42016-91-1

Usage

Uses

Used in Organic Synthesis:
3,5-Diiodosalicyloyl chloride is utilized as a building block in organic synthesis for the preparation of various biologically active compounds and pharmaceutical products. Its unique structure and functional groups make it a valuable intermediate in the creation of new molecules with therapeutic potential.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 3,5-Diiodosalicyloyl chloride is used as a key component in the development of new drugs. Its presence in the molecular structure can contribute to the desired pharmacological properties, such as enhanced bioavailability, target specificity, and therapeutic efficacy.
Used in Dye and Pigment Production:
3,5-Diiodosalicyloyl chloride is employed as a raw material in the production of dyes and pigments. Its chemical properties allow for the creation of vibrant and stable colorants used in various applications, including textiles, plastics, and printing inks.
Used in Specialty Chemicals:
3,5-Diiodosalicyloyl chloride is also used in the manufacturing of specialty chemicals, where its unique characteristics can be leveraged to develop products with specific applications, such as in the fields of materials science, coatings, and adhesives.
Used in Medical Applications:
3,5-Diiodosalicyloyl chloride is used as an antimicrobial and antifungal agent in medical applications. Its ability to inhibit the growth of harmful microorganisms makes it a potential candidate for use in disinfectants, antiseptics, and other healthcare products.
Used in Agricultural Applications:
In agriculture, 3,5-Diiodosalicyloyl chloride is used for its antimicrobial and antifungal properties to protect crops from diseases and pests. Its application can help improve crop yields and ensure food safety by reducing the reliance on harmful chemical pesticides.

InChI:InChI=1/C7H3ClI2O2/c8-7(12)4-1-3(9)2-5(10)6(4)11/h1-2,11H

Upstream product

• 133-91-5 3,5-diiodosalicylic acid 

Downstream Products

• 50274-07-2 N-[5-chloro-4-(4-chlorobenzoyl)-2-methylphenyl]-3,5-diiodo-2-hydroxybenzamide 
• 212135-77-8 [2-[2-Chloro-4-(2-hydroxy-3,5-diiodo-benzoylamino)-5-methyl-phenyl]-2-(4-chloro-phenyl)-ethyl]-carbamic acid tert-butyl ester 
• 42016-80-8 2-hydroxy-3,5-diiodo-benzoic acid-(3,4-dichloro-anilide) 
• 61438-44-6 N-{4-[α-cyano-α-(4-methoxyphenyl)methyl]-3-(trifluoromethyl)phenyl}-2-hydroxy-3,5-diiodobenzamide 
• 61438-32-2 N-{4-[α-cyano-α-(2,6-dichlorophenyl)methyl]-3-(trifluoromethyl)phenyl}-2-hydroxy-3,5-diiodobenzamide 
• 57808-65-8 closantel 
• 61438-35-5 N-{4-[α-(4-chlorophenyl)-α-cyanomethyl]-3-cyanophenyl}-2-hydroxy-3,5-diiodobenzamide 
• 61438-38-8 N-[4-(α-cyano-α-phenylmethyl)phenyl]-2-hydroxy-3,5-diiodobenzamide 
• 61438-43-5 N-{4-[α-(4-chlorphenyl)-α-cyanomethyl]-3-(trifluoromethyl)phenyl}-2-hydroxy-3,5-diiodobenzamide 
• 61438-61-7 N-{5-chloro-4-[α-(4-chlorophenyl)-α-cyanomethyl]-2-(1,1-dimethylethyl)phenyl}-2-hydroxy-3,5-diiodobenzamide 
• 292637-51-5 C₁₄H₁₁I₂NO₂ 
• 14437-46-8 N-(4-Chlorophenyl)-2-hydroxy-3,5-diiodobenzamide 
• 290366-63-1 C₁₄H₁₁I₂NO₃ 
• 19503-64-1 2-hydroxy-3,5-diiodo-N-phenyl-benzamide 

Relevant academic research and scientific papers

Development of a novel probe for measuring drug binding to the F1*S variant of human alpha 1-acid glycoprotein

