Insight into 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamides as peripheral benzodiazepine receptor ligands: Synthesis, biological evaluation and 3D-QSAR investigation

Selleri, Silvia; Gratteri, Paola; Costagli, Chiara; Bonaccini, Claudia; Costanzo, A.; Melani, Fabrizio; Guerrini, Gabriella; Ciciani, Giovanna; Costa, Barbara; Spinetti, Francesca; Martini, Claudia; Bruni, F.

doi:10.1016/j.bmc.2005.05.015

Cited by 56 publications

(31 citation statements)

References 37 publications

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“…10, Table 4), whilst others showed clear antagonistic attributes. The GRID/Golpe model provided useful insights on the necessary features required for stereoselectivity at the PBR binding site and supported the concept of an asymmetric site containing two individual cavities [42].…”

Section: Phenoxyphenyl-acetamide Derivativesmentioning

confidence: 99%

“…Fig. 2b depicts the molecular interaction fields important for PBR binding as constructed via the use of the GRID/Golpe model [42].…”

Section: Synthetic Ligandsmentioning

confidence: 99%

“…This, along with the high affinity, selectivity and potential therapeutic role suggests that they represent useful tools for elucidating the exact biochemical role of the PBR. PK 11195 ----9.3 [19] Recently, further research has been conducted focusing on the 3-position in an attempt to determine the importance of the amide moiety and key structural features regarding the number and length of alkyl substituents on the amide nitrogen [42]. A 3D-QSAR model using GRID/Golpe procedure was implemented to assess the outcome of the substitution on the acetamide chain.…”

Section: Phenoxyphenyl-acetamide Derivativesmentioning

confidence: 99%

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Development of Ligands for the Peripheral Benzodiazepine Receptor

James¹,

Selleri²,

Kassiou

2006

CMC

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Abstract:The peripheral benzodiazepine receptor (PBR) initially characterised as a high affinity binding site for diazepam, is densely distributed in most peripheral organs whilst only moderately expressed in the healthy brain. The predominant cell type expressing the PBR at regions of central nervous system (CNS) pathology are activated microglial cells. Under neuroinflammatory conditions there is an over-expression of PBR binding sites indicating that measurements of PBR density can act as a useful index of brain disease activity. The PBR is now considered a significant therapeutic and diagnostic target which has provided the impetus for PBR ligand development. There are several classes of PBR ligands available including benzodiazepines (Ro5 -4864), isoquinoline carboxamides (PK 11195), indoleacetamides (FGIN-1-27), phenoxyphenyl-acetamides (DAA1106) and pyrazolopyrimidines (DPA-713). Subsequent conformationally restrained isoquinoline and indoleacetamide analogues have been synthesised in an attempt to yield PBR ligands with superior affinity and brain kinetics. Even though the PBR has been linked to a number of biochemical processes, including cell proliferation, apoptosis, steroidogenesis, porphyrin transport and immunomodulation, its exact physiological role is yet to be deciphered. Selective PBR ligands with favourable in vivo binding properties and kinetics is required to gain a more complete understanding on the normal functioning of the PBR and the chemical pathways underlying several pathological conditions. Novel PBR ligands with unique binding properties and functional activity may also generate information on the localisation of the PBR and the possibility of PBR subtypes. This review highlights the main classes of PBR ligands to date. In addition the biological activity and therapeutic potential of certain PBR ligands is discussed.

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Section: Phenoxyphenyl-acetamide Derivativesmentioning

confidence: 99%

“…Fig. 2b depicts the molecular interaction fields important for PBR binding as constructed via the use of the GRID/Golpe model [42].…”

Section: Synthetic Ligandsmentioning

confidence: 99%

Section: Phenoxyphenyl-acetamide Derivativesmentioning

confidence: 99%

See 1 more Smart Citation

Development of Ligands for the Peripheral Benzodiazepine Receptor

James¹,

Selleri²,

Kassiou

2006

CMC

Self Cite

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show abstract

“…Several compounds of this class show interesting antitrypanosomal [20] and antischistosomal activities [21]. They are used as HMG-CoA reductase inhibitors [22], COX-2 selective inhibitors [23], 30:50-cyclic-AMP phosphodiesterase inhibitors [24], CRF1 antagonists [25], selective peripheral benzodiazepine receptor ligands [26], potassium channel openers (KCO's) [27], and histamine-3 receptor ligands [28].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Evaluation of the Anticancer Properties of a Novel Series of α‐(Benzoylamino)‐β‐substituted Acrylic Amide Derivatives of Pyrazolo[1,5‐a]pyrimidine

Sasikumar

Mohanasrinivasan

Kumar

et al. 2017

Journal of Heterocyclic Chem

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A novel series of α‐(benzoylamino)‐β‐substituted acrylic amide derivatives of pyrazolo[1,5‐a]pyrimidine has been synthesized using a convergent multistep synthesis. The synthesized compounds were characterized by 1H NMR, 13C NMR, ESI‐MS, and IR analyses. Those new compounds were screened for their in vitro antiproliferative activity using an MTT assay analysis. Out of nine derivatives synthesized in the current study, compounds 13g, 13d, 13h, and 13i exhibited the greatest anticancer activities in HeLa and HepG2 cell lines. The in vitro anticancer activity of compound 13g against HeLa, HepG2, and MCF‐7 cell lines is superior to the marketed drugs paclitaxel and SAHA.

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“…Several compounds of this class display interesting antitrypanosomal [4] and antischistosomal activities [6]. They are used as HMG-CoA reductaseinhibitors [7], COX-2 selective inhibitors [8], 30,50-cyclic-AMP phosphodiesteraseinhibitors [9], CRF1 antagonists [10][11], selective peripheral benzodiazepine receptor ligands [12][13][14][15][16], potassium channel [17] and histamine-3 receptor ligands [18], CDK9 inhibitor [19]and antianxiety agents [20].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization and Biological Evaluation of some Novel Pyrazolo[1,5-a]Pyrimidine Derivatives

Thumar¹,

Kaneria²,

Vadodaria³

et al. 2016

ILCPA

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A convenient synthesis of substituted Pyrazolo[1,5-a]pyrimidine was carried out by the reaction of different ketene dithioacetals with different aromatic amine in isopropanol in the presence of potassium carbonate. The newly synthesized compound were characterized by 1 H NMR, IR, Mass and screened for their antimicrobial activity against various strains of bacteria and fungi. From the synthesized different NCEs, compounds 8a, 8d and 8e are broad spectrum drug which can inhibit the growth of gram positive, gram negative bacteria and fungi.

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Insight into 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamides as peripheral benzodiazepine receptor ligands: Synthesis, biological evaluation and 3D-QSAR investigation

Cited by 56 publications

References 37 publications

Development of Ligands for the Peripheral Benzodiazepine Receptor

Development of Ligands for the Peripheral Benzodiazepine Receptor

Design, Synthesis, and Evaluation of the Anticancer Properties of a Novel Series of α‐(Benzoylamino)‐β‐substituted Acrylic Amide Derivatives of Pyrazolo[1,5‐a]pyrimidine

Synthesis, Characterization and Biological Evaluation of some Novel Pyrazolo[1,5-a]Pyrimidine Derivatives

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