131372-64-0

Upstream product

• 4728-12-5 2,2-dimethyl-5-hydroxymethyl-1,3-dioxane 
• 124-63-0 methanesulfonyl chloride 

Downstream Products

• 131372-62-8 5-amino-4-aminocarbonyl-1-(2,2-dimethyl-1,3-dioxan-5-yl)methoxyimidazole 
• 97827-17-3 5-iodomethyl-2,2-dimethyl-1,3-dioxane 
• 179096-67-4 (2,2-Dimethyl-[1,3]dioxan-5-ylmethyl)-(1-methyl-1-phenyl-ethyl)-amine 
• 1010701-28-6 N-benzyl(2,2-dimethyl-1,3-dioxan-5-yl)methanamine 
• 1414575-97-5 3-((2,2-dimethyl-1,3-dioxan-5-yl)methoxy)-4-methyl-1-phenyl-1H-pyrazol-5-amine 
• 875012-97-8 (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-(2,2-dimethyl-[1 ,3]dioxan-5-ylmethoxy)-3,5-dimethyl-benzylamide 
• 133384-75-5 2,2-dimethyl-5-(2'-carbethoxy-2'diphenylmethylimino-ethane)-1,3-dioxane 
• 1027196-80-0 2-(4-{2-[[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-(1-ethyl-cyclopentyl)-carbamoyl]-phenyl}-2-hydroxy-butyl)-N-(2,2-dimethyl-[1,3]dioxan-5-ylmethyl)-5-methyl-N-(1-methyl-1-phenyl-ethyl)-benzamide 
• 1026429-40-2 2-(4-{2-[[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-(1-ethyl-cyclopentyl)-carbamoyl]-phenyl}-2-oxo-butyl)-N-(2,2-dimethyl-[1,3]dioxan-5-ylmethyl)-5-methyl-N-(1-methyl-1-phenyl-ethyl)-benzamide 
• 179096-72-1 N-(1-ethylcyclopentyl)-[2-(4-{2-[(2,2-dimethyl[1,3]dioxan-5-yl)methyl](1-methyl-1-phenylethyl)carbamoyl}-4-methylphenyl)-3-hydroxybutyl]-N-(2-hydroxyethyl)benzamide 
• 179096-68-5 N-(2,2-Dimethyl-[1,3]dioxan-5-ylmethyl)-2,5-dimethyl-N-(1-methyl-1-phenyl-ethyl)-benzamide 

Relevant academic research and scientific papers

GDC-9545 (Giredestrant): A Potent and Orally Bioavailable Selective Estrogen Receptor Antagonist and Degrader with an Exceptional Preclinical Profile for ER+ Breast Cancer

Breast cancer remains a leading cause of cancer death in women, representing a significant unmet medical need. Here, we disclose our discovery efforts culminating in a clinical candidate, 35 (GDC-9545 or giredestrant). 35 is an efficient and potent selective estrogen receptor degrader (SERD) and a full antagonist, which translates into better antiproliferation activity than known SERDs (1, 6, 7, and 9) across multiple cell lines. Fine-tuning the physiochemical properties enabled once daily oral dosing of 35 in preclinical species and humans. 35 exhibits low drug-drug interaction liability and demonstrates excellent in vitro and in vivo safety profiles. At low doses, 35 induces tumor regressions either as a single agent or in combination with a CDK4/6 inhibitor in an ESR1Y537S mutant PDX or a wild-type ERα tumor model. Currently, 35 is being evaluated in Phase III clinical trials.

SSAO INHIBITORS AND USE THEREOF

Provided are a compound of formula (I') or (I), a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which modulates the activity of SSAO, a pharmaceutical composition comprising a compound of formula (I') or (I), and a method of treating or preventing a disease in which SSAO plays a role.

POLY(PHOSPHOESTERS) FOR DELIVERY OF NUCLEIC ACIDS

Disclosed are polymers comprising the moiety A, which is a moiety of formula I: and pharmaceutically acceptable salts thereof, wherein R, R1, R2, L, n1 and n2 are as defined herein. These polymers are useful for delivering nucleic acids to subject. These polymers and pharmaceutically acceptable compositions comprising such polymers and nucleic acids can be useful for treating various diseases, disorders and conditions.

CRYSTAL OF CYCLIC PHOSPHONIC ACID SODIUM SALT AND METHOD FOR MANUFACTURING SAME

An object of the present invention is to provide a crystal of a cyclic phosphonic acid sodium salt (2ccPA) with high purity and excellent storage stability and a method for producing the crystal. The present invention provides a crystal of a cyclic phosphonic acid sodium salt (2ccPA) represented by formula (1):

ASH1L INHIBITORS AND METHODS OF TREATMENT THEREWITH

Provided herein are small molecule inhibitors of ASH1L activity and small molecules that facilitate ASH1L degradation and methods of use thereof for the treatment of disease, including acute leukemia, solid cancers and other diseases dependent on activity of ASH1L.

4,6-SUBSTITUTED-PYRAZOLO[1,5-a]PYRAZINES AS JANUS KINASE INHIBITORS

Compounds of Formula I: and stereoisomers and pharmaceutically acceptable salts and solvates thereof in which R1, R2, R3 and R4 have the meanings given in the specification, are inhibitors of one or more JAK kinases and are useful in the treatment of JAK kinase-associated diseases and disorders, such as autoimmune diseases, inflammatory diseases, rejection of transplanted organs, tissues and cells, as well as hematologic disorders and malignancies and their co-morbidities.

BICYCLIC HETEROARYL UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS

Compounds of Formula I or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis and pelvic pain syndrome.

Transition state analogue inhibitors of human methylthioadenosine phosphorylase and bacterial methylthioadenosine/S-adenosylhomocysteine nucleosidase incorporating acyclic ribooxacarbenium ion mimics

Several acyclic hydroxy-methylthio-amines with 3-5 carbon atoms were prepared and coupled via a methylene link to 9-deazaadenine. The products were tested for inhibition against human MTAP and Escherichia coli and Neisseria meningitidis MTANs and gave Ki values as low as 0.23 nM. These results were compared to those obtained with 1st and 2nd generation inhibitors (1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-methylthio-d-ribitol (MT-Immucillin-A, 3) and (3R,4S)-1-[9-deazaadenin-9-yl)methyl]3-hydroxy-4- methylthiomethylpyrrolidine (MT-DADMe-Immucillin-A, 4). The best inhibitors were found to exhibit binding affinities of approximately 2- to 4-fold those of 3 but were significantly weaker than 4. Cleavage of the 2,3 carbon-carbon bond in MT-Immucillin-A (3) gave an acyclic product (79) with a 21,500 fold loss of activity against E. coli MTAN. In another case, N-methylation of a side chain secondary amine resulted in a 250-fold loss of activity against the same enzyme [(±)-65 vs (±)-68]. The inhibition results were also contrasted with those acyclic derivatives previously prepared as inhibitors for a related enzyme, purine nucleoside phosphorylase (PNP), where some inhibitors in the latter case were found to be more potent than their cyclic counterparts.

Design, synthesis and X-ray crystallographic study of new nonsecosteroidal vitamin D receptor ligands

We designed and synthesized nonsecosteroidal vitamin D receptor (VDR) ligands that formed H-bonds with six amino acid residues (Tyr143, Ser233, Arg270, Ser274, His301 and His393) of the VDR ligand-binding domain. The ligand YR335 exhibited potent transