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Parekh V.,University of Warwick | Ramsden J.A.,Dr Reddys Laboratories | Wills M.,University of Warwick
Tetrahedron Asymmetry | Year: 2010

The first report of an asymmetric transfer hydrogenation, in formic acid/triethylamine, of quinolines is described. Using a Ru(II) catalyst containing a 4-carbon tether, products of up to 73% ee were formed, whilst a Rh(III)-tethered catalyst gave products of up to 94% ee. © 2010 Elsevier Ltd. All rights reserved.

Thom S.,Imperial College London | Poulter N.,Imperial College London | Field J.,Imperial College London | Patel A.,George Institute for Global Health | And 9 more authors.
JAMA - Journal of the American Medical Association | Year: 2013

IMPORTANCE: Most patients with cardiovascular disease (CVD) do not take recommended medications long-term. The use of fixed-dose combinations (FDCs) improves adherence in several clinical areas. Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment. OBJECTIVE: To assess whether FDC delivery of aspirin, statin, and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors, systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C). DESIGN, SETTING, AND PARTICIPANTS: The UMPIRE trial, a randomized, open-label, blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe. The trial follow-up concluded in July 2012. INTERVENTIONS: Participants were randomly assigned (1:1) to an FDC-based strategy (n=1002) containing either (1) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol or (2) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide or to usual care (n=1002). MAIN OUTCOMES AND MEASURES: Adherence to medication (defined as self-reported use of antiplatelet, statin, and ≥2 BP-lowering medications) and changes in SBP and LDL-C from baseline. RESULTS: At baseline, mean BP was 137/78mmHg, LDL-C was 91.5mg/dL, and 1233 (61.5%) of 2004 participants reported use of antiplatelet, statin, and 2 or more BP-lowering medications. Median follow-up was 15 months (interquartile range, 12-18 months). The FDC group had improved adherence vs usual care (86%vs 65%; relative risk [RR] of being adherent, 1.33; 95%CI, 1.26-1.41; P < .001) with concurrent reductions in SBP (-2.6mmHg; 95%CI, -4.0 to -1.1mmHg; P < .001) and LDL-C (-4.2 mg/dL; 95%CI, -6.6 to -1.9 mg/dL; P < .001) at the end of the study. Although there was consistency of effects across predefined subgroups, evidence existed of larger benefits in patients with lower adherence at baseline. In this subgroup of 727 participants (36%), adherence at the end of study was 77%vs 23% (RR, 3.35; 95%CI, 2.74-4.09; P < .001 for interaction), SBP was reduced by 4.9mmHg (95% CI 7.3-2.6mmHg; P = .01 for interaction), and LDL-C was reduced by 6.7mg/dL (95%CI, 10.5-2.8mg/dL; P = .11 for interaction). There were no significant differences in serious adverse events or cardiovascular events (50 [5%] in the FDC group and 35 [3.5%] in the usual care group; RR, 1.45; 95%CI, 0.94-2.24; P=.09) between the groups. CONCLUSIONS AND RELEVANCE: Among patients with or at high risk of CVD, use of an FDC strategy for blood pressure, cholesterol, and platelet control vs usual care resulted in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01057537.

Heiss A.,Dr Reddys Laboratories
Chimica Oggi/Chemistry Today | Year: 2015

High potency API (HPAPI) production is currently the fastest growing segment of the pharmaceutical market: the global market is predicted to double in value from approximately $9bn in 2011 to $18bn by 2018. The rising demand for drugs with increasing potencies is leading to a number of questions for manufacturing. This article reviews current trends and challenges for innovators and contract manufacturers involved in high potency production.

Gutam K.J.,Indian Institute of Science | Gutam K.J.,Dr Reddys Laboratories | Mehandia V.,Indian Institute of Science | Nott P.R.,Indian Institute of Science
Physics of Fluids | Year: 2013

The cylindrical Couette device is commonly employed to study the rheology of fluids, but seldom used for dense granular materials. Plasticity theories used for granular flows predict a stress field that is independent of the shear rate, but otherwise similar to that in fluids. In this paper we report detailed measurements of the stress as a function of depth, and show that the stress profile differs fundamentally from that of fluids, from the predictions of plasticity theories, and from intuitive expectation. In the static state, a part of the weight of the material is transferred to the walls by a downward vertical shear stress, bringing about the well-known Janssen saturation of the stress in vertical columns. When the material is sheared, the vertical shear stress changes sign, and the magnitudes of all components of the stress rise rapidly with depth. These qualitative features are preserved over a range of the Couette gap and shear rate, for smooth and rough walls and two model granular materials. To explain the anomalous rheological response, we consider some hypotheses that seem plausible a priori, but show that none survive after careful analysis of the experimental observations. We argue that the anomalous stress is due to an anisotropic fabric caused by the combined actions of gravity, shear, and frictional walls, for which we present indirect evidence from our experiments. A general theoretical framework for anisotropic plasticity is then presented. The detailed mechanics of how an anisotropic fabric is brought about by the above-mentioned factors is not clear, and promises to be a challenging problem for future investigations. © 2013 AIP Publishing LLC.

Parekh V.,University of Warwick | Ramsden J.A.,Dr Reddys Laboratories | Wills M.,University of Warwick
Catalysis Science and Technology | Year: 2012

A new type of Ru(ii)/TsDPEN catalyst containing an ether-based linking tether has been prepared and shown to exhibit excellent activity in asymmetric transfer hydrogenation reactions of ketones. Related complexes containing a hydroxyl-terminated alkyl chain have also been prepared and tested as asymmetric catalysts. In some cases the activity of the new catalyst type complements that of the closely related alkyl-chain tethered complexes. © 2012 The Royal Society of Chemistry.

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