1478126-83-8

Basic information

• Product Name: 7,8-dihydro-5H-pyrano[4,3-d]pyrimidine-2,4-diol
• Synonyms: 7,8-dihydro-5H-pyrano[4,3-d]pyrimidine-2,4-diol;2H-Pyrano[4,3-d]pyrimidine-2,4(3H)-dione, 1,5,7,8-tetrahydro-;EOS-61082;1H,2H,3H,4H,5H,7H,8H-pyrano[4,3-d]pyrimidine-2,4-dione
• CAS NO: 1478126-83-8
• Molecular Formula: C₇H₈N₂O₃
• Molecular Weight: 168.15002
• Mol File: 1478126-83-8.mol
• Article Data: 6

Chemical Properties

• Appearance: /
• Density: 1.44±0.1 g/cm3(Predicted)
• PKA: 9.82±0.20(Predicted)
• CAS DataBase Reference: 7,8-dihydro-5H-pyrano[4,3-d]pyrimidine-2,4-diol(CAS DataBase Reference)
• NIST Chemistry Reference: 7,8-dihydro-5H-pyrano[4,3-d]pyrimidine-2,4-diol(1478126-83-8)
• EPA Substance Registry System: 7,8-dihydro-5H-pyrano[4,3-d]pyrimidine-2,4-diol(1478126-83-8)

Safety Data

• Hazardous Substances Data: 1478126-83-8(Hazardous Substances Data)

Upstream product

• 1542711-49-8 methyl 4-amino-5,6-dihydro-2H-pyran-3-carboxylate 
• 3019-71-4 Trichloroacetyl isocyanate 
• 127956-11-0 4-oxotetrahydro-2H-pyran-3-carboxylic acid methyl ester 
• 29943-42-8 Tetrahydro-4H-pyran-4-one 

Downstream Products

• 1542706-34-2 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxylic acid 
• 1542706-15-9 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-N,2-dimethyl-1H-indole-4-carboxamide 
• 1542706-38-6 1-[4-(benzylamino)-5H,7H,8H-pyrano[4,3-d]pyrimidin-2-yl]-2-methyl-1H-indole-4-sulfonamide 
• 1542706-62-6 N-benzyl-2-(2-methyl-4-(1H-tetrazol-5-yl)-1H-indol-1-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine 
• 1542712-01-5 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-cyclopropyl-1H-indole-4-carbonitrile 
• 1542706-80-8 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-cyclopropyl-1H-indole-4-carboxamide 
• 944902-88-9 2,4-dichloro-7,8-dihydro-5H-pyrano[4,3-d]pyrimidine 
• 1542711-55-6 N-benzyl-2-chloro-7,8-di-hydro-5H-pyrano[4,3-d]pyrimidin-4-amine 
• 1542705-83-8 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carbonitrile 
• 1542705-92-9 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide 
• 1542706-33-1 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carbonitrile 
• 1542706-09-1 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide 

Relevant articles and documents

Discovery and Optimization of Glucose Uptake Inhibitors

Aerobic glycolysis, originally identified by Warburg as a hallmark of cancer, has recently been implicated in immune cell activation and growth. Glucose, the starting material for glycolysis, is transported through the cellular membrane by a family of glucose transporters (GLUTs). Therefore, targeting glucose transporters to regulate aerobic glycolysis is an attractive approach to identify potential therapeutic agents for cancers and autoimmune diseases. Herein, we describe the discovery and optimization of a class of potent, orally bioavailable inhibitors of glucose transporters, targeting both GLUT1 and GLUT3.

TREATMENT OF INFECTIOUS DISEASES WITH GLUCOSE UPTAKE INHIBITORS

Provided are methods of treating infectious diseases in mammals comprising administering a compound that inhibits glucose uptake. Particular infectious diseases that may be treated include malaria, leishmaniasis, African trypanosomiasis, tuberculosis, HIV, HCMV or herpes virus. In a first aspect, the invention features a method of treating infectious diseases in a mammal, comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a compound or prodrug thereof, or pharmaceutically acceptable salt or ester of said compound or prodrug, wherein the compound is an inhibitor of glucose uptake.

Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083)

The AAA-ATPase p97 plays vital roles in mechanisms of protein homeostasis, including ubiquitin-proteasome system (UPS) mediated protein degradation, endoplasmic reticulum-associated degradation (ERAD), and autophagy. Herein we describe our lead optimization efforts focused on in vitro potency, ADME, and pharmaceutical properties that led to the discovery of a potent, ATP-competitive, D2-selective, and orally bioavailable p97 inhibitor 71, CB-5083. Treatment of tumor cells with 71 leads to significant accumulation of markers associated with inhibition of UPS and ERAD functions, which induces irresolvable proteotoxic stress and cell death. In tumor bearing mice, oral administration of 71 causes rapid accumulation of markers of the unfolded protein response (UPR) and subsequently induces apoptosis leading to sustained antitumor activity in in vivo xenograft models of both solid and hematological tumors. 71 has been taken into phase 1 clinical trials in patients with multiple myeloma and solid tumors.