Synthesis and biological evaluation of (E)-cinnamic acid, (E)-2-styrylthiazole and (E)-2-[2-(naphthalen-1-yl)vinyl]thiazole derivatives

Olawode, Emmanuel O.; Tandlich, Roman; Prinsloo, Earl; Isaacs, Michelle; Hoppe, Heinrich C.; Seldon, Ronnett; Warner, Digby F.; Steenkamph, Vanessa; Kaye, Perry T.

doi:10.24820/ark.5550190.p009.905

Cited by 5 publications

(5 citation statements)

References 37 publications

(45 reference statements)

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“…Compounds 2 – 4 were made by routes based on a recently published method for synthesizing pitolisant (Scheme ). Known cinnamic acids 5 – 7 were synthesized by Knoevenagel condensations , and reduced by standard methods to provide the corresponding known hydrocinnamyl alcohols 8 – 10 . These intermediates were converted into targets 2 – 4 by adding KO- t -Bu and spirocyclic ammonium bromide 11 , which is produced by the reaction of piperidine with 1-bromo-3-chloropropane. , The corresponding hydrochloride salts were made by standard reactions and were crystallized by methods used for pitolisant hydrochloride.…”

Section: Resultsmentioning

confidence: 99%

Exploring Polymorphism: Hydrochloride Salts of Pitolisant and Analogues

Patel,

Leduc,

Nunez Avila

et al. 2024

Crystal Growth & Design

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Pitolisant hydrochloride is used to treat excessive daytime sleepiness in adults with narcolepsy. The drug is formulated as a crystalline solid, and a monoclinic P2 1 form has been claimed in patents, but little additional information about the structure and polymorphism of the compound has been published. No new forms were obtained when we grew crystals from solution under various conditions. Re-examination of the crystals revealed a disordered and partially hydrated structure that resembles the one reported earlier but is not identical. Further insight was obtained by synthesizing analogues of pitolisant with its Cl substituent replaced by Me, F, and Br, followed by structural analysis of the hydrochloride salts by X-ray diffraction. Pitolisant hydrochloride and its three analogues showed very similar solid-state behavior, and each compound yielded new metastable forms when crystallized from melts. The lifetime of metastable form III of pitolisant hydrochloride could be extended significantly by adding small amounts of the fluoro analogue, but none of the metastable forms could be obtained as single crystals suitable for structural analysis. Computational predictions of the polymorphic landscapes of pitolisant hydrochloride and its analogues identified possible structures of the metastable forms. Dual experimental and computational approaches are already widely used in polymorphic screening, but our work shows the value of broadening these searches to include sets of structural analogues.

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Section: Resultsmentioning

confidence: 99%

Exploring Polymorphism: Hydrochloride Salts of Pitolisant and Analogues

Patel,

Leduc,

Nunez Avila

et al. 2024

Crystal Growth & Design

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“…2‐Styrylthiazole‐4‐carboxylic acid was prepared according to the reported procedures. [ 18 ] 2.0 g of l ‐Histidine methyl ester dihydrochloride (8.26 mmol) was dispersed in dry dichloromethane (250 mL). To this solution, 2.09 g of triethylamine (20.66 mmol) were added.…”

Section: Methodsmentioning

confidence: 99%

Alkaline‐Earth Metal Ion Turn‐On Circularly Polarized Luminescence and Encrypted Selective Recognition of AMP

