3757-53-7

Usage

Uses

Used in Pharmaceutical Industry:
5-METHYL-1H-PYRROLE-2-CARBOXYLIC ACID is used as a reactant for the preparation of coumarin-carboxylic acids, which are known to act as inhibitors of gyrase B. Gyrase B is an essential enzyme in bacterial DNA replication, and its inhibition can lead to the development of novel antibiotics targeting bacterial infections.
Used in Chemical Synthesis:
5-METHYL-1H-PYRROLE-2-CARBOXYLIC ACID can also be utilized as a building block in the synthesis of various organic compounds, including pharmaceuticals, agrochemicals, and other specialty chemicals. Its unique structure and reactivity make it a valuable intermediate in the development of new molecules with potential applications in different fields.

InChI:InChI=1/C6H7NO2/c1-4-2-3-5(7-4)6(8)9/h2-3,7H,1H3,(H,8,9)

Upstream product

• 3284-51-3 ethyl 5-methyl-1H-pyrrole-2-carboxylate 
• 625-84-3 2,5-Dimethylpyrrole 
• 689-89-4 (2E,4E)-methylhexa-2,4-dienoate 
• 821-10-3 1,4-Dichloro-2-butyne 
• 1068-90-2 2-acetylaminomalonic acid diethyl ester 
• 1194-97-4 methyl 5-methyl-1H-pyrrole-2-carboxylate 
• 82698-67-7 2-(4-Methoxycarbonyl-phenyl)-3-methyl-3,6-dihydro-2H-[1,2]oxazine-6-carboxylic acid methyl ester 
• 82698-69-9 1-(4-Methoxycarbonyl-phenyl)-5-methyl-1H-pyrrole-2-carboxylic acid methyl ester 

Downstream Products

• 1194-97-4 methyl 5-methyl-1H-pyrrole-2-carboxylate 
• 245729-77-5 5-methyl-1H-pyrrole-2-carboxylic acid 6-(4-benzhydryloxy-8-methyl-2-oxo-2H-chromen-7-yloxy)-5-hydroxy-3-methoxy-2,2-dimethyl-tetrahydro-pyran-4-yl ester 
• 4434-05-3 coumermycin A1 

Relevant academic research and scientific papers

Stereochemical determination of the leupyrrins and total synthesis of leupyrrin A1

The stereochemical determination of the potent antifungal agents leupyrrin A1 and B1 and the total synthesis of leupyrrin A1 are reported. The relative and absolute configuration was determined by a combination of high field NMR studies, molecular modeling, and chemical derivatization. The expedient total synthesis involves a one-pot sequential Zr-mediated oxidative diyne-cyclization/regioselective opening sequence for preparation of the unique dihydrofuran ring, a highly stereoselective one-pot approach to the butyrolactone, a challenging sp2-sp3 Suzuki coupling and a high-yielding Shiina macrolactonization.

Gatekeeping Ketosynthases Dictate Initiation of Assembly Line Biosynthesis of Pyrrolic Polyketides

Assembly line biosynthesis of polyketide natural products involves checkpoints where identities of thiotemplated intermediates are verified before polyketide extension reactions are allowed to proceed. Determining what these checkpoints are and how they operate is critical for reprogramming polyketide assembly lines. Here we demonstrate that ketosynthase (KS) domains can perform this gatekeeping role. By comparing the substrate specificities for polyketide synthases that extend pyrrolyl and halogenated pyrrolyl substrates, we find that KS domains that need to differentiate between these two substrates exercise high selectivity. We additionally find that amino acid residues in the KS active site facilitate this selectivity and that these residues are amenable to rational engineering. On the other hand, KS domains that do not need to make selectivity decisions in their native physiological context are substrate-promiscuous. We also provide evidence that delivery of substrates to polyketide synthases by non-native carrier proteins is accompanied by reduced biosynthetic efficiency.

Total Synthesis of Leupyrrins A1 and B1, Highly Potent Antifungal Agents from the Myxobacterium Sorangium cellulosum

Full details on the design, elaboration, and application of efficient strategies for the high-yielding total syntheses of leupyrrins A1 and B1, unique antifungal agents from the myxobacterium Sorangium cellulosum, are reported. A sequential zirconocene-mediated diyne-cyclization, and regioselective opening of the zirconacyclopentadiene intermediate enabled a concise entry into the unique dihydrofuran fragment, whereas another domino reaction was developed for the butyrolactone involving a one-pot lactol opening, stereoselective aldehyde addition and in situ lactonization. Furthermore, an innovative sp2-sp3-cross-coupling for pyrrole functionalization and an optimized HATU-mediated amide coupling protocol of two elaborate fragments were established. In addition, an unusual protective group strategy, involving a Teoc-acetonide protected amine in combination with tert-butyl and acetate esters, was successfully elaborated. These tactics and strategies are generally useful and may be also applied in the synthesis of other functionalized compounds. It is expected that the material which was obtained by these total syntheses will enable the further exploration of the biological profile of these potent antifungal agents.

NOVEL COMPOUNDS USEFUL FOR THE TREATMENT OF BACTERIAL INFECTIOUS DISEASES

Compounds are disclosed that have a formula represented by the following: wherein A, B, R1, R2 and R3 are as defined herein. Novel compounds of the invention may be prepared as a pharmaceutical composition, and may be useful in the treatment of infectious diseases, in particular bacterial infectious diseases. The compounds may be active against a specific enzyme in the bacterial DNA replicative process, DNA polymerase IIIE.

