1254036-83-3

Upstream product

• 1254036-94-6 6-chloro-4-iodo-1-(phenylsulfonyl)-1H-indazole 
• 118994-89-1 oxazol-5-yl-carboxylic acid ethyl ester 
• 924-44-7 glyoxylic acid ethyl ester 
• 38622-91-2 [(p-methylphenyl)sulfonylmethyl]isonitrile 
• 1254036-82-2 methyl 2-[6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-oxazole-5-carboxylate 
• 870606-29-4 5-chloro-3-iodo-2-methylaniline 
• 294190-16-2 2-iodo-4-chloro-6-nitrotoluene 
• 219312-44-4 5-chloro-2-methyl-3-nitro-aniline 
• 35572-79-3 5-chloro-2-methyl-1,3-dinitro-benzene 
• 606-20-2 2,6-dinitrotoluene 
• 1254036-80-0 6-chloro-1-(phenylsulfonyl)-4-(trimethylstannanyl)-1H-indazole 
• 885519-56-2 6-chloro-4-iodo-1H-indazole 
• 98-09-9 benzenesulfonyl chloride 
• 1254036-81-1 ethyl 2-[6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-oxazole-5-carboxylate 

Downstream Products

• 1254036-84-4 4-[5-(bromomethyl)-1,3-oxazol-2-yl]-6-chloro-1-(phenylsulfonyl)-1H-indazole 
• 1254036-85-5 6-chloro-4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole 
• 1361970-55-9 N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide 
• 1361970-34-4 N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide tosylate salt 
• 1361970-37-7 N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide mesitylenesulfonate salt 
• 1254036-87-7 N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide 
• 1254036-91-3 6-chloro-4-(5-{[(2R,6R)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole 
• 1254036-68-4 N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide 
• 1364799-92-7 C₇H₈O₃S*C₂₆H₂₈N₆O 
• 1364802-72-1 6-(1H-indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole 
• 1254036-86-6 6-chloro-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole 

Relevant academic research and scientific papers

Application of C-H Functionalization in the Development of a Concise and Convergent Route to the Phosphatidylinositol-3-kinase Delta Inhibitor Nemiralisib

This paper describes the development of an improved and scalable method for the manufacture of nemiralisib, a phosphatidylinositol-3-kinase delta inhibitor. Incorporation of three consecutive catalytic reactions, including a palladium-catalyzed C-H functionalization and an iridium-catalyzed borylation, significantly simplified and shortened the synthetic sequence. The revised route was successfully implemented in a pilot plant on a multikilogram scale to deliver >100 kg of product.

Development of Flexible and Scalable Routes to Two Phosphatidinylinositol-3-kinase Delta Inhibitors via a Common Intermediate Approach

This paper describes the discovery and development of a flexible route to two candidate drug molecules by a common intermediate approach. Key reactions include Negishi and Suzuki couplings to form biaryl bonds. Conditions for a Miyaura borylation of heteroaryl bromides were also developed. Heteroaryl trifluoroborates and aryl chlorides were used as coupling partners in the Suzuki reaction, thereby minimizing detrimental side reactions such as protodeboronation and oxidative homocoupling. A complementary set of reaction conditions using pinacolboronates with potassium bifluoride as an additive were also developed and used to make 5 kg of drug substance for use in early-phase clinical trials.

Indazole derivatives for use in the treatment of influenza virus infection

The present invention is directed to compounds for use in the treatment or prevention of influenza virus infection.

Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease

Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3Kδ potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (GSK2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3Kδ over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.

Polymorphs and Salts

The present invention is directed to a polymorph of a compound and salts of a compound and polymorphs thereof, which compound is an inhibitor of kinase activity.

POLYMORPHS AND SALTS OF N- [5- [4- (5- { [(2R,6S) -2, 6 - DIMETHYL - 4 -MORPHOLINYL] METHYL} - 1, 3 - OXAZOL - 2 - YL) - 1H- INDA ZOL-6-YL] -2- (METHYLOXY) - 3 - PYRIDINYL] METHANESULFONAMIDE

The present invention is directed to novel polymorphs and salts of a compound which is an inhibitor of kinase activity.

POLYMORPHS AND SALTS OF 6-(1H-INDOL-4-YL)-4-(5- { [4-(1-METHYLETHYL)-1-PI PERAZINYL] METHYL} -1,3-OXAZOL-2-YL)-1H-INDAZOLE AS PI3K INHIBITORS FOR USE IN THE TREATMENT OF E.G. RESPIRATORY DISORDERS

The present invention is directed to a polymorph of a compound of formula (II) and salts and polymorphs thereof, which is an inhibitor of PI3 kinase activity.

OXAZOLE SUBSTITUTED INDAZOLES AS PI3-KINASE INHIBITORS

The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I): and salts thereof. The compounds of the invention are inhibitors of kinase activity, in particular PI3-kinase activity.