Structure-Guided Drug Design of 6-Substituted Adenosine Analogues as Potent Inhibitors of Mycobacterium tuberculosis Adenosine Kinase was written by Crespo, Roberto A.;Dang, Qun;Zhou, Nian E.;Guthrie, Liam M.;Snavely, Thomas C.;Dong, Wen;Loesch, Kimberly A.;Suzuki, Takao;You, Lanying;Wang, Wei;O’Malley, Theresa;Parish, Tanya;Olsen, David B.;Sacchettini, James C.. And the article was included in Journal of Medicinal Chemistry in 2019.Formula: C11H13IN4O4 The following contents are mentioned in the article:
Mycobacterium tuberculosis adenosine kinase (MtbAdoK) is an essential enzyme of Mtb and forms part of the purine salvage pathway within mycobacteria. Evidence suggests that the purine salvage pathway might play a crucial role in Mtb survival and persistence during its latent phase of infection. In these studies, we adopted a structural approach to the discovery, structure-guided design, and synthesis of a series of adenosine analogs that displayed inhibition constants ranging from 5 to 120 nM against the enzyme. Two of these compounds exhibited low micromolar activity against Mtb with half maximal effective inhibitory concentrations of 1.7 and 4.0 μM. Our selectivity and preliminary pharmacokinetic studies showed that the compounds possess a higher degree of specificity against MtbAdoK when compared with the human counterpart and are well tolerated in rodents, resp. Finally, crystallog. studies showed the mol. basis of inhibition, potency, and selectivity and revealed the presence of a potentially therapeutically relevant cavity unique to the MtbAdoK homodimer. This study involved multiple reactions and reactants, such as (2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4Formula: C11H13IN4O4).
(2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4) belongs to tetrahydrofuran derivatives. THF (Tetrahydrofuran) is water-miscible and has a low viscosity making it a highly versatile solvent used in a variety of industries. Tetrahydrofuran can also be produced, or synthesised, via catalytic hydrogenation of furan. This process involves converting certain sugars into THF by digesting to furfural. An alternative to this method is the catalytic hydrogenation of furan with a nickel catalyst.Formula: C11H13IN4O4
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem