5584-18-9

Usage

Uses

Used in Coordination Chemistry:
Picolinic acid, 6-amino-, hydrazide (7CI,8CI) is used as a ligand in the synthesis of metal complexes. This application is crucial for various purposes in coordination chemistry, as metal complexes play a significant role in areas such as catalysis, materials science, and supramolecular chemistry.
Used in Metal Toxicity Treatment:
As a chelating agent, picolinic acid, 6-amino-, hydrazide (7CI,8CI) has been studied for its potential use in the treatment of metal toxicity. Chelation therapy is essential for the removal of toxic metal ions from the body, and Picolinic acid, 6-amino-, hydrazide (7CI,8CI) may offer a promising approach to addressing metal-related health issues.
Used in Antimicrobial Applications:
Picolinic acid, 6-amino-, hydrazide (7CI,8CI) has been investigated for its antimicrobial properties, making it a potential candidate for use in the development of new antimicrobial agents. This application is particularly relevant in the context of increasing antibiotic resistance and the need for novel antimicrobial compounds.
Used in Pharmaceutical Industry:
The potential use of picolinic acid, 6-amino-, hydrazide (7CI,8CI) in pharmaceuticals is another area of interest. Its diverse chemical properties and potential applications in various fields make it a promising candidate for the development of new drugs and therapeutic agents.

Upstream product

• 36052-26-3 methyl 6-aminopyridine-2-carboxylate 

Downstream Products

• 1448428-05-4 5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide 
• 1262043-91-3 6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-amine 

Relevant academic research and scientific papers

Discovery of CNS-Penetrant Apoptosis Signal-Regulating Kinase 1 (ASK1) Inhibitors

Apoptosis signal-regulating kinase 1 (ASK1) is a key mediator in the apoptotic and inflammatory cellular stress response. To investigate the therapeutic value of modulating this pathway in neurological disease, we have completed medicinal chemistry studie

Structure-guided optimization of a novel class of ASK1 inhibitors with increased sp3 character and an exquisite selectivity profile

Apoptosis Signal-Regulating Kinase-1 (ASK1) is a known member of the Mitogen-Activated Protein Kinase Kinase Kinase (MAP3K) family and upon stimulation will activate the p38- and JNK-pathways leading to cardiac apoptosis, fibrosis, and hypertrophy. Using Structure-Based Drug Design (SBDD) in parallel with deconstruction of a published compound, a novel series of ASK1 inhibitors was optimized, which incorporated a saturated heterocycle proximal to the hinge-binding motif. This yielded a unique chemical series with excellent selectivity across the broader kinome, and desirable drug-like properties. The lead compound (10) is highly soluble and permeable, and exhibits a cellular EC50 = 24 nM and Kd 50 ≤ 500 nM for only eight of them. This paper will describe the design hypotheses behind this series, key data points during the optimization phase, as well as a possible structural rationale for the kinome selectivity. Based on crystallographic data, the presence of an aliphatic cycle adjacent to the hinge-binder in the active site of the protein kinase showed up in 5000 structures in the Protein Data Bank, potentially conferring the selectivity seen in this series.

Structure-based discovery of 1H-indole-2-carboxamide derivatives as potent ASK1 inhibitors for potential treatment of ulcerative colitis

Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase (MAPK) family, is implicated in many human diseases. Here, we describe the structural optimization of hit compound 7 and conduct further structure-activity relationship (SAR) studies that result in the development of compound 19 with a novel indole-2-carboxamide hinge scaffold. Compound 19 displays potent anti-ASK1 kinase activity and stronger inhibitory effect on ASK1 in AP1-HEK293 cells than previously described ASK1 inhibitor GS-4997. Besides improved in vitro activity, compound 19 also exhibits an appropriate in vivo PK profile. In a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC), compound 19 shows significant anti-UC efficacy and markedly attenuates DSS-induced body weight loss, colonic shortening, elevation in disease activity index (DAI) and inflammatory cell infiltration in colon tissues. Mechanistically, compound 19 represses the phosphorylation of ASK1-p38/JNK signaling pathways and suppresses the overexpression of inflammatory cytokines. Together, these findings suggest that ASK1 inhibitors can potentially be used as a therapeutic strategy for UC.

FORMAMIDE COMPOUND, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF

The present invention relates to a formamide compound, a preparation method therefor and an application thereof. The structure of the compound is shown in formula (I), and the definition of each variable in the formula is as provided in the description. The compound is capable of inhibiting the activity of ASK1 kinase. The compound of the present invention may be used in the treatment/prevention of diseases associated with ASK1 kinase, such as inflammatory diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, neurodegenerative diseases, cancers and other diseases.

ASK1 INHIBITING AGENTS

Provided are compounds of Formula (I): Formula (I), including compounds of Formulas (II), (III), (IV), (V) and (VI), wherein X, R1, R2, R3, R4 and n are as defined herein,and pharmaceutically acceptable salts thereof, and methods for their use and production. These compounds can be useful, e.g., in the treatment of disorders responsive to the inhibition of apoptosis signal-regulating kinase 1 (ASK1).

2,3-DIHYDRO-1H-PYRROLO[3,4-C]PYRIDIN-1-ONE DERIVATIVES AS HPK1 INHIBITORS FOR THE TREATMENT OF CANCER

This invention relates to 2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one derivatives of general Formula (I) and pharmaceutically acceptable salts thereof, as hematopoietic progenitor kinase 1 (HPK1) inhibitors, in which R1, R1a, R2, R3, R4, and (R5)a are as defined herein, to pharmaceutical compositions comprising such compounds and and to compositions for the treatment of abnormal cell growth, including cancer. A specific exemplary compound is e.g. 4-[(methylamino)methyl]-6- [methyl(propan-2-yl)amino]-2-[6-(4-propyl-4H-l,2,4-triazol-3-yl) pyridin-2-yl]-2,3-dihydro-lH-pyrrolo[3,4-c]pyridin-l-one. The present description discloses the preparation of exemplary compounds as well as pharmacological data thereof (e.g. pages 82 to 211; examples 1 to 188; tables 1 to 5).

NOVEL APOPTOSIS SIGNAL-REGULATING KINASE 1 INHIBITORS

The present invention relates to inhibitors of apoptosis signal-regulating kinase 1 ("ASK1"), a process for synthesis of the compounds of the present invention, composition comprising the compounds and use of the compounds for inhibition of ASK1.

APOPTOSIS SIGNAL-REGULATING KINASE 1 INHIBITORS AND METHODS OF USE THEREOF

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof: which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

Indole ASK1 small-molecule inhibitor and preparation method and application thereof

The invention discloses an indole ASK1 small-molecule inhibitor and a preparation method and application thereof. The inhibitor comprises a compound as shown in a general formula (I) and a stereoisomer or pharmaceutically acceptable salt thereof. Experime

AMIDE DERIVATIVE INHIBITOR AND PREPARATION METHOD AND APPLICATION THEREOF

An amide derivative inhibitor and a preparation method and an application thereof. Specifically relating to the compound shown in general formula (I), a preparation method for same, a pharmaceutical composition comprising said compound, and an application of same as an ASK inhibitor for the treatment of neurodegenerative disease, cardiovascular disease, inflammation, autoimmune and metabolic disease, each of the substituents in the general formula (I) being as defined in the description.