16130-32-8

Upstream product

• 53-86-1 [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid 
• 873657-14-8 N-(4-chlorobenzoyl)-2-iodo-4-methoxyaniline 
• 191348-14-8 2-iodo-4-methoxylaniline 
• 122-01-0 4-chloro-benzoyl chloride 
• 873657-15-9 3-(tert-butyldimethylsiloxy)ethyl-1-(4-chlorobenzoyl)-5-methoxy-2-methylindole 

Downstream Products

• 138561-27-0 C₂₉H₃₅ClN₂O₇ 
• 22789-46-4 1-(4-chlorobenzoyl)-3-ethyl-5-methoxy-2-methylindole 
• 910457-38-4 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methylindol-3-yl}ethyl methanesulfonate 
• 1414702-04-7 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)ethyl 2-(1H-pyrrol-3-yl)acetate 
• 1376615-38-1 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetaldehyde O-methyl oxime 
• 1376615-37-0 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetaldehyde oxime 
• 138561-28-1 N-{2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-1-ethyl}hydroxylamine 
• 53-86-1 [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid 
• 1026313-08-5 C₃₀H₃₁ClN₄O₆S 
• 24438-49-1 <1-(4-chlorobenzoyl)-2-methyl-5-methoxyindol-3-yl>acetaldehyde 

Relevant academic research and scientific papers

Design of multifaceted antioxidants: Shifting towards anti-inflammatory and antihyperlipidemic activity

Oxidative stress and inflammation are two conditions that coexist in many multifactorial diseases such as atherosclerosis and neurodegeneration. Thus, the design of multifunctional compounds that can concurrently tackle two or more therapeutic targets is an appealing approach. In this study, the basic NSAID structure was fused with the antioxidant moieties 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHB), its reduced alcohol 3,5-di-tert-butyl- 4-hydroxybenzyl alcohol (BHBA), or 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), a hydrophilic analogue of α-tocopherol. Machine learning algorithms were utilized to validate the potential dual effect (anti-inflammatory and antioxidant) of the designed analogues. Derivatives 1-17 were synthesized by known esterification methods, with good to excellent yields, and were pharmacologically evaluated both in vitro and in vivo for their antioxidant and anti-inflammatory activity, whereas selected compounds were also tested in an in vivo hyperlipidemia protocol. Furthermore, the activity/binding affinity of the new compounds for lipoxygenase-3 (LOX-3) was studied not only in vitro but also via molecular docking simulations. Experimental results demonstrated that the antioxidant and anti-inflammatory activities of the new fused molecules were increased compared to the parent molecules, while molecular docking simulations validated the improved activity and revealed the binding mode of the most potent inhibitors. The purpose of their design was justified by providing a potentially safer and more efficient therapeutic approach for multifactorial diseases.

SYNTHESIS OF DEUTERATED ALDEHYDES

Described are methods for preparing a deuterated aldehyde using N-heterocyclic carbene catalysts in a solvent comprising D2O. The methods may be used to convert a wide variety of aldehydes (e.g., aryl, alkyl, or alkenyl aldehydes) to C-1 deuterated aldehydes under mild reaction conditions without functionality manipulation.

Photoinduced NaI-Promoted Radical Borylation of Alkyl Halides and Pseudohalides

A method for photoinduced NaI-promoted radical borylation of aliphatic halides and pseudohalides with bis(catecholato)diboron (B2cat2) as the boron source is introduced. The borylation reaction is operationally simple and shows high

Silver-Promoted Direct Phosphorylation of Bulky C(sp2)-H Bond to Build Fully Substituted β-Phosphonodehydroamino Acids

A general and practical cross-dehydrogenative coupling protocol between readily available trisubstituted α,β-dehydro α-amino carboxylic esters and H-phosphites is described. This C(sp2)-H phosphorylation reaction proceeds with absolute Z-selectivity promoted by silver salt in a radical relay manner. The bulky tetrasubstituted β-phosphonodehydroamino acids were obtained in grams and added new modules to the toolkit for peptide modifications.

DRUG DERIVATIVES

The present invention relates to derivatives of known active pharmaceutical compounds. These derivatives are differentiated from the parent active compound by virtue of being redox derivatives of the active compound. This means that one or more of the functional groups in the active compound has been converted to another group in one or more reactions which may be considered to represent a change of oxidation state. We refer to these compounds generally as redox derivatives. The derivatives of the invention may be related to the original parent active pharmaceutical compound by only a single step transformation, or may be related via several synthetic steps including one or more changes of oxidation state. In certain cases, the functional group obtained after two or more transformations may be in the same oxidation state as the parent active compound (and we include these compounds in our definition of redox derivatives). In other cases, the oxidation state of the derivative of the invention may be regarded as being different from that of the parent compound. In many cases, the compounds of the invention have inherent therapeutic activity on their own account. In some cases, this activity relative to the same target or targets of the parent compound is as good as or better than the activity which the parent compound has against the target or targets.

