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51.
52.
Charlne Gadais Justyna Piekielna-Ciesielska Jolien De Neve Charlotte Martin Anna Janecka Steven Ballet 《Molecules (Basel, Switzerland)》2021,26(17)
Opioid agonists are well-established analgesics, widely prescribed for acute but also chronic pain. However, their efficiency comes with the price of drastically impacting side effects that are inherently linked to their prolonged use. To answer these liabilities, designed multiple ligands (DMLs) offer a promising strategy by co-targeting opioid and non-opioid signaling pathways involved in nociception. Despite being intimately linked to the Substance P (SP)/neurokinin 1 (NK1) system, which is broadly examined for pain treatment, the neurokinin receptors NK2 and NK3 have so far been neglected in such DMLs. Herein, a series of newly designed opioid agonist-NK2 or -NK3 antagonists is reported. A selection of reported peptidic, pseudo-peptidic, and non-peptide neurokinin NK2 and NK3 ligands were covalently linked to the peptidic μ-opioid selective pharmacophore Dmt-DALDA (H-Dmt-d-Arg-Phe-Lys-NH2) and the dual μ/δ opioid agonist H-Dmt-d-Arg-Aba-βAla-NH2 (KGOP01). Opioid binding assays unequivocally demonstrated that only hybrids SBL-OPNK-5, SBL-OPNK-7 and SBL-OPNK-9, bearing the KGOP01 scaffold, conserved nanomolar range μ-opioid receptor (MOR) affinity, and slightly reduced affinity for the δ-opioid receptor (DOR). Moreover, NK binding experiments proved that compounds SBL-OPNK-5, SBL-OPNK-7, and SBL-OPNK-9 exhibited (sub)nanomolar binding affinity for NK2 and NK3, opening promising opportunities for the design of next-generation opioid hybrids. 相似文献
53.
In this paper, we study the existence, continuation and bifurcation from infinity of2π-periodic solutions of autonomous Newtonian systems. We underline that the resonant case is considered. To prove the results, we apply the degree for S1-equivariant gradient maps defined by Rybicki (1994) in [15] and the angle condition introduced by Bartsch and Li (1997) in [16]. 相似文献
54.
Bis- and tris(methylated) derivatives of 3,3'-bis(N-confused porphyrin) were obtained. Methylation of C21 stabilizes the geometry of the axially chiral system allowing separation of enantiomers and assignment of an absolute configuration by X-ray methods. 相似文献
55.
Juice made from sea-buckthorn berries (Hippophae rhamnoides L.) is a valuable source of bioactive compounds, vitamins, as well as micro- and macronutrients. By applying defatted sea-buckthorn juice, it is possible to enhance wheat beer and change its sensory properties and the contents of bioactive compounds in the finished product. A sensory assessment showed that wheat beers with a 5% v/v addition of sea-buckthorn juice were characterised by a balanced taste and aroma (overall impression). Physicochemical analyses showed that, compared to the control samples, wheat beers enhanced with defatted sea-buckthorn juice at a rate of 5% v/v or 10% v/v had high total acidity with respective mean values of 5.30 and 6.88 (0.1 M NaOH/100 mL), energy values lower on average by 4.04% and 8.35%, respective polyphenol contents of 274.1 mg GAE/L and 249.7 mg GAE/L, as well as higher antioxidant activity (measured using DPPH, FRAP, and ABTS assays). The findings show that the samples of wheat beer enhanced with sea-buckthorn juice had average ascorbic acid contents of 2.5 and 4.5 mg/100 mL (in samples with 5% v/v and 10% v/v additions, respectively) and contained flavone glycosides, e.g., kaempferol-3-O-glucuronide-7-O-hexoside. Based on the current findings, it can be concluded that wheat beer enhanced with sea-buckthorn juice could emerge as a new trend in the brewing industry. 相似文献
56.
Justyna Sikorska 《Journal of Mathematical Analysis and Applications》2008,345(2):650-660
We study a generalized stability problem for Cauchy and Jensen functional equations satisfied for all pairs of vectors x,y from a linear space such that γ(x)=γ(y) or γ(x+y)=γ(x−y) with a given function γ. 相似文献
57.
Balances of multiple varying forces must be the basis for the unusually great dynamic stability of swimming pufferfishes.
We used high-speed digital video recordings to study biomechanics and kinematics of rectilinear swimming at different speeds
of five porcupine puffers in a water tunnel. We measured critical swimming speeds (U
crit); fin biomechanics, kinematics, and coordination; recoil movements; and gait changes. Major propulsors were pectoral fins
at lower speeds; dorsal, anal, and caudal fins at higher speeds. Precise coordination of fin movements produced small recoil
movements at speeds below U
crit. The unusual body shape probably contributes to unconscious stability control. 相似文献
58.
Zygmuntowicz Justyna Wiecinska Paulina Miazga Aleksandra Konopka Katarzyna Szafran Mikolaj Kaszuwara Waldemar 《Journal of Thermal Analysis and Calorimetry》2018,133(1):303-312
Journal of Thermal Analysis and Calorimetry - Composite material with a gradient concentration of the metallic phase was prepared by the novel gel-centrifugal casting method. This method combines... 相似文献
59.
60.
Jan Epsztajn Adam Bieniek Justyna A. Kowalska Jacek Ścianowski 《Monatshefte für Chemie / Chemical Monthly》1992,123(12):1125-1134
Summary The lithiation (Bu
nLi/THF) of 2-chloro- (1), 3-chloro- (2) and 4-chlorobenzanilides (3) and the subsequent reactions of the corresponding bis-lithiated anilides4–6 with electrophiles (MeI, CH2=CH-CH2Br,Me
3SiCl,MeCHO,o-MeOC6H4CHO,p-MeOC6H4CHO,Me
2NCHO andp-MeOC6H4CONMe
2) towards the synthesis of theortho substituted chlorobenzoesic acids derivatives12–14 have been described. The effect of the chlorine substituent upon the generation and stability of the bis-lithiated chloro-anilides4–6 has been studied. It has been found that the bis-lithiated chloro-anilide5 derived fromm-chloro-benzanilide (2) at a temperature above –30°C converts into the corresponding benzyne9. The anilide moiety (masking group) of the formedortho-substituted chlorobenzanilides appeared to be effectively removable on acid-driven hydrolysis.
Anwendungen von Organolithium und verwandten Reagenzien in organischen Synthesen, 10. Mitt. Metallierung und nachfolgende elektrophile Substitution sekundärer Chlorbenzamide
Zusammenfassung Die Lithiierung (Bu nLi/THF) der 2-Chlor-(1), 3-Chlor- (2) and 4-Chlorbenzanilide (3) und nachfolgende Reaktion der entsprechenden doppellithiierten Anilide4–6 mit elektrophilen Reagenzien (MeI, CH2=CH-CH2Br,Me 3SiCl,MeCHO,o-MeOC6H4CHO,p-MeOC6H4CHO,Me 2NCHO undp-MeOC6H4CONMe 2) zur Synthese vonortho-substituierten Benzoesäurederivaten12–14 wird beschrieben. Der Einfluß des Chlorsubstituierten auf die Bildung und Stabilität der doppellithiierten Chloranilide4–6 wurde untersucht. Es wurde festgestellt, daß das doppellithiierte, vomm-Chlorbenzanilid erhaltene Chloranilid5 bei Temperaturen über –30°C das entsprechende Arin9 bildet. Der Anilidrest (eine maskierende Gruppe) der gebildetenortho-substituierten Chloranilide kann durch saure Hydrolyse abgespalten werden.相似文献