82302-32-7

Upstream product

• 10236-60-9 (2,3-dichlorophenyl)acetic acid 

Downstream Products

• 366456-31-7 N-(2-benzoyl-4-nitrophenyl)-2-(2,3-dichlorphenyl)acetamide 
• 849069-39-2 2-(2,3-dichloro-phenyl)-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)-ethanone 
• 1434517-96-0 (R)-4-benzyl-3-(2-(2,3-dichlorophenyl)acetyl)oxazolidin-2-one 
• 1434517-76-6 (R)-2-(2,3-dichlorophenyl)-N-(2-(pyridine-4-yl)benzo[d]oxazol-5-yl)propanamide 
• 1239016-39-7 (R)-2-(2,3-dichlorophenyl)propanoic acid 
• 1434517-97-1 (4R)-4-benzyl-3-(2-(2,3-dichlorophenyl)propanoyl)oxazolidin-2-one 
• 1428640-56-5 C₁₂H₉Cl₂N₅ 
• 1428640-45-2 C₁₅H₁₆Cl₂N₄ 
• 956026-43-0 1-tert-butyl-3-(2,3-dichlorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 
• 1428640-32-7 C₁₅H₁₅Cl₂N₅ 
• 1026186-53-7 Methyl 4-(2,3-dichlorophenyl)-3-oxobutyrate 
• 366456-63-5 N-[3-benzoyl-4-[2-(2,3-dichlorophenyl)acetylamino]phenyl]-N^α-tert-butyloxycarbonyl-S-tritylcysteinamide 
• 366456-49-7 N-(4-amino-2-benzoylphenyl)-2-(2,3-dichlorphenyl)acetamide 
• 1446450-25-4 2-(2,3-dichlorophenyl)-1-hydroxyethylidenebisphosphonic acid 

Relevant academic research and scientific papers

Discovery of a potent protein kinase D inhibitor: insights in the binding mode of pyrazolo[3,4-d]pyrimidine analogues

In this study, we set out to rationally optimize PKD inhibitors based on the pyrazolo[3,4-d]pyrimidine scaffold. The lead compound for this study was 1-NM-PP1, which was previously found by us and others to inhibit PKD. In our screening we identified one compound (3-IN-PP1) displaying a 10-fold increase in potency over 1-NM-PP1, opening new possibilities for specific protein kinase inhibitors for kinases that show sensitivity towards pyrazolo[3,4-d]pyrimidine derived compounds. Interestingly the observed SAR was not in complete agreement with the commonly observed binding mode where the pyrazolo[3,4-d]pyrimidine compounds are bound in a similar fashion as PKD's natural ligand ATP. Therefore we suggest an alternate binding mode where the compounds are flipped 180 degrees. This possible alternate binding mode for pyrazolo[3,4-d]pyrimidine based compounds could pave the way for a new class of specific protein kinase inhibitors for kinases sensitive towards pyrazolo[3,4-d]pyrmidines.

COMPOUNDS AND METHODS FOR TREATING MAMMALIAN GASTROINTESTINAL MICROBIAL INFECTIONS

Disclosed are compounds and pharmaceutically acceptable salts thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound selectively inhibits a parasitic IMPDH versus a host IMPDH. Also disclosed are pharmaceutical compositions comprising one or more compounds of the invention. Related methods of treating various parasitic and bacterial infections in mammals are disclosed. Moreover, the compounds may be used alone or in combination with other therapeutic or prophylactic agents, such as anti-virals, anti-inflammatory agents, antimicrobials and immunosuppressants.

Optimizing small molecule inhibitors of calcium-dependent protein kinase 1 to prevent infection by toxoplasma gondii

Toxoplasma gondii is sensitive to bulky pyrazolo [3,4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1). Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1). The potency of PP analogues in inhibiting CDPK1 enzyme activity in vitro (low nM IC50 values) and blocking parasite growth in host cell monolayers in vivo (low μM EC 50 values) were highly correlated and occurred in a CDPK1-specific manner. Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity. Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model. Collectively, the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis and perhaps related parasitic diseases.

Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5′-monophosphate dehydrogenase

Cryptosporidium parvum is an enteric protozoan parasite that has emerged as a major cause of diarrhea, malnutrition, and gastroenteritis and poses a potential bioterrorism threat. C. parvum synthesizes guanine nucleotides from host adenosine in a streamlined pathway that relies on inosine 5′-monophosphate dehydrogenase (IMPDH). We have previously identified several parasite-selective C. parvum IMPDH (CpIMPDH) inhibitors by high-throughput screening. In this paper, we report the structure-activity relationship (SAR) for a series of benzoxazole derivatives with many compounds demonstrating CpIMPDH IC50 values in the nanomolar range and >500-fold selectivity over human IMPDH (hIMPDH). Unlike previously reported CpIMPDH inhibitors, these compounds are competitive inhibitors versus NAD +. The SAR study reveals that pyridine and other small heteroaromatic substituents are required at the 2-position of the benzoxazole for potent inhibitory activity. In addition, several other SAR conclusions are highlighted with regard to the benzoxazole and the amide portion of the inhibitor, including preferred stereochemistry. An X-ray crystal structure of a representative E·IMP·inhibitor complex is also presented. Overall, the secondary amine derivative 15a demonstrated excellent CpIMPDH inhibitory activity (IC 50 = 0.5 ± 0.1 nM) and moderate stability (t1/2 = 44 min) in mouse liver microsomes. Compound 73, the racemic version of 15a, also displayed superb antiparasitic activity in a Toxoplasma gondii strain that relies on CpIMPDH (EC50 = 20 ± 20 nM), and selectivity versus a wild-type T. gondii strain (200-fold). No toxicity was observed (LD 50 > 50 μM) against a panel of four mammalian cells lines.

Synthesis and evaluation of effective inhibitors of plant δ1-pyrroline-5-carboxylate reductase

Analogues of previously studied phenyl-substituted aminomethylene- bisphosphonic acids were synthesized and evaluated as inhibitors of Arabidopsis thaliana δ1-pyrroline-5-carboxylate reductase. With the aim of improving their effectiveness, two main modifications were introduced into the inhibitory scaffold: the aminomethylenebisphosphonic moiety was replaced with a hydroxymethylenebisphosphonic group, and the length of the molecule was increased by replacing the methylene linker with an ethylidene chain. In addition, chlorine atoms in the phenyl ring were replaced with various other substituents. Most of the studied derivatives showed activity in the micromolar to millimolar range, with two of them being more effective than the lead compound, with concentrations inhibiting 50% of enzyme activity as low as 50 μM. Experimental evidence supporting the ability of these inhibitors to interfere with proline synthesis in vivo is also shown.

PHENOXYACETIC ACID DERIVATIVES USEFUL FOR TREATING RESPIRATORY DISEASES

The invention relates to substituted phenoxyacetic acids as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation.Formula (I)

COMPOSITIONS USEFUL AS INHIBITORS OF PROTEIN KINASES

The present invention relates to compounds useful of inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.