Synthesis of novel pyrrolyl-indomethacin derivatives

In the present work, we report the synthesis of the novel esters of indomethacin (IDMC) and an ester of reduced IDMC. For this purpose, IDMC is covalently bound by using a spacer chain to the pyrrole (Py) in the 3-position. The innovative pyrrole-indomethacin (3-Py-IDMC) derivates show no cytotoxic effects in primary calvarial osteoblasts. The designed IDMC derivates have been studied because they could be injected locally as a component of polymeric micro-particles. In fact, the new 3-Py-IDMC derivatives will assure their further polymerization since the 2- and 5-monomer positions are free.

DRUG DERIVATIVES

The present invention relates to derivatives of known active pharmaceutical compounds. These derivatives are differentiated from the parent active compound by virtue of being redox derivatives of the active compound. This means that one or more of the functional groups in the active compound has been converted to another group in one or more reactions which may be considered to represent a change of oxidation state. We refer to these compounds generally as redox derivatives. The derivatives of the invention may be related to the original parent active pharmaceutical compound by only a single step transformation, or may be related via several synthetic steps including one or more changes of oxidation state. In certain cases, the functional group obtained after two or more transformations may be in the same oxidation state as the parent active compound (and we include these compounds in our definition of redox derivatives). In other cases, the oxidation state of the derivative of the invention may be regarded as being different from that of the parent compound. In many cases, the compounds of the invention have inherent therapeutic activity on their own account. In some cases, this activity relative to the same target or targets of the parent compound is as good as or better than the activity which the parent compound has against the target or targets.

Structure-based design, synthesis, and biological evaluation of indomethacin derivatives as cyclooxygenase-2 inhibiting nitric oxide donors

Indomethacin, a nonselective cyclooxygenase (COX) inhibitor, was modified in three distinct regions in an attempt both to increase cyclooxygenase-2 (COX-2) selectivity and to enhance drug safety by covalent attachment of an organic nitrate moiety as a nitric oxide donor. A human whole-blood COX assay shows the modifications on the 3-acetic acid part of the indomethacin yielding an amide-nitrate derivative 32 and a sulfonamide-nitrate derivative 61 conferred COX-2 selectivity. Along with their respective des-nitrate analogs, for example, 31 and 62, the nitrates 32 and 61 were effective antiinflammatory agents in the rat air-pouch model. After oral dosing, though, only 32 increased nitrate and nitrite levels in rat plasma, indicating that its nitrate tether served as a nitric oxide donor in vivo. In a rat gastric injury model, examples 31 and 32 both show a 98% reduction in gastric lesion score compared to that of indomethacin. In addition, the nitrated derivative 32 inducing 85% fewer gastric lesions when coadministered with aspirin as compared to the combination of aspirin and valdecoxib.

2-METHYL INDOLE CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE

The invention describes compositions and kits comprising 2-methyl indole cyclooxygenase 2 (COX-2) selective inhibitors or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The 2-methyl indole cyclooxygenase 2 selective inhibitors can be optionally substituted with at least one nitric oxide enhancing group. The invention also provides methods for (a) treating inflammation, pain and fever; (b) treating gastrointestinal disorders and/or improving the gastrointestinal properties of COX-2 selective inhibitors; (c) facilitating wound healing; (d) treating renal and/or respiratory toxicities; (e) treating disorders resulting from elevated levels of cyclooxygenase-2; (f) improving the cardiovascular profile of COX-2 selective inhibitors; (g) treating diseases resulting from oxidative stress; (h) treating endothelial dysfunctions; (j) treating diseases caused by endothelial dysfunctions; (k) treating inflammatory disease states and/or disorders; (1) treating ophthalmic disorders; and (m) treating peripheral vascular diseases. The nitric oxide enhancing groups are organic nitrates, organic nitrites, nitrosothiols, thionitrites, thionitrates, NONOates, heterocyclic nitric oxide donors and/or nitroxides. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.

A new entry to the synthesis of 2,3-disubstituted indoles

(Chemical Equation Presented) The Stille coupling of N-acyl-2-iodoanilines with the 1-(tributylstannyl)-1-substituted allenes affected the successive one-step formation of the 2-methyl-3-substituted indoles. Alternatively, the other type of 2-alkyl-3-substituted indoles could be synthesized in a one-pot operation, which consists of the Stille coupling reaction with the 1-(tributylstannyl)-1,3-disubstituted allenes, followed by TBAF treatment. This procedure could be applied to the synthesis of indomethacin.