P.R. Maulik

Vapor-Phase Processable Novel Nonplanar Donor−Acceptor Quateraryls for Blue OLEDs#

A novel series of thermally stable blue light emitting quateraryls with a piperidine donor and a nitrile acceptor was prepared from a ketene- S, S-acetal under mild conditions without using an organometal catalyst. The performance of a blue quateraryl 6e was investigated by fabricating a multilayer OLED with a configuration of ITO/PEDOT:PSS (40 nm)/quateraryl (60 nm)/BCP (6 nm)/Alq(3) (20 nm)/LiF (0.5 nm)/Al (200 nm), which exhibited blue emission with a low turn on voltage of 4 V at a brightness of 0.22 cd/m(2).

Peganine hydrochloride dihydrate an orally active antileishmanial agent.

Protozoic infections caused by genus Leishmania pose an enormous public health threat in developing countries, compounded by the toxicity and resistance to current therapies. Under the aegis of our ongoing program on drug discovery and development on antileishmanial agents from plants, we carried out bioassay guided fractionation on Peganum harmala seeds which resulted in the isolation of 1 as an antileishmanial agent. 2D-NMR spectral data and single crystal X-ray crystallography data indicated 1 as peganine hydrochloride in dihydrated form. The compound 1 exhibited in-vitro activity against both extracellular promastigotes as well as intracellular amastigotes residing within murine macrophages in Leishmania donovani. Furthermore, 1 also exhibited in-vivo activity, 79.6 (+/-8.07)% against established VL in hamsters at a dose of 100mg/kgb.wt.

Design and synthesis of ERα/ERβ selective coumarin and chromene derivatives as potential anti-breast cancer and anti-osteoporotic agents

Several new coumarin and chromene prototype derivatives have been synthesised and evaluated for their ERα and ERβ selective activity. Coumarin prototype compounds 18 & 19 were found to be ERα selective and the most active, exhibiting potential antiproliferative activity against both ER +ve & ER −ve breast cancer cell lines. The surprise finding of the series, however, are the novel prototype III chromenes 45 & 46, with aroyl substitution at the 6th position. Both the compounds have shown potent antiproliferative activity against both the breast cancer cell lines, promote alkaline phosphatase activity, enhance osteoblast mineralization in vitro, significantly decrease ERE–ERα dependent transactivation and induce ERβ activity. This specific upregulation of ERβ isoform activity of compound 45 may be responsible for the antiosteoporotic activity at picomolar concentration. In addition, both the compounds were also devoid of any estrogenic activity, which correlates to their antiestrogenic behaviour in the two breast cancer cell lines. Assessment of selectivity using specific SiRNAs for ERα and ERβ revealed that most of the compounds showed ERα and ERβ-mediated action, except compound 28, which showed selectivity to ERα only. Computational docking analysis of active compounds 18 and 45 was conducted to correlate the interaction with the two receptors and it was found that the docked conformations of the coumarin prototype, compound 18 at ERα and ERβ active sites were more or less superimposable on each other. However, the unique orientation of the aminoalkoxy side chain of novel chromene (prototype III) compound 45 in the ERβ binding cavity may be responsible for its potential biological response.

Resolution, molecular structure and biological activities of the D- and L-enantiomers of potent anti-implantation agent, DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran.

Compound 1 (DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran, CDRI 85/287) a potent anti-estrogen and anti-implantation agent has been successfully resolved into its pure D- and L-enantiomers. Biological studies showed L-enantiomer to be the active form, exhibiting a fivefold higher receptor affinity for the rat uterine cytosolic estrogen receptor, 100% contraceptive efficacy at 1.3 mg/kg dose in single day schedule and 89% inhibition of estradiol induced increase of uterine weight at its contraceptive dose. The absolute stereochemistry determined by X-ray crystallographic analysis showed that the L-enantiomer has 2R configuration at its asymmetric centre.

Regioselective synthesis of densely functionalized, enantiopure, sugar–pyrazole hybrids as potential scaffolds for drug discovery

A versatile new synthetic strategy utilizing MBH chemistry for the assembly of highly functionalized enantiopure sugar–pyrazole hybrid molecules with multiple sites for structural diversification and a non-flat skeleton as potential drug scaffolds is reported. Four representative hybrid molecules were screened for in vitro anti-cancer activity, wherein three of them were found to exhibit good anti-cancer activity.

Amide Derivatives of 2,3-diarylacrylophenone as Estrogen Receptor Binding Ligands

Substituted amidoalkyl derivatives of 2,3-diarylacrylophenones carrying the amide chain on the 3-aryl residue have been prepared by reacting corresponding phenolic 2,3-diarylacrylophenones with haloalkyl carboxylic acid esters, their hydrolysis and subsequent treatment with different alkyl amines. Compounds thus prepared were evaluated for their relative binding affinity (RBA) towards estrogen receptors (ER), estrogen agonistic and antagonistic activities. Out of eleven amide derivatives thus prepared, compounds 7, 13, 15-19, 23, 24 showed significant estrogen antagonistic activity. Interestingly the phenolic compound 7 and the acid ester 18 also exhibited estrogen inhibiting property. Majority of the dimethoxy derivatives (R = OCH(3)) showed significantly high estrogenic activity. In order to throw light on their SAR, In silico docking of the acrylophenone derivatives in the ligand binding site of the ERalpha and their comparison with pure steroidal estrogen antagonist ICI-164,384 and the non-steroidal antiestrogen raloxifene, was carried out. Crystal structure of compound 6 revealed relative trans-geometry of the 2(B) and 3(C) phenyl rings.

Synthesis of 3-phenyl-4-phenylvinyl Benzopyranones and the Corresponding 2,2-dimethyl-benzopyrans with Structural Similarity to Estradiol, as Estrogen Receptor Ligands

7-Methoxy-3-phenyl-4-phenylvinyl benzopyran-2-ones and the corresponding 2,2-dimethyl-benzopyrans, substituted with different alkylamino residues were synthesized. Except compound 13e, all compounds showed high level of estrogen agonistic activity (>81 %) whereas, compounds 13 b-e and 15a showed significant estrogen antagonistic activity (>20 %). X-Ray analysis of a 7-methoxy-3-phenyl-4-phenylvinyl benzopyran-2-one derivative 13d showed its structural resemblance to endogenous estrogen, 17beta-estradiol. Estrogenic and antiestrogenic activities of these derivatives demonstrate their estrogen receptor (ER) binding ability. The lack of hydroxyl groups at appropriate positions resulted in poor Relative Binding Affinity (RBA).

Naphtho[2,1- h ]isoquinolines: a new class of partially reduced polycyclic aromatic nucleus

An efficient de novo synthesis of partially reduced naphtho[2,1-h]isoquinolines has been developed through base catalyzed ring transformation of 2-oxo-4-sec-amino-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles by a carbanion, generated in situ from 1-substituted-4-piperidones in DMF and powdered KOH, in excellent yields. The effect of nitrogen insertion in the D ring of partially reduced benzo[c]phenanthrene on conformational changes has also been studied by X-ray diffraction analysis.

An unusual conformational change in the folded trimethylene/leonard linker pyrazolo[3,4-d]pyrimidine analogue of the theophylline compound due to structural changes

The title compound C29H28N8O4, 1,1′-(propane-1,3-diyl)bis(5-benzyl-7-methyl-1H-pyrazolo[3,4-d]••pyrimidine-4,6(5H,7H)-dione) is characterized by single crystal X-ray diffraction. It crystallizes in the centrosymmetric space group P

Reusable resin Amberlyst 15 catalyzed new convenient protocol for accessing arylated benzene scaffolds

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