102147-75-1

Isopentenyladenosine (iPA), a member of the cytokinin family of plant hormones, exerts a marked antiproliferative activity on some leukemic and epithelial cancer cell lines. To characterize the molecular moieties required for the in vitro antitumor activity of the molecule and to obtain cytostatic iPA derivatives potentially useful as chemotherapeutic agents, N9-acyclic analogues have been synthesized using regioselective Mitsunobu reaction and characterized by elemental analyses, 1H and 13C NMR. These compounds were analyzed for their activity on human bladder cancer cell lines. In this study, we report that iPA inhibited the proliferation but not the migration of human bladder cancer cells, while the newly synthesized analogues revealed no significant cytostatic activity apart from the compound with a saturated double bond of the isopentenyl chain. These results indicate that the integrity of the ribose ring is required for the cytostatic activity of iPA.

Alkylation of 2-amino-6-chloropurine with 5-(2-bromoethyl)-2,2-dimethyl-1,3-dioxan (7) and subsequent acid hydrolysis provides an improved procedure for synthesis of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (3).

Lipid nanoparticle compositions for delivery of nucleic acids are described. In various embodiments the lipid nanoparticle contains an ionizable lipid of the Formula (I). Methods of using such lipid nanoparticle compositions to achieve targeted delivery of therapeutic cargo without the need for a targeting ligand are also provided.

Lipid nanoparticle compositions for delivery of nucleic acids are described. The lipid nanoparticle may contain a conformationally constrained ionizable lipid as part of the composition. These compositions may allow for delivery of cargo without the need for a targeting ligand.

A flame retardant itaconic acid-based compound, a process for forming a flame retardant polymer, and an article of manufacture comprising a material that contains a flame retardant itaconic acid-based polymer are disclosed. The flame retardant itaconic acid-based compound has variable moieties, which include methylene bridge groups, carbonyl groups, vinyl groups, functionalized groups, phenyl-substituted flame retardant groups, and/or functionalized flame retardant groups. The process for forming the flame retardant polymer includes forming a phosphorus-based flame retardant molecule, forming an itaconic acid derivative, chemically reacting the phosphorus-based flame retardant molecule and the itaconic acid derivative to form a flame retardant itaconic acid-based compound, and incorporating the itaconic acid-based flame retardant compound into a polymer to form the flame retardant polymer.

NAmPRTase (PBEF/Visfatin) plays a pivotal role in the salvage pathway of NAD+ biosynthesis. NAmPRTase has been an attractive target for anti-cancer agents that induce apoptosis of tumor cells via a declining plasma NAD+ level. In this report, a series of structural analogs of FK866 (1), a known NAmPRTase inhibitor, was synthesized and tested for inhibitory activities against the proliferation of cancer cells and human NAmPRTase. Among them, compound 7 showed similar anti-cancer and enzyme inhibitory activities to compound 1. Further investigation of compound 7 with X-ray analysis revealed a co-crystal structure in complex with human NAmPRTase, suggesting that Asp219 in the active site of the enzyme could contribute to an additional interaction with the pyrrole nitrogen of compound 7.

An object of the present invention is to provide a novel chemical compound useful as a therapeutic or prophylactic agent for acid-related diseases, having an excellent inhibitory effect against gastric acid secretion, an excellent effect of maintaining the inhibitory effect against gastric acid secretion, thereby maintaining intragastric pH high for a long time, and having more safety and appropriate physicochemical stability. Provided is a compound represented by where R1 and R3 may be the same or different and each represent a hydrogen atom or a C1-C6 alkyl group; R2 represents (5,5-dimethyl-1,3-dioxan-2-yl)methoxy group, 5,7-dioxaspiro[2.5]oct-6-ylmethoxy group, 1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy group, or (2,2-dimethyl-1,3-dioxan-5-yl)methoxy group; R4, R5, R6 and R7 represent a hydrogen atom, halogen atom, C1-C6 alkyl group, C1-C6 haloalkyl group, C1-C6 alkoxy group or C1-C6 haloalkoxy group; and W1 represents a single bond, methylene or ethylene group, a salt thereof or a solvate of these.

Nucleoside chemical compounds, which interact with specific structures of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) are disclosed. The compounds interfere with the activities of telomerase and reverse transcriptase, and are useful as antivirals, antibacterials and anticancer agents. Methods of treating or preventing cancers in patients involving administration of a therapeutically effective amount of a composition having an inhibitor or antagonist of the reverse transcriptases (RTs) expressed in cells of the patients are also disclosed. Method of using nucleoside analogs and other inhibitors of RTs in conjunction with DNA damaging agents such as genotoxic agents or radiation or photodynamic therapy or combinations these for the treatment of various cancers are also disclosed.

Deoxyuridine derivatives of the formula (I) where R1 is H or various substituents; D is -NHCO-, -CONH-, -0-, -C(=O)-, -CH=CH, -CΞC-, -NR5-; R4 is hydrogen or various substituents; R5 is H, C1-C4 alkyl, C1-C4 alkanoyl; E is Si or C; R6, R7 and R8 are independently selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl or a stable monocyclic, bicyclic or tricyclic ring system; G is -O-, -S-, -CHR10-, -C(=O)-; J is -CH2-, or when G is CHR10 may also be -O- or -NH-; R10 is H, F, -CH3, -CH2NH2, -CH2OH; -OH R11 is H, F, -CH3, -CH2 NH2, -CH2OH, CH(OH)CH3, CH(NH3)CH3; or R10 and R11 together define an olefinic bond, or together form a -CH2-group, thereby defining a cis or trans cyclopropyl group; have utility in the prophylaxis or treatment of protozoal diseases such as malaria.

An improved total synthesis of [18F]FHBG starting from triethyl-1,1,2-ethanetricarboxylate and 2-amino-6-chloropurine is reported. [18F]FHBG was prepared by nucleophilic substitution of the appropriate precursor with [18F]KF/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with a simplified Silica Sep-Pak solid-phase extraction (SPE) method in 20-25% radiochemical yield.

Positron emission tomography (PET) herpes simplex virus thymidine kinase (HSV-tk) gene reporter probes 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy) methyl]guanine ([18F]FHPG) and 9-(4-[18F]fluoro-3- hydroxymethylbutyl)guanine ([18F]FHBG) were prepared by nucleophilic substitution of the appropriate tosylated precursors with [18F]KF/ Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with a simplified dual Silica Sep-Pak solid-phase extraction (SPE) method in 15-30% radiochemical yield.

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Alkylation of 2-amino-6-chloropurine with 5-(2-bromoethyl)-2,2-dimethyl-1,3-dioxane (5) provided 2-amino-6-chloro-9-purine (6) in high yield.This aminochloropurine 6 readily converted to the antiviral acyclonucleoside 9-guanine (1) and to its 6-chloro (10), 6-thio (11), 6-alkoxy (12-17), 6-amino (20), and 6-deoxy (21) purine analogues.The guanine derivative 1 was converted to its xanthine analogue 9.Similarly, alkylation of 6-chloropurine with 5 provided a route to 8, the hypoxanthine analogue of 1.Of these 9-substituted purines, the guanine derivative 1 showed the highest activity against herpes simplex virus types 1 and 2 in cell cultures, and in some tests it was more active than acyclovir, with no evidence of toxicity for the cells.A series of monoesters (30-33) and diesters (24-27, 29) of 1 were prepared, and some of these also showed antiherpes virus activity in cell cultures, the most active ester being the dihexanoate 27.