keyword
MENU ▼
Read by QxMD icon Read
search

2-Chloro-4-[[(1R,2R)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile

keyword
https://www.readbyqxmd.com/read/27078757/discovery-of-a-potent-selective-orally-bioavailable-and-efficacious-novel-2-pyrazol-4-ylamino-pyrimidine-inhibitor-of-the-insulin-like-growth-factor-1-receptor-igf-1r
#1
S├ębastien L Degorce, Scott Boyd, Jon O Curwen, Richard Ducray, Christopher T Halsall, Clifford D Jones, Franck Lach, Eva M Lenz, Martin Pass, Sarah Pass, Catherine Trigwell
Optimization of cellular lipophilic ligand efficiency (LLE) in a series of 2-anilino-pyrimidine IGF-1R kinase inhibitors led to the identification of novel 2-(pyrazol-4-ylamino)-pyrimidines with improved physicochemical properties. Replacement of the imidazo[1,2-a]pyridine group of the previously reported inhibitor 3 with the related pyrazolo[1,5-a]pyridine improved IGF-1R cellular potency. Substitution of the amino-pyrazole group was key to obtaining excellent kinase selectivity and pharmacokinetic parameters suitable for oral dosing, which led to the discovery of (2R)-1-[4-(4-{[5-chloro-4-(pyrazolo[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}-3,5-dimethyl-1H-pyrazol-1-yl)-1-piperidinyl]-2-hydroxy-1-propanone (AZD9362, 28), a novel, efficacious inhibitor of IGF-1R...
May 26, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/26683992/2-chloro-4-1r-2r-2-hydroxy-2-methyl-cyclopentyl-amino-3-methyl-benzonitrile-a-transdermal-selective-androgen-receptor-modulator-sarm-for-muscle-atrophy
#2
Ashraf Saeed, Grant M Vaught, Kostas Gavardinas, Donald Matthews, Jonathan E Green, Pablo Garcia Losada, Heather A Bullock, Nathan A Calvert, Nita J Patel, Stephanie A Sweetana, Venkatesh Krishnan, Judith W Henck, John G Luz, Yong Wang, Prabhakar Jadhav
A transdermal SARM has a potential to have therapeutic benefit through anabolic activity in muscle while sparing undesired effects of benign prostate hyperplasia (BPH) and liver-mediated decrease in HDL-C. 2-Chloro-4-[(2-hydroxy-2-methyl-cyclopentyl)amino]-3-methyl-benzonitrile 6 showed the desired muscle and prostate effects in a preclinical ORX rat model. Compound 6 had minimal effect on HDL-C levels in cynomolgus monkeys and showed human cadaver skin permeability, thus making it an effective tool for proof-of-concept studies in a clinical setting...
January 28, 2016: Journal of Medicinal Chemistry
1
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"