Imidazopyridazinones as novel PDE7 inhibitors: SAR and in vivo studies in Parkinson’s disease model

Banerjee, Abhisek; Patil, Saiprasad; Pawar, Mahesh Y.; Gullapalli, Srinivas; Gupta, Praveen Kumar; Gandhi, Maulik N.; Bhateja, Deepak; Bajpai, Malini; Sangana, Ramachandra; Gudi, Girish; Khairatkar-Joshi, Neelima; Gharat, Laxmikant A.

doi:10.1016/j.bmcl.2012.07.077

Cited by 31 publications

(15 citation statements)

References 19 publications

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“…C57BL/6j 11 (Mabrouk et al, 2010;Shiozaki et al, 1999;Banerjee et al, 2012;Greenbaum et al, 2012;Cannella et al, 2015;Hagino et al, 2015;Celorrio et al, 2016;Koranda et al, 2016;Celorrio et al, 2017;Charvin et al, 2017;Cortés et al, 2017) BALB/cJ 4 (Atack et al, 2014;Shook et al, 2010;Striem et al, 1997;Ionov & Severtsev, 2012b) Others 40 (Greco et al, 2010;Mihara et al, 2007;Shiozaki et al, 1999;Himori et al, 1994;Kanda et al, 1994;Kinoshita et al, 1994;Haraguchi et al, 1996;Haraguchi et al, 1997;Kobayashi et al, 1997;Matsuo et al, 2000;Nasu et al, 2000;Wang et al, 2000;Araki et al, 2001;El Yacoubi et al, 2001;Xu et al, 2002;Karasawa et al, 2003;Pires et al, 2003;Tsujikawa et al, 2003;Stasi et al, 2006;Marazziti et al, 2007;Kasture, Barhate, et al, 2009;Ardayfio et al, 2010;Bateup et al, 2010;Fink-Jensen et al, 2011;Manikandaselvi et al, 2012;Golden et al, 2013;…”

Section: Number Of Studies Referencesmentioning

confidence: 99%

Haloperidol‐induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies

Waku

Magalhães

Alves

et al. 2021

Eur J of Neuroscience

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Several useful animal models for parkinsonism have been developed so far. Haloperidol‐induced catalepsy is often used as a rodent model for the study of motor impairments observed in Parkinson's disease and related disorders and for the screening of potential antiparkinsonian compounds. The objective of this systematic review is to identify publications that used the haloperidol‐induced catalepsy model for parkinsonism and to explore the methodological characteristics and the main questions addressed in these studies. A careful systematic search of the literature was carried out by accessing articles in three different databases: Web of Science, PubMed and SCOPUS. The selection and inclusion of studies were performed based on the abstract and, subsequently, on full‐text analysis. Data extraction included the objective of the study, study design and outcome of interest. Two hundred and fifty‐five articles were included in the review. Publication years ranged from 1981 to 2020. Most studies used the model to explore the effects of potential treatments for parkinsonism. Although the methodological characteristics used are quite varied, most studies used Wistar rats as experimental subjects. The most frequent dose of haloperidol used was 1.0 mg/kg, and the horizontal bar test was the most used to assess catalepsy. The data presented here provide a framework for an evidence‐based approach to the design of preclinical research on parkinsonism using the haloperidol‐induced catalepsy model. This model has been used routinely and successfully and is likely to continue to play a critical role in the ongoing search for the next generation of therapeutic interventions for parkinsonism.

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Section: Number Of Studies Referencesmentioning

confidence: 99%

Haloperidol‐induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies

Waku

Magalhães

Alves

et al. 2021

Eur J of Neuroscience

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“…Of note, PDE7 may act as a therapeutic remyelination agent for the treatment of MS . In a follow-up study, TC3.6 and VP1.15 have been demonstrated to possess potent neuroprotective and anti-inflammatory effects in other neurological disorders, including AD, PD, spinal cord injury, and MS. , ASB16165, exhibiting an IC 50 value of 15 nM for human PDE7A, suppressed IL-12-induced IFN-γ production by T lymphoblasts and the induction of activated CD4 + /CD8 + T cells. These findings indicated that ASB16165 may be beneficial for the treatment of immunological disorders .…”

Section: Overview Of the Phosphodiesterase (Pde) Superfamilymentioning

confidence: 99%

Advances in Cyclic Nucleotide Phosphodiesterase-Targeted PET Imaging and Drug Discovery

et al. 2021

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Cyclic nucleotide phosphodiesterases (PDEs) control the intracellular concentrations of cAMP and cGMP in virtually all mammalian cells. Accordingly, the PDE family regulates a myriad of physiological functions, including cell proliferation, differentiation and apoptosis, gene expression, central nervous system function, and muscle contraction. Along this line, dysfunction of PDEs has been implicated in neurodegenerative disorders, coronary artery diseases, chronic obstructive pulmonary disease, and cancer development. To date, 11 PDE families have been identified; however, their distinct roles in the various pathologies are largely unexplored and subject to contemporary research efforts. Indeed, there is growing interest for the development of isoform-selective PDE inhibitors as potential therapeutic agents. Similarly, the evolving knowledge on the various PDE isoforms has channeled the identification of new PET probes, allowing isoform-selective imaging. This review highlights recent advances in PDE-targeted PET tracer development, thereby focusing on efforts to assess disease-related PDE pathophysiology and to support isoform-selective drug discovery.

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“…6-Methyltetrahydropyridazin-3(2H)-one (5b). The title compound was prepared according to the above general procedure from 6-methyl-4,5-dihydropyridazin-3(2H)-one 18 (474.8 mg, 4.2 mmol, 1 equiv) and NaBH 3 CN (532.0 mg, 8.5 mmol, 2 equiv) in MeOH (19.7 mL, 0.2 M) in 6 h. Flash column chromatography over silica gel (CH 2 Cl 2 /MeOH 94:6 v/v) afforded the title compound as a white powder (299.4 mg, 82%). R f = 0.17 (CH 2 Cl 2 /MeOH 94:6 v/v).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

The Catalytic Regio- and Stereoselective Synthesis of 1,6-Diazabicyclo[4.3.0]nonane-2,7-diones

et al. 2021

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A straightforward synthesis of original 1,6-diazabicyclo[4.3.0]nonane-2,7-diones was achieved through a DBU-organocatalyzed multicomponent Knoevenagel-aza-Michael-Cyclocondensation (KMC) reaction which takes advantage of an unprecedented highly regio-and diastereoselective conjugate addition of pyridazinones to alkylidene Meldrum's acid intermediates. The key reactive intermediates of this complex process were analyzed by means of electrospray ionization mass spectrometry coupled to ion mobility spectrometry (ESI-IMS-MS) allowing to valid the proposed mechanism.

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Imidazopyridazinones as novel PDE7 inhibitors: SAR and in vivo studies in Parkinson’s disease model

Cited by 31 publications

References 19 publications

Haloperidol‐induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies

Haloperidol‐induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies

Advances in Cyclic Nucleotide Phosphodiesterase-Targeted PET Imaging and Drug Discovery

The Catalytic Regio- and Stereoselective Synthesis of 1,6-Diazabicyclo[4.3.0]nonane-2,7-diones

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