715-68-4

Upstream product

• 5845-41-0 acetic acid 4-(6-aminopurin-9-yl)-butyl ester 
• 87-42-3 6-chloro-7H-purine 
• 411225-21-3 4-(6-chloro-9H-purin-9-yl)butyl acetate 
• 87-42-3 6-chloropurine 
• 114978-79-9 4-(6-Amino-purin-9-yl)-but-2-yn-1-ol 
• 114987-15-4 N⁹-(4-Chloro-2-butyn-1-yl)adenine 
• 66224-66-6 adenine 
• 302908-38-9 9-[(4-tetrahydropyranyloxy)butyl]adenine 
• 41785-06-2 6-Amino-9H-purine-9-butanoic acid ethyl ester 
• 121683-05-4 9-(4'-benzyloxybutyl) adenine 
• 114987-18-7 adenallene 

Downstream Products

• 69293-19-2 N⁹-(4-chlorobutyl)adenine 
• 123156-31-0 9-(4-diethoxyphosphonylbutyl)-N⁶-benzoyladenine 
• 123156-30-9 9-(4-bromobutyl)-N⁶-benzoyladenine 
• 302908-42-5 8-Bromo-9-[4-(tosyloxy)butyl]adenine 
• 55343-30-1 4-(6-benzoylamino-purin-9-yl)-butan-1-ol 

Relevant academic research and scientific papers

Cyclic adenosine 5′-diphosphate ribose analogs without a southern ribose inhibit ADP-ribosyl cyclase-hydrolase CD38

Cyclic adenosine 5′-diphosphate ribose (cADPR) analogs based on the cyclic inosine 5′-diphosphate ribose (cIDPR) template were synthesized by recently developed stereo- and regioselective N1-ribosylation. Replacing the base N9-ribose with a butyl chain generates inhibitors of cADPR hydrolysis by the human ADP-ribosyl cyclase CD38 catalytic domain (shCD38), illustrating the nonessential nature of the southern ribose for binding. Butyl substitution generally improves potency relative to the parent cIDPRs, and 8-amino-N9-butyl-cIDPR is comparable to the best noncovalent CD38 inhibitors to date (IC50 = 3.3 μM). Crystallographic analysis of the shCD38:8-amino-N9-butyl-cIDPR complex to a 2.05 ? resolution unexpectedly reveals an N1-hydrolyzed ligand in the active site, suggesting that it is the N6-imino form of cADPR that is hydrolyzed by CD38. While HPLC studies confirm ligand cleavage at very high protein concentrations, they indicate that hydrolysis does not occur under physiological concentrations. Taken together, these analogs confirm that the northern ribose is critical for CD38 activity and inhibition, provide new insight into the mechanism of cADPR hydrolysis by CD38, and may aid future inhibitor design.

ADENINE DERIVATIVES AS PROTEIN KINASE INHIBITORS

The present invention relates to a compound suitable for use as a kinase inhibitor according to general formula (I) [compound (C), herein after], or the N- oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof, formula (I) wherein A, R1, R2, R3, R3', R4, R4', X, Y, Z, T are as defined in the claims. The invention further relates to an in vitro method of inhibiting protein kinase activity which comprises contacting a protein kinase with a compound of formula (I), or the N-oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof. The invention further relates to the compounds of formula (I) per se, as well as to their use as a medicament, and for use or in a method of treatment of a disease mediated by a protein kinase selected from cancer, inflammatory disorders, cardiovascular diseases, viral induced diseases, circulatory diseases, fibro-proliferative diseases and pain sensitization disorders.

Synthesis and Pharmacological Evaluation of Novel Adenine-Hydrogen Sulfide Slow Release Hybrids Designed as Multitarget Cardioprotective Agents

This work deals with the design, synthesis, and evaluation of the cardioprotective properties of a number of novel hybrid compounds combining the adenine nucleus with a suitable H2S slow-releasing moiety, coupled via a stable ether bond. The H2S release rate of the hybrids and their ability to increase cGMP were estimated in vitro. The most promising derivatives 4 and 11, both containing 4-hydroxythiobenzamide moiety as H2S donor, were selected for further in vivo evaluation. Their ability to release H2S in vivo was recorded using a new fully validated UPLC-DAD method. Both compounds reduced significantly the infarct size when administered at the end of sustained ischemia. Mechanistic studies showed that they conferred enhanced cardioprotection compared to adenine or 4-hydroxythiobenzamide. They activate the PKG/PLN pathway in the ischemic myocardium, suggesting that the combination of both pharmacophores results in synergistic cardioprotective activity through the combination of both molecular pathways that trigger cardioprotection.

