107754-19-8

Basic information

• Product Name: 4-[[5-[[(Cyclopentyloxy)carbonyl]aMino]-1-Methyl-1H-indol-3-yl]Methyl]-3-Methoxy-benzoic Acid Methyl Ester
• Synonyms: 4-[[5-[[(Cyclopentyloxy)carbonyl]aMino]-1-Methyl-1H-indol-3-yl]Methyl]-3-Methoxy-benzoic Acid Methyl Ester
• CAS NO: 107754-19-8
• Molecular Formula: C₂₅H₂₈N₂O₅
• Molecular Weight: 438.5161
• Product Categories: Heterocycles, Impurities, Inhibitors, Pharmaceuticals, Intermediates & Fine Chemicals, Sulfur & Selenium Compounds
• Mol File: 107754-19-8.mol

Chemical Properties

• Melting Point: 128-132 °C
• Boiling Point: 581.9±50.0 °C(Predicted)
• Appearance: /
• Density: 1.25±0.1 g/cm3(Predicted)
• PKA: 14.52±0.43(Predicted)
• CAS DataBase Reference: 4-[[5-[[(Cyclopentyloxy)carbonyl]aMino]-1-Methyl-1H-indol-3-yl]Methyl]-3-Methoxy-benzoic Acid Methyl Ester(CAS DataBase Reference)
• NIST Chemistry Reference: 4-[[5-[[(Cyclopentyloxy)carbonyl]aMino]-1-Methyl-1H-indol-3-yl]Methyl]-3-Methoxy-benzoic Acid Methyl Ester(107754-19-8)
• EPA Substance Registry System: 4-[[5-[[(Cyclopentyloxy)carbonyl]aMino]-1-Methyl-1H-indol-3-yl]Methyl]-3-Methoxy-benzoic Acid Methyl Ester(107754-19-8)

Safety Data

• Hazardous Substances Data: 107754-19-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-[[5-[[(Cyclopentyloxy)carbonyl]amino]-1-Methyl-1H-indol-3-yl]Methyl]-3-Methoxy-benzoic Acid Methyl Ester is used as an impurity in the production of Zafirlukast (Z125000) for the treatment of asthma and allergic rhinitis. As an impurity, it is important to monitor and control its presence in the final product to ensure the safety and efficacy of the medication.
In the pharmaceutical industry, the control and management of impurities like 4-[[5-[[(Cyclopentyloxy)carbonyl]amino]-1-Methyl-1H-indol-3-yl]Methyl]-3-Methoxy-benzoic Acid Methyl Ester are crucial for maintaining the quality and safety of drugs. 4-[[5-[[(Cyclopentyloxy)carbonyl]aMino]-1-Methyl-1H-indol-3-yl]Methyl]-3-Methoxy-benzoic Acid Methyl Ester serves as an example of the need for thorough analysis and purification processes in the development and manufacturing of pharmaceutical products.

Upstream product

• 70264-94-7 methyl 4-(bromomethyl)-3-methoxybenzoate 
• 7151-68-0 3-methoxy-p-toluic acid 
• 29906-67-0 1-methyl-5-nitro-1H-indole 
• 3556-83-0 methyl 4-methyl-3-methoxybenzoate 
• 6146-52-7 5-nitroindole 
• 107754-15-4 3-methoxy-4-(1-methyl-5-nitroindol-3-ylmethyl)-benzoic acid methyl ester 
• 107786-36-7 4-[5-nitro-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid methylester 
• 50715-28-1 cyclopentyl chloroformate 
• 107754-14-3 methyl 4-<(5-amino-1-methylindol-3-yl)methyl>-3-methoxybenzoate 

Downstream Products

• 126502-34-9 {3-[4-(2-Bromo-benzenesulfonylaminocarbonyl)-2-methoxy-benzyl]-1-methyl-1H-indazol-5-yl}-carbamic acid cyclopentyl ester 
• 126502-33-8 {3-[4-(2-Chloro-benzenesulfonylaminocarbonyl)-2-methoxy-benzyl]-1-methyl-1H-indazol-5-yl}-carbamic acid cyclopentyl ester 
• 126502-32-7 {3-[2-Methoxy-4-(toluene-2-sulfonylaminocarbonyl)-benzyl]-1-methyl-1H-indazol-5-yl}-carbamic acid cyclopentyl ester 
• 107753-78-6 ZAFIRLUKAST 
• 107753-53-7 N-[4-[5-(cyclopentyloxycarbonyl)amino-1-methylindazol-3-ylmethyl]-3-methoxybenzoyl]benzenesulphonamide 
• 107754-31-4 cyclopentyl N-[3-({4-[(benzenesulfonyl)carbamoyl]-2-methoxyphenyl}methyl)-1-methyl-1H-indol-5-yl]carbamate 
• 107786-91-4 methyl 4-[2-(acetoxyimino)-2-[5-(cyclopentyloxycarbonyl)amino-2-(methylamino)phenyl]ethyl]-3-methoxybenzoate 
• 107786-93-6 methyl 4-<2-<5-<<(cyclopentyloxy)carbonyl>amino>-2-(methylamino)phenyl>-2-(hydroxyimino)ethyl>-3-methoxybenzoate 
• 107786-90-3 methyl 4-<<5-<<(cyclopentyloxy)carbonyl>amino>-1-methylindazol-3-yl>methyl>-3-methoxybenzoate 
• 107786-94-7 4-[5-(cyclopentyloxycarbonyl)amino-1-methylindazol-3-ylmethyl]-3-methoxybenzoic acid 
• 107786-92-5 methyl 4-<2-<5-<<(cyclopentyloxy)carbonyl>amino>-2-(N-formyl-N-methylamino)phenyl>-2-oxoethyl>-3-methoxybenzoate 
• 107754-20-1 4-[5-(cyclopentyloxycarbonylamino)-1-methyl-indol-3-yl-methyl]-3-methoxy-benzoic acid 

