199604-34-7

Upstream product

• 3770-50-1 2-carbethoxyindole 
• 104-83-6 1-Chloro-4-(chloromethyl)benzene 
• 622-95-7 4-chlorobenzyl bromide 
• 1477-50-5 Indole-2-carboxylic acid 

Downstream Products

• 1401619-07-5 5-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)octahydro-1H-pyrrolo[3,4-c]pyridin-1-one 
• 1401619-08-6 2-benzyl-5-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)octahydro-1H-pyrrolo[3,4-c]pyridin-1-one 
• 1401619-11-1 (1-(4-chlorobenzyl)-1H-indol-2-yl)(4-(piperidin-1-ylmethyl)piperidin-1-yl)methanone 
• 1401619-12-2 (4-benzylpiperazin-1-yl)(1-(4-chlorobenzyl)-1H-indol-2-yl)methanone 
• 1401618-79-8 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)-N-((2,3-dihydrofuro[2,3-c]pyridin-3-yl)methyl)piperidine-4-carboxamide 
• 1401618-55-0 (1-(4-chlorobenzyl)-1H-indol-2-yl)(4-(pyrrolidine-1-carbonyl)piperidin-1-yl)methanone 
• 1401619-06-4 rac-1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)-N-((2,3-dihydro-1H-inden-1-yl)methyl)piperidine-4-carboxamide 
• 1401619-05-3 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)-N-(1-(2,3-dihydro-1H-inden-2-yl)ethyl)piperidine-4-carboxamide 
• 1401619-04-2 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)-N-((2,3-dihydro-1H-inden-2-yl)methyl)piperidine-4-carboxamide 
• 1401619-03-1 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)-N-(2,3-dihydro-1H-inden-2-yl)piperidine-4-carboxamide 
• 1401619-02-0 rac-(1-(4-chlorobenzyl)-1H-indol-2-yl)(4-(3-phenylpyrrolidine-1-carbonyl)piperidin-1-yl)methanone 
• 1401619-01-9 (1-(4-chlorobenzyl)-1H-indol-2-yl)(4-(2-phenylpyrrolidine-1-carbonyl)piperidin-1-yl)methanone 
• 1401619-00-8 (1-(4-chlorobenzyl)-1H-indol-2-yl)(4-(isoindoline-2-carbonyl)piperidin-1-yl)methanone 
• 1401618-82-3 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)-N-(4-isopropylphenethyl)piperidine-4-carboxamide 

Relevant academic research and scientific papers

Identification of indole scaffold-based dual inhibitors of NOD1 and NOD2

NOD1 and NOD2 are important members of the pattern recognition receptor family and play a crucial role within the context of innate immunity. However, overactivation of NODs, especially of NOD1, has also been implicated in a number of diseases. Surprisingly, NOD1 remains a virtually unexploited target in this respect. To gain additional insight into the structure–activity relationships of NOD1 inhibitors, a series of novel analogs has been designed and synthesized and then screened for their NOD1-inhibitory activity. Selected compounds were also investigated for their NOD2-inhibitory activity. Two compounds 4 and 15, were identified as potent mixed inhibitors of NOD1 and NOD2, displaying a balanced inhibitory activity on both targets in the low micromolar range. The results obtained have enabled a deeper understanding of the structural requirements for NOD1 and NOD2 inhibition.

Novel inhibitors of neurotropic alphavirus replication that improve host survival in a mouse model of acute viral encephalitis

Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoxicity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells. Furthermore, we demonstrate improved outcomes (both symptoms and survival) following treatment with indole analogue 9h (CCG-203926) in an in vivo mouse model of alphaviral encephalitis that closely correlate with the enantiospecific in vitro antiviral activity. These results represent a substantial advancement in the early preclinical development of a promising class of novel antiviral drugs against virulent neurotropic alphaviruses.

ARBOVIRUS INHIBITORS AND USES THEREOF

The present invention relates to chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides compounds as inhibitors of arboviruses.

AMIDE COMPOUND

[Problems] A compound, which is useful as an active ingredient of a pharmaceutical composition, for example, a pharmaceutical composition for treating chronic renal failure and/or diabetic nephropathy, is provided. [Solving Means] The present inventors have conducted extensive studies on a compound having an EP4 receptor antagonistic activity, and confirmed that the amide compound of the present invention has an EP4 receptor antagonistic activity, thereby completing the present invention. The amide compound of the present invention has an EP4 receptor antagonistic activity, and can be used as an active ingredient of a pharmaceutical composition for preventing and/or treating various EP4-related diseases, for example, chronic renal failure and/or diabetic nephropathy, and the like.

Factor Xa inhibitors based on a 2-carboxyindole scaffold: SAR of neutral P1 substituents

A series of novel, highly potent 2-carboxyindole-based factor Xa inhibitors is described. Structural requirements for neutral ligands, which bind in the S1 pocket of factor Xa were investigated with the 2-carboxyindole scaffold. This privileged fragment assembly approach yielded a set of equipotent, selective inhibitors with structurally diverse neutral P1 substituents.

N-Benzylindole-2-carboxylic acids: Potent functional antagonists of the CCR2b chemokine receptor

Screening of the corporate database led to the discovery of a novel series of N-benzylindole-2-carboxylic acid CCR2b chemokine receptor antagonists. These compounds demonstrate high affinity and functional inhibition of the CCR2b receptor. A discussion of

Monocyte chemoattractant protein-1 inhibitor compounds

The invention concerns the use of a compound of the formula (I) in which Z, X, T, A, R1, R2, p and q have any of the meanings defined herein, and their pharmaceutically acceptable salts or in vivo hydrolysable esters, in the treatment of a disease or condition mediated by monocyte chemoattractant protein-1 (MCP-1). Certain of the components of formula (I) are novel and are provided, together with pharmaceutical compositions thereof, as further features of the invention.

Synthesis of Substituted 3-Amino-4-cyano-1-oxo-1,2,5,10-tetrahydroazepino[3,4-b]indoles

The preparation of 3-amino- and 3-dialkylamino-4-cyanoazepino[3,4-b]indoles bearing substituents on the aromatic nucleus and N10 is outlined. Starting from suitable substituted ethyl 3-formylindole-2-carboxylates 2, condensation with malononitrile (3) and subsequent sodium borohydride-reduction yielded ethyl 3-(2,2-dicyanoethyl)indole-2-carboxyIates 5 and 19, respectively, which were cyclized in boiling alkoxides to 3-alkoxy-4-cyanoazepino[3,4-b]indoles 10,11,20 and 21. This sequence constitutes a novel and flexible route to functional azepino[3,4-b]indoles. The aminolysis of 10,11,20 and 21 with different amines and ammonia yielded the title compounds which were screened for their possible biological activity.