4136-97-4

Basic information

• Product Name: METHYL 4-AMINOSALICYLATE
• Synonyms: METHYL 4-AMINOSALICYLATE;METHYL 4-AMINO-2-HYDROXYBENZENECARBOXYLATE;METHYL 4-AMINO-2-HYDROXYBENZOATE;P-AMINO METHYL SALICYLATE;4-amino-2-hydroxy-benzoicacimethylester;amino-salicylicacimethylester;methylp-aminosalicylate;p-aminosalicylicacidmethylester
• CAS NO: 4136-97-4
• Molecular Formula: C₈H₉NO₃
• Molecular Weight: 167.16
• EINECS: 223-958-3
• Mol File: 4136-97-4.mol

Chemical Properties

• Melting Point: 120-123°C
• Boiling Point: 329.5 °C at 760 mmHg
• Flash Point: 153.1 °C
• Appearance: /Powder
• Density: 1.305±0.06 g/cm3 (20 ºC 760 Torr)
• Vapor Pressure: 9.21E-05mmHg at 25°C
• Refractive Index: 1.605
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 9.81±0.10(Predicted)
• Water Solubility: Slightly soluble in water.
• CAS DataBase Reference: METHYL 4-AMINOSALICYLATE(CAS DataBase Reference)
• NIST Chemistry Reference: METHYL 4-AMINOSALICYLATE(4136-97-4)
• EPA Substance Registry System: METHYL 4-AMINOSALICYLATE(4136-97-4)

Safety Data

• RTECS: VO1683000
• HazardClass: IRRITANT
• Hazardous Substances Data: 4136-97-4(Hazardous Substances Data)

Usage

Uses

Methyl 4-aminosalicylate is used as pharmaceutical intermediate.

InChI:InChI=1/C8H9NO3/c1-12-8(11)6-3-2-5(9)4-7(6)10/h2-4,10H,9H2,1H3

Upstream product

• 186581-53-3 diazomethane 
• 65-49-6 4-Aminosalicylic acid 
• 13684-28-1 2-hydroxy-4-nitro-benzoic acid methyl ester 
• 67-56-1 methanol 
• 2597-56-0 4-nitro-o-anisic acid 
• 144-55-8 sodium hydrogencarbonate 
• 7440-44-0 pyrographite 
• 1336-21-6 ammonium hydroxide 
• 7664-93-9 sulfuric acid 
• 77-78-1 dimethyl sulfate 
• 619-19-2 2-hydroxy-4-nitrobenzoic acid 
• 39614-82-9 2-hydroxy-4-nitrobenzoyl chloride 

Downstream Products

• 6950-58-9 2-hydroxy-4-(2-hydroxy-ethylamino)-benzoic acid methyl ester 
• 114554-96-0 N-(3-hydroxy-4-methoxycarbonyl-phenyl)-maleamic acid 
• 105106-30-7 N-(3-hydroxy-4-methoxycarbonyl-phenyl)-succinamic acid 
• 4093-28-1 methyl 4-acetamido-2-hydroxybenzoate 
• 38059-73-3 5-acetylamino-2-methoxycarbonyl-1-acetoxybenzene 
• 28744-43-6 4-amino-2-hydroxy-benzoic acid-(2-hydroxy-ethylamide) 
• 858479-96-6 4-[(N-acetyl-sulfanilyl)-amino]-2-hydroxy-benzoic acid methyl ester 
• 54245-53-3 4-(2,2-dichloro-acetylamino)-2-hydroxy-benzoic acid methyl ester 
• 108128-42-3 2-amino-5-hydroxy-benzothiazole-6-carboxylic acid methyl ester 
• 98953-36-7 2-hydroxy-4-thioureido-benzoic acid methyl ester 
• 59393-77-0 5-amino-2-hydroxy-benzoic acid amide 
• 35352-91-1 4-aminosalicylhydroxamic acid 
• 5985-89-7 4-amino-2-hydroxybenzamide 
• 6946-29-8 4-aminosalicylic acid hydrazide 

Relevant articles and documents

FePd alloy nanoparticles assembled on reduced graphene oxide as a catalyst for selective transfer hydrogenation of nitroarenes to anilines using ammonia borane as a hydrogen source

Addressed herein is a facile protocol for the synthesis and assembly of FePd alloy nanoparticles (NPs) on reduced graphene oxide (rGO) to catalyze transfer hydrogenation of nitroarenes to anilines under ambient conditions. 3.5 nm FePd NPs were synthesized by using a surfactant-assisted co-reduction method that allowed NP composition control. FePd NPs were then assembled on rGO via a liquid-phase self-assembly method and studied as catalysts to promote hydrogen transfer from ammonia borane (AB) to numerous nitroarenes in aqueous methanol solutions at room temperature. Among three different rGO-FePd, the commercial C-Pd and rGO-Pd catalysts tested, rGO-Fe48Pd52 showed the highest efficiency in converting nitroarenes to anilines, achieving >90% yields within 10-20 min of reactions. Our work demonstrates an efficient and selective approach to transfer hydrogenation of nitroarenes to anilines.

