Structure elucidation and identification of a common metabolite for naphthoylindole-based synthetic cannabinoids using LC-TOF and comparison to a synthetic reference standard.

The identification of a predominate metabolite found in urine specimens which test positive for naphthoylindole-based synthetic cannabinoids is reported. The presence of this new metabolite was detected at the Air Force Drug Testing Lab Investigations Division during screening analysis for metabolites of JWH-018 and JWH-073, because it shares the same MRM transitions as the JWH-073 N-(3-hydroxybutyl) metabolite. However, the detected peak is chromatographically distinguished from other metabolites due to differences in retention time.

High-throughput bioanalytical method for analysis of synthetic cannabinoid metabolites in urine using salting-out sample preparation and LC-MS/MS.

Herbal smoking mixtures which are sold as incense or potpourri and often referred to as 'Spice' are actually inactive plant matter adulterated with alkylamino indole based synthetic cannabinoids such as JWH-018 and JWH-073. Due to the inclusion of five synthetic cannabinoids, including JWH-018 and JWH-073, as Schedule I drugs by the Drug Enforcement Agency (DEA) in March 2011, it has become necessary for forensic laboratories to develop analytical methods to test for the presence of metabolites of synthetic cannabinoids. When a new analyte of interest emerges, most laboratories strive to develop a sample preparation procedure and validate an analytical method as quickly as possible and therefore, rely on effective but time consuming traditional protocols such as solid phase and liquid-liquid extraction.

Targeting HER2-positive cancer with dolastatin 15 derivatives conjugated to trastuzumab, novel antibody-drug conjugates.

Purpose: Targeting tubulin binders to cancer cells using antibody-drug conjugates (ADCs) has great potential to become an effective cancer treatment with low normal tissue toxicity. The nature of the linker used to tether the tubulin binder to the antibody and the conjugation sites on the antibody and the small molecule are important factors in the ADC stability and effectiveness.

Methods: We explored the use of tubulin-targeting dolastatin 15 derivatives (Dol15) tethered covalently to a representative antibody, trastuzumab, via cleavable and non-cleavable linkers at varying antibody reactive sites (i.

Bone marrow CFU-GM and human tumor xenograft efficacy of three antitumor nucleoside analogs.

Nucleoside analogs are rationally designed anticancer agents that disrupt DNA and RNA synthesis. Fludarabine and cladribine have important roles in the treatment of hematologic malignancies. Clofarabine is a next generation nucleoside analog which is under clinical investigation.

Synthetic studies on formamidopyrimidines related to clofarabine.

Degradation of clofarabine (3) in 0.9% saline solution at 100 degrees C afforded three degradation products which were determined to be formamidopyrimidines 4-6. Compounds 4 and 5 were assigned as C(1') anomers on the basis of one-dimensional and two-dimensional NMR experiments, whereas 6 was found to be the formamidopyrimidine lacking the sugar moiety.

Formal synthesis of angiogenesis inhibitor NM-3.

We report the formal synthesis of angiogenesis inhibitor NM-3 (1) in six steps from either of the 2,4-dimethoxyhalobenzenes 13a,b or 3,5-dimethoxychlorobenzene (13c). The first key reaction is the regiospecific alkylation/rearrangement between the aryne derived from 13a-c with sodium diethylmalonate in THF to produce diester 11, which after hydrolysis and cyclization affords homophthalic anhydride 3. The second is the reaction of anhydride 3 with either ethyl 2-methylmalonate (28a), in the presence of 1,1'-carbonyldiimidazole, or ethyl-2-methylmalonyl chloride (28b) under basic conditions to afford key isocoumarin 27.