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18. Analysis of sustainable pastureland farming in tropics of Deccan Plateau.

Author

BIRADAR, NAGARATNA, KUMAR, ANIL, NATARAJAN, S., CHANDRA, AMARESH, and TRIVEDI, B. K.

Abstract

The article presents an analysis of sustainable pastureland farming in tropics of the Deccan Plateau in India. It says the study was conducted to examine the Kangayam grasslands to determine their vegetative composition and dry matter production potential. Among the cited methods used in this study were survey of grasslands, market study and stakeholder interviews. It discusses the differences in accessions of Cenchrus ciliaris, the most commonly grown grass in the pastures.

Published
2012
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22. Eco-restoration of Degraded Lands Through Watershed Development.

Author

Pathak, P. S., Suresh, G., and Trivedi, B. K.

Abstract

The article describes the development and eco-restoration efforts in 72 ha of Rammadhi watershed, at Jhansi, Uttar Pradesh, India as an example of productive utilization of non-arable degraded lands. Increasing area under degraded lands in India has attracted the attention of scientists and the policy makers during the past 20 years with the creation of the National Wasteland Development Board. Land degradation was recognized as a major challenge affecting land productivity and livelihood, and efforts have been made to arrest it. Watershed management is considered to be the most viable tool for repair of such degraded lands so that they are restored to their normal production potential maintaining the natural resource base. This has been used as a tool for developing and managing the land resource at the Indian Grassland and Fodder Research Institute, Jhansi. Worldwide about 1.96 million hectares land are affected by human-induced soil degradation, mainly caused by water and wind erosion. The degradation of natural resources in India is equally grim among the Asian countries. In India out of a total geographical area of 329 million hectares, 70 percent of cultivated land falls under the rain-fed areas. Most of the arid and semi-arid regions have high concentrations of eroded and degraded natural resources. Excessive biotic and abiotic interferences have caused considerable degradation of the natural resources of land, water, vegetation and ground water aquifers.

Published
2004

26. Novel Nonpeptide CCK-B Antagonists:  Design and Development of Quinazolinone Derivatives as Potent, Selective, and Orally Active CCK-B Antagonists<SUP>1</SUP><BBR RID="jm970373jb00001">

Author

Padia, J. K., Field, M., Hinton, J., Meecham, K., Pablo, J., Pinnock, R., Roth, B. D., Singh, L., Suman-Chauhan, N., Trivedi, B. K., and Webdale, L.

Abstract

We have designed a novel series of CCK-B receptor antagonists by combining key pharmacophores, an arylurea moiety of 1 and a quinazolinone ring of 3, from two known series. Our earlier studies showed that compounds with methylene linkers in our “target” produced moderate binding affinity and selectivity for CCK-B receptors, whereas its higher and lower homologues resulted in loss of affinity. Introduction of −NH− as a linker dramatically enhanced binding affinity and selectivity for CCK-B receptors, thus providing several compounds with single-digit nanomolar binding affinity and excellent selectivity. Analogous to the earlier studies of the series of quinazolinone derivatives 3, we also found 3-isopropoxyphenyl as a preferred substitution on the N-3 quinazolinone. Electron-withdrawing substitutions on the urea terminal phenyl ring enhanced the CCK-B potency. Representative compounds of this series were tested in the functional assay and showed pure antagonist profiles. Compounds 51 and 61 were orally active in the elevated rat X-maze test. These compounds were also evaluated for their pharmacokinetic profile. The absolute oral bioavailability of compound 61 was 22% in rats.

Published
1998

27. Second Generation “Peptoid” CCK-B Receptor Antagonists:  Identification and Development of N-(Adamantyloxycarbonyl)-α-methyl-(R)-tryptophan Derivative (CI-1015) with an Improved Pharmacokinetic Profile

Author

Trivedi, B. K., Padia, J. K., Holmes, A., Rose, S., Wright, D. S., Hinton, J. P., Pritchard, M. C., Eden, J. M., Kneen, C., Webdale, L., Suman-Chauhan, N., Boden, P., Singh, L., Field, M. J., and Hill, D.

Abstract

We have previously described the design and development of CI-988, a peptoid analogue of CCK-4 with excellent binding affinity and selectivity for the CCK-B receptor. Due to its anxiolytic profile in animal models of anxiety, this compound was developed as a clinical candidate. However, during its development, it was determined that CI-988 had low bioavailability in both rodent and nonrodent species. In the clinic, it was further established that CI-988 had poor bioavailability. Thus, there was a need to identify an analogue with an improved pharmacokinetic (PK) profile. The poor bioavailability was attributed to poor absorption and efficient hepatic extraction. We envisaged that reducing the molecular weight of the parent compound (5, MW = 614) would lead to better absorption. Thus, we synthesized a series of analogues in which the key α-methyltryptophan and adamantyloxycarbonyl moieties, required for receptor binding, were kept intact and the C-terminus was extensively modified. This SAR study led to the identification of tricyclo[3.3.1.13,7]dec-2-yl [1S-[1α(S*)2β]-[2-[(2-hydroxycyclohexyl)amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamate (CI-1015, 31) with binding affinities of 3.0 and 2900 nM for the CCK-B and CCK-A receptors, respectively. The compound showed CCK-B antagonist profile in the rat ventromedial hypothalamus assay with a Ke of 34 nM. It also showed an anxiolytic like profile orally in a standard anxiety paradigm (X-maze) with a minimum effective dose (MED) of 0.1 μg/kg. Although the compound is less water soluble than CI-988, oral bioavailability in rat was improved nearly 10 times relative to CI-988 when dosed in HPβCD. The blood−brain permeability of CI-1015 (31) was also enhanced relative to CI-988 (5). On the basis of the overall improved pharmacokinetic profile as well as enhanced brain penetration, CI-1015 (31) was chosen as a development candidate.

Published
1998

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