A novel probe was developed to measure drug association with the F1*S variant of the human serum protein alpha 1-acid glycoprotein (AGP). The molecule 2-hydroxy-3,5-diiodo-N-[2(diethylamino)ethyl]benzamide (DEDIC) binds to AGP, quenching its native fluorescence. This quenching was fitted to a two-site model giving apparent dissociation constants of 0.049 ± 0.005 and 12 ± 2 μM (mean ± SEM). Quenching of each of the separate variants of AGP by DEDIC was itself described by a two-site model, giving for the F1*S variant KD(F1*S)1 = 0.041 ± 0.010 μM and KD(F1*S)2 = 29 ± 7 μM; and for the A variant KD(A)1 = 0.31 ± 0.18 μM and KD(A)2 = 8.8 ± 0.7 μM. The utility of DEDIC in probing drug interactions with isolated variants was demonstrated in competition experiments with the model drugs amitriptyline and bupivacaine. In addition, the selectivity of DEDIC for variant F1*S rendered it capable of probing the binding of drugs (including the variant A-selective drug amitriptyline) to F1*S in a mixture of variants, such as occurs naturally in whole AGP. DEDIC is unique as an F1*S variant-selective probe of drug binding to whole AGP that is also sufficiently soluble to serve as a probe of drug binding to the lower affinity sites on isolated A and F1*S variants.

INHIBITORS OF PROTEIN ARGININE DEIMINASE 1 AND METHODS OF PREPARATION AND USE THEREOF

The invention provides novel inhibitors or inactivators of protein arginine deiminase 1, pharmaceutical compositions and methods of use thereof. The invention also relates to molecular probes based on such compounds and methods of use thereof.

Iodinated 1,2-diacylhydrazines, benzohydrazide-hydrazones and their analogues as dual antimicrobial and cytotoxic agents

Hydrazide-hydrazones have been described as a scaffold with antimicrobial and cytotoxic activities as well as iodinated compounds. A resistance rate of bacterial and fungal pathogens has increased considerably. That is why we synthesized and screened twenty-two iodinated hydrazide-hydrazones 1 and 2, ten 1,2-diacylhydrazines 3 and their three reduced analogues 4 for their antibacterial, antifungal, and cytotoxic properties. Hydrazide-hydrazones were prepared by condensation of 4-substituted benzohydrazides with 2-/4-hydroxy-3,5-diiodobenzaldehydes, diacylhydrazines from identical benzohydrazides and 3,5-diiodosalicylic acid via its chloride. These compounds were investigated in vitro against eight bacterial and eight fungal strains. The derivatives were found potent antibacterial agents against Gram-positive cocci including methicillin-resistant Staphylococcus aureus with the lowest values of minimum inhibitory concentrations (MIC) of 7.81 μM. Four compounds inhibited also human pathogenic fungi (MIC of ≥1.95 μM). The derivatives had different degrees of cytotoxicity for HepG2 and HK-2 cell lines (IC50 values from 11.72 and 26.80 μM, respectively). Importantly, normal human cells exhibited lower sensitivity. The apoptotic effect was also investigated. In general, the presence of 3,5-diiodosalicylidene scaffold (compounds 1) is translated into enhanced both antimicrobial and cytotoxic properties whereas its 4-hydroxy isomers 2 share a low biological activity. N′-Benzoyl-2-hydroxy-3,5-diiodobenzohydrazides 3 have a non-homogeneous activity profile. Focusing on 4-substituted benzohydrazide part, the presence of an electron-withdrawing group (F, Cl, CF3, NO2) was found to be beneficial.

Halogen Bonding Increases the Potency and Isozyme Selectivity of Protein Arginine Deiminase 1 Inhibitors

Protein arginine deiminases (PADs) hydrolyze the side chain of arginine to form citrulline. Aberrant PAD activity is associated with rheumatoid arthritis, multiple sclerosis, lupus, and certain cancers. These pathologies established the PADs as therapeutic targets and multiple PAD inhibitors are known. Herein, we describe the first highly potent PAD1-selective inhibitors (1 and 19). Detailed structure–activity relationships indicate that their potency and selectivity is due to the formation of a halogen bond with PAD1. Importantly, these inhibitors inhibit histone H3 citrullination in HEK293TPAD1 cells and mouse zygotes with excellent potency. Based on this scaffold, we also developed a PAD1-selective activity-based probe that shows remarkable cellular efficacy and proteome selectivity. Based on their potency and selectivity we expect that 1 and 19 will be widely used chemical tools to understand PAD1 biology.

METHODS FOR TREATMENT OF CLOSTRIDIUM DIFFICILE INFECTIONS

In this study, we capitalized on the antimicrobial property and low oral bioavailability of known salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen. The anthelmintics displayed excellent potency against C. difficile strains 630 and 4118 (with MIC values as low as 0.06 - 0.13 μg/mL for rafoxanide) via a membrane depolarization mechanism, interestingly, closantel, rafoxanide and compound 8 were bactericidal against logarithmic- and stationary-phase cultures of the BI/NAP1/027 strain 4118. Further evaluation of the salicylanilides showed their preferential activity against Gram-positive over Gram-negative bacteria. Moreover, the salicylanilides were non-hemolytic and were non- toxic to mammalian cell lines HepG2 and HEK 293T/17 within the range of their in vitro MICs and MBCs. The salicylanilide anthelmintics exhibit desirable bactericidal and pharmacokinetic properties and are amenable to repositioning as anti-C. difficile agents.

