39787-83-2

Usage

InChI:InChI=1/C8H6ClNO4/c1-14-7-4-5(10(12)13)2-3-6(7)8(9)11/h2-4H,1H3

Upstream product

• 2597-56-0 4-nitro-o-anisic acid 
• 101084-96-2 2-methoxy-4-nitrobenzonitrile 
• 39106-79-1 methyl 2-methoxy-4-nitrobenzoate 
• 79-37-8 oxalyl dichloride 
• 619-19-2 2-hydroxy-4-nitrobenzoic acid 

Downstream Products

• 91568-19-3 N-(2-methoxy-4-nitro-benzoyl)-DL-threonine 
• 62726-03-8 2-methoxy-4-nitrobenzamide 
• 476615-23-3 N-(2-diethylamino-ethyl)-4-nitro-2-methoxybenzamide 
• 102471-83-0 2-methoxy-4-nitro-benzoic acid-(3-diethylamino-2-hydroxy-propylamide) 
• 110663-15-5 2-methoxy-4-nitro-benzoic acid-(3-diethylamino-propylamide) 
• 129175-86-6 diethyl N-(2-methoxy-4-nitrobenzoyl)-L-glutamate 
• 247237-91-8 7-chloro-1-(2-methoxy-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 109721-91-7 2-methoxy-4-nitro-benzoic acid-[3-(2-methyl-piperidino)-propylamide]; hydrochloride 
• 190276-81-4 (2-methoxy-4-nitro-phenyl)-(5,6,7,8-tetrahydro-thieno[3,2-b]azepin-4-yl)-methanone 

Relevant academic research and scientific papers

Exploiting the HSP60/10 chaperonin system as a chemotherapeutic target for colorectal cancer

Over the past few decades, an increasing variety of molecular chaperones have been investigated for their role in tumorigenesis and as potential chemotherapeutic targets; however, the 60 kDa Heat Shock Protein (HSP60), along with its HSP10 co-chaperone, have received little attention in this regard. In the present study, we investigated two series of our previously developed inhibitors of the bacterial homolog of HSP60/10, called GroEL/ES, for their selective cytotoxicity to cancerous over non-cancerous colorectal cells. We further developed a third “hybrid” series of analogs to identify new candidates with superior properties than the two parent scaffolds. Using a series of well-established HSP60/10 biochemical screens and cell-viability assays, we identified 24 inhibitors (14%) that exhibited > 3-fold selectivity for targeting colorectal cancer over non-cancerous cells. Notably, cell viability EC50 results correlated with the relative expression of HSP60 in the mitochondria, suggesting a potential for this HSP60-targeting chemotherapeutic strategy as emerging evidence indicates that HSP60 is up-regulated in colorectal cancer tumors. Further examination of five lead candidates indicated their ability to inhibit the clonogenicity and migration of colorectal cancer cells. These promising results are the most thorough analysis and first reported instance of HSP60/10 inhibitors being able to selectively target colorectal cancer cells and highlight the potential of the HSP60/10 chaperonin system as a viable chemotherapeutic target.

Synthesis of N-(2-diethylamino-ethyl)-4-(4-fluoro-benzamido)-2-methoxybenzamide (desiodo-MIP-1145) by coupling technique and its radioiodination: a potential melanoma imaging agent

Radioiodinated MIP-1145, which specifically targets melanin, is an ideal candidate for targeted therapy of melanoma. An analogue of MIP-1145 lacking the iodo-substituent (desiodo-MIP-1145) was synthesized as a labeling precursor in three simple steps. The radioiodination of desiodo-MIP-1145 by iodine-125 was carried out via an electrophilic substitution reaction. An optimization study for the iodination reaction was carried out. The labeled compound was isolated and purified by means of electrophoresis and HPLC. The maximum radiochemical yield, 76%, was obtained with radiochemical purity greater than 99%. The log P value for [125I]MIP-1145 was measured as 4.5.

IMIDAZO-OXADIAZOLE AND IMIDAZO-THIADIAZOLE DERIVATIVES

The present invention provides compounds of Formula (I) used as Amyloid beta lowering agent for the treatment of neurodegenerative diseases.

Efficient synthesis of anacardic acid analogues and their antibacterial activities

Anacardic acid derivatives exhibit a broad range of biological activities. In this report, an efficient method for the synthesis of anacardic acid derivatives was explored, and a small set of salicylic acid variants synthesised retaining a constant hydrophobic element (a naphthyl tail). The naphthyl side chain was introduced via Wittig reaction and the aldehyde installed using directed ortho-metalation reaction of the substituted o-anisic acids. The failure of ortho-metalation using unprotected carboxylic acid group compelled us to use directed ortho-metalation in which a tertiary amide was used as a strong ortho-directing group. In the initial route, tertiary amide cleavage during final step was challenging, but cleaving the tertiary amide before Wittig reaction was beneficial. The Wittig reaction with protected carboxylic group (methyl ester) resulted in side-products whereas using sodium salt resulted in higher yields. The novel compounds were screened for antibacterial activity and cytotoxicity. Although substitution on the salicylic head group enhanced antibacterial activities they also enhanced cytotoxicity.

