1670-82-2

Usage

Uses

Indole-6-carboxylic acid is used as a reactant in the preparation of D-glutamic acid-based inhibitors of E. coli MurD ligase. It is also used as a reactant for the preparation of indolylindazoles and indolylpyrazolopyridines, which are interleukin-2 inducible T cell kinase inhibitors.
Used in Pharmaceutical Industry:
Indole-6-carboxylic acid is used as a reactant for the preparation of amide conjugates with ketoprofen, which act as inhibitors of Gli1-mediated transcription in the Hedgehog pathway. It is also used as a reactant for the preparation of piperazine-bisamide analogs, which are human growth hormone secretagogue receptor antagonists for the treatment of obesity.
Used in Antiviral Applications:
Indole-6-carboxylic acid is used as a reactant for the preparation of pyridinyl carboxylates via esterification with chlorohydroxypyridine, which are SARS-CoV 3CL proinhibitors.
Used in Anticoagulant Applications:
Indole-6-carboxylic acid is used as a reactant for the preparation of (indolecarbonyl)-D-phenylglycinamide amides, which are factor Xa inhibitors.

Synthesis Reference(s)

Journal of Medicinal Chemistry, 35, p. 2419, 1992 DOI: 10.1021/jm00091a010

InChI:InChI=1/C9H7NO2/c11-9(12)7-2-1-6-3-4-10-8(6)5-7/h1-5,10H,(H,11,12)/p-1

Upstream product

• 15861-36-6 1H-Indole-6-carbonitrile 
• 50820-65-0 indole-6-carboxylic acid methyl ester 
• 106851-27-8 3-Amino-4-(2,2-dimethoxy-ethyl)-benzoic acid 
• 7356-11-8 4-methyl-3-nitro-benzoic acid methyl ester 
• 104447-80-5 (E)-1-(dimethylamino)-2-[4-(methoxycarbonyl)-2-nitrophenyl]ethene 
• 14719-83-6 methyl 3-nitro-4-chlorobenzoate 
• 106851-22-3 4-(2,2-Dimethoxy-ethyl)-3-nitro-benzoic acid 
• 106867-41-8 methyl 4-(2-(trimethylsilyl)ethynyl)-3-nitrobenzoate 
• 96-98-0 4-methyl-3-nitrobenzoic acid 
• 93247-78-0 methyl 1H-indole-7-carboxylate 

Downstream Products

• 104447-78-1 6-indole 
• 955132-88-4 N-((1-(4-iodophenyl)-1H-imidazol-4-yl)methyl)-1H-indole-6-carboxamide 
• 251106-49-7 4-benzylpiperidinyl-indole-6-carboxamide 
• 50820-65-0 indole-6-carboxylic acid methyl ester 
• 494799-16-5 3-(cyclohex-1-en-1-yl)-1H-indole-6-carboxylic acid 
• 1204-32-6 methyl 1-methylindole-6-carboxylate 
• 219507-60-5 N₄-Acetyl-N₂-(4-t-butylbenzoyl)-N₁-(6-indolylcarbonyl)-1,2,4-benzenetriamine 
• 319474-35-6 3-formyl-1H-indazole-6-carboxylic acid 
• 1224699-05-1 3-chloro-1H-indole-5-carboxylic acid 
• 400653-16-9 1-Cbz-3-[(6-indolyl)carbonyl]aminopyrrolidine 
• 1221403-84-4 C₂₁H₂₀BrN₃O₂ 
• 1221403-83-3 C₂₁H₂₀BrN₃O₂ 

Relevant academic research and scientific papers

Nickel-Catalyzed Dearomative Arylboration of Indoles: Regioselective Synthesis of C2- And C3-Borylated Indolines

Indole dearomatization is an important strategy to access indolines: a motif present in a variety of natural products and biologically active molecules. Herein, a method for transition-metal catalyzed regioselective dearomative arylboration of indoles to

Indole carboxylic acid esters of melampomagnolide B are potent anticancer agents against both hematological and solid tumor cells

A series of novel, heteroaryl carboxylic acid conjugates of the sesquiterpene melampomagnolide-B (MMB, 3) has been evaluated as antitumor agents against an NCI panel of 64 human hematopoetic and solid tumor cell lines. The indole-3-acrylic acid conjugate 7j and the indole-3-carboxylic acid conjugate 7k were found to be the most potent analogs in the series. Compounds 7j and 7k exhibited remarkable growth inhibition, with GI50 values in the range 0.03–0.30?μM and 0.04–0.28?μM, respectively, against the cell lines in the leukemia sub-panel, and GI50 values of 0.05–0.40?μM and 0.04–0.61?μM, respectively, against 90% of the solid tumor cell lines in the NCI panel. Compound 7a was particularly effective against the sub-panel of breast cancer cell lines with GI50 values in the range 50 value of 720?nM, and exhibited the greatest cytotoxicity against a collection of primary AML stem cell specimens, which included a specimen that was unresponsive to PTL, affording EC50 values in the range 0.33–1.0?μM in three out of four specimens. The results from this study provide further evidence that analogs of the sesquiterpene MMB can be designed to afford molecules with significantly improved anticancer activity. Thus, both 7j and 7k are considered potential lead molecules in the search for new anticancer agents that can be used as treatments for both hematopoetic and solid tumors.

Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D2 Receptor Through Fragmentation of a Bitopic Ligand

Recently, we have demonstrated that N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652) (1) adopts a bitopic pose at one protomer of a dopamine D2 receptor (D2R) dimer to negatively modulate the binding of dopamine at the other protomer. The 1H-indole-2-carboxamide moiety of 1 extends into a secondary pocket between the extracellular ends of TM2 and TM7 within the D2R protomer. To target this putative allosteric site, we generated and characterized fragments that include and extend from the 1H-indole-2-carboxamide moiety of 1. N-Isopropyl-1H-indole-2-carboxamide (3) displayed allosteric pharmacology and sensitivity to mutations of the same residues at the top of TM2 as was observed for 1. Using 3 as an "allosteric lead", we designed and synthesized an extensive fragment library to generate novel SAR and identify N-butyl-1H-indole-2-carboxamide (11d), which displayed both increased negative cooperativity and affinity for the D2R. These data illustrate that fragmentation of extended compounds can expose fragments with purely allosteric pharmacology.

HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK

Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.

New adenosine receptor ligands and uses thereof

The present invention provides new compounds with high affinity for adenosine A2A receptors. It also provides antagonists of adenosine A2A receptors and their use as medicaments for the treatment and/or prophylaxis of diseases and di

Novel indolyl derivatives which are L-CPT1 inhibitors

The invention is concerned with novel heterobicyclic derivatives of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, A, X and Y are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit L-CPT1 and can be used as medicaments.

1,3,6-Trisubstituted indoles as peptidoleukotriene antagonists: Benefits of a second, polar, pyrrole substituent

1,6-Substituted and 3,5-substituted indoles and indazoles containing acylamino and N-arylsulfonyl amide appendages are potent antagonists of the peptidoleukotrienes LTD4 and LTE4. A compound from the 3,5-substituted indole series, N-[4-[[5-[[(cyclopentyloxy)carbonyl]amino]-1-methylindol-3- yl]methyl]-3-methoxybenzoyl]-2-methyl-benzenesulfonamide (ICI 204,219), is undergoing clinical evaluation for asthma. Two new elements of structural diversity were introduced to this series of antagonists. An investigation of pyrrole substituents in the 1,6-substituted indoles demonstrated that substitution at C-2 was detrimental to biological activity, but the incorporation of hydrophilic groups at C-3 was beneficial. The introduction of a propionamide moiety at C-3 enhanced activity by 1 order of magnitude; N- [4-[[6-(cyclopentylacetamido)-3-[2-(N-methylcarbamoyl)ethyl]indol-1- yl]methyl]-3-methoxybenzoyl]benzenesulfonamide (15c) has a pK(B) of 10.7 at the LTD4 receptor on guinea pig trachea. Modifications of the acylamino portion of the disubstituted antagonists demonstrated that a transposition of the amide CO and NH atoms was viable. N-Cyclopentylmethyl amides in both the 1,6- and 3,5-disubstituted indole series were 1 order of magnitude less potent than the corresponding cyclopentylacetamides. In both series this potency loss could be regained by the incorporation of a propionamide substituent at either C-3 or N-1, respectively. For example, N-[4-[[6-[N- (cyclopentylmethyl)carbamoyl]-3-[2-(pyrrolidin-1-ylcarbonyl)ethyl]indol-1- yl]methyl]-3-methoxybenzoyl]-2-methylbenzenesulfonamide (39c) has a pK(B) of 9.5.

Heterocyclic carboxamides

This invention provides a series of novel heterocyclic carboxamides of formula I in which the group --Y--Z is selected from --C(Ra)=C, --N=C, and --CH(Ra)--CH and the other radicals have the meanings defined in the following specification. The compoun

6-SUBSTITUTED INDOLES FROM o-HALONITROBENZENES

o-Chloro- and o-bromonitrobenzenes are efficiently converted to 6-substituted indoles in a four step synthesis, proceeding through o-trimethylsilylethynylnitrobenzenes, o-nitrophenylacetaldehyde dimethylacetals and o-aminophenylacetaldehyde dimethylacetal