83-18-1

Usage

Uses

Used in Pharmaceutical Industry:
2,5-DIMETHYL-1-PHENYLPYRROLE-3-CARBOXALDEHYDE is used as a reagent for the discovery of pyrrolone antimalarials, which are compounds with potential therapeutic applications in the treatment of malaria. Its unique structure allows for the development of new and effective antimalarial drugs, addressing the need for novel treatments against drug-resistant strains of the malaria parasite.

InChI:InChI=1/C13H19NO/c1-10-8-12(9-15)11(2)14(10)13-6-4-3-5-7-13/h8-9,13H,3-7H2,1-2H3

Upstream product

• 83-24-9 2,5-dimethyl-1-phenyl-1H-pyrrole 
• 77287-34-4 formamide 
• 68-12-2 N,N-dimethyl-formamide 
• 110-13-4 2,5-hexanedione 
• 62-53-3 aniline 
• 32570-10-8 N-(3′-methylphenyl)-2,5-dimethylpyrrole 

Downstream Products

• 115121-44-3 1-ethyl-2-[2-(2,5-dimethyl-1-phenyl-pyrrol-3-yl)-vinyl]-6,7-dihydro-4H-pyrano[4,3-d]thiazolium; iodide 
• 35648-29-4 (E)-2-(2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)vinyl)-6-(dimethylamino)-1-methylquinolin-1-ium iodide 
• 102311-27-3 3ξ-(2,5-dimethyl-1-phenyl-pyrrol-3-yl)-2-phenyl-acrylonitrile 

Relevant academic research and scientific papers

Synthesis, structure and in vitro anti-trypanosomal activity of non-toxic arylpyrrole-based chalcone derivatives

With an intention of identifying chalcone derivatives exhibiting anti-protozoal activity, a cohort of relatively unexplored arylpyrrole-based chalcone derivatives were synthesized in moderate to good yields. The resultant compounds were evaluated in vitro for their potential activity against a cultured Trypanosoma brucei brucei 427 strain. Several compounds displayed mostly modest in vitro anti-trypanosomal activity with compounds 10e and 10h emerging as active candidates with IC50 values of 4.09 and 5.11 μM, respectively. More importantly, a concomitant assessment of their activity against a human cervix adenocarcinoma (HeLa) cell line revealed that these compounds are non-toxic.

ANDROGEN RECEPTOR ANTAGONISTS

Compounds that inhibit the androgen receptor, pharmaceutical compositions comprising one or more of the compounds, as well as methods of treating cancer using such compounds are described.

Direct Synthesis of Pyrroles via Heterogeneous Catalytic Condensation of Anilines with Bioderived Furans

Given the wide applications of pyrroles in agriculture, pharmaceuticals, and supramolecular and materials chemistry, a mild and eco-friendly route to produce functionalized pyrroles from bioderived feedstocks is highly desirable. Described herein is a mild and convenient synthesis of pyrroles via direct condensation of an equimolar amount of structurally diverse anilines with biobased furans catalyzed by a simple and efficient solid acid H form zeolite Y catalyst. The protocol tolerates a large variety of functional groups and offers a general and versatile method for scale-up synthesis of a variety of N-substituted pyrrole compounds. Most importantly, the bioactive pyrrole-derived drug pyrvinium, which has lately been confirmed as highly effective in curing colon cancer, can be obtained by this method.

Discovery and optimisation studies of antimalarial phenotypic hits

There is an urgent need for the development of new antimalarial compounds. As a result of a phenotypic screen, several compounds with potent activity against the parasite Plasmodium falciparum were identified. Characterization of these compounds is discussed, along with approaches to optimise the physicochemical properties. The in vitro antimalarial activity of these compounds against P. falciparum K1 had EC50 values in the range of 0.09e29 mM, and generally good selectivity (typically >100-fold) compared to a mammalian cell line (L6). One example showed no significant activity against a rodent model of malaria, and more work is needed to optimise these compounds.

New synthesis of pyrvinium that inhibits the β-catenin/Tcf4 pathway

A new and converged route is described for synthesis of pyrvinium, an anthelmintic and antitumor agent. This method uses easily obtained materials and simple and practical reactions, including the key Friedlaender condensation, to form the quinoline ring. The final product is generated through eight steps, with 23% yield and 96.6% purity (HPLC). This synthetic pyrvinium effectively inhibits β-catenin/Tcf4 driven TOP-luciferase activity, with an IC50 value 50 of 0.54 ± 0.06 μM.

Discovery, synthesis and SAR analysis of novel selective small molecule S1P4-R agonists based on a (2Z,5Z)-5-((pyrrol-3-yl)methylene)-3- alkyl-2-(alkylimino)thiazolidin-4-one chemotype

High affinity and selective S1P4 receptor (S1P4-R) small molecule agonists may be important proof-of-principle tools used to clarify the receptor biological function and effects to assess the therapeutic potential of the S1P4-R in diverse disease areas including treatment of viral infections and thrombocytopenia. A high-throughput screening campaign of the Molecular Libraries-Small Molecule Repository was carried out by our laboratories and identified (2Z,5Z)-5-((1-(2-fluorophenyl)-2,5-dimethyl-1H- pyrrol-3-yl)methylene)-3-methyl-2-(methylimino) thiazolidin-4-one as a promising S1P4-R agonist hit distinct from literature S1P4-R modulators. Rational chemical modifications of the hit allowed the identification of a promising lead molecule with low nanomolar S1P4-R agonist activity and exquisite selectivity over the other S1P 1-3,5-Rs family members. The lead molecule herein disclosed constitutes a valuable pharmacological tool to explore the effects of the S1P4-R signaling cascade and elucidate the molecular basis of the receptor function.

SMALL-MOLECULE INHIBITORS OF THE ANDROGEN RECEPTOR

The present invention provides a method of inhibiting an androgen receptor by administering a compound of Formula I: or a compound of Formula II: wherein R1, R2, R3 and R8 are each independently hydrogen or C1-6 alkyl. R4 is absent or is hydrogen, C1-6 alkyl or C1-6 alkyl-OH. R5 is hydrogen, C1-6 alkyl or —NR6R7. R6 and R7 are each independently hydrogen or C1-6 alkyl, or are combined with the nitrogen to which they are attached to form a heterocycloalkyl having from 5 to 7 ring members. L is a linker of C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene or C3-6 cycloalkylene. The compounds of Formula I include the salts, hydrates and prodrugs thereof. Each R9 is H, C1-6 alkyl, —OH or —O—C1-6 alkyl. The compounds of Formulas I and II include the salts, hydrates and prodrugs thereof. By administering the compound of Formula I or II, the method inhibits the androgen receptor.

NOVEL QUINOLINIUM SALTS AND DERIVATIVES

The present invention relates generally to the synthesis of novel quinolinium salts and derivative compounds. Such salts and compounds are useful for inhibiting the growth of cancer cells.