Formula: C8H18O3. Recently I am researching about OPTIMIZATION; IMPAIRMENTS; AGONIST; SERIES, Saw an article supported by the NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) – USA; NIMHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) – USANIH National Institute of Mental Health (NIMH) [MH082867, MH106839]; EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENTUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) – USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [U54HD083211] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF MENTAL HEALTHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) – USANIH National Institute of Mental Health (NIMH) [R01MH082867, U19MH106839] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGINGUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) – USANIH National Institute on Aging (NIA) [R01AG051626] Funding Source: NIH RePORTER. Published in AMER CHEMICAL SOC in WASHINGTON ,Authors: Engers, JL; Bender, AM; Kalbfleisch, JJ; Cho, HP; Lingenfelter, KS; Luscombe, VB; Han, CH; Melancon, BJ; Blobaum, AL; Dickerson, JW; Rook, JM; Niswender, CM; Emmitte, KA; Conn, PJ; Lindsley, CW. The CAS is 78-39-7. Through research, I have a further understanding and discovery of 1,1,1-Triethoxyethane
This Letter describes the chemical optimization of a new series of muscarinic acetylcholine receptor subtype 1 (MO positive allosteric modulators (PAMs) based on novel tricyclic triazolo- and imidazopyridine lactam cores, devoid of M-1 agonism, e.g., no M-1 ago-PAM activity, in high expressing recombinant cell lines. While all the new tricyclic congeners afforded excellent rat pharmacokinetic (PK) properties (CLp < 8 mL/min/kg and t(1/2) > 5 h), regioisomeric triazolopyridine analogues were uniformly not CNS penetrant (K-p < 0.05), despite a lack of hydrogen bond donors. However, removal of a single nitrogen atom to afford imidazopyridine derivatives proved to retain the excellent rat PK and provide high CNS penetration (K-p > 2), despite inclusion of a basic nitrogen. Moreover, 24c was devoid of M-1 agonism in high expressing recombinant cell lines and did not induce cholinergic seizures in vivo in mice. Interestingly, all of the new M-1 PAMs across the diverse tricyclic heterocyclic cores possessed equivalent CNS MPO scores (>4.5), highlighting the value of both medicinal chemist’s eye and experimental data, e.g., not sole reliance (or decision bias) on in silico calculated properties, for parameters as complex as CNS penetration.
Formula: C8H18O3. About 1,1,1-Triethoxyethane, If you have any questions, you can contact Engers, JL; Bender, AM; Kalbfleisch, JJ; Cho, HP; Lingenfelter, KS; Luscombe, VB; Han, CH; Melancon, BJ; Blobaum, AL; Dickerson, JW; Rook, JM; Niswender, CM; Emmitte, KA; Conn, PJ; Lindsley, CW or concate me.
Reference:
Thiazolidine – Wikipedia,
,Thiazolidine – ScienceDirect.com