Chromene Scaffold Research Articles

Microwave-assisted synthesis of substituted 4-chloro-8-methyl-2-phenyl-1,5-dioxa-2H-phenanthren-6-ones and their antimicrobial activity

Chromene and coumarin scaffolds are known for their potential antimicrobial activity. Herein, we have synthesized hybrid compounds containing both, substituted 4-chloro-8-methyl-2-phenyl-1,5-dioxa-2H-phenanthren-6-ones, 3a–o have been synthesized from substituted (E)-1-(7-Hydroxy-4-methyl-8-coumarinyl)-3-phenyl-2-propen-1-ones, 2a–o in good yield using the microwave-assisted Vilsmeier–Haack reaction. All the synthesized compounds were tested in vitro for their antimicrobial activity. The compounds 3e, 3f and 3g were found to be potent against tested fungal and bacterial strains.

Natural Product Derived Antiprotozoal Agents: Synthesis, Biological Evaluation, and Structure–Activity Relationships of Novel Chromene and Chromane Derivatives

Various natural products with the chromane and chromene scaffold exhibit high antiprotozoal activity. The natural product encecalin (7) served as key intermediate for the synthesis of different ethers 9, amides 11, and amines 12. The chromane analogues 14 and the phenols 15 were obtained by reductive amination of ketones 13 and 6, respectively. Angelate 3, ethers 9, and amides 11 did not show considerable antiprotozoal activity. However, the chromene and chromane derived amines 12, 14, and 15 revealed promising antiprotozoal activity and represent novel lead compounds. Whereas benzylamine 12a and α-methylbenzylamine 12g were active against P. falciparum with IC50 values in the range of chloroquine, the analogous phenols 15a and 15b were unexpectedly 10- to 25-fold more potent than chloroquine with selectivity indexes of 6760 and 1818, respectively. The phenylbutylamine 14d based on the chromane scaffold has promising activity against T. brucei rhodesiense and L. donovani.

ChemInform Abstract: An Organic Molecule Modulated Chemoselective Cyclization of Alkynyl Nitriles Tethered to 2‐Alkyl Substituted Chromones with Multireactive Sites.

AbstractOptimized conditions including a benzylcyanide as anion transfer reagent allow the preparation of novel tetracyclic and tricyclic chromene scaffolds.

New chromene scaffolds for adenosine A2A receptors: Synthesis, pharmacology and structure–activity relationships

In silico screening of a collection of 1584 academic compounds identified a small molecule hit for the human adenosine A2A receptor (pKi = 6.2) containing a novel chromene scaffold (3a). To explore the structure–activity relationships of this new chemical series for adenosine receptors, a focused library of 43 2H-chromene-3-carboxamide derivatives was synthesized and tested in radioligand binding assays at human adenosine A1, A2A, A2B and A3 receptors. The series was found to be enriched with bioactive compounds for adenosine receptors, with 14 molecules showing submicromolar affinity (pKi ≥ 6.0) for at least one adenosine receptor subtype. These results provide evidence that the chromene scaffold, a core structure present in natural products from a wide variety of plants, vegetables, and fruits, constitutes a valuable source for novel therapeutic agents.

An efficient synthesis of 6 H,7 H-chromeno[4,3- b]chromenes and 6,7-dihydrothio chromeno[3,2- c]chromenes as 9-substituted xanthene like analogs

An efficient synthetic route with good overall yields to access 7-aryl/heteroaryl/alkyl substituted 6 H,7 H-chromeno[4,3- b]chromene, and 6,7-dihydrothiochromeno[3,2- c]chromene scaffolds has been developed. The route to these xanthene-like analogs involves a three-step reaction sequence: (1) Michael addition of readily available phenol and thiophenol to 4-chloro-2,2-dimethyl-2 H-chromene-3-carbaldehyde, (2) Grignard reaction of different aryl, heteroaryl and alkyl magnesium bromides on the resulting carbaldehydes followed by (3) FeCl 3 catalyzed spontaneous intramolecular Friedel–Craft’s reaction on the diarylmethyl carbinols.

Synthesis of novel chromene scaffolds for adenosine receptors

A one-pot procedure was developed for the synthesis of novel 3-[amino(methoxy)methylene]-2-oxo-3,4-dihydro-2H-chromen-4-yl)-3-cyanoacetamides and chromeno[3,4-c]pyridine-1-carbonitriles from the reaction of 2-oxo-2H-chromene-3-carbonitriles and cyanoacetamides. These chromene derivatives were identified as new scaffolds for adenosine receptors and the hits 3a, 3c, 5a, and 5b were found.

Identification and Structure−Activity Relationships of Chromene-Derived Selective Estrogen Receptor Modulators for Treatment of Postmenopausal Symptoms

As part of a program aimed at the development of selective estrogen receptor modulators (SERMs), novel chromene scaffolds, benzopyranobenzoxapanes, were discovered. Many compounds showed binding affinity as low as 1.6-200 nM, displayed antagonist behaviors in the MCF-7 human breast adenocarcinoma cell line as well in Ishikawa cell line with IC(50) values in the range 0.2-360 nM. On the basis of the side chain substitution, various compounds demonstrated strong inhibitory activity in anti-uterotropic assay. Compound 7-(R) and its major metabolites 5-(R) and 6-(R) were evaluated in several in vivo models of estrogen action. Relative to a full estrogen agonist (ethynyl estradiol) and the SERM raloxifene, 7-(R) was found to be a potent SERM that behaved as antagonist in the uterus and exhibited estrogen agonistic activity on bone, plasma lipids, hot flush, and vagina. The overall pharmacokinetic profile and stability were significantly improved compared to those of the phase 2 development compound 9-(R).

Catalysis of Salicylaldehydes and Two Different CH Acids with Electricity: First Example of an Efficient Multicomponent Approach to the Design of Functionalized Medicinally Privileged 2‐Amino‐4H‐Chromene Scaffold

AbstractElectrochemically induced multicomponent transformation of salicylaldehydes and two different CH acids in alcohols in an undivided cell in the presence of sodium bromide as an electrolyte results in the efficient and selective formation of diversely functionalized, medicinally privileged 2‐amino‐4H‐chromene scaffolds in 65–86% yields. The developed electrocatalytic system affords the distinction between two CH acids according to their reactivity, and offers an efficient approach to the 2‐amino‐4H‐chromene scaffold with a predefined arrangement of desired substituents. The electrocatalytic multicomponent reaction smoothly proceeds with salicylaldehydes bearing both electron‐donating and electron‐withdrawing groups. Thus, fifteen previously inaccessible, close structural analogues of the tumor antagonists HA14‐1 and MX58151 have been synthesized. The electrocatalytic process was found to be advantageous in terms of selectivity and yields compared to classic chemical base catalysis, and includes a remarkable mechanistic feature that is promising for the further development of 2‐amino‐4H‐chromene chemistry. The application of this convenient electrocatalytic multicomponent method to the formation of medicinally relevant 2‐amino‐4H‐chromenes is also beneficial from the viewpoint of diversity‐oriented large‐scale processes and represents a novel, facile and environmentally benign synthetic concept for multicomponent reaction strategy.