259809-79-5

Usage

Uses

Used in Pharmaceutical Industry:
TERT-BUTYL 7,8-DIHYDRO-2-(METHYLSULFONYL)PYRIDO[4,3-D]PYRIMIDINE-6(5H)-CARBOXYLATE is used as a potential drug candidate for its potential therapeutic effects, which are currently under investigation. Its unique molecular structure may offer novel avenues for the treatment of various diseases and conditions.
Used in Biochemical Research:
In the field of biochemical research, TERT-BUTYL 7,8-DIHYDRO-2-(METHYLSULFONYL)PYRIDO[4,3-D]PYRIMIDINE-6(5H)-CARBOXYLATE serves as a valuable precursor in the synthesis of pharmaceuticals. Its complex structure allows researchers to explore its interactions with biological systems and its potential role in the development of new drugs.
Used in Medicinal Research:
TERT-BUTYL 7,8-DIHYDRO-2-(METHYLSULFONYL)PYRIDO[4,3-D]PYRIMIDINE-6(5H)-CARBOXYLATE is utilized in medicinal research to study its potential applications in treating specific medical conditions. Its unique chemical properties may contribute to the discovery of new therapeutic agents and the advancement of medical treatments.

InChI:InChI=1/C13H19N3O4S/c1-13(2,3)20-12(17)16-6-5-10-9(8-16)7-14-11(15-10)21(4,18)19/h7H,5-6,8H2,1-4H3

Upstream product

• 157327-41-8 t-butyl-3-[(dimethylamino)methylidene]-4-oxopiperidine-1-carboxylate 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 259809-78-4 t-butyl-2-(methylthio)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-6-carboxylate 

Downstream Products

• 1567965-09-6 tert-butyl 2-(cyclopropylamino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate 
• 1567964-27-5 6-(5'-chloro-3,5-dimethyl-2,4'-bipyridin-2'-yl)-N-phenyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine 
• 124458-31-7 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine 
• 869198-95-8 2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-carboxylic acid tert-butyl ester 
• 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 
• 1365154-07-9 N,N-dimethyl-6-(4-(methylamino)cyclohexyl)-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 
• 1365155-89-0 6-(4-(Benzyl(methyl)amino)cyclohexyl)-N,N-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-2-amine 
• 578713-43-6 N,N-Dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine 

Relevant academic research and scientific papers

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.

HEDGEHOG PATHWAY SIGNALING INHIBITORS AND THERAPEUTIC APPLICATIONS THEREOF

The hedgehog (Hh) signaling pathway is a pathway which regulates patterning, growth and cell migration during embryonic development, but in adulthood is limited to tissue maintenance and repair. Mutational inactivation of the inhibitory pathway components leads to constitutive ligand-independent activation of the Hh signaling pathway, results in cancers such as basal cell carcinoma and medulloblastoma. Ligand-dependent activation of Hh signaling is involved in prostate cancer, pancreatic cancer, breast cancer and blood cancers. Therefore, inhibition of the aberrant Hh signaling represents a promising approach toward novel anticancer therapy. The invention provides novel molecules of formula I that inhibit hedgehog pathway signaling and provides therapeutic applications for the treatment of malignancies (basal cell carcinoma, medulloblastoma, glioblastoma, non-small cell lung cancer, prostate cancer, pancreatic cancer, blood cancers, mesenchymal cancers, etc.), prevention of tumor regrowth, sensitization of radio-chemo therapies, and other diseases (inflammation, fibrosis and immune disorders).

Substituted Benzamide Compounds

Substituted benzamide compounds corresponding to formula (I) in which R5, R6, R7, R8, a, b, c, d, t, D and X have defined meanings, a process for their preparation, pharmaceutical compositions comprising such compounds, and a method of using such compounds to treat pain and other conditions mediated at least in part via the bradykinin 1 receptor.