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Usage

Uses

Used in Pharmaceutical Industry:
Pyrido[4,3-d]pyrimidin-2-amine, 5,6,7,8-tetrahydro(9CI) is utilized as a key intermediate in the synthesis of new drugs. Its unique structure allows for the development of compounds with potential therapeutic applications, targeting various diseases and conditions. Pyrido[4,3-d]pyrimidin-2-amine, 5,6,7,8-tetrahydro(9CI)'s versatility in chemical reactions makes it a valuable asset in medicinal chemistry for creating innovative pharmaceutical agents.
Used in Chemical Industry:
In the chemical industry, Pyrido[4,3-d]pyrimidin-2-amine, 5,6,7,8-tetrahydro(9CI) serves as a building block for the construction of more complex organic molecules. Its heterocyclic amine nature facilitates its integration into larger molecular frameworks, contributing to the advancement of material science and the creation of new chemical entities with diverse applications.
Further research and development are essential to fully explore the potential uses and properties of Pyrido[4,3-d]pyrimidin-2-amine, 5,6,7,8-tetrahydro(9CI), ensuring its optimal application across various fields and industries.

InChI:InChI=1/C7H10N4/c8-7-10-4-5-3-9-2-1-6(5)11-7/h4,9H,1-3H2,(H2,8,10,11)

Upstream product

• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 259809-79-5 tert-butyl 2-(methylsulfonyl)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate 
• 259809-78-4 t-butyl-2-(methylthio)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-6-carboxylate 
• 869198-95-8 2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-carboxylic acid tert-butyl ester 
• 157327-41-8 t-butyl-3-[(dimethylamino)methylidene]-4-oxopiperidine-1-carboxylate 
• 593-85-1 guanidine carbonate 

Downstream Products

• 1609485-44-0 (2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)(5-chloro-2,4-dihydroxyphenyl)methanone 

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).

Identification and optimization of novel Hsp90 inhibitors with tetrahydropyrido[4,3-d]pyrimidines core through shape-based screening

Rapid Overlay of Chemical Structures (ROCS), which can rapidly identify potentially active compounds by shape comparison, is recognized as a powerful virtual screening tool. By ROCS, a class of novel Hsp90 inhibitors was identified. The calculated binding mode of the most potent hit 36 guided us to design and synthesize a series of analogs (57a-57h). Over 100-fold improvement was achieved in the target-based assay. The most potent compound 57h inhibited Hsp90 with IC50 0.10 ± 0.01 μM. It also showed much improved cell potency and ligand efficiency. Our study showed that ROCS is efficient in the identification of novel cores of Hsp90 inhibitors. 57h can be ideal leads for further optimization.

Heterocycylic-substituted quinoline-carboxylic acids

1-Substituted-6-fluoro-7-heterocyclic-1,4-dihydroquino-1-(or dihydronaphthyridin)-4-one carboxylic acids have antibacterial properties. The 7-heterocyclic group is a bicyclic group, one of the rings of which is saturated and the other ring of which is unsaturated.