An acyl-SAM analog as an affinity ligand for identifying quorum sensing signal synthases

N-Acylhomoserine lactones (AHLs) are quorum sensing signals produced by Gram-negative bacteria. We here report the affinity purification of AHL synthases using beads conjugated with an enzyme inhibitor, which was designed based on the catalytic intermediate acyl-SAM. the Partner Organisations 2014.

Structure-activity relationship of adenosine 5′-diphosphoribose at the transient receptor potential melastatin 2 (TRPM2) channel: Rational design of antagonists

Adenosine 5′-diphosphoribose (ADPR) activates TRPM2, a Ca 2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure-activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2′-deoxy-ADPR (86, IC50 = 3 μM), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfamate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.

Adenine-based acyclic nucleotides as novel P2X3 receptor ligands

A new series of acyclic nucleotides based on the adenine skeleton and bearing in 9-position a phosphorylated four carbon chain has been synthesized. Various substituents were introduced in 2-position of the adenine core. The new compounds were evaluated o

Synthesis of acyclic adenine 8,N-anhydronucleosides

9-(4-Hydroxybutyl)adenine (10) was obtained by reaction of adenine with 4-[(2-tetrahydropyran-2-yl)oxy]butyl chloride (7) in the presence of DBU. 8-Bromo-9-(4-hydroxybutyl)adenine (13) was prepared by bromination of 10 or by alkylation of 8-bromoadenine (11) with 4-bromoethyl acetate followed by methanolysis. Tosylation of compound 13 afforded the 4-tosyloxy derivative 15 which gave on heating with methylamine or cyclopropylamine 6-methyl-(17a) or 6-cyclopropyl-7,8,9,10-tetrahydro-6H-[1,3]diazepino[1,2-e]purin-4-amine (17b), while the reaction with hydrazine afforded 7,8,9,10-tetrahydro-6H-[1,3]diazepino-[1,2-e]purine-4,6-diamine (17d). Treatment of compound 13 with thionyl chloride gave 9-(4-chlorobutyl)-8-chloroadenine (18) as the main product which was transformed to 17b, 6-propyl-7,8,9,10-tetrahydro-6H-[1,3]diazepino[1,2-e]purin-4-amine (17c) or 7,8,9,10-tetrahydro-6H-[1,3]diazepino[1,2-e]purin-4-amine (17e) by reaction with cyclopropylamine, propylamine or ammonia, respectively. Compound 17e was quite stable both in acid and alkaline solutions, at room temperature or at 90 °C. Compound 13 was converted to 9-(4-hydroxybutyl)-8-methylaminoadenine (19) by reaction with methylamine. Compound 19 failed to undergo intramolecular cyclization to diazepine 17a on treatment with diphenyl carbonate, bis(4-nitrophenyl) carbonate or 1,1′-carbonyldiimidazole.

Intramolecular cyclization of some acyclic nucleoside analogs

Reaction of stereoisomeric 8-bromo-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines (8) with concentrated aqueous ammonia, sodium hydride, potassium tert-butoxide, or 1,8-diazabicyclo-[5,4,0]undec-7-ene afforded 4′-O,8-anhydro-9-(2,3-O-isopropyliden

Solid-Liquid Phase Transfer Catalysis II: A Convenient Approach to the Synthesis of ACV, HBG and Related Compounds

When solid-liquid phase transfer catalysis is conducted in the presence of potassium tert-butoxide as base, 18-crown-6 ether or tetraglyme as catalyst, DMF as solvent and at temperature of 0 deg C, the N-alkylation takes place at the N-1 and N-9 in pyrimidine and purine heterocyclic respectively.

Unsaturated acyclic analogues of 2'-deoxyadenosine and thymidine containing fluorine: Synthesis and biological activity

The syntheses and biological activities of fluorobutynol 11 and (E)- and (Z)-fluorobutenols 8a,d and 9a,d are described. Alkylation of adenine with bromofluorobutyne 13a afforded intermediate 14 which was converted to fluorobutynol 11. Aldehyde 16a and (c