Relevant articles and documents

Dual Farnesoid X Receptor/Soluble Epoxide Hydrolase Modulators Derived from Zafirlukast

The nuclear farnesoid X receptor (FXR) and the enzyme soluble epoxide hydrolase (sEH) are validated molecular targets to treat metabolic disorders such as non-alcoholic steatohepatitis (NASH). Their simultaneous modulation in vivo has demonstrated a triad of anti-NASH effects and thus may generate synergistic efficacy. Here we report dual FXR activators/sEH inhibitors derived from the anti-asthma drug Zafirlukast. Systematic structural optimization of the scaffold has produced favorable dual potency on FXR and sEH while depleting the original cysteinyl leukotriene receptor antagonism of the lead drug. The resulting polypharmacological activity profile holds promise in the treatment of liver-related metabolic diseases.

Boosting Anti-Inflammatory Potency of Zafirlukast by Designed Polypharmacology

Multitarget design offers access to bioactive small molecules with potentially superior efficacy and safety. Particularly multifactorial chronic inflammatory diseases demand multiple pharmacological interventions for stable treatment. By minor structural changes, we have developed a close analogue of the cysteinyl-leukotriene receptor antagonist zafirlukast that simultaneously inhibits soluble epoxide hydrolase and activates peroxisome proliferator-activated receptor γ. The triple modulator exhibits robust anti-inflammatory activity in vivo and highlights the therapeutic potential of designed multitarget agents.

Breathing new life into West Nile virus therapeutics; discovery and study of zafirlukast as an NS2B-NS3 protease inhibitor

The West Nile virus (WNV) has spread throughout the world causing neuroinvasive diseases with no treatments available. The viral NS2B-NS3 protease is essential for WNV survival and replication in host cells and is a promising drug target. Through an enzymatic screen of the National Institute of Health clinical compound library, we report the discovery of zafirlukast, an FDA approved treatment for asthma, as an inhibitor for the WNV NS2B-NS3 protease. Zafirlukast was determined to inhibit the protease through a mixed mode mechanism with an IC50 value of 32 μM. A structure activity relationship study of zafirlukast revealed the cyclopentyl carbamate and N-aryl sulfonamide as structural elements crucial for NS2B-NS3 protease inhibition. Replacing the cyclopentyl with a phenyl improved inhibition, resulting in an IC50 of 22 μM. Experimental and computational docking analysis support the inhibition model of zafirlukast and analogs binding at an allosteric site on the NS3 protein, thereby disrupting the NS2B cofactor from binding, resulting in protease inhibition.

An improved and scalable process for zafirlukast: An asthma drug

An improved and scalable process for the large-scale production of zafirlukast (Accolate), an important drug for asthma, is discussed along with impurity and scale-up-related issues.

SUBSTITUTED INDOLES

Disclosed herein are substituted indole cysteinyl leukotriene receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

PROCESSES FOR PREPARING ZAFIRLUKAST

An improved process for the preparation of substantially pure zafirlukast and pharmaceutical compositions thereof.

Evolution of a series of peptidoleukotriene antagonists: Synthesis and structure/activity relationships of 1,3,5-substituted indoles and indazoles

1,3,5-Substituted indoles and indazoles have been studied as receptor antagonists of the peptidoleukotrienes. The best of these compounds generally had a methyl group at the N1 position, a [(cyclopentyloxy)carbonyl]amino or 2-cyclopentylacetamido or N'-cyclopentylureido group at the C-5 position, and an arysulfonyl amide group as part of the acidic chain at the C-3 position of the ring. Such compounds had in vitro dissociation constants K(B) in the range 10-9-10-11 M on guinea pig trachea against LTE4 as agonist and inhibition constants (K(i)) ≤ 10-9 M on guinea pig parenchymal membranes against [3H]LTD4. A number of compounds were orally effective at doses ≤1 mg/kg in blocking LTD4-induced 'dyspnea' in guinea pigs. Compound 45 [N-[4-[[5-[[cyclopentyloxy)carbonyl]amino]-1-methylindol-3-yl]methyl]- 3-methoxybenzoyl]-2-methyl]benzenesulfonamide, ICI 204,219; pK(B) = 9.67 ± 0.13, K(i) = 0.3 ± 0.03 nM, po ED50 = 0.3 mg/kg] is currently under clinical investigation for asthma. In the indole series, certain alkylsulfonyl amides possessing a 3-cyanobenzyl substituent at the N-1 position (60, 61) were produced that had K(B) ≤ 10-9 M on guinea pig trachea.

Indole and indazole keto sulphones as leukotriene antagonists

This invention provides a series of novel keto sulfones of formula I STR1 in which the group =A-- is selected from =C(Ra)-- and =N-- and the other radicals have the meanings defined in the following specification. The compounds of formula I are leukotriene antagonists. The invention also provides pharmaceutically acceptable salts of the formula I compounds; pharmaceutical compositions containing the formula I compound, or their salts, for use in the treatment of, for example, allergic or inflammatory diseases, or endotoxic or traumatic shock conditions; and processes for the manufacture of the formula I compounds, as well as intermediates for use in such manufacture.

Heterocyclic amide derivatives and pharmaceutical use

The invention concerns novel, pharmaceutically useful, amide derivatives of certain benzoheterocyclylalkanoic acids (and related tetrazoles and acylsulphonamides) of the formula I and salts thereof, wherein the radicals R1, R2, L, X, Y, Z, A1, Q, A2 and M have the meanings set out in the specification. The invention also includes pharmaceutical compositions incorporating a formula I compound or a salt thereof, a process for the manufacture of the said compound, together with intermediates for use in the latter process. STR1