1238697-26-1

Basic information

• Product Name: TAK-063
• Synonyms: TAK-063;1-[2-Fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one;Balipodect
• CAS NO: 1238697-26-1
• Molecular Formula: C₂₃H₁₇FN₆O₂
• Molecular Weight: 428.4184832
• Product Categories: Inhibitors
• Mol File: 1238697-26-1.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 612.3±65.0 °C(Predicted)
• Appearance: /
• Density: 1.37±0.1 g/cm3(Predicted)
• PKA: -0.34±0.12(Predicted)
• CAS DataBase Reference: TAK-063(CAS DataBase Reference)
• NIST Chemistry Reference: TAK-063(1238697-26-1)
• EPA Substance Registry System: TAK-063(1238697-26-1)

Safety Data

• Hazardous Substances Data: 1238697-26-1(Hazardous Substances Data)

Usage

Description

TAK-063 is a potent and selective inhibitor of phosphodiesterase 10A (PDE10A) with an IC50 value of 0.3 nM. It demonstrates high selectivity for PDE10A over other phosphodiesterase enzymes and shows minimal inhibition of 91 receptors, ion channels, and enzymes at a concentration of 10 μM. TAK-063 has the ability to increase cAMP and cGMP levels in the striatum of mice, and it can reverse hyperlocomotion induced by certain agents in wild-type mice. However, it does not affect PDE10A knockout mice or influence plasma prolactin or glucose levels in rats.

Uses

Used in Pharmaceutical Industry:
TAK-063 is used as a therapeutic agent for the treatment of neurological disorders, particularly those involving the dysregulation of cAMP and cGMP levels. Its ability to selectively inhibit PDE10A makes it a promising candidate for the development of targeted treatments with minimal side effects.
Used in Research Applications:
TAK-063 serves as a valuable research tool for studying the role of PDE10A in various biological processes and disease states. Its high selectivity and potency allow researchers to investigate the specific functions of PDE10A and its interactions with other cellular components.
Used in Drug Development:
TAK-063 can be utilized in the development of new drugs targeting PDE10A for the treatment of neurological disorders. Its selectivity and efficacy in animal models provide a foundation for further optimization and refinement of PDE10A inhibitors as potential therapeutic agents.

Upstream product

• 1126-00-7 1-phenylpyrazole 
• 1357192-19-8 1-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)-propan-2-ol 
• 1357191-82-2 3-[3-(dimethylamino)prop-2-enoyl]-1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxypyridazin-4(1H)-one 
• 100-63-0 phenylhydrazine 
• 29632-74-4 2-fluro-4-iodoaniline 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 1357192-20-1 1-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)propan-2-one 
• 288-13-1 NH-pyrazole 
• 1238695-54-9 1-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one 

Relevant articles and documents

Practical Preparation of a 1,3,5-Trisubstituted Pyridazin-4(1 H)-one Using Selective C1 Unit Insertion and Cyclization

A novel and practical preparation of the selective phosphodiesterase 10A (PDE10A) inhibitor 1 having the core moiety of a 1,3,5-trisubstituted pyridazin-4(1H)-one has been achieved. The facile preparation of 1 in 42% overall yield involves the following key features: (1) the finding that filling the headspace of the reaction vessel with Ar gas and controlling the flow rate of the gas were found to be important to complete the substitution of an aryl iodide with pyrazole; (2) synthesis of a 3-acetyl-5-methoxy-substituted pyridazin-4(1H)-one via regioselective dimethylaminomethylenation of a diazo compound and simultaneous cyclization; and (3) regioselective ring formation of a 1,5-disubstituted pyrazole through reaction of a dimethylaminomethylene group with phenylhydrazine. In addition, an alternative synthesis of 1 via selective alkylation of 1-phenylpyrazole has been discovered.

Discovery of 1-[2-Fluoro-4-(1 H -pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1 H -pyrazol-5-yl)pyridazin-4(1 H)-one (TAK-063), a highly potent, selective, and orally active phosphodiesterase 10A (PDE10A) inhibitor

A novel series of pyridazinone-based phosphodiesterase 10A (PDE10A) inhibitors were synthesized. Our optimization efforts using structure-based drug design (SBDD) techniques on the basis of the X-ray crystal structure of PDE10A in complex with hit compound 1 (IC50 = 23 nM; 110-fold selectivity over other PDEs) led to the identification of 1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (27h). Compound 27h has potent inhibitory activity (IC50 = 0.30 nM), excellent selectivity (>15000-fold selectivity over other PDEs), and favorable pharmacokinetics, including high brain penetration, in mice. Oral administration of compound 27h to mice elevated striatal 3,5-cyclic adenosine monophosphate (cAMP) and 3,5-cyclic guanosine monophosphate (cGMP) levels at 0.3 mg/kg and showed potent suppression of phencyclidine (PCP)-induced hyperlocomotion at a minimum effective dose (MED) of 0.3 mg/kg. Compound 27h (TAK-063) is currently being evaluated in clinical trials for the treatment of schizophrenia.

Pyridazinone compounds

The present invention provides a compound which has the effect of PDE inhibition, and which is useful as a medicament for preventing or treating schizophrenia or so on. A compound of formula (I0): wherein R1 represents a substituent, R2 represents a hydrogen atom, or a substituent, R3 represents a hydrogen atom, or a substituent, Ring A represents an aromatic ring which can be substituted, and Ring B represents a 5-membered heteroaromatic ring which can be substituted, or a salt thereof.