203195-42-0Relevant articles and documents
Discovery of Novel, Potent, Brain-Permeable, and Orally Efficacious Positive Allosteric Modulator of α7 Nicotinic Acetylcholine Receptor [4-(5-(4-Chlorophenyl)-4-methyl-2-propionylthiophen-3-yl)benzenesulfonamide]: Structure-Activity Relationship and Preclinical Characterization
Sinha, Neelima,Karche, Navnath P.,Verma, Mahip Kalyan,Walunj, Sameer S.,Nigade, Prashant B.,Jana, Gourhari,Kurhade, Sanjay P.,Hajare, Anil K.,Tilekar, Ajay R.,Jadhav, Ganesh R.,Thube, Baban R.,Shaikh, Javed S.,Balgude, Sudhakar,Singh, Lairikyengbam Bikramjit,Mahimane, Vijaya,Adurkar, Shridhar K.,Hatnapure, Girish,Raje, Firoj,Bhosale, Yogesh,Bhanage, Dnyaneshwar,Sachchidanand, Sachchidanand,Dixit, Ruchi,Gupta, Rajesh,Bokare, Anand M.,Dandekar, Manoj,Bharne, Ashish,Chatterjee, Manavi,Desai, Sagar,Koul, Sarita,Modi, Dipak,Mehta, Maneesh,Patil, Vinod,Singh, Minakshi,Gundu, Jayasagar,Goel, Rajan N.,Shah, Chirag,Sharma, Sharad,Bakhle, Dhananjay,Kamboj, Rajender Kumar,Palle, Venkata P.
, p. 944 - 960 (2019/12/30)
The discovery of a series of thiophenephenylsulfonamides as positive allosteric modulators (PAM) of α7 nicotinic acetylcholine receptor (α7 nAChR) is described. Optimization of this series led to identification of compound 28, a novel PAM of α7 nicotinic acetylcholine receptor (α7 nAChR). Compound 28 showed good in vitro potency, with pharmacokinetic profile across species with excellent brain penetration and residence time. Compound 28 robustly reversed the cognitive deficits in episodic/working memory in both time-delay and scopolamine-induced amnesia paradigms in the novel object and social recognition tasks, at very low dose levels. Additionally, compound 28 has shown excellent safety profile in phase 1 clinical trials and is being evaluated for efficacy and safety as monotherapy in patients with mild to moderate Alzheimer's disease.
HETEROARYL DERIVATIVES AS ALPHA7 NACHR MODULATORS
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Paragraph 0359-0362, (2014/01/08)
Disclosed is a compound of formula (I), wherein Z, m and R1-R6 are as described herein, as a modulator of nicotinic acetylcholine receptors particularly the α7 subtype, in a subject in need thereof, as well as analogues, prodrugs, isotopically substituted analogs, metabolites, pharmaceutically acceptable salts, polymorphs, solvates, isomers, clathrates, and co-crystal thereof, for use either alone or in combinations with suitable other medicaments, and pharmaceutical compositions containing such compounds and analogues. Also disclosed are a process of preparation of the compounds and the intended uses thereof in therapy, particularly in the prophylaxis and therapy of disorders such as Alzheimer's disease, mild cognitive impairment, senile dementia, and the like.