Serendipitous discovery of potent human head and neck squamous cell carcinoma anti-cancer molecules: A fortunate failure of a rational molecular design

Histone deacetylase inhibitors (HDACis) play an important role as valuable drugs targeted to cancer therapy: several HDACis are currently being tested in clinical trials. Two new potential HDACis 1a and 1d, characterized by the presence of a biphenyl-4-sulfonamide group as a connection unit between the N-{4-[(E)-(2-formylhydrazinylidene)methyl]-3-hydroxyphenyl} and the 2-hydroxy-N-(trifluoroacetyl)benzamide moiety, respectively, as two zinc-binding group (ZBG), have been designed, synthesized and tested for their biological activity. Surprisingly, compounds 1a and 12, this last exclusively obtained in place of 1d, exhibited a very low HDAC inhibitory activity. A serendipitous assay of these two compounds, conducted on three chemoresistant cell lines of head and neck squamous cell carcinoma (HNSCC), showed their antiproliferative activity at low nanomolar concentrations, better than cisplatin. In vitro, biological assays indicated that compounds 1a and 12 are able to increase acetylation of histone H3 and to interfere with the PI3K/Akt/mTOR pathway by inducing the accumulation of PTEN protein.

Synthesis, colon-targeted studies and pharmacological evaluation of an anti-ulcerative colitis drug 4-Aminosalicylic acid-β-O-glucoside

A glycoside prodrug of 4-aminosalicylic acid (4-ASA) with d-glucose was synthesized for targeted drug delivery to inflammatory bowel. The in vitro assessment of 4-aminosalicylic acid-β-O-glucoside (4-ASA-Glu) as a colon-specific prodrug was studied using colitis rat with the healthy one as control. The stability studies in aqueous buffers (pH 1.2, 6.8 and 7.4) indicated that 4-ASA-Glu was stable over a period of 12 h. The incubation of 4-ASA-Glu with cecal or colonic contents of healthy rats at 37 °C released 4-ASA in 77 or 80% of the dose in 12 h, respectively. The amount of 4-ASA liberated from the incubation of 4-ASA-Glu in cecal or colonic contents of colitis rats at 37 °C was 69 or 79% in 12 h respectively, while less than 9% 4-ASA was detected from the incubation of 4-ASA-Glu with the homogenates of stomach or small intestine. The curative effect of 4-ASA-Glu was evaluated in 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) induced experimental colitis model in male Sprague-Dawley (SD) rats. It was found that 4-ASA-Glu possess significantly ameliorate effect than sulfasalazine, oral 4- and 5-aminosalicylic acid.

Synthesis and biological evaluation of orally active prodrugs and analogs of para-aminosalicylic acid (PAS)

Tuberculosis (TB) is one of the world's most deadly infectious diseases resulting in nearly 1.3 million deaths annually and infecting nearly one-quarter of the population. para-Aminosalicylic acid (PAS), an important second-line agent for treating drug-resistant Mycobacterium tuberculosis, has moderate bioavailability and rapid clearance that necessitate high daily doses of up to 12 g per day, which in turn causes severe gastrointestinal disturbances presumably by disruption of gut microbiota and host epithelial cells. We first synthesized a series of alkyl, acyloxy and alkyloxycarbonyloxyalkyl ester prodrugs to increase the oral bioavailability and thereby prevent intestinal accumulation as well as undesirable bioactivation by the gut microbiome to non-natural folate species that exhibit cytotoxicity. The pivoxyl prodrug of PAS was superior to all of the prodrugs examined and showed nearly quantitative absorption. While the conceptually simple prodrug approach improved the oral bioavailability of PAS, it did not address the intrinsic rapid clearance of PAS mediated by N-acetyltransferase-1 (NAT-1). Thus, we next modified the PAS scaffold to reduce NAT-1 catalyzed inactivation by introduction of groups to sterically block N-acetylation and fluorination of the aryl ring of PAS to attenuate N-acetylation by electronically deactivating the para-amino group. Among the mono-fluorinated analogs prepared, 5-fluoro-PAS, exhibited the best activity and an 11-fold decreased rate of inactivation by NAT-1 that translated to a 5-fold improved exposure as measured by area-under-the-curve (AUC) following oral dosing to CD-1 mice. The pivoxyl prodrug and fluorination at the 5-position of PAS address the primary limitations of PAS and have the potential to revitalize this second-line TB drug.

