1010701-75-3

Upstream product

• 1010701-76-4 5-[(benzyloxy)methyl]-7-bromo-4-chloro-5H-pyrrolo[3,2-d]pyrimidine 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 1010823-84-3 2-((5-(benzyloxymethyl)-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)-2-(methylthiomethyl)propane-1,3-diol 
• 1010823-87-6 ({5-[(benzyloxy)methyl]-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)[(2S)-2-hydroxy-3-(methylsulfanyl)propyl]amine 
• 1010823-96-7 (2R,3R)-2-[({5-[(benzyloxy)methyl]-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-4-(methylsulfanyl)butane-1,3-diol 
• 1010824-04-0 (2R,3S)-2-[({5-[(benzyloxy)methyl]-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-4-(methylsulfanyl)butane-1,3-diol 
• 1010824-13-1 (2R,3S)-2-(((5-(benzyloxymethyl)-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)(methyl)amino)-4-(methylthio)butane-1,3-diol 
• 1396317-21-7 2-[({5-[(benzyloxy)methyl]-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-3-(methylsulfanyl)propan-1-ol 
• 1396317-22-8 (2S)-2-[({4-amino-5-[(benzyloxy)methyl]-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-3-(methylsulfanyl)propan-1-ol 
• 1396317-96-6 2-[({4-amino-5-[(benzyloxy)methyl]-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-3-(methylsulfanyl)propan-1-ol 
• 1396317-08-0 3-[({4-amino-5-[(benzyloxy)methyl]-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-2-[(methylsulfanyl)methyl]propan-1-ol 
• 1010824-05-1 (2R,3S)-2-[({4-amino-5-[(benzyloxy)methyl]-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-4-(methylsulfanyl)butane-1,3-diol 
• 1010824-10-8 (2S,3R)-2-[({4-amino-5-[(benzyloxy)methyl]-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-4-(methylsulfanyl)butane-1,3-diol 
• 1010823-97-8 (2R,3R)-2-[({4-amino-5-[(benzyloxy)methyl]-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-4-(methylsulfanyl)butane-1,3-diol 
• 1010824-38-0 (2S,3S)-2-[({4-amino-5-[(benzyloxy)methyl]-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-4-(methylsulfanyl)butane-1,3-diol 
• 1010823-85-4 2-[({4-amino-5-[(benzyloxy)methyl]-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-2-[(methylsulfanyl)methyl]propane-1,3-diol 

Relevant academic research and scientific papers

Transition state analogue inhibitors of human methylthioadenosine phosphorylase and bacterial methylthioadenosine/S-adenosylhomocysteine nucleosidase incorporating acyclic ribooxacarbenium ion mimics

Several acyclic hydroxy-methylthio-amines with 3-5 carbon atoms were prepared and coupled via a methylene link to 9-deazaadenine. The products were tested for inhibition against human MTAP and Escherichia coli and Neisseria meningitidis MTANs and gave Ki values as low as 0.23 nM. These results were compared to those obtained with 1st and 2nd generation inhibitors (1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-methylthio-d-ribitol (MT-Immucillin-A, 3) and (3R,4S)-1-[9-deazaadenin-9-yl)methyl]3-hydroxy-4- methylthiomethylpyrrolidine (MT-DADMe-Immucillin-A, 4). The best inhibitors were found to exhibit binding affinities of approximately 2- to 4-fold those of 3 but were significantly weaker than 4. Cleavage of the 2,3 carbon-carbon bond in MT-Immucillin-A (3) gave an acyclic product (79) with a 21,500 fold loss of activity against E. coli MTAN. In another case, N-methylation of a side chain secondary amine resulted in a 250-fold loss of activity against the same enzyme [(±)-65 vs (±)-68]. The inhibition results were also contrasted with those acyclic derivatives previously prepared as inhibitors for a related enzyme, purine nucleoside phosphorylase (PNP), where some inhibitors in the latter case were found to be more potent than their cyclic counterparts.

ACYCLIC AMINE INHIBITORS OF NUCLEOSIDE PHOSPHORYLASES AND HYDROLASES

The invention relates to compounds of the general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNPs) and/or nucleoside hydrolases (NHs). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.