Improved stability of proline-derived direct thrombin inhibitors through hydroxyl to heterocycle replacement

Modification of the previously disclosed (S)-N-(2-(aminomethyl)-5-chlorobenzyl)-1-((R)-2-hydroxy-3,3-dimethylbutanoyl)pyrrolidine-2-carboxamide 2 by optimization of the P3 group afforded novel, low molecular weight thrombin inhibitors. Heterocycle replace

BRANIMYCIN DERIVATIVES AND THEIR USE FOR THE TREATMENT OF BACTERIAL INFECTIOUS DISEASES

Compounds are disclosed that have a formula represented by Formula (I) wherein A, B, R1, R2 and R3 are as defined herein. Novel compounds of the invention may be prepared as a pharmaceutical composition, and may be useful in the treatment of infectious diseases, in particular bacterial infectious diseases. The compounds may be active against a specific enzyme in the bacterial DNA replicative process, DNA polymerase IIIE.

Synthesis and biological evaluation of novobiocin analogues as potential heat shock protein 90 inhibitors

Recent studies have shown that novobiocin (NB), a member of the coumermycin (CA) family of antibiotics with demonstrated DNA gyrase inhibitory activity, inhibits Heat shock protein 90 (HSP90) by binding weakly to a putative ATP-binding site within its C-terminus. To develop more potent HSP90 inhibitors that target this site and to define structure-activity relationships (SARs) for this class of compounds, we have synthesized twenty seven 3-amido-7- noviosylcoumarin analogues starting from NB and CA. These were evaluated for evidence of HSP90 inhibition using several biological assays including inhibition of cell proliferation and cell cycle arrest, induction of the heat shock response, inhibition of luciferase-refolding in vitro, and depletion of the HSP90 client protein c-erbB-2/HER-2/neu (HER2). This SAR study revealed that a substantial increase in biological activity can be achieved by introduction of an indole-2-carboxamide group in place of 4-hydroxy-isopentylbenzamido group at C-3 of NB in addition to removal/derivatization of the 4-hydroxyl group from the coumarin ring. Methylation of the 4-hydroxyl group in the coumarin moiety moderately increased biological activity as shown by compounds 11 and 13. Our most potent new analogue 19 demonstrated biological activities consistent with known HSP90-binding agents, but with greater potency than NB.

Synthesis, biological evaluation and molecular modelling of N-heterocyclic dipeptide aldehydes as selective calpain inhibitors

A series of N-heterocyclic dipeptide aldehydes 4-13 have been synthesised and evaluated as inhibitors of ovine calpain 1 (o-CAPN1) and ovine calpain 2 (o-CAPN2). 5-Formyl-pyrrole 9 (IC50 values of 290 and 25 nM against o-CAPN1 and o-CAPN2, respectively) was the most potent and selective o-CAPN2 inhibitor, displaying >11-fold selectivity. The amino acid sequences of o-CAPN1 and o-CAPN2 have been determined. Because of the lack of available structural information on the ovine calpains, in silico homology models of the active site cleft of o-CAPN1 and o-CAPN2 were developed based on human calpain 1 (h-CAPN1) X-ray crystal structure (PDB code 1ZCM). These models were used to rationalise the observed SAR for compounds 4-13 and the selectivity observed for 9. The o-CAPN2 selective inhibitor 9 (CAT0059) was assayed in an in vitro ovine lens culture system and shown to successfully protect the lens from calcium-induced opacification.

PHENYL-3-{ (3- (1H- PYRROL- 2 -YL) - [1 , 2 , 4] 0XADIAZ0L-5-YL] PIPERIDIN-1-YL}-METHANONE DERIVATIVES AND RELATED COMPOUNDS AS POSITIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS

The present invention provides new compounds of formula (I) as positive allosteric modulators of metabotropic receptors - subtype 5 ("mGluR5") which are useful for the treatment or prevention of central nervous system disorders such as for example, cognitive decline, both positive and negative symptoms in schizophrenia as well as other central or peripheral nervous system disorders in which the mGluR5 subtype of glutamate metabotropic receptor is involved. The invention is also directed to pharmaceutical compounds and compositions in the prevention or treatment of such diseases in which mGluKi is involved. W represents (C4-C7)cycloalkyl, (C3-C7)heterocycloalkyl , (C3-C7)heterocycloalkyl-(C1-C3)alkyl or (C3-C7)heterocycloalkenyl ring; represents a (C5-C7)heteroeycloalkyl, (C5-C7)heterocycloalkeiiyl ring or a heteroaryl group of formula (a), (b), (c), (d), (e), (f), (g), (i). Q denotes a cycloalkyl, an aryl or heteroaryl group of formula (j), (k), (l), (m), (n). A is azo -N=N-, ethyl, ethenyl, ethynyl, -NR8C(=O)-, -NR8C(=O)-O-, -NR8C(=O)-NR9, NR8S(=O)2-, -C(=O)NR8-, -O-C(=O)NR8-, -S-, -S(=O)-, -S(=O)2-, -S(C=O)2NR8-, -C(=0)-0-, -0-C(=0)-, -C(=NR8)NR9-, C(C=NOR8)NR9- , -NR8C(=NOR9)-, =N-0-, -0-N=CH- or a group aryl or heteroaryl of formula, (o), (p), (q), (r), (s), (t), (u), (v), (w), (x). The other substituents are defined in the claims.

Synthesis of coumermycin A1

A concise synthesis of the antibiotic coumermycin A1, a natural product isolated from streptomyces, was achieved. In a key step, a selectively protected noviose sugar was prepared from novobiocin through a transglycosylation reaction with aceto