1609259-46-2Relevant academic research and scientific papers
Synthesis and Pharmacological Evaluation of Noncatechol G Protein Biased and Unbiased Dopamine D1 Receptor Agonists
Wang, Pingyuan,Felsing, Daniel E.,Chen, Haiying,Raval, Sweta R.,Allen, John A.,Zhou, Jia
, p. 792 - 799 (2019)
Noncatechol heterocycles have recently been discovered as potent and selective G protein biased dopamine 1 receptor (D1R) agonists with superior pharmacokinetic properties. To determine the structure-activity relationships centered on G protein or β-arrestin signaling bias, systematic medicinal chemistry was employed around three aromatic pharmacophores of the lead compound 5 (PF2334), generating a series of new molecules that were evaluated at both D1R Gs-dependent cAMP signaling and β-arrestin recruitment in HEK293 cells. Here, we report the chemical synthesis, pharmacological evaluation, and molecular docking studies leading to the identification of two novel noncatechol D1R agonists that are a subnanomolar potent unbiased ligand 19 (PW0441) and a nanomolar potent complete G protein biased ligand 24 (PW0464), respectively. These novel D1R agonists provide important tools to study D1R activation and signaling bias in both health and disease.
Crisaborole intermediate, preparation method and application of crisaborole intermediate in preparation of crisaborole
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Paragraph 0151-0162, (2021/04/03)
The invention discloses a crisaborole intermediate, a preparation method and application of the crisaborole intermediate in preparation of crisaborole. The crisaborole intermediate has a structure asshown in a formula I in the specification. The preparation method comprises the following steps: carrying out Grignard reaction on a compound shown in a structural formula VI in an organic solvent A or carrying out exchange reaction with a metal Grignard reagent, and reacting with borate to obtain a compound shown in a structural formula V; reacting the obtained compound with the structural formula V with pinacol in an organic solvent B to obtain a compound with a structural formula IV; removing a protecting group from the compound shown in the structural formula IV in an organic solvent C toobtain a compound shown in a structural formula III; and carrying out a coupling reaction on the compound shown in the structural formula III and 4-halogenated cyanophenyl shown in the structural formula II in an organic solvent D under an alkaline condition to obtain the crisaborole intermediate shown in the structural formula I. The method effectively solves the problems of high production costand low product purity, and is suitable for industrial large-scale production.
HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS
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Page/Page column 118-119, (2015/11/10)
The present invention provides, in part, compounds of Formula (I) and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating D1-mediated (or D1 -associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), schizotypal personality disorder, cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, Parkinson's disease, anxiety, and depression.
HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS
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Page/Page column 96; 98, (2015/11/16)
The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating D1-mediated (or D1 -associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), schizotypal personality disorder, cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, Parkinson's disease, anxiety, and depression.
HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS
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Page/Page column 128; 129; 130, (2015/11/16)
The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating D1-mediated (or D1 -associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), schizotypal personality disorder, cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, Parkinson's disease, anxiety, and depression.
HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS
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Page/Page column 86; 92; 93, (2015/01/16)
The present invention provides, in part, compounds of Formula (I) and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating D1 -mediated (or D1 -associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), age-related cognitive decline, dementia, and Parkinson's disease.
HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS
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Paragraph 0349; 0352, (2014/05/20)
The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof and N-oxides of the foregoing; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, salts or N-oxides, and their uses for treating D1-mediated (or D1-associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, impulsivity, compulsive gambling, overeating, autism spectrum disorder, MCI, age-related cognitive decline, dementia, RLS, Parkinson's disease, Huntington's chorea, anxiety, depression, MDD, TRD, and bipolar disorder.
