934-05-4

Usage

Uses

Used in Pharmaceutical Industry:
Methyl 4-bromopyrrole-2-carboxylate is used as a synthetic intermediate for the development of potent melanin-concentrating hormone (MCH-R1) antagonists based on pyrazolopiperazinone. These antagonists have potential applications in the treatment of various disorders, including obesity, anxiety, and depression, by modulating the MCH-R1 receptor.
Used in Organic Synthesis:
Methyl 4-bromopyrrole-2-carboxylate is also used as a key building block in the synthesis of various organic compounds, including pharmaceuticals, agrochemicals, and other specialty chemicals. Its unique structure and functional groups make it a valuable component in the development of novel molecules with diverse applications.

InChI:InChI=1/C6H6BrNO2/c1-10-6(9)5-2-4(7)3-8-5/h2-3,8H,1H3

Upstream product

• 72652-32-5 1-(4-bromo-1H-pyrrol-2-yl)-2,2,2-trichloroethanone 
• 124-41-4 sodium methylate 
• 1193-62-0 methyl Pyrrole-2-carboxylate 
• 35302-72-8 pyrrol-2-yl trichloromethyl ketone 
• 67-56-1 methanol 
• 110-86-1 pyridine 
• 192197-56-1 4-bromo-1H-pyrrole-2-carboxylic acid chloride 

Downstream Products

• 86288-94-0 4-Bromo-1-((E)-styryl)-1H-pyrrole-2-carboxylic acid 
• 157425-54-2 5-acetyl-4-bromo-1H-pyrrole-2-carboxylic acid methyl ester 
• 156237-78-4 4-bromopyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 86288-56-4 4-Bromo-1-phenethyl-1H-pyrrole-2-carboxylic acid methyl ester 
• 220231-01-6 3,4-bis-(3,4,5-trimethoxyphenyl)-1H-pyrrole-2,5-dicarboxylic acid dimethyl ester 
• 1207173-02-1 3,4-bis-(1-benzenesulfonyl-1H-indol-3-yl)-1H-pyrrole-2,5-dicarboxylic acid dimethyl ester 
• 1207172-99-3 3-(1-benzenesulfonyl-1H-indol-3-yl)-1H-pyrrole-2,5-dicarboxylic acid dimethyl ester 
• 1036355-90-4 3-(3,4,5-trimethoxyphenyl)-1H-pyrrole-2,5-dicarboxylic acid dimethyl ester 
• 1036355-92-6 3-iodo-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole-2,5-dicarboxylic acid dimethyl ester 

Relevant academic research and scientific papers

Substrate Controlled Regioselective Bromination of Acylated Pyrroles Using Tetrabutylammonium Tribromide (TBABr3)

Electrophilic bromination of pyrroles bearing carbonyl substituents at C-2 typically results in a mixture of the 4- and 5-brominated species, generally favoring the 4-position. Herein, we describe a substrate-controlled regioselective bromination in which

Non-basic azolotriazinone MCHR1 antagonists for the treatment of obesity: An empirical brain-exposures-driven candidate selection for in vivo efficacy studies

Non-basic azolotriazinones were explored using an empirical free brain exposures-driven approach to identify potent MCHR1 antagonists for evaluation in in vivo efficacy studies. An optimized lead from this series, 1j (rMCHR1 Ki = 1.8 nM), demonstrated a 6.9% reduction in weight gain relative to vehicle in a rat model at 30 mg/kg after 4 days of once-daily oral treatment as a glycine prodrug. Despite a promising efficacy profile, an assessment of the biliary toxicity risk of this compound rendered this compound non-progressible.

Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a] quinoxaline derivatives as inhibitors of the human protein kinase CK2

Herein we describe the synthesis and properties of substituted phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was designed and synthesized using

Vanadate-dependent bromoperoxidases from Ascophyllum nodosum in the synthesis of brominated phenols and pyrroles

Bromoperoxidases from the brown alga Ascophyllum nodosum, abbreviated as VBrPO(AnI) and VBrPO(AnII), show 41% sequence homology and differ by a factor of two in the percentage of α-helical secondary structures. Protein monomers organize into homodimers for VBrPO(AnI) and hexamers for VBrPO(AnII). Bromoperoxidase II binds hydrogen peroxide and bromide by approximately one order of magnitude stronger than VBrPO(AnI). In oxidation catalysis, bromoperoxidases I and II turn over hydrogen peroxide and bromide similarly fast, yielding in morpholine-4-ethanesulfonic acid (MES)-buffered aqueous tert-butanol (pH 6.2) molecular bromine as reagent for electrophilic hydrocarbon bromination. Alternative compounds, such as tribromide and hypobromous acid are not sufficiently electrophilic for being directly involved in carbon-bromine bond formation. A decrease in electrophilicity from bromine via hypobromous acid to tribromide correlates in a frontier molecular orbital (FMO) analysis with larger energy gaps between the π-type HOMO of, for example, an alkene and the σ*Br,X-type LUMO of the bromination reagent. By using this approach, the reactivity of substrates and selectivity for carbon-bromine bond formation in reactions mediated by vanadate-dependent bromoperoxidases become predictable, as exemplified by the synthesis of bromopyrroles occurring naturally in marine sponges of the genera Agelas, Acanthella, and Axinella. The Royal Society of Chemistry.

Molecular cloning, structure, and reactivity of the second bromoperoxidase from Ascophyllum nodosum

The sequence of bromoperoxidase II from the brown alga Ascophyllum nodosum was determined from a full length cloned cDNA, obtained from a tandem mass spectrometry RT-PCR-approach. The clone encodes a protein composed of 641 amino-acids, which provides a mature 67.4 kDa-bromoperoxidase II-protein (620 amino-acids). Based on 43% sequence homology with the previously characterized bromoperoxidase I from A. nodosum, a tertiary structure was modeled for the bromoperoxidase II. The structural model was refined on the basis of results from gel filtration and vanadate-binding studies, showing that the bromoperoxidase II is a hexameric metalloprotein, which binds 0.5 equivalents of vanadate as cofactor per 67.4 kDa-subunit, for catalyzing oxidation of bromide by hydrogen peroxide in a bi-bi-ping-pong mechanism (kcat = 153 s-1, 22 °C, pH 5.9). Bromide thereby is converted into a bromoelectrophile of reactivity similar to molecular bromine, based on competition kinetic data on phenol bromination and correlation analysis. Reactivity provided by the bromoperoxidase II mimics biosynthesis of methyl 4-bromopyrrole-2-carboxylate, a natural product isolated from the marine sponge Axinella tenuidigitata.

PYRROLOPYRIDAZINE JAK3 INHIBITORS AND THEIR USE FOR THE TREATMENT OF INFLAMMATORY AND AUTOIMMUNE DISEASES

Disclosed are compounds of formula (I) and pharmaceutically acceptable salts thereof. The compounds of formula (I) inhibit tyrosine kinase activity of JAK3, thereby making them useful for the treatment of inflammatory and autoimmune diseases.

PYRROLOPYRIDAZINE JAK3 INHIBITORS AND THEIR USE FOR THE TREATMENT OF INFLAMMATORY AND AUTOIMMUNE DISEASES

Disclosed are compounds of Formula (I), and pharmaceutically acceptable salts thereof. The compounds of formula (I) inhibit tyrosine kinase activity of JAK3, thereby making them useful for the treatment of inflammatory and autoimmune diseases.

Parameters for bromination of pyrroles in bromoperoxidase-catalyzed oxidations

Ester-, cyano-, and carboxamide-substituted 1H-pyrroles undergo electrophilic aromatic bromination, if treated with hydrogen peroxide and sodium bromide at pH 6.2 and 20 °C. Oxidation of bromide under such conditions is catalyzed by a vanadate(V)-dependent bromoperoxidase, in a substrate/enzyme ratio of 32-63 μmol %. To obtain maximum yields of bromopyrroles (up to 91%) by spending least amount of substrates and catalyst, hydrogen peroxide and sodium bromide have to be added continuously to the enzyme and the 2-acceptor-substituted pyrrole (1.5 mmol) in a solution of morpholine-4- ethanesulfonic acid buffer. This technique was applied to prepare two marine natural products under biomimetic conditions, that is, methyl 4,5-dibromopyrrole-2-carboxylate (from Agelas oroides) and 4,5-dibromopyrrole-2- carboxamide (from Acanthella carteri).