et al. 2020

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Circularly polarized luminescence (CPL) is an important luminescence phenomenon that provides the complementary chiral and conformational information about the excited state of the studied chiral molecular systems, thus accelerating its development as both an attractive chiroptical property and a promising sensing technology in several chemistry frontiers. [1] Especially, developing stimuliresponsive chiroptical functional materials with CPL has gained a lot of attention. Among them, CPL switch, which can selectively emit two different CPL signals in one individual system under certain stimuli, [2] is gradually showing great value for designing smart chiroptical materials and detection technologies. In the past several years, although several examples of CPL switch based on molecular or supramolecular systems have been reported by incorporating stimuli-responsive groups into the backbone of building blocks, [3] their further applications utilizing the intrinsic chiroptical properties of the two different switching states has been rarely investigated. Integrating CPL signal into such a switchable supramolcular system can not only build multiple information channels to improve variable performance, but also might bring encrypted recogniton ability for chiral analytes such as bioactive compounds. [4] Adenosines and their derivatives are widely observed in cells and play a crucial role in life systems. [5] Due to the significant contributions of adenosines in a series of physiological activities and metabolism, qualitative and/or quantitative detection of adenosines both in vitro and in vivo could provide insights into the precise understanding of complex biological processes. However, different adenosines play different roles, and how to selectively and efficiently identify them is essential for the development of accurate adenosine detection technologies. [6] Adenosine monophosphate (AMP), as one of the three adenosines, is also a critical component in the synthesis of RNA. [7] Selective discriminating and sensing AMP are useful not only for mechanistic studies of energy metabolism but also for understanding the structural basis of RNA folding and recognition, [8] however, such sensing systems are currently rare, especially in terms of the physiological AMP concentration. [9] Here, by encrypting CPL information into a STH/Mg 2+ metal complex, we report a chiral self-assembly system for selective Circularly polarized luminescence (CPL) provides fundamental insights into the chiral structural information of luminescent materials at their excited states, thus contributing to the possibility of encrypting both chirality and luminescence information into functional materials for multipurpose applications such as smart chiroptical devices and encrypted recognition systems. Here, by coordination of alkali-earth metal ions with a chiral histidine-functionalized amphiphile (methyl (E)-(2-styrylthiazole-4-carbonyl)-l-histidinate, abbreviated as STH), both fluorescence (FL), and CPL signals are encoded into the STH metal comp...

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“…All the chemical intermediates (3a-j) were obtained by the reaction between corresponding aldehydes (1) and malonic acid (2), via Doebner-Knoevenagel condensation ( Figure 3), with yields ranging from 45 to 94% [76,77]. Additionally, 1 H Nuclear Magnetic Resonance (NMR) spectra revealed that the intermediates (3a-j) were obtained in an (E)-configuration, confirmed by large vinylic coupling constant (J) values, ranging from 15.8 to 16.1 Hz [77,78]. Moreover, 1 H NMR analysis showed that the chemical shifts (δ) for the hydroxyl (OH) from the carboxylic acid can appear between 12.38 and 12.71 ppm.…”

Section: Chemistrymentioning

confidence: 99%

“…These procedures are adaptations from works previously reported [107][108][109]. In general, an adaptation of methods described by Luo and collaborators (2015) was used [110], through a Knoevenagel condensation Doebner modification reaction [77]. In a bottom flask (50 mL) containing 6 mL pyridine, the corresponding aldehydes (1.0 eq.)…”

Section: Elemental Analysis (Chn)mentioning

confidence: 99%

Computer-Aided Design, Synthesis, and Antiviral Evaluation of Novel Acrylamides as Potential Inhibitors of E3-E2-E1 Glycoproteins Complex from Chikungunya Virus

et al. 2020

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Chikungunya virus (CHIKV) causes an infectious disease characterized by inflammation and pain of the musculoskeletal tissues accompanied by swelling in the joints and cartilage damage. Currently, there are no licensed vaccines or chemotherapeutic agents to prevent or treat CHIKV infections. In this context, our research aimed to explore the potential in vitro anti-CHIKV activity of acrylamide derivatives. In silico methods were applied to 132 Michael’s acceptors toward the six most important biological targets from CHIKV. Subsequently, the ten most promising acrylamides were selected and synthesized. From the cytotoxicity MTT assay, we verified that LQM330, 334, and 336 demonstrate high cell viability at 40 µM. Moreover, these derivatives exhibited anti-CHIKV activities, highlighting the compound LQM334 which exhibited an inhibition value of 81%. Thus, docking simulations were performed to suggest a potential CHIKV-target for LQM334. It was observed that the LQM334 has a high affinity towards the E3-E2-E1 glycoproteins complex. Moreover, LQM334 reduced the percentage of CHIKV-positive cells from 74.07 to 0.88%, 48h post-treatment on intracellular flow cytometry staining. In conclusion, all virtual simulations corroborated with experimental results, and LQM334 could be used as a promising anti-CHIKV scaffold for designing new drugs in the future.

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Synthesis and biological evaluation of (E)-cinnamic acid, (E)-2-styrylthiazole and (E)-2-[2-(naphthalen-1-yl)vinyl]thiazole derivatives

Cited by 5 publications

References 37 publications

Exploring Polymorphism: Hydrochloride Salts of Pitolisant and Analogues

Exploring Polymorphism: Hydrochloride Salts of Pitolisant and Analogues

Alkaline‐Earth Metal Ion Turn‐On Circularly Polarized Luminescence and Encrypted Selective Recognition of AMP

Computer-Aided Design, Synthesis, and Antiviral Evaluation of Novel Acrylamides as Potential Inhibitors of E3-E2-E1 Glycoproteins Complex from Chikungunya Virus

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