259809-78-4

Basic information

• Product Name: 2-Methylsulfanyl-7,8-dihydro-5H-pyrido[4,3-d]pyriMidine -6-carboxylic acid tert-butyl ester
• Synonyms: 2-Methylsulfanyl-7,8-dihydro-5H-pyrido[4,3-d]pyriMidine -6-carboxylic acid tert-butyl ester;tert-Butyl 2-(methylthio)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate;tert-butyl 7,8-dihydro-2-(methylthio)pyrido[4,3-d]pyrimidine-6(5H)-carboxylate
• CAS NO: 259809-78-4
• Molecular Formula: C₁₃H₁₉N₃O₂S
• Molecular Weight: 281.37386
• Mol File: 259809-78-4.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 420.4±45.0 °C(Predicted)
• Appearance: /
• Density: 1.23±0.1 g/cm3 (20 ºC 760 Torr)
• PKA: 1.52±0.20(Predicted)
• CAS DataBase Reference: 2-Methylsulfanyl-7,8-dihydro-5H-pyrido[4,3-d]pyriMidine -6-carboxylic acid tert-butyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Methylsulfanyl-7,8-dihydro-5H-pyrido[4,3-d]pyriMidine -6-carboxylic acid tert-butyl ester(259809-78-4)
• EPA Substance Registry System: 2-Methylsulfanyl-7,8-dihydro-5H-pyrido[4,3-d]pyriMidine -6-carboxylic acid tert-butyl ester(259809-78-4)

Safety Data

• Hazardous Substances Data: 259809-78-4(Hazardous Substances Data)

Upstream product

• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 157327-41-8 t-butyl-3-[(dimethylamino)methylidene]-4-oxopiperidine-1-carboxylate 
• 147895-43-0 S-methylisothiourea hemisulphate 
• 867-44-7 S-Methylisothiourea sulfate 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 

Downstream Products

• 259809-79-5 tert-butyl 2-(methylsulfonyl)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate 
• 578713-43-6 N,N-Dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine 
• 1365155-89-0 6-(4-(Benzyl(methyl)amino)cyclohexyl)-N,N-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-2-amine 
• 1365155-94-7 tert-Butyl 4-(2-(dimethylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)cyclohexyl(methyl)carbamate 
• 1365154-07-9 N,N-dimethyl-6-(4-(methylamino)cyclohexyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-2-amine 
• 1454656-61-1 6-(2-methanesulfinyl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl)-pyridine-2-carboxylic acid (4-isopropyl-phenyl)-amide 
• 1454656-47-3 6-{2-amino-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl}-N-[4-(isopropyl)phenyl]pyridine-2-carboxamide 
• 1454656-60-0 N-(4-isopropylphenyl)-6-[2-(methylthio)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]pyridine-2-carboxamide 
• 1454657-51-2 methyl-4-methyl-3-[2-(methylsulfanyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]benzoate 
• 1454656-93-9 3-[2-(methylthio)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-N-[3-(trifluoromethyl)phenyl]benzamide 
• 1454656-96-2 N-(3-isopropylphenyl)-4-methyl-3-[2-(methylthio)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]benzamide 
• 1454657-06-7 3-(7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-N-[3-(trifluoromethyl)phenyl]benzamide 
• 1567965-09-6 tert-butyl 2-(cyclopropylamino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate 
• 1567963-78-3 6-(5-chloro-4-(quinolin-2-yl)pyridin-2-yl)-N-cyclopropyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine 

Relevant articles and documents

Design, Synthesis, and Structure-Activity Relationship of Tetrahydropyrido[4,3-d]pyrimidine Derivatives as Potent Smoothened Antagonists with in Vivo Activity

Medulloblastoma is one of the most prevalent brain tumors in children. Aberrant hedgehog (Hh) pathway signaling is thought to be involved in the initiation and development of medulloblastoma. Vismodegib, the first FDA-approved cancer therapy based on inhibition of aberrant hedgehog signaling, targets smoothened (Smo), a G-protein coupled receptor (GPCR) central to the Hh pathway. Although vismodegib exhibits promising therapeutic efficacy in tumor treatment, concerns have been raised from its nonlinear pharmacokinetic (PK) profiles at high doses partly due to low aqueous solubility. Many patients experience adverse events such as muscle spasms and weight loss. In addition, drug resistance often arises among tumor cells during treatment with vismodegib. There is clearly an urgent need to explore novel Smo antagonists with improved potency and efficacy. Through a scaffold hopping strategy, we have identified a series of novel tetrahydropyrido[4,3-d]pyrimidine derivatives, which exhibited effective inhibition of Hh signaling. Among them, compound 24 is three times more potent than vismodegib in the NIH3T3-GRE-Luc reporter gene assay. Compound 24 has a lower melting point and much greater solubility compared with vismodegib, resulting in linear PK profiles when dosed orally at 10, 30, and 100 mg/kg in rats. Furthermore, compound 24 showed excellent PK profiles with a 72% oral bioavailability in beagle dogs. Compound 24 demonstrated overall favorable in vitro safety profiles with respect to CYP isoform and hERG inhibition. Finally, compound 24 led to significant regression of subcutaneous tumor generated by primary Ptch1-deficient medulloblastoma cells in SCID mouse. In conclusion, tetrahydropyrido[4,3-d]pyrimidine derivatives represent a novel set of Smo inhibitors that could potentially be utilized to treat medulloblastoma and other Hh pathway related malignancies.

KINASE INHIBITORS

The present invention relates to compounds of formulae I and II wherein the variables are as defined herein. These compounds are capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.

METABOTROPIC GLUTAMATE RECEPTOR MODULATORS

The invention relates to heterocyclic derivatives as well as their pharmaceutically acceptable salts. The invention further relates to a process for the preparation of such compounds. The compounds of the invention are m GluR5 modulators and are therefore useful for the control and prevention of acute and/or chronic neurological disorders.