The recyclizations of 5‐amino‐ and 5‐hydrazine‐1,3‐oxazoles mainly with electron‐withdrawing group in 4th position are considered. The chemical behavior of these heterocycles is due to the presence ...of two hidden amide fragments; therefore, the recyclization processes include a stage of nucleophile attack on 2nd or 5th position of the oxazole cycle. When the nitrile group is present in 4th position, it is often involved in the recyclization forming α‐aminoazoles. 5‐Amino/hydrazine‐1,3‐oxazoles undergo recyclization both in nucleophilic (amines, hydrazine, thionating agents) and electrophilic medium ((trifluoro)acetic acid, other acylating agents). The numerous types of functionalized heterocycles can be easily obtained with the usage of these recyclizations, such as the derivatives of 3‐amino‐6,7‐dihydro‐5H‐pyrrolo1,2–aimidazole, imidazolidine‐2,4‐dione, 1H‐pyrazole‐3,4,5‐triamine, 5,6‐diamino‐2,3‐diphenylpyrimidin‐4(3H)‐one, 2‐(2‐R‐7‐oxo‐5‐(trifluoromethyl)oxazolo5,4–dpyrimidin‐6(7H)‐yl)acetic acid, 2‐R‐4‐(5‐R′‐1,3,4‐oxadiazol‐2‐yl)oxazol‐5‐amine, (amino(5‐amino‐1,3,4‐thiadiazol‐2‐yl)methyl)phosphonate.
The recyclizations of 5‐amino‐ and 5‐hydrazine‐1,3‐oxazoles mainly with electron‐withdrawing group in 4th position in nucleophilic and electrophilic medium are considered. This personal account summarized original explorations of the Department of Chemistry of Bioactive Nitrogen Heterocyclic Bases of V. P. Kukhar IBOPC of the NAS of Ukraine.
An approach to a series of new 5‐amino‐4‐cyanoxazoles is described. Synthesis of the title compounds relied on a two‐step sequence including heterocyclization of 2‐amido‐3,3‐dichloroacrylonitriles ...with aliphatic secondary amines (dimethylamine, morpholine), primary aliphatic amines with active functional groups (2‐aminoethanol and glycine ethyl ester), and aniline. An efficient and straightforward protocol introduces a carboxylate group at the C‐2 position of 5‐amino‐4‐cyanoxazoles, connected to the heterocycle directly or through an aliphatic linker. This carboxylic group is an attractive motif that can be found in a variety of drug‐relevant compounds and also used for further modifications. Furthermore, efficient transformations of selected trisubstituted compounds were used to demonstrate their rich synthetic potential – e. g., as precursors to 2‐(4‐cyano‐5‐(dimethylamino)oxazol‐2‐yl)acetamides, oxazole‐containing macrocyclic structures, 2‐(oxazol‐2‐yl)acetamides, amino pyrazoles, 3‐(4‐cyano‐5‐aminoxazol‐2‐yl)coumarins, and oxazole amino acids.
An approach for the synthesis of new 5‐amino‐4‐cyanoxazoles with carboxylate group at the C‐2 position, connected to the heterocycle directly or through an aliphatic linker, was developed. This process features readily available starting materials, simple operations, and good to high yields. Wide synthetic applicability of the obtained compounds was also successfully demonstrated by further modifications.
In this study, we report the development of efficient synthetic strategies for the preparation of novel 2'-carboxyl isoflavones and their recyclization products, pyrazoles and oxazoles. Utilizing ...readily accessible starting materials and mild reaction conditions, the synthesis affords valuable compounds with good to excellent yields. The presence of diverse functional groups, including hydroxyl, carboxyl, and carboxamido moieties, renders these molecules attractive for biological screening and targeted structural modifications. This work unveils new avenues for the design of compounds exhibiting a wide range of beneficial properties and opens new opportunities for future research into intramolecular interactions of proximal functional groups.
