352672-60-7

Upstream product

• 38875-53-5 5-bromo-pyridine-2,3-diamine 
• 100-52-7 benzaldehyde 

Downstream Products

• 65147-89-9 6-bromo-2-phenyl-1H-imidazo<4,5-b>pyridine 

Relevant academic research and scientific papers

SOLID FORMS OF A BET INHIBITOR

The present disclosure relates to a mesylate salt/co-crystal of a BET bromodomain inhibitor, l-benzyl-6-(3,5-dimethylisoxazol-4-yl)-N-methyl-lH-imidazo[4,5-b]pyridine-2-amine, that modulates or inhibits the activity of BET bromodomain-containing proteins, pharmaceutical compositions, therapeutic uses, and processes for making a mesylate salt/co-crystal of said BET bromodomain inhibitor. These inhibitors have the potential to cure, treat, or improve the lives of subjects suffering from diseases such as cancer, inflammatory and cardiovascular diseases.

METHOD OF MANUFACTURING A SOLID FORM OF A BET BROMODOMAIN INHIBITOR

The invention relates to solid crystalline forms of Compound (I), such as e.g., Form VII, including pharmaceutical compositions thereof and processes for preparing crystalline Compound (I), Form VII. Compound (I) modulates or inhibits the activity of BET bromodomain-containing proteins, and is useful in the treatment of diseases such as cancer, inflammatory and cardiovascular diseases.

COMBINATION THERAPY FOR THE TREATMENT OF PROSTATE CANCER

The invention provides methods for treating prostate cancer, including metastatic castration-resistant prostate cancer, comprising administering to a subject in need thereof a BET faromadomain inhibitor in combination with a second agent.

COMBINATION THERAPY FOR THE TREATMENT OF TRIPLE-NEGATIVE BREAST CANCER

The invention provides methods for treating triple negative breast cancer (TBNC), by co-administration of a BET bromodomain inhibitors selected from 1-benzyl-6-(3, 5 -dimethylisoxazol-4-yl)-Nmethyl- 1 H-imidazo [4,5 -b]pyridin-2-amine (Compound I), 1-benzyl-6-(3,5- dimethylisoxazol-4-yl)-1H-imidazo[4,5-b]pyridin-2-amine, and pharmaceutically acceptable salts/co-crystals thereof, and a second therapeutic agent to a subject in need thereof. The second therapeutic agent is a PARP inhibitor, preferably talazoparib, olaparib or veliparib.

COMBINATION THERAPY FOR THE TREATMENT OF ESTROGEN-RECEPTOR POSITIVE BREAST CANCER

Methods for treating estrogen receptor positive (ER+) breast cancer, comprising administering to a subject in need thereof, a BET bromodomain inhibitor in combination with a second agent, selected from a selective-estrogen receptor degrader (SERD), a selective-estrogen receptor modulator (SERM) and a selective CDK4/6 inhibitor. The BET bromodomain inhibitor is selected from 1-benzyl-6-(3, 5-dimethylisoxazol-4-yl)- N-methyl-1H-imidazo[4,5-b]pyridin-2-amine (Compound I), 1-benzyl-6-(3,5- dimethylisoxazol-4-yl)-1H-imidazo[4,5-b]pyridin -2-amine, and pharmaceutically acceptable salts/co-crystals thereof.

Synthesis and antiproliferative activity in vitro of new 2-thioxoimidazo[4,5-b]pyridine derivatives

Two series of 2-thioxoimidazo[4,5-b]pyridine derivatives have been synthesized from 2,3-diaminopyridine (1) and 5-halogenosubstituted-2,3-diaminopyridines 2, 3. Mannich bases 7 - 12 and 24 - 29, derivatives of 1-arylamino-6-halogeno-2-thioxoimidazo[4,5-b]pyridine were obtained with selected secondary amines: morpholine, piperidine, 2-methoxyphenylpiperazine, pyrimidyn-2-yl-piperazine and formaldehyde in ethanol. The structures 7 - 12 and 24 - 29 were confirmed by the results of elementary analysis and their IR,1H-NMR and MS spectra. All given structures 7 - 12 have been optimized to get the most stable low energy conformers. Synthesized compounds were of interest for biological studies or can be substrates for further synthesis. The selected compounds 7 - 10, 12 - 17, 22, 25, 27 - 29 were screened for their antiproliferative activity in vitro against human cancer and normal mouse fibroblast cell lines.

NOVEL BICYCLIC BROMODOMAIN INHIBITORS

The invention relates to substituted bicyclic compounds, which are useful for inhibition of BET protein function by binding to bromodomains, pharmaceutical compositions comprising these compounds, and use of the compounds and compositions in therapy.

Unambiguous structural assignment of monoanils obtained from 2,3-pyridinediamines

The reaction of 2,3-pyridinediamine la and its 5-bromo analogue lb independently with aromatic aldehydes results in the formation of 2-amino-and 5-bromo-2-amino-3-arylideneaminopyridines (2a and 2b) respectively. The structure of 2 has been confirmed by single crystal X-ray analysis, thereby ruling out the alternate structure for these compounds.

Structure and reactions of monoanils obtained from 2,3-pyridinediamines

The reaction of 2,3-pyridinediamines 1 with aromatic aldehydes results in the formation of 2-amino-3-arylideneaminopyridines 2 respectively. Dehydrogenative cyclisation of 2 with different reagents give 2-aryl-1H-imidazo[4,5-b]pyridines 4. Reactions of 2 with different reagents have been described.