Vanadate(v)-dependent bromoperoxidase immobilized on magnetic beads as reusable catalyst for oxidative bromination

Vanadate(v)-dependent bromoperoxidase I (Ascophyllum nodosum) was immobilized on magnetic micrometre-sized particles in quantitative yields, with up to 40% retention of initial bromoperoxidase (BPO) activity. The immobilized enzyme was stable with a half-life time of about 160 days. It served as reusable catalyst for bromide oxidation with H2O2 in up to 14 consecutive experiments. Reactivity that resulted from enzymatic bromide oxidation was applicable for methyl pyrrole-2-carboxylate conversion into derivatives of naturally occurring compounds (e.g. from Agelas oroides) with product selectivity of up to 75%.

AZOLOTRIAZINONE MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS

The present application provides compounds that are useful as MCHR1 antagonists, especially for the treatment of obesity, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I, wherein R1, is selected from the group consisting of monocyclic aryl or monocyclic heteroaryl; W is selected from the group consisting of a direct bond, -O-, and -N(R6)-; provided that if W is a direct bond, D is a cyclic amine that is attached to A via the nitrogen atom of the cyclic amine; D is selected from the group consisting of a direct bond, substituted or unsubstituted C1 to C4 alkyl, substituted or unsubstituted C3 to C7 cycloalkyl, cycloalkylalkyl, and 4- to 6-membered cyclic amines, provided that if D is a direct bond, R2a, R2b, and R2c must be selected from H, alkyl, or cycloalkyl; E and G are independently N or CH provided that both are not N; R1 is substituted or unsubstituted phenyl or substituted or unsubstituted monocyclic heteroaryl; R2a, R2b, and R2c are independently selected from the group consisting of hydrogen, halo, cyano, hydroxyl, -NR5R5a, -SO2R34, -CO2R35 -NR5CO2R21, -NR5COR21, substituted or unsubstituted C1 to C4 alkyl, substituted or unsubstituted C3 to C7 cycloalkyl, substituted or unsubstituted 4- to 6-membered cyclic amines wherein said cyclic amine is optionally substituted with -OH, carbonylamino, alkoxycarbonylamino, or at least one of R2a, R2b, and R2c is a prodrug moiety selected from amino acid esters or phosphoric acid esters wherein said amino acid ester has the formula -OC(O)CH(NH2)R31, wherein R31 is H or C1 to C4 alkyl; or any two of R2a, Rb, or R2c, may be taken together to form a ring; R3 and R3a are each independently selected from the group consisting of hydrogen, hydroxyl, lower alkoxy, halo, CN, substituted or unsubstituted C1 to C4 alkyl, perfluoroalkyl, substituted or unsubstituted C3 to C7 cycloalkyl, cycloalkoxy, amino, alkylamino, dialkylamino, and aminoalkyl, wherein R3 or R3a and D may optionally be taken together with the atoms to which they are attached to form a 5- to 7-membered ring; R5 and R5a are the same or different and are independently selected from the group consisting of hydrogen, substituted or unsubstituted lower alkyl, hydroxyalkyl, hydroxyalkylcycloalkyl, substituted or unsubstituted heterocycloalkyl, acyl, alkoxycarbonyl, carboxyalkyl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted cycloalkylalkyl, wherein the R5 and R5a groups and the N atom to which they are attached may form a ring; R21 and R31 are each H or C1 to C4 alkyl; R34 is alkyl; R35 is H or alkyl; and R6 is selected from the group consisting of H, C1 to C4 alkyl and C3 to C7 cycloalkyl.