This research focuses on the synthesis and
in vitro
anticancer evaluation of functionalized 2-aryl-5-(4-piperazin-1-yl)oxazoles and 5-(4-arylsulfonyl) piperazin-1-yl-2-phenyloxazoles. Oxazoles are a ...versatile class of compounds with diverse biological activities, making them attractive targets in medicinal chemistry. We incorporated amino and sulfonamide functionalities into the oxazole scaffold, as they have shown potential for interacting with biological targets. The synthesis of target oxazole derivatives was accomplished using 2-aroylamino-3,3-dichloroacrylonitriles as starting materials and employing efficient reaction conditions. The resulting compounds exhibited structural features that make them promising candidates for further chemical modifications and biological evaluations. Additionally, a series of sulfonamides were synthesized from 5-(piperazin-1-yl)oxazole-4-carbonitrile hydrochloride, offering diverse bioactivity and versatile structural characteristics. However, no potent inhibitors of malignant cell growth were identified among the tested compounds. Nevertheless, we categorized the investigated substances into two distinct groups based on their activity profile. Group A, comprising sulfonamides, displayed pronounced anticancer activity against breast cancer and melanoma cell lines. On the other hand, group B, the 2-aryl-5-(4-R-piperazin-1-yl)oxazole-4-carbonitriles, exhibited a moderate effect primarily on renal cancer cell lines. These findings provide valuable insights for further structural modifications in the quest for more potent anticancer agents.
An efficient and practical synthetic procedure for libraries of diversified 1,2-dihydrochromeno2,3-
c
pyrrole-3,9-diones using a multicomponent process is presented. A convenient synthetic procedure ...for obtaining functionalized 3-(2-hydroxyphenyl)-4,5-dihydropyrrolo3,4-
c
pyrazol-6(1
H
)-ones via ring-opening strategy has also been developed. This protocol was found to be compatible with a wide range of substituents and paves the way for the practical synthesis of title compounds with a broad range of substituents under mild condition. The products can be easily isolated by crystallization without the use of chromatography.
Graphic abstract
A convenient method was developed for the synthesis of novel isoquinolin-1(2
H
)-ones, 1-chloroisoquinolines, and 1-aminoisoquinolines with a heterocyclic substituent in position 3
via
a ...recyclization of 3-hetarylisocoumarins with (NH
4
)
2
CO
3
. 1-Aminoisoquinolines were efficiently obtained from corresponding 1-chloro-3-hetarylisoquinolines (obtained by interaction of isoquinolin-1(2
H
)-ones with POCl
3
) and cyclic secondary amines (morpholine or 1-methylpiperazine). Literature data and preliminary results of biological assays allow to consider 1-amino-3-hetarylisoquinolines a promising family of anticancer compounds.
Functionalization of heterocyclic systems with sulfur- and phosphorus-containing pharmacophores has long shown itself as an effective method for construction of new bioactive substances. At the same ...time, some types of the compounds are represented by only a few examples, and it prevents further evaluation of the contribution of certain structural elements to biological effects of the sulfonyl- and phosphoryl-substituted heterocyclic derivatives studied. Therefore, a relevant task for organic and medicinal chemistry still remains development of new methods for the synthesis of heterocyclic compounds with sulfonyl and phosphoryl groups, as well as determination of the biological activity of these substances. A structural variety of sulfonyl- and phosphoryl-substituted heterocycles can be achieved by using heterofunctional low-molecular compounds with sulfonyl and phosphoryl groups. This review highlights the information on biologically active heterocyclic compounds synthesized from acrylonitriles and enamines of sulfones, phosphine oxides, and phosphonates series.
A convenient method for the synthesis of novel sulfonic cytosine derivatives, 8-(methyl(phenyl)sulfonyl)-2,6-dihydroimidazo1,2-
c
-pyrimidin-5(3
Н
)-ones and ...9-(methyl(phenyl)sulfonyl)-2,3,4,7-tetrahydro-6
H
-pyrimido1,6-
a
pyrimidin-6-ones, has been developed based on the reaction of 3-amino-2-(methyl(phenyl)sulfonyl)acrylonitriles with 2-chloroethyl isocyanate and 3-chloropropyl isocyanate. The resulting heteryl sulfones possess antiviral activity.
Obtained by the interaction of 2-amino-3,3-dichloroacrylonitrile and chlorosulphonyl isocyanate (Z)-(5-(dichloromethylene)-2-oxoimidazolidin-4-ylidene)sulfamoyl chloride reacts easily with excess of ...the aliphatic amine to form new (Z)-N-(5-(dichloromethylene)-2-oxoimidazolidin-4-ylidene)-N'-substituted sulfonamides. According to the National Cancer Institute (USA) examinations, two of the six synthesized sulfonamides showed a high anticancer activity.
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