6290-50-2Relevant academic research and scientific papers
Practical Preparation of a 1,3,5-Trisubstituted Pyridazin-4(1 H)-one Using Selective C1 Unit Insertion and Cyclization
Suzuki, Akihiro,Fukuda, Naohiro,Kajiwara, Takeshi,Ikemoto, Tomomi
, p. 484 - 492 (2019/02/14)
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.
IMIDAZOPYRIDINE EZH2 INHIBITORS
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Page/Page column 114; 115, (2016/07/27)
The present invention relates to imidazopyridines of general formula (I), to a method for their preparation, to intermediates for their preparation, to pharmaceutical compositions comprising at least one of those compounds, and to the use thereof.
Synthesis of diverse acyclic precursors to pyrroles for studies of prebiotic routes to tetrapyrrole macrocycles
Chandrashaker, Vanampally,Ptaszek, Marcin,Taniguchi, Masahiko,Lindsey, Jonathan S.
, p. 8786 - 8808 (2016/10/13)
A chemical model for the origin of tetrapyrrole macrocycles under prebiotic conditions entails the condensation of acyclic dicarbonyl compounds and α-aminoketones to form pyrroles that are equipped for subsequent self-condensation. Development and exploration of the scope of the chemical model (including combinatorial reactions, studies of the effects of structurally defective substrates, and reactions in aqueous or organic media) have relied on the availability of diverse starting materials prepared by traditional chemical synthesis methods. Here the synthesis of all acyclic dicarbonyl compounds and α-aminoketones used in the prior prebiotic model studies is described. There are five sets of acyclic dicarbonyl compounds including (i) β-ketoesters bearing diverse 4-substituents, (ii) levulinic acid derivatives bearing selected 5-substituents (i.e., analogues of δ-aminolevulinic acid, ALA), (iii) meso-substituted β-ketoesters, (iv) meso-substituted β-diketones that contain one 4-substituent, and (v) hybrid molecules that contain both the β-ketoacyl unit and the levulinic acid skeleton (or homologue thereof). A variety of α-aminoketones (homologues of ALA) also have been prepared. Altogether, the synthesis of 53 compounds is described, encompassing 28 new compounds as well as 25 known compounds that have been more fully characterized or prepared via alternative routes. The ability to convert selected acyclic compounds directly via pyrroles to porphyrinogens in a single-flask process may also prove useful in mainstream syntheses of diverse tetrapyrroles regardless of possible prebiotic relevance.
SUBSTITUTED PYRROLO[1,2-A]PYRIMIDINES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
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Paragraph 00269, (2016/06/28)
The invention provides substituted pyrrolo[l,2-a]pyrimi dines and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrrolo[1,2-a]pyrimidines compounds described herein include substituted 2,4-dimethyl-N-phenylpyrrolo[l,2-a]pyrimidine-8-carboxamide compounds and variants thereof.
METHOD OF TREATMENT
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Paragraph 0784, (2014/09/29)
The present invention relates to a method of treating T cell mediated inflammatory immune diseases or T cell mediated hypersensitivity diseases, which comprises administering to a human in need thereof an effective amount of a compound which inhibits EZH2 and/or EZH1, or a pharmaceutically acceptable salt thereof.
ENHANCER OF ZESTE HOMOLOG 2 INHIBITORS
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Page/Page column 59, (2013/12/03)
This invention relates to novel substituted benzamide according to Formula (I) which are inhibitors of Enhancer of Zeste Homolog 2 (EZH2), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the treatment of cancers.
