936691-31-5

Upstream product

• 5198-86-7 (2-bromo-1,3-thiazol-4-yl)methanol 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 100367-77-9 ethyl 2-bromothiazole-4-carboxylate 
• 5198-88-9 2-bromothiazole-4-carboxylic Acid 

Relevant academic research and scientific papers

Design, Synthesis, and Cytotoxic Activity of New Tubulysin Analogues

Synthesis of tubulysin analogues, containing an N-methyl substituent on tubuvaline-amide together with the replacement of either the hydrophobic N-terminal N-methyl pipecolic acid (Mep) or at both N- and C- terminal peptides with available heteroaromatic

Synthesis and evaluation of novel and potent protease activated receptor 4 (PAR4) antagonists based on a quinazolin-4(3H)-one scaffold

Protease activated receptor 4 (PAR4) is an important target in antiplatelet therapy to reduce the risk of heart attack and thrombotic complications in stroke. PAR4 antagonists can prevent harmful and stable thrombus growth, while retaining initial thrombus formation, by acting on the late diffusion stage of platelet aggregation, and may provide a safer alternative to other antiplatelet agents. To date, only two PAR4 antagonists, BMS-986120 and BMS-986141 have entered clinical trials for thrombosis. Thus, the development of a potent and selective PAR4 antagonist with a novel chemotype is highly desirable. In this study, we explored the activity of quinazolin-4(3H)-one-based PAR4 antagonists, beginning with their IDT analogues. By repeated structural optimisation, we developed a series of highly selective PAR4 antagonists with nanomolar potency on human platelets. Of these, 13 and 30g, with an 8-benzo[d]thiazol-2-yl-substituted quinazolin-4(3H)-one structure, showed optimal activity (h. PAR4-AP PRP IC50 = 19.6 nM and 6.59 nM, respectively) on human platelets. Furthermore, 13 and 30g showed excellent selectivity for PAR4 versus PAR1 and other receptors (IC50s > 10 μM) on human platelets. And 13 and 30g were lack of cross-reactivity for PAR1 or PAR2 (PAR1 AP FLIPR IC50 > 3162 nM, PAR2 AP FLIPR IC50 > 1000 nM) in the calcium mobilization assays. Metabolic stability assays and cytotoxicity tests of 13 and 30g indicated that these compounds could sever as promising drug candidates for the development of novel PAR4 antagonists. In summary, the quinazolin-4(3H)-one-based analogues are the first reported chemotypes with excellent activity and selectivity against PAR4, and, in the current study, we expanded the structural diversity of PAR4 antagonists. The two compounds, 13 and 30g, found in our study could be promising starting points with great potential for further research in antiplatelet therapy.

SULFONIMIDAMIDE COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured: (Formula AA) or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formula A can be as defined anywhere herein.

METHODS OF TREATING CANCER

The present disclosure relates to methods of treating cancer in a patient using a combination of an inhibitor of an immune checkpoint protein and an indole compound or its phosphate derivative.

NLRP MODULATORS

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured: or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formula A can be as defined anywhere herein.

NLRP MODULATORS

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured: or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formula A can be as defined anywhere herein, useful to treat connected to the modulation of NRLP3.

METHODS OF TREATMENT WITH AMINOLEVULINIC ACID SYNTHASE 2 (ALAS2) MODULATORS

Described herein is a compound of Formula I or a pharmaceutically acceptable salt thereof: wherein Ring A R1, R2, a, b, and n are as defined herein. Also described is a method of treating a subject having a disorder in need of treatment, comprising inhibiting aminolevulinic acid synthase 2 (ALAS2) in the subject by administering a compound of Formula (I) or a pharmaceutically acceptable salt thereof. Disorders that are of particular interest are blood disorders, such as porphyria and anemia.

INDOLE COMPOUNDS AND THEIR USE

The present disclosure relates to indole compounds and pharmaceutical compositions thereof, and their use in stimulating the immune system of patients in need thereof and in treating cancer.

COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured. The variables shown in Formula AA are as defined in the claims. The compounds of formula AA are NLRP3 activity modulators and, as such, can be used in the treatment of metabolic disorders (e.g. Type 2 diabetes, atherosclerosis, obesity or gout), a disease of the central nervous system (e.g. Alzheimer's disease, multiple sclerosis, Amyotrophic Lateral Sclerosis or Parkinson's disease), lung disease (e.g. asthma, COPD or pulmonary idiopathic fibrosis), liver disease (e.g. NASH syndrome, viral hepatitis or cirrhosis), pancreatic disease (e.g. acute pancreatitis or chronic pancreatitis), kidney disease (e.g. acute kidney injury or chronic kidney injury), intestinal disease (e.g. Crohn's disease or Ulcerative Colitis), skin disease (e.g. psoriasis), musculoskeletal disease (e.g. scleroderma), a vessel disorder (e.g. giant cell arteritis), a disorder of the bones (e.g. osteoarthritis, osteoporosis or osteopetrosis disorders), eye disease (e.g. glaucoma or macular degeneration), a disease caused by viral infection (e.g. HIV or AIDS), an autoimmune disease (e.g. Rheumatoid Arthritis, Systemic Lupus Erythematosus or Autoimmune Thyroiditis), cancer or aging.

Imidazo ring PAR4 antagonist and medical applications thereof

The invention relates to an imidazo ring compound represented by formula (I) or formula (II), or a pharmaceutically acceptable salt or ester or solvate thereof. The compound disclosed by the inventioncan be used for preparing medicines for preventing or treating thromboembolic diseases.