1005403-35-9

Upstream product

• 1382182-62-8 C₁₆H₂₅BO₆S 
• 41720-98-3 (R)-2-methylpyrrolidine hydrochloride 
• 269409-70-3 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol 
• 889865-32-1 2-[4-(3-chloropropoxy)phenyl]-4,4,5,5,-tetramethyl[1,3,2]dioxaborolane 
• 957061-13-1 2-[4-(3-bromopropoxy)phenyl]-4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane 

Downstream Products

• 1174675-06-9 (R)-2-methyl-1-{3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-propyl}-pyrrolidine hydrochloride 
• 1174674-56-6 3-chloro-6-{4-[3-((R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}pyridazine 
• 1005398-61-7 Irdabisant hydrochloride 
• 1005401-17-1 4-methoxy-2-methoxymethyl-5-(4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl)-2H-pyridazin-3-one 
• 1005401-18-2 5-methoxy-2-methoxymethyl-4-(4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl)-2H-pyridazin-3-one 
• 1005402-07-2 5-methoxy-4-(4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl)-2H-pyridazin-3-one 
• 1349798-19-1 C₁₉H₂₄N₂O₂ 
• 1349798-31-7 C₂₄H₂₈N₂O₂ 

Relevant academic research and scientific papers

Synthesis and evaluation of 4- and 5-pyridazin-3-one phenoxypropylamine analogues as histamine-3 receptor antagonists

A novel series of 4-pyridazin-3-one and 5-pyridazin-3-one analogues were designed and synthesized as H3R antagonists. Structure-activity relationship revealed the 5-pyridazin-3-ones 8a and S-methyl 8b had excellent human and rat H3R affinities, and acceptable pharmacokinetic properties. In vivo evaluation of 8a showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG/EMG model.

Discovery and characterization of 6-{4-[3-(R)-2-methylpyrrolidin-1-yl) propoxy]phenyl}-2H-pyridazin-3-one (CEP-26401, irdabisant): A potent, selective histamine H3 receptor inverse agonist

Optimization of a novel series of pyridazin-3-one histamine H3 receptor (H3R) antagonists/inverse agonists identified 6-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2H-pyridazin-3-one (8a, CEP-26401; irdabisant) as a lead candid

Synthesis and evaluation of pyridone-phenoxypropyl-R-2-methylpyrrolidine analogues as histamine H3 receptor antagonists

6-{4-[3-(R)-2-Methylpyrrolidin-1-yl)propoxy]-phenyl}-2H-pyridazin-3-one 6 (Irdabisant; CEP-26401) was recently reported as a potent H3R antagonist with excellent drug-like properties and in vivo activity that advanced into clinical evaluation. A series of pyridone analogs of 6 was synthesized and evaluated as H3R antagonists. Structure-activity relationships revealed that the 5-pyridone regiomer was optimal for H 3R affinity. N-Methyl 9b showed excellent H3R affinity, acceptable pharmacokinetics and pharmaceutical properties. In vivo evaluation of 9b showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG model.

SUBSTITUTED PYRIDAZINE DERIVATIVES WHICH HAVE HISTAMINE H3 ANTAGONIST ACTIVITY

The present invention is directed to compounds having histamine H3 antagonist activity, as well as methods of their use and preparation.