426463-01-6Relevant articles and documents
Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the Treatment of Atopic Dermatitis
Ko, Kwangseok,Kim, Hye-Jung,Ho, Pil-Su,Lee, Soon Ok,Lee, Ji-Eun,Min, Cho-Rong,Kim, Yu Chul,Yoon, Ju-Han,Park, Eun-Jung,Kwon, Young-Jin,Yun, Jee-Hun,Yoon, Dong-Oh,Kim, Jung-Sook,Park, Woul-Seong,Oh, Seung-Su,Song, Yu-Mi,Cho, Woon-Ki,Morikawa, Kazumi,Lee, Kyoung-June,Park, Chan-Hee
supporting information, p. 2949 - 2961 (2018/04/23)
The histamine H4 receptor (H4R), a member of the G-protein coupled receptor family, has been considered as a potential therapeutic target for treating atopic dermatitis (AD). A large number of H4R antagonists have been disclosed, but no efficient agents controlling both pruritus and inflammation in AD have been developed yet. Here, we have discovered a novel class of orally available H4R antagonists showing strong anti-itching and anti-inflammation activity as well as excellent selectivity against off-targets. A pharmacophore-based virtual screening system constructed in-house successfully identified initial hit compound 9, and the subsequent homology model-guided optimization efficiently led us to discover pyrido[2,3-e]tetrazolo[1,5-a]pyrazine analogue 48 as a novel chemotype of a potent and highly selective H4R antagonist. Importantly, orally administered compound 48 exhibits remarkable efficacy on antipruritus and anti-inflammation with a favorable pharmacokinetic (PK) profile in several mouse models of AD. Thus, these data strongly suggest that our compound 48 is a promising clinical candidate for treatment of AD.
NOVEL HETEROCYCLIC DERIVATIVES AND THEIR USES
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Paragraph 0742-0744, (2014/10/29)
The present invention relates to novel heterocyclic compounds useful in preparing drugs for treatment of diseases associated with various functions of the histamine 4 receptor. Especially, the said drugs are useful for treatment of inflammatory diseases, allergy, pain, nasal polyps, rhinitis, chronic sinusitis, nasal congestion, nasal itch, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, atopic dermatitis, psoriasis, eczema, pruritus, itchy skin, urticaria, idiopathic chronic urticaria, scleroderma, conjunctivitis, keratoconjunctivitis, ocular inflammation, dry eye, cardiac dysfunction, arrhythmia, atherosclerosis, multiple sclerosis, inflammatory bowel disease (including colitis, Crohn's disease, ulcerative colitis), inflammatory pain, neuropathic pain, osteoarthritic pain, autoimmune thyroid disease, immune-mediated (also known as type I) diabetes, lupus, post-operative adhesions, vestibular disorders and cancer.
Compounds and methods for promoting smoking cessation
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, (2008/06/13)
Compounds and methods for promoting smoking cessation. The compounds may be used to treat a variety of other conditions and disease states.
Synthesis and biological evaluation of pyrido[2,3-b]pyrazine and pyrido[2,3-b]pyrazine-N-oxide as selective glycine antagonists
Cugola, Alfredo,Donati, Daniele,Guarneri,Micheli, Fabrizio,Missio, Andrea,Pecunioso, Angelo,Reggiani, Angelo,Tarzia,Zanirato
, p. 2749 - 2754 (2007/10/03)
Pyrido[2,3-b]pyrazines and pyrido[2,3-b]pyrazines-N-oxides have been synthesized and evaluated for in vitro/in vivo antagonistic activity at the glycine site on the NMDA receptor.