195055-03-9

Basic information

• Product Name: R-121,919
• Synonyms: R-121,919;3-(6-(DIMETHYLAMINO)-4-METHYLPYRIDIN-3-YL)-2,5-DIMETHYL-N,N-DIPROPYLPYRAZOLO[1,5-A]PYRIMIDIN-7-AMINE;NBI 30775;3-[6-(diMethylaMino)-4-Methyl-3-pyridinyl]-2,5-diMethyl-N,N-dipropyl-pyrazolo[2,3-a]pyriMidine-7-aMine;3-(6-(Dimethylamino)-4-methylpyridin-3-yl)-2,5-dimethyl-N,N-dipropylpyrazolo[1,5-a]pyrimidin-7-am;3-[6-(DiMethylaMino)-4-Methyl-3-pyridinyl]-2,5-diMethyl-N,N-dipropylpyrazolo[1,5-a]pyriMidin-7-aMine;-2,5-dimethyl-N,N-dipropylpyrazolo[1,5-a]pyrimidin-7-amine;-4-methylpyridin-3-yl)
• CAS NO: 195055-03-9
• Molecular Formula: C22H32N6
• Molecular Weight: 380.53
• Mol File: 195055-03-9.mol

Chemical Properties

• Appearance: /
• Density: 1.114g/cm³
• Refractive Index: 1.595
• CAS DataBase Reference: R-121,919(CAS DataBase Reference)
• NIST Chemistry Reference: R-121,919(195055-03-9)
• EPA Substance Registry System: R-121,919(195055-03-9)

Safety Data

• Hazardous Substances Data: 195055-03-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
R-121,919 is used as a therapeutic agent for the treatment of alcoholism. It functions by acting as a CRF1 receptor antagonist, which helps in reducing the negative emotional symptoms of acute and protracted alcohol withdrawal, thereby aiding in the recovery process for individuals struggling with alcohol dependence.
Additionally, due to its receptor antagonist properties, R-121,919 may have potential applications in other areas of medicine where CRF1 receptors play a role, although the provided materials do not specify these additional uses.

InChI:InChI=1/C22H32N6/c1-8-10-27(11-9-2)20-13-16(4)24-22-21(17(5)25-28(20)22)18-14-23-19(26(6)7)12-15(18)3/h12-14H,8-11H2,1-7H3

Upstream product

• 142-84-7 di-n-propylamine 
• 195055-65-3 3-(4-methyl-6-dimethylaminopyridin-3-yl)-2,5-dimethyl-7-chloropyrazolo[1,5-a]pyrimidine 
• 20173-72-2 2-(N,N-dimethylamino)-4-methylpyridine 
• 764651-69-6 2-dimethylamino-4-methyl-5-formylpyridine 
• 764651-68-5 5-bromo-2-dimethylamino-4-methylpyridine 
• 764651-70-9 2-dimethylamino-4-methyl-5-(cyanomethyl)pyridine 
• 764651-65-2 1-cyano-1-(6-dimethylamino-4-methylpyridin-3-yl)acetone 
• 764651-66-3 3-amino-4-(6-dimethylamino-4-methylpyridin-3-yl)-5-methylpyrazole 
• 764651-67-4 3-(4-methyl-6-dimethylaminopyridin-3-yl)-2,5-dimethyl-7-hydroxypyrazolo[1,5-a]pyrimidine 

Relevant articles and documents

Design of 2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylamino- pyrazolo[1,5-a]pyrimidine (NBI 30775/R121919) and structure-activity relationships of a series of potent and orally active corticotropin-releasing factor receptor antagonists

We previously shown that 3-phenylpyrazolo[1,5-a]pyrimidines exemplified by 8 were potent antagonists of the human corticotropin-releasing factor-1 receptor. A series of 3-pyridylpyrazolo-[1,5-a]pyrimidines 15, 25-30, 34, and 35 containing a weakly basic pyridine ring at the 3-position of the bicyclic nucleus was designed to reduce lipophilicity from the initial leads such as 7. Here, we showed that these 3-pyridyl compounds exhibited potent antagonists at the human CRF1 receptor. Moreover, the hydrophilic and weakly basic pyridine moiety increased the water solubility of some analogues. Compound 26h exhibited good binding affinity at the human CRF1 receptor with a Ki value of 3.5 nM. As a functional antagonist, it dose-dependently inhibited CRF-stimulated cAMP production in cells expressing the CRF1 receptor (IC50 = 50 nM), and CRF-stimulated ACTH release from cultured rat pituitary cells (IC50 = 20 nM). 26h had a log P value of 4.9 and water solubility of greater than 10 mg/mL. Pharmacokinetic studies in rats showed that 26h was orally bioavailable and able to penetrate into the brain. 26h has been demonstrated in vivo efficacy in animal behavioral models that measure anxiolytic activity. These results suggest that analogues from this series were potent CRF1 receptor antagonists with proper physicochemical properties and good pharmacokinetic profiles. 26h was developed into a clinical compound and exhibited efficacy in patients with major depression.

PYRAZOLOPYRIMIDINES AS CRF RECEPTOR ANTAGONISTS

This invention concerns compounds of formula including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R1 is NR4R5 or OR5; R2 is C1-6alkyl, C