Scaffold Diversity Inspired by the Natural Product Evodiamine: Discovery of Highly Potent and Multitargeting Antitumor Agents

A critical question in natural product-based drug discovery is how to translate the product into drug-like molecules with optimal pharmacological properties. The generation of natural product-inspired scaffold diversity is an effective but challenging strategy to investigate the broader chemical space and identify promising drug leads. Extending our efforts to the natural product evodiamine, a diverse library containing 11 evodiamine-inspired novel scaffolds and their derivatives were designed and synthesized. Most of them showed good to excellent antitumor activity against various human cancer cell lines. In particular, 3-chloro-10-hydroxyl thio-evodiamine (66c) showed excellent in vitro and in vivo antitumor efficacy with good tolerability and low toxicity. Antitumor mechanism and target profiling studies indicate that compound 66c is the first-in-class triple topoisomerase I/topoisomerase II/tubulin inhibitor. Overall, this study provided an effective strategy for natural product-based drug discovery. (Figure Presented).

Dual protonophore-chitinase inhibitors dramatically affect O. Volvulus molting

The L3-stage-specific chitinase OvCHT1 has been implicated in the development of Onchocerca volvulus, the causative agent of onchocerciasis. Closantel, a known anthelmintic drug, was previously discovered as a potent and specific OvCHT1 inhibitor. As closantel is also a known protonophore, we performed a simple scaffold modulation to map out the structural features that are relevant for its individual or dual biochemical roles. Furthermore, we present that either OvCHT1 inhibition or protonophoric activity was capable of affecting O. volvulus L3 molting and that the presence of both activities in a single molecule yielded more potent inhibition of the nematode's developmental process.

Design, synthesis, and biological activities of closantel analogues: Structural promiscuity and its impact on onchocerca volvulus

Onchocerciasis, or river blindness, is a neglected tropical disease that affects more than 37 million people worldwide, primarily in Africa and Central and South America. We have disclosed evidence that the larval-stage-specific chitinase, OvCHT1, may be a potential biological target for affecting nematode development. On the basis of screening efforts, closantel, a known anthelmintic drug, was discovered as a potent and highly specific OvCHT1 inhibitor. Originally, closantel's anthelmintic mode of action was believed to rely solely on its role as a proton ionophore; thus, the impact of each of its biological activities on O. volvulus L3moltingwas investigated. Structure-activity relationship studies on an active closantel fragment are detailed, and remarkably, by use of a simple salicylanilide scaffold, compounds acting only as protonophores or chitinase inhibitors were identified. From these data, unexpected synergistic protonophore and chitinase inhibition activities have also been found to be critical for molting in O. volvulus L3 larvae.

Identification of halosalicylamide derivatives as a novel class of allosteric inhibitors of HCV NS5B polymerase

Halosalicylamide derivatives were identified from high-throughput screening as potent inhibitors of HCV NS5B polymerase. The subsequent structure and activity relationship revealed the absolute requirement of the salicylamide moiety for optimum activity. Methylation of either the hydroxyl group or the amide group of the salicylamide moiety abolished the activity while the substitutions on both phenyl rings are acceptable. The halosalicylamide derivatives were shown to be non-competitive with respect to elongation nucleotide and demonstrated broad genotype activity against genotype 1-3 HCV NS5B polymerases. Inhibitor competition studies indicated an additive binding mode to the initiation pocket that is occupied by the thiadiazine class of compounds and an additive binding mode to the elongation pocket that is occupied by diketoacids, but a mutually exclusive binding mode with respect to the allosteric thumb pocket that is occupied by the benzimidazole class of inhibitors. Therefore, halosalicylamides represent a novel class of allosteric inhibitors of HCV NS5B polymerase.

ANTHELMINTIC BENZO[D]ISOXAZOLYL BENZAMIDE DERIVATIVES

The present invention is concerned with novel anthelmintic N-benzo[d]isoxazol-6-yl-benzamide derivatives and the pharmaceutically acceptable acid addition salts thereof, compositions comprising said novel Compounds, processes for preparing said Compounds and compositions, and the use thereof as a medicine, in particular in treatment, control and prevention of endo- and ectoparasite infections in warm-blooded animals.