Oligophenylenaminones as scaffolds for α-helix mimicry

The design and synthesis of small molecule α-helix mimetics has been a productive field over the past decade. These compounds have performed well in a variety of biological systems as functional disruptors of α-helix- mediated protein-protein interactions. In our studies we have continued to develop novel, more biologically compatible scaffolds, which are often easier to assemble and capable of mimicking longer and/or more diverse helices. To this end, we have constructed a new series of i, i+4, i+7 α-helix mimics based on the enaminone scaffold. These molecules represent a step forward in the pursuit of idealized monofacial α-helix mimetics.

Aminothiazoles as γ-secretase modulators

We herein report the discovery of a new γ-secretase modulator class with an aminothiazole core starting from a HTS hit (3). Synthesis and SAR of this series are discussed. These novel compounds demonstrate moderate to good in vitro potency in inhibiting amyloid beta (Aβ) peptide production. Overall c-secretase is not inhibited but the formation of the aggregating, toxic Aβ42 peptide is shifted to smaller non-aggregating Ab peptides. Compound 15 reduced brain Abβ42 in vivo in APPSwe transgenic mice at 30 mg/kg p.o.

Discovery of phosphoric acid mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)- 3,5-difluorobenzoylimino]-thiazol-3-ylmethyl} Ester (Lu AA47070): A phosphonooxymethylene prodrug of a potent and selective hA2A receptor antagonist

The discovery and structure-activity relationship of a series of hA 2A receptor antagonists is described. Compound 28 was selected from the series as a potent and selective compound and was shown to be efficacious in an in vivo model of Parkinson's disease. It had acceptableADME properties; however, the low intrinsic solubility of this compound was limiting for its developability, because the oral bioavailability from dosing in suspension was significantly lower than the oral bioavailability from solution dosage. As a consequence, prodrugs of 28 were prepared with dramatically increased aqueous solubility. The prodrugs efficiently delivered 28 into systemic circulation, with no detectable levels of prodrug in plasma samples. From this investigation, we selected 32 (Lu AA47070), a phosphonooxymethylene prodrug of 28, as a drug candidate.

Synthesis and Antimicrobial Evaluation of Nitazoxanide-Based Analogues: Identification of Selective and Broad Spectrum Activity

A library composed of nitazoxanide-based analogues was synthesized and assayed for increased antibacterial efficacy against the pyruvate-ferredoxin oxidoreductase (PFOR) using microorganisms Helicobacter pylori, Campylobacter jejuni and Clostridium difficile. Derivatives were found to recapitulate and improve activity against these organisms and select analogues were tested for their ability to disrupt the PFOR enzyme directly. The library was also screened for activity against staphylococci and resulted in the identification of analogues capable of inhibiting both staphylococci and all PFOR organisms at low micromolar minimum inhibitory concentrations with low toxicity to human foreskin cells. Hitting them where it hurts! A library of nitazoxanide-based analogues was synthesized and assayed for antibacterial efficacy against pyruvate-ferredoxin oxidoreductase (PFOR) utilizing microorganisms. Derivatives were found to recapitulate and improve activity against these organisms, and select analogues were screened for activity against staphylococci resulting in the identification of analogues capable of inhibiting both staphylococci and all PFOR organisms at low micromolar minimum inhibitory concentrations.

NOVEL SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS AS GAMMA SECRETASE MODULATORS

The present invention is concerned with substituted bicyclic heterocyclic compounds of Formula (I) wherein Het1, Het2, A1, A2, A3 and A4 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

2-ARYLCARBOXAMIDE-NITROGENEOUS HETEROCYCLE COMPOUND

A compound represented bv the formula [I]: [wherein R1 and R2 are the same or different and each represents C1-6 alkyl, C3-8 cycloalkyl, et al; R3a, R3b, and R4 are the same or different and each represents hydrogen, C1-6 alkyl, et al; X represents -N-, -CH-, et al; Y1 represents a single bond, C1-3 alkylene, et al; Y2 represents C1-4 alkylene, oxy(C1-4 alkylene), et al; Ar1 represents a monocyclic aromatic carbocyclic group, monocyclic aromatic heterocyclic group, et al; and Ar2 represents a 5- or 6-membered aromatic carbocyclic group, aromatic heterocyclic group, et al]. This compound functions as a melanin-concentrating hormone receptor antagonist and is useful as, e.g., a therapeutic agent for obesity, et al.