New dual ATP-competitive inhibitors of bacterial DNA gyrase and topoisomerase IV active against ESKAPE pathogens

The rise in multidrug-resistant bacteria defines the need for identification of new antibacterial agents that are less prone to resistance acquisition. Compounds that simultaneously inhibit multiple bacterial targets are more likely to suppress the evolution of target-based resistance than monotargeting compounds. The structurally similar ATP binding sites of DNA gyrase and topoisomerase Ⅳ offer an opportunity to accomplish this goal. Here we present the design and structure-activity relationship analysis of balanced, low nanomolar inhibitors of bacterial DNA gyrase and topoisomerase IV that show potent antibacterial activities against the ESKAPE pathogens. For inhibitor 31c, a crystal structure in complex with Staphylococcus aureus DNA gyrase B was obtained that confirms the mode of action of these compounds. The best inhibitor, 31h, does not show any in vitro cytotoxicity and has excellent potency against Gram-positive (MICs: range, 0.0078–0.0625 μg/mL) and Gram-negative pathogens (MICs: range, 1–2 μg/mL). Furthermore, 31h inhibits GyrB mutants that can develop resistance to other drugs. Based on these data, we expect that structural derivatives of 31h will represent a step toward clinically efficacious multitargeting antimicrobials that are not impacted by existing antimicrobial resistance.

Synthesis and biological evaluation of salicylic acid analogues of celecoxib as a new class of selective cyclooxygenase-1 inhibitor

A series of salicylic acid analogues of celecoxib where the phenylsulfonamide moiety in the structure of celecoxib is replaced by salicylic acid moiety was synthesized and tested for in vitro cyclooxygenase (COX)-1 and COX-2 enzyme inhibition. Among the series, 5-substituted-2-hydroxy-benzoic acid analogues (7a–7h) generally showed better inhibitory activities on both enzymes than 4-substituted-2-hydroxy-ben-zoic acid analogues (12a–12h). In particular, the chloro analogue 7f which had the highest inhibitory effect (IC50=0.0057μM) to COX-1 with excellent COX-1 selectivity (SI=768) can be classified as a new potent and selective COX-1 inhibitor. The high inhibitory potency of 7f was rationalized through the docking simulation of this analogue in the active site of COX-1 enzyme.

Fluoroquinolone derivative of p-aminosalicylic acid as well as intermediate, preparation method and application of fluoroquinolone derivative

The invention discloses a fluoroquinolone derivative of p-aminosalicylic acid as well as an intermediate, a preparation method and application of the fluoroquinolone derivative, and belongs to the technical field of drug synthesis. The structural formula of the fluoroquinolone derivative of p-aminosalicylic acid is shown in the specification. An in-vitro antibacterial activity determination resultshows that the target compound has good inhibition activity on bacteria as a whole; most compounds have good antibacterial activity on pichia pastoris, and some compounds have activity even strongerthan that of positive control drugs; the inhibitory activity of the two intermediates on mycobacterium smegmatis is higher than that of most positive control drugs; part of the target compounds have inhibitory activity on citrus germs. The fluoroquinolone derivative of p-aminosalicylic acid and the intermediate have potential application prospects in the fields of bacterium resistance, fungus resistance, tuberculosis resistance and citrus pathogen resistance.

P-aminosalicylic acid fluoroquinolone derivative as well as intermediate, preparation method and application thereof

The invention discloses a p-aminosalicylic acid fluoroquinolone derivative and an intermediate, a preparation method and application thereof, and belongs to the technical field of drug synthesis. Thestructural formula of the p-aminosalicylic acid fluoroquinolone derivative is shown in the specification. In-vitro activity determination results show that part of fluoroquinolone aminosalicylate derivatives (compounds for short) and intermediates have inhibition effects on mycobacterium smegmatis; the compounds and intermediates have good inhibition activity on common pathogenic bacteria as a whole; most compounds and intermediates have better antibacterial activity on pichia pastoris as a whole; part of the compounds have good inhibitory activity on citrus canker pathogens. The p-aminosalicylic acid fluoroquinolone derivative and the intermediate thereof have potential application prospects in the fields of tuberculosis resistance, bacteria resistance, fungus resistance and citrus pathogen resistance.

Cystobactamid 507: Concise Synthesis, Mode of Action, and Optimization toward More Potent Antibiotics

Lack of new antibiotics and increasing antimicrobial resistance are among the main concerns of healthcare communities nowadays, and these concerns necessitate the search for novel antibacterial agents. Recently, we discovered the cystobactamids—a novel natural class of antibiotics with broad-spectrum antibacterial activity. In this work, we describe 1) a concise total synthesis of cystobactamid 507, 2) the identification of the bioactive conformation using noncovalently bonded rigid analogues, and 3) the first structure–activity relationship (SAR) study for cystobactamid 507 leading to new analogues with high metabolic stability, superior topoisomerase IIA inhibition, antibacterial activity and, importantly, stability toward the resistant factor AlbD. Deeper insight into the mode of action revealed that the cystobactamids employ DNA minor-groove binding as part of the drug–target interaction without showing significant intercalation. By designing a new analogue of cystobactamid 919-2, we finally demonstrated that these findings could be further exploited to obtain more potent hexapeptides against Gram-negative bacteria.

NEW CLASS OF DNA GYRASE AND/OR TOPOISOMERASE IV INHIBITORS WITH ACTIVITY AGAINST GRAM-POSITIVE AND GRAM-NEGATIVE BACTERIA

The present invention relates to compounds having a structure of general formula (I), processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment of bacterial infections in humans and warm-blooded animals.