1,2,4-benzothiadiazine-1,1-dioxides and their spiro derivatives

A green and general synthesis of 1,2,4-benzothiadiazine-1,1-dioxides possessing a spiro group or a substituent at C-3 has been achieved first time via an Amberlyst-15 mediated reaction under ultrasound in water. The reaction is operationally simple and can be performed at room temperature in an open flask to give a range of products that do not require any chromatographic purification. The catalyst is recyclable.

A Pd-catalyzed direct entry to 11-substituted 6H-isoindolo[2,1-a]indol-6-one derivatives as potential anticancer agents

We describe Pd-mediated one-step synthesis of 11-substituted 6H-isoindolo[2,1-a]indol-6-ones via a sequential intramolecular Heck reaction of the corresponding dihalo N-allyl substituted N-arylbenzamide derivatives. Several of these compounds showed promising antiproliferative properties when tested against a number of cancer cell lines in vitro.

1,2,3-Triazoles derived from olanzapine: their synthesis via an ultrasound assisted CuAAC method and evaluation as inhibitors of PDE4B

The antipsychotic drug olanzapine which does not inhibit PDE4 can be converted into the inhibitor of PDE4B via linking its N-10 position with an appropriately N-substituted 1,2,3-triazole moiety through a methylene linker. All these compounds were conveniently prepared by a CuAAC method under ultrasound irradiation at room temperature and evaluated for their PDE4 inhibitory potential in vitro. Three of them were identified as selective inhibitors of PDE4B (IC50 ∼ 5–6 μM) over PDE4D. Overall, the present research reports one of the few examples of an ultrasound assisted CuAAC method used in medicinal chemistry.