Piramal Life science Ltd.

Mumbai, India

Piramal Life science Ltd.

Mumbai, India
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Khandare J.,Piramal Life science Ltd | Calderon M.,Free University of Berlin | Dagia N.M.,Piramal Life science Ltd | Haag R.,Free University of Berlin
Chemical Society Reviews | Year: 2012

Nanotechnology has resulted in materials that have greatly improved the effectiveness of drug delivery because of their ability to control matter on the nanoscale. Advanced forms of nanomedicine have been synthesized for better pharmacokinetics to obtain higher efficacy, less systemic toxicity, and better targeting. These criteria have long been the goal in nanomedicine, in particular, for systemic applications in oncological disorders. Now, the "holy grail" in nanomedicine is to design and synthesize new advanced macromolecular nanocarriers and to translate them from lab to clinic. This review describes the current and future perspectives of nanomedicine with particular emphasis on the clinical targets in cancer and inflammation. The advanced forms of liposomes and polyethylene glycol (PEG) based nanocarriers, as well as dendritic polymer conjugates will be discussed with particular attention paid to designs, synthetic strategies, and chemical pathways. In this critical review, we also report on the current status and perspective of dendritic polymer nanoconjugate platforms (e.g. polyamidoamine dendrimers and dendritic polyglycerols) for cellular localization and targeting of specific tissues (192 references). © 2012 The Royal Society of Chemistry.


Background: Fenofibrate, a PPAR-α agonist and rosiglitazone, a PPAR-γ agonist, reduce triglycerides and fatty acids in humans and in animal disease models. The efficacy of PPAR-α agonists in mouse model of human atherosclerosis disease has shown mixed results, and efficacy of PPAR-γ and liver X receptor (LXR) agonists has not been evaluated in cholesterol ester transfer protein (CETP) producing animal models. Methods and results: The efficacy of PPAR-α, PPAR-γ and LXR agonists on lipid lowering and antiatherosclerotic activities was studied in atherosclerosis-susceptible F 1B hamster that showed greater responsiveness to dietary fat and cholesterol (HFHC) diet and increased severity of atherosclerosis compared to Golden Syrian (GS) hamsters (aortic lesion 0.3% in GS vs 5% in F 1B). F 1B hamsters were fed HFHC diet and simultaneously treated with fenofibrate, rosiglitazone, and T0901317 (a pan LXR agonist) for 8 weeks. Fenofibrate lowered triglycerides and LDL-C by >80%, rosiglitazone did not significantly impact plasma lipid levels, and as expected, T0901317 increased triglycerides by 3-fold and HDL-C by 50%. The lesions in the aortic arch area as measured by en face method, decreased by 81%, 38% and 35%, following fenofibrate, rosiglitazone, and T0901317 treatments, respectively. In F 1B hamster regression model, fenofibrate decreased levels of triglycerides and LDL-C by >85%, and LDL-C by >70%, respectively, which resulted in ∼50% regression of aortic lesions compared to vehicle treated group, and ∼36% compared to baseline. Conclusions: These results demonstrate that: (a) F 1B hamster is more sensitive to developing diet-induced hyperlipidemia and atherosclerosis; and (b) the greater antiatherosclerotic efficacy of fenofibrate occurred primarily via reductions in proatherogenic lipoproteins. Thus, PPAR-α selective agonist shows a greater anti-atherosclerotic response compared to PPAR-γ and LXR agonists in diet-induced atherosclerosis-susceptible F 1B hamster. © 2010 Elsevier Ireland Ltd.


Patent
Piramal Life science Ltd | Date: 2010-08-11

Compounds of formula 1: are disclosed, wherein V is CH_(2); W is S(O)_(m); m is the integer 0, 1 or 2; U is O, C(O), CR_(13)R_(14 )or NR_(15); where R_(13 )is H, alkyl; R_(14 )is H, OH, OR_(13 )or OCOR_(13); R_(15 )is H, alkyl, cycloalkyl, alkenyl, C(O)R_(13), C(O)OR_(13 )or alkylaminocarbonyl; R_(1), R_(2), R_(3), R_(4), R_(5), R_(6), R_(7 )and R_(5 )are as defined herein. These compounds are inhibitors of tumor necrosis factor-alpha (TNF-) and are useful as medicaments for the treatment and prevention of disorders caused by increased TNF- activity, in particular inflammations.


Synergistic combinations of gemcitabine with P276-00 or P1446A and their use in the treatment of cancer are disclosed. The invention further describes novel and unique gene signatures comprising gene markers used to monitor the drug response in a subject treated with the said combinations.


The present invention provides novel compounds represented by the general formula (I): their stereoisomers, pharmaceutically acceptable salts and their pharmaceutically acceptable solvates thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia. The invention also relates to a process for the manufacture of compounds of formula (I) and pharmaceutical compositions containing them.


Patent
PIRAMAL LIFE science Ltd | Date: 2011-04-22

The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.


Patent
Piramal Life science Ltd and Satyam | Date: 2010-12-29

The invention provides the compounds of formula (I) or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutical compositions comprising one or more compounds of formula I or intermediates thereof and one more of pharmaceutically acceptable carriers, vehicles or diluents. The invention further provides methods of preparation and methods of use of prodrugs including NO-releasing prodrugs, double prodrugs and mutual prodrugs comprising the compounds of formula 1.


Patent
PIRAMAL LIFE science Ltd | Date: 2010-12-09

The present invention relates to a method employing Interferon Epsilon (IFNE1) as a therapeutic response, prognostic, or pharmacodynamic marker for cancer chemotherapeutic treatment involving the use of cyclin dependent kinase (CDK) inhibitors. The inventors have identified IFNE1 as a biomarker transcript that is upregulated when cancer cells are treated with CDK inhibitors. In an embodiment, the method of the invention includes measuring a level of IFNE1 mRNA or IFNE1 protein in a subjects tumor, blood or other tissue. An increase in the level of IFNE1 compared to control level can indicate that the CDK inhibitor has produced a therapeutic response or can determine whether a tumor is sensitive to a CDK inhibitor.


Patent
Piramal Life science Ltd and Satyam | Date: 2011-01-05

The invention provides the compounds of formula (I) or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutical compositions comprising one or more compounds of formula I or intermediates thereof and one more of pharmaceutically acceptable carriers, vehicles or diluents. The invention further provides methods of preparation and methods of use of prodrugs including NO-releasing prodrugs, double prodrugs and mutual prodrugs comprising the compounds of formula 1.


Patent
PIRAMAL LIFE science LTD. | Date: 2011-02-14

The present invention relates to novel compounds for the inhibition of cyclin-dependent kinases, and more particularly, to chromenone derivatives of formula (Ia), wherein R_(1), R_(2), R_(3), R_(4), R_(5), R_(6), R_(7 )and A have the meanings indicated in the claims. The invention also relates to processes for the preparation of the compounds of formula (Ia), to methods of inhibiting cyclin-dependent kinases and of inhibiting cell proliferation, to the use of the compounds of formula (Ia) in the treatment and prophylaxis of diseases, which can be treated or prevented by the inhibition of cyclin-dependent kinases such as cancer, to the use of the compounds of formula (Ia) in the preparation of medicaments to be applied in such diseases. The invention further relates to compositions containing a compound of formula (Ia) either alone or in combination with another active agent, in admixture or otherwise in association with an inert carrier, in particular pharmaceutical compositions containing a compound of formula (Ia) either alone or in combination with another active agent, together with pharmaceutically acceptable carrier substances and auxiliary substances.

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