78287-52-2

Upstream product

• 95656-84-1 benzyl 4-((tert-butoxycarbonyl)amino)butanoate 
• 100-39-0 benzyl bromide 
• 100-51-6 benzyl alcohol 
• 56-12-2 4-amino-n-butyric acid 

Downstream Products

• 869541-41-3 benzyl 4-(2-oxohexadecanamido)butanoate 
• 121667-28-5 nicotinoyl chloride 
• 1356018-30-8 benzyl 4-formamidobutanoate 
• 105449-18-1 benzyl (S)-4-(2-((tert-butoxycarbonyl)amino)propanamido)butanoate 
• 1356018-26-2 benzyl 4-(2-((S)-N-((S)-2,6-dioxo-1-phenethylpiperidin-3-yl)-2-methylbutanamido)acetamido)butanoate 
• 1345855-73-3 benzyl 4-isocyanobutanoate 
• 869541-08-2 benzyl 4-(2-hydroxyhexadecanamido)butanoate 

Relevant academic research and scientific papers

Development of 99mTc-labeled asymmetric urea derivatives that target prostate-specific membrane antigen for single-photon emission computed tomography imaging

Prostate-specific membrane antigen (PSMA) is expressed strongly in prostate cancers and is, therefore, an attractive diagnostic and radioimmunotherapeutic target. In contrast to previous reports of PMSA-targeting 99mTc-tricarbonyl complexes that are cationic or lack a charge, no anionic 99mTc-tricarbonyl complexes have been reported. Notably, the hydrophilicity conferred by both cationic and anionic charges leads to rapid hepatobiliary clearance, whereas an anionic charge might better enhance renal clearance relative to a cationic charge. Therefore, an improvement in rapid clearance would be expected with either cationic or anionic charges, particularly anionic charges. In this study, we designed and synthesized a novel anionic 99mTc-tricarbonyl complex ([99mTc]TMCE) and evaluated its use as a single-photon emission computed tomography (SPECT) imaging probe for PSMA detection. Direct synthesis of [99mTc]TMCE from dimethyl iminodiacetate, which contains both the asymmetric urea and succinimidyl moiety important for PSMA binding, was performed using our microwave-assisted one-pot procedure. The chelate formation was successfully achieved even though the precursor included a complicated bioactive moiety. The radiochemical yield of [99mTc]TMCE was 12-17%, with a radiochemical purity greater than 98% after HPLC purification. [99mTc]TMCE showed high affinity in vitro, with high accumulation in LNCaP tumors and low hepatic retention in biodistribution and SPECT/CT studies. These findings warrant further evaluation of [99mTc]TMCE as an imaging agent and support the benefit of this strategy for the design of other PSMA imaging probes.

ANTIBACTERIAL ANTISENSE AGENTS

The invention relates to improved ANTISENSE agents for the treatment of gram-negative bacterial infections. Compounds of the invention utilise an Antibiotic-Assisted Translocation; AAT' platform to improve influx into bacterial cells through enhanced permeability, providing improved intracellular exposure of the ANTISENSE AGENT and superior treatment of the infection.

Synthesis and biological evaluation of Santacruzamate-A based analogues

Several derivatives of Santacruzamate-A, a natural product that is structurally related to SAHA, were synthesized to explore the potential of carbamates and oxalylamides as novel biasing element for targeting the catalytic site of zinc-dependent histone deacetylases (HDACs). An additional class of Santacruzamate-A derivatives was synthesized to investigate the influence of the cap group and the linker element on HDAC inhibitory activity. All compounds were evaluated in dose response for their in vitro cytotoxic activity in MTT assay in HCT116 cells. HDAC inhibitory activity was evaluated in vitro by western blot analysis for histone hyperacetylation assay and biochemically for representative human HDACs isoforms. Two novel compounds were identified to exhibit potent time dependent anti proliferative activity. However, unlike hydroxamic acid analogues, the tested Santacruzamate-A derivatives showed no noticeable HDAC inhibitory activity. The ethylcarbamate moiety as unusual zinc-binding group displayed no ability to coordinate the zinc ion and thus, presumably, was not able to reproduce known inhibitor-substrate zinc-binding group interactions with the HDAC catalytic site. This study confirmed that the accommodation of the zinc-binding group is deeply critical of the positioning of the linker and the projection of the cap group toward the different surface pockets of the enzyme.

