- Hyperpolarisation of Mirfentanil by SABRE in the Presence of Heroin
-
Mirfentanil, a fentanyl derivative that is a μ-opioid partial agonist, is hyperpolarised via Signal Amplification By Reversible Exchange (SABRE), a para-hydrogen-based technique. [Ir(IMes)(COD)Cl] (IMes=1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene, C
- Robertson, Thomas B. R.,Gilbert, Nicolas,Sutcliffe, Oliver B.,Mewis, Ryan E.
-
p. 1059 - 1064
(2021/05/17)
-
- Structure-activity relationships for a series of (Bis(4-fluorophenyl)methyl)sulfinylethyl-aminopiperidines and -piperidine amines at the dopamine transporter: Bioisosteric replacement of the piperazine improves metabolic stability
-
Despite considerable efforts to develop medications to treat psychostimulant use disorders, none have proven effective, leaving an underserved patient population and unanswered questions as to what mechanism(s) of action should be targeted for developing
- Giancola, JoLynn B.,Bonifazi, Alessandro,Cao, Jianjing,Ku, Therese,Haraczy, Alexandra J.,Lam, Jenny,Rais, Rana,Coggiano, Mark A.,Tanda, Gianluigi,Newman, Amy Hauck
-
-
- The identification and use of robust transaminases from a domestic drain metagenome
-
Transaminases remain one of the most promising biocatalysts for use in chiral amine synthesis, however their industrial implementation has been hampered by their general instability towards, for example, high amine donor concentrations and organic solvent content. Herein we describe the identification, cloning and screening of 29 novel transaminases from a household drain metagenome. The most promising enzymes were fully characterised and the effects of pH, temperature, amine donor concentration and co-solvent determined. Several enzymes demonstrated good substrate tolerance as well as an unprecedented robustness for a wild-type transaminase. One enzyme in particular readily accepted IPA as an amine donor giving the same conversion with 2-50 equivalents, as well as being tolerant to a number of co-solvents, and operational in up to 50% DMSO-a characteristic as yet unobserved in a wild-type transaminase. This work highlights the value of using metagenomics for biocatalyst discovery from niche environments, and here has led to the identification of one of the most robust native transaminases described to date, with respect to IPA and DMSO tolerance.
- Leipold, Leona,Dobrijevic, Dragana,Jeffries, Jack W.E.,Bawn, Maria,Moody, Thomas S.,Ward, John M.,Hailes, Helen C.
-
-
- ATYPICAL INHIBITORS OF MONOAMINE TRANSPORTERS; METHOD OF MAKING; AND USE THEREOF
-
Disclosed herein are a series of modafinil analogue compounds that bind with moderate to high affinity to the dopamine (DA) transporter (DAT) and several analogues also having affinity for the serotonin (5-HT) transporter (SERT) and/or sigma-1 receptor. E
- -
-
-
- 2-PHENYL-3H-IMIDAZO[4,5-B]PYRIDINE DERIVATES USEFUL AS INHIBITORS OF MAMMALIAN TYROSINE KINASE ROR1 ACTIVITY
-
A compound of formula (I′) or (I′′) or a pharmaceutically acceptable salt thereof. The compound is an inhibitor of mammalian kinase enzyme activity, including ROR1 tyrosine kinase activity and may be used in the treatment of disorders associated with such activity.
- -
-
Page/Page column 96-97
(2016/09/22)
-
- SUBSTITUTED 1-ARYLETHYL-4-ACYLAMINOPIPERIDINE DERIVATIVES AS OPIOID/ALPHA-ADRENORECEPTOR MODULATORS AND METHOD OF THEIR PREPARATION
-
The invention provides compounds that bind with high affinities to the μ-, δ- and κ- opioid receptors and α2 - adrenoreceptor. In addition to providing these compounds with novel pharmacological binding properties, the invention also describes detailed novel methods for the preparation of representative compounds and a scheme for the synthesis of related compounds that bind to the opioid receptors and/or α2 - adrenoreceptor.
- -
-
-
- Anti-prion activities and drug-like potential of functionalized quinacrine analogs with basic phenyl residues at the 9-amino position
-
In this paper, we report the synthesis and cell-based anti-prion activity of quinacrine analogs derived by replacing the basic alkyl side chain of quinacrine with 4-(4-methylpiperazin-I-yl)phenyl, (1-benzylpiperidin-4-yl) and their structural variants. Several promising analogs were found that have a more favorable anti-prion profile than quinacrine in terms of potency and activity across different prion-infected murine cell models. They also exhibited greater binding affinities for a human prion protein fragment (hPrP121-231) than quinacrine, and had permeabilities on the PAMPA-BBB assay that fall within the range of CNS permeant candidates. When evaluated on bidirectional assays on a Pgp overexpressing cell line, one analog was less susceptible to Pgp efflux activity compared to quinacrine. Taken together, the results point to an important role for the substituted 9-amino side chain attached to the acridine, tetrahydroacridine and quinoline scaffolds. The nature of this side chain influenced cell-based potency, PAMPA permeability and binding affinity to hPrP121-231.
- Nguyen, Thuy,Sakasegawa, Yuji,Doh-Ura, Katsumi,Go, Mei-Lin
-
experimental part
p. 2917 - 2929
(2011/07/08)
-
- New 4-(heteroanilido)piperidines, structurally related to the pure opioid agonist fentanyl, with agonist and/or antagonist properties
-
A research program based on certain heterocyclic modifications (12-50) of the fentanyl (1) molecule has generated a novel class of opioids. In the mouse hot-place test, these compounds were weaker analgesics than 1. Two types of antagonists were observed
- Bagley,Wynn,Rudo,Doorley,Spencer,Spaulding
-
p. 663 - 671
(2007/10/02)
-
- New antihistaminic N-heterocyclic 4-piperidinamines. 1. Synthesis and antihistaminic activity of N-(4-piperidinyl)-1H-benzimidazol-2-amines
-
The synthesis of a series N-(4-piperidinyl)-1H-benzimidazol-2-amines and the preliminary evaluation of their in vitro and in vivo antihistaminic activity are described. Cyclodesulfurization of (2-aminophenyl) thioureas with mercury(II) oxide resulted in 2-aminobenzimidazole intermediates, which were monoalkylated on the endo-nitrogen atom. After deprotection of the piperideine nitrogen atom with 48% aqueous hydrobromic acid solution, the title compounds were obtained by three different methods, viz. alkylation, reductive amination, or oxirane ring-opening reactions. The in vivo antihistaminic activity was evaluated by the compound 48/80 induced lethality test in rats and histamine-induced lethality test in guinea pigs after oral and/or subcutaneous administration. The duration of action, for a selected number of compounds, was studied in the guinea pig. The phenylethyl derivatives showed the most potent antihistamine properties after oral administration in both animal species.
- Janssens,Torremans,Janssen,Stokbroekx,Luyckx
-
p. 1925 - 1933
(2007/10/02)
-
- 4H-1,2,4-TRIAZOL-3-YL COMPOUNDS
-
The present invention provides novel 4-phenyl-triazol-3-yl-and 3-phenyl-triazol-4-yl-piperidines which are useful as analgesics.
- -
-
-
- Opiate receptor interaction of compounds derived from or structurally related to fentanyl
-
The opiate receptor affinity of compounds derived from or structurally related to fentanyl (1) was determined by in vitro receptor binding assays. The relatively high affinity of fentanyl (3 times morphine) was hardly influenced by the introduction of a 2
- Lobbezoo,Soudijn,Van Wijngaarden
-
p. 777 - 782
(2007/10/02)
-