Results 221 to 230 of about 4,657 (257)

Evolution and synthesis of novel orally bioavailable inhibitors of PDE10A

Bioorganic & Medicinal Chemistry Letters, 2015
The design and synthesis of highly potent, selective orally bioavailable inhibitors of PDE10A is reported. Starting with an active compound of modest potency from a small focused screen, we were able to evolve this series to a lead molecule with high potency and selectivity versus other PDEs using structure-based design. A systematic refinement of ADME
Lee W. Herman, Michael C. Hewitt, Philip Jones, Douglas F. Burdi, Sufang Zhao, Jianfeng Wei, Una Campbell, Patrick Koch, Liming Shao, Jun Wang, John Emmerson Campbell, Hua Zhong   +11 more
openaire   +3 more sources

Brain PET measurement of PDE10A occupancy by TAK‐063, a new PDE10A inhibitor, using [¹¹C]T‐773 in nonhuman primates

Synapse, 2016
AbstractBecause phosphodiesterase 10A (PDE10A) degrades both cyclic adenosine monophosphate and cyclic guanosine monophosphate and is distributed mainly in the striatum, PDE10A inhibitors have been considered to potentially be useful therapeutic agents for psychiatric and neurodegenerative diseases such as schizophrenia and Huntington's disease.
Nahid Amini, Haruhide Kimura, Akihiro Takano, Balázs Gulyás, Vladimir Stepanov, Ryuji Nakao, Christer Halldin   +6 more
openaire   +3 more sources

Design and synthesis of potent and selective pyridazin-4(1H)-one-based PDE10A inhibitors interacting with Tyr683 in the PDE10A selectivity pocket

Bioorganic & Medicinal Chemistry, 2016
Utilizing structure-based drug design techniques, we designed and synthesized phosphodiesterase 10A (PDE10A) inhibitors based on pyridazin-4(1H)-one. These compounds can interact with Tyr683 in the PDE10A selectivity pocket. Pyridazin-4(1H)-one derivative 1 was linked with a benzimidazole group through an alkyl spacer to interact with the OH of Tyr683 ...
Kosuke Nakashima, Takahiko Taniguchi, Makoto Fushimi, Tomoaki Hasui, Hideyuki Oki, Jun Kunitomo, Takenori Hitaka, Hironori Kokubo, Masato Yoshikawa   +8 more
openaire   +3 more sources

Familial choreoathetosis due to novel heterozygous mutation in PDE10A

American Journal of Medical Genetics Part A, 2017
PDE10A encodes a dual cAMP‐cGMP phosphodiesterase that is enriched in the medium spiny neurons of the corpus striatum in the brain and plays an important role in basal ganglia circuitry. Three unrelated patients with childhood onset chorea and striatal abnormalities on MRI brain with heterozygous de novo variants in PDE10A have been described ...
Dipti Deshpande, Dipti Deshpande, Aneek Das Bhowmik, Dandu R Varma, Ashwin Dalal, Dhanya Lakshmi Narayanan   +5 more
openaire   +2 more sources

Alterations in gene regulation following inhibition of the striatum-enriched phosphodiesterase, PDE10A

Neuropharmacology, 2010
PDE10A is a member of the phosphodiesterase superfamily highly enriched within medium spiny neurons (MSN) in mammalian striatum. We have used inhibitors of PDE10A and quantitative measures of mRNA to demonstrate that PDE10A controls striatal gene expression by regulating MSN cyclic nucleotide signaling pathways.
Frank S. Menniti, Larry C. James, Seeger Thomas Francis, Christine A. Strick, Christopher J. Schmidt, Carol B. Fox   +5 more
openaire   +3 more sources

Current Understanding of PDE10A in the Modulation of Basal Ganglia Circuitry

2017
The basal ganglia are a forebrain network of interconnected nuclei that are involved in action selection, reward circuits and coordinating movement. PDE10A inhibition has been proposed as a novel way to modulate basal ganglia circuitry and to ameliorate symptoms in Huntington's disease, Parkinson's disease and Schizophrenia.
Nicholas J. Brandon, Jan-Philip Schülke
openaire   +3 more sources

Development of a series of novel carbon‐11 labeled PDE10A inhibitors

Journal of Labelled Compounds and Radiopharmaceuticals, 2015
Phosphodiesterase 10A (PDE10A) is a member of the PDE family of enzymes that degrades cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Our aim was to label a series of structurally related PDE10A inhibitors with carbon‐11 and evaluate them as potential positron emission tomography (PET) radioligands for PDE10A using ...
Christer Halldin, Takanobu Kuroita, Tomoaki Hasui, Nahid Amini, Kosuke Nakashima, Akihiro Takano, Haruhide Kimura, Ryuji Nakao, Vladimir Stepanov, Takahiko Taniguchi, Shotaro Miura, Shotaro Miura   +11 more
openaire   +3 more sources

Design and optimization of purine derivatives as in vivo active PDE10A inhibitors

Bioorganic & Medicinal Chemistry, 2017
Phosphodiesterases are important enzymes regulating signal transduction mediated by second messenger molecules cAMP or cGMP. PDE10A is a unique member in the PDE family because of its selective expression in medium spiny neurons. It is recognized as anti-psychotic drug target.
Liu Chen, Danqi Chen, Le Tang, Jing Ren, Jiaojiao Chen, Xuechu Zhen, Yu-Chih Liu, Chenhua Zhang, Haibin Luo, Jingkang Shen, Bing Xiong   +10 more
openaire   +3 more sources

PDE10A Mutation as an Emerging Cause of Childhood-Onset Hyperkinetic Movement Disorders: A Review of All Published Cases

Neuropediatrics, 2023
S. Kalampokini, Georgia Xiromerisiou, P. Bargiotas, V. Anastasiadou, Paul Costeas, G. Hadjigeorgiou   +5 more
semanticscholar   +1 more source

Expanding the genotype-phenotype landscape of PDE10A-associated movement disorders.

Parkinsonism & Related Disorders, 2023
S. Bohlega, Ali H. Abusrair, Zainah Al-Qahtani, Francisco J. Guzmán-Vega, R. Ramakrishnan, Haya Aldosari, A. Aldakheel, Salma Al-Qahtani, D. Monies, S. Arold   +9 more
semanticscholar   +1 more source