36256-45-8Relevant academic research and scientific papers
Cell-permeable lanthanide-platinum(iv) anti-cancer prodrugs
Baldwin, Andrew J.,Christensen, Kirsten E.,Farrer, Nicola J.,Faulkner, Stephen,Holdship, Philip,Howarth, Alison,Karunanithy, Gogulan,Thompson, Amber L.,Yao, Kezi
, p. 8761 - 8767 (2021)
Platinum compounds are a vital part of our anti-cancer arsenal, and determining the location and speciation of platinum compounds is crucial. We have synthesised a lanthanide complex bearing a salicylic group (Ln = Gd, Eu) which demonstrates excellent cellular accumulation and minimal cytotoxicity. Derivatisation enabled access to bimetallic lanthanide-platinum(ii) and lanthanide-platinum(iv) complexes. Luminescence from the europium-platinum(iv) system was quenched, and reduction to platinum(ii) with ascorbic acid resulted in a “switch-on” luminescence enhancement. We used diffusion-based1H NMR spectroscopic methods to quantify cellular accumulation. The gadolinium-platinum(ii) and gadolinium-platinum(iv) complexes demonstrated appreciable cytotoxicity. A longer delay following incubation before cytotoxicity was observed for the gadolinium-platinum(iv) compared to the gadolinium-platinum(ii) complex. Functionalisation with octanoate ligands resulted in enhanced cellular accumulation and an even greater latency in cytotoxicity.
Formation of platinum (II) as a six member ring for sustained polymeric delivery
Senadheera, Sanjeewa N.,Zhang, Ti,Groer, Chad E.,Forrest, M. Laird
, p. 452 - 456 (2017)
A new pH-activated polymer chelate of cisplatin was synthesized using a scalable and green aqueous technique. Synthesis of the chelate was based on formation of a 6-member ring of platinum(II) with acetyl-homo-Lysine (Ac-homo-Lys), which was accomplished under completely aqueous conditions using a traceless photocleavable protection chemistry. Synthesis preceded by, first, amidation of a photocaged homo-Ac-Lys with hyaluronic acid (HA) in water using a p-hydroxyphenacyl (pHP) group as the photoremovable protecting group, followed by reaction of cisplatin (diaqua form) in water to form the reversible chelate. Platinum drug release was pH rate controlled, with more rapid release (t1/2 20?h) at acidic pH similar to the tumor microenvironment yet slower release (t1/2 35?h) at normal physiological pH.
Structural isomers of saligenin-based β2-agonists: Synthesis and insight into the reaction mechanism
Kne?evi?, Anamarija,Novak, Jurica,Bosak, Anita,Vinkovi?, Marijana
, p. 9675 - 9688 (2020/12/28)
Salmeterol and albuterol are well-known β2-adenoreceptor agonists widely used in the treatment of inflammatory respiratory diseases, such as bronchial asthma and chronic obstructive pulmonary disease. Here we report the preparation of structural isomers of salmeterol and albuterol, which can be obtained from the same starting material as the corresponding β2-agonists, depending on the synthetic approach employed. Using 1D and various 2D NMR measurements, we determined that the structure of prepared isomers holds the β-aryl-β-aminoethanol moiety, in contrast to the α-aryl-β-aminoethanol moiety found in salmeterol and albuterol. We investigated the reaction of β-halohydrin and amines responsible for the formation of β-aryl-β-amino alcohol-both experimentally and using computational methods. The structure of β-halohydrin with the methyl salicylate moiety imposes the course of the reaction. The solvent plays a relevant, yet ambiguous role in the direction of the reaction, while the strength of the base influences the reaction yield and isomer ratio in a more evident way. Using computational methods, we have shown that the most probable reaction intermediate responsible for the formation of the unexpected isomer is the corresponding para-quinone methide, which can be formed due to phenol present in the methyl salicylate moiety. After successful preparation of albuterol and salmeterol isomers, we tested their inhibition potency to human acetylcholinesterase (AChE) and usual and atypical butyrylcholinesterase (BChE). Kinetic studies revealed that both isomers are low-potency reversible inhibitors of human cholinesterases.
DRUG DELIVERY COMPOSITIONS AND METHODS
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Page/Page column 53, (2017/08/01)
One aspect of the present invention is directed to conjugates that comprise a linear polymer carrier, a linker and one or more drugs or imaging agents, as well as pharmaceutical compositions that include such conjugates. The drug may be a platinum-containing drug with a linker comprised of a modified amino acid. The conjugate may alternatively include a metal complexing ligand with a metal used for imaging or chemotherapeutic purposes. Another aspect of the invention is directed to formulations and processes for lyophilization of hyaluronan conjugates. Another aspect of the invention is directed to methods for treating and/or inhibiting cancer utilizing the conjugates and compositions described herein.
P-Hydroxyphenacyl photoremovable protecting groups Robust photochemistry despite substituent diversity
Givens, Richard S.,Stensrud, Kenneth,Conrad, Peter G.,Yousef, Abraham L.,Perera, Chamani,Senadheera, Sanjeewa N.,Heger, Dominik,Wirz, Jakob
scheme or table, p. 364 - 384 (2011/06/22)
A broadly based investigation of the effects of a diverse array of substituents on the photochemical rearrangement of p-hydroxyphenacyl esters has demonstrated that common substituents such as F, MeO, CN, CO2R, CONH2, and CH3 have little effect on the rate and quantum efficiencies for the photo-Favorskii rearrangement and the release of the acid leaving group or on the lifetimes of the reactive triplet state. A decrease in the quantum yields across all substituents was observed for the release and rearrangement when the photolyses were carried out in buffered aqueous media at pHs that exceeded the ground-state pKa of the chromophore where the conjugate base is the predominant form. Otherwise, substituents have only a very modest effect on the photoreaction of these robust chromophores.
DERIVATIVES OF THIAZOLE AND THIADIAZOLE INHIBITORS OF TYROSINE PHOSPHATASES
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Page/Page column 67, (2010/10/20)
Provided herein are compounds and compositions for modulation of tyrosine phosphatase activity. In one embodiment, compounds and compositions for inhibiting protein tyrosine phosphatase activity are provided. In another embodiment, provided herein are compounds and compositions that are useful in the treatment, prevention, or amelioration of one or more symptoms of diseases caused by dysfunctional signal transduction, or in which dysfunctional signal transduction is implicated. In another embodiment, provided herein are compounds and compositions for treatment, prevention, or amelioration of one or more symptoms of diabetes. The compounds have following formulas: (II), (I), (III), and (IV).
Improved synthesis of 13C,2H3- and 2H3-salmeterol by Cs2CO3-mediated monoalkylation of a primary amine
Molinski, Tadeusz F.,Stanley, Scott D.
, p. 755 - 762 (2007/10/03)
An abbreviated synthesis of isotopically labelled salmeterol has been achieved. The key improvement utilizes a highly selective Cs2CO3-mediated one-pot alkylation of benzylamine by 6-bromo-1-(4′-phenylbutoxy)hexane to prepare the limiting reagent, 6-N-benzylamino-1-(4′-phenylbutoxy)hexane without overalkylation. The method was applied to synthesis of the title compounds in >97 at% isotopic purity. Copyright
Synthesis and Structure-Activity Relationships among α-Adrenergic Receptor Agonists of the Phenylethanolamine Type
Leclerc, Gerard,Bizec, Jean Claude,Bieth, Nicole,Schwartz, Jean
, p. 738 - 744 (2007/10/02)
Nineteen arylethanolamine derivatives related to norepinephrine were prepared and tested for α-adrenergic stimulant activity.In one series the analogues possess a p-hydroxy function, while the meta position is substituted by methyl, ethyl, isopropyl, cyclohexyl, fluoro, chloro, iodo, carboxy, carbomethoxy, and methylsulfamido groups.The other series is meta hydroxylated with the para position substituted by the same groups.The influence of these groups upon the α-adrenergic activity is discussed, and the compounds are compared to octopamine, normetanephrine,norepinephrine, and norphenylephrine.It has been found that the introduction of an isopropyl, cyclohexyl, and fluoro group in the meta position of octopamine improves its affinity by three, five, and six times, respectively, whereas when these groups are introduced in the para position of norphenylephrine their effects are always detrimental.The most active compound, α-(aminomethyl)-(4-fluoro-3-hydroxyphenyl)methanol (44), has about one-hundreth the affinity and the same intrinsic activity as norepinephrine.