COMPOSITIONS AND METHODS OF USING THE COMPOSITIONS FOR PLAQUE SOFTENING

Disclosed herein is a compound for use in a composition applied to a blood vessel, wherein the compound softens and/or disrupts the crystalline matrix of calcified plaque. Methods of treatment comprising applying the disclosed composition are also disclosed. Plaque-softening compounds are also disclosed.

Synthesis of (-)-julocrotine and a diversity oriented Ugi-approach to analogues and probes

An improved total synthesis of (-)-julocrotine in three steps from Cbz-glutamine, in 51% overall yield, is presented. To demonstrate the potential of the heterocyclic moiety for diversity oriented synthesis, a series of (-)-julocrotine analogues was synthesized by employing the heterocyclic precursor as an amino input in Ugi four-component reactions (Ugi-4CR) [1].

Synthesis and biological evaluation of GABA derivatives able to cross the blood-Brain barrier in rats

Two new GABA derivatives, 1 and 2, were synthesized and tested for their capacity to display CNS activity, which was assessed by determining the effects on the duration of pentobarbital-induced hypnosis in rats. Compound 1, peripherally injected, significantly prolonged the hypnosis time, a typical GABA-mimetic effect, while both intracerebroventricular and intravenous administration of compound 2 surprisingly shortened the hypnotic effect in an atropine-sensitive way. The study was extended also to compounds 1a, 1b and 2a, putative oxidative/hydrolytic metabolites of 1 and 2.

DC107 derivatives

DC107 derivatives represented by formula (I) or pharmaceutically acceptable salts thereof which have antimicrobial activity and antitumor activity are provided: STR1 wherein R1 represents hydrogen, lower alkoxyalkyl, aralkyloxyalkyl, lower alkoxyalkoxyalkyl, lower alkoxyalkoxyalkoxyalkyl, aralkyl, tetrahydropyranyl, COR4, or the like; R2 represents hydrogen or COR6 ; R3 represents --CH2 OCOR7, phthalimidomethyl, or the like; and W represents oxygen or NR8 (wherein R8 represents hydroxy, lower alkoxy, lower alkenyloxy, aralkyloxy, substituted or unsubstituted arylsulfonylamino, or lower alkoxycarbonylamino).

Benzo-fused macrocycles promote release of growth hormone

There are disclosed certain novel compounds identified as benzo-fused macrocycles which promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to increase the stature of those afflicted with a lack of a normal secretion of natural growth hormone. Growth promoting compositions containing such benzo-fused macrocycles as the active ingredient thereof are also disclosed.

Lariat-bearing cyclophosphazenes: potential molecular sepulchers for magnetic resonance imaging agents

Lariat-bearing cyclophosphazenes were prepared by aminolysis of hexachlorocyclotriphosphazene with amino ester hydrochlorides followed by standard alkaline hydrolysis.These cryptands are actually capable complexing gadolinium cations with stability constants larger than 1E28; this is much larger than the values for classical magnetic resonance imaging agents.Unfortunately, these cryptates are much too insoluble in physiological serum to be used for clinical purposes in a facile way.

Brain-specific drug delivery

The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are: (a) compounds of the formula wherein [D] is a centrally acting drug species, and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine pyridinium salt redox carrier, with the proviso that when [DHC] is STR1 wherein R is lower alkyl or benzyl and [D] is a drug species containing a single NH2 or OH functional group, the single OH group when present being a primary or secondary OH group, said drug species being linked directly through said NH2 or OH function group to the carbonyl function of [DHC], then [D] must be other than a sympathetic stimulant, steroid sex hormone or long chain alkanol; and (b) non-toxic pharmaceutically acceptable salts of compounds of formula (I) wherein [D] is a centrally acting drug species and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine pyridinium salt redox carrier. The corresponding ionic pyridinium salt type drug/carrier entitles [D--QC]+ X- are also disclosed.