118811-07-7Relevant articles and documents
Discovery and optimization of a potent and selective indazolamine series of IRAK4 inhibitors
Zhai, Wenqiang,Lu, Yongping,Zhu, Yabo,Zhou, Mengguang,Ye, Cheng,Shi, Zheng-Zheng,Qian, Wenjian,Hu, Taishan,Chen, Lei
, (2021)
IRAK4 is a key mediator of innate immunity. There is a high interest in identifying novel IRAK4 inhibitors for the treatment of inflammatory autoimmune diseases. We describe here a highly potent and selective IRAK4 inhibitor (HS271) that exhibited superio
Thienopyrimidine derivatives and preparation method thereof
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Paragraph 0128-0129; 0146-0147, (2021/09/08)
Disclosed are a thienopyrimidine derivative and a preparation method therefor. Provided is a method for preparing a compound as shown in formula B, which method is characterized by comprising the following steps: subjecting a compound as shown in formula
1-[2-(1-Cyclobutylpiperidin-4-yloxy)-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl]propan-1-one: a Histamine H3 Receptor Inverse Agonist with Efficacy in Animal Models of Cognition
Achanta, Pramod Kumar,Badange, Rajesh Kumar,Benade, Vijay,Bojja, Kumar,Choudary Palacharla, Raghava,Jayarajan, Pradeep,Kagita, Narendra,Lingavarapu, Bujji Babu,Manchineella, Sravanthi,Mohammed, Abdul Rasheed,Nirogi, Ramakrishna,Rao Doguparthi, Mallikarjuna,Rao Muddana, Nageswara,Reballi, Veena,Shinde, Anil Karbhari,Subramanian, Ramkumar,Thentu, Jagadeesh Babu,Yarra, Sivasekhar
, (2021/11/23)
A series of chemical optimizations, which was guided by in vitro affinity at histamine H3 receptor (H3R), modulation of lipophilicity, ADME properties and preclinical efficacy resulted in the identification of 1-[2-(1-cyclobutylpiperidin-4-yloxy)-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl]propan-1-one (45 e) as a potent and selective (Ki=4.0 nM) H3R inverse agonist. Dipsogenia induced by (R)-α-methylhistamine was dose dependently antagonized by 45 e, confirming its functional antagonism at H3R. It is devoid of hERG and phospholipidosis issues. Compound 45 e has adequate oral exposures and favorable half-life in both rats and dogs. It has demonstrated high receptor occupancy (ED80=0.22 mg/kg) and robust efficacy in object recognition task and, dose dependently increased acetylcholine levels in brain. The sub-therapeutic doses of 45 e in combination with donepezil significantly increased acetylcholine levels. The potent affinity, selectivity, in vivo efficacy and drug like properties together with safety, warrant for further development of this molecule for potential treatment of cognitive disorders associated with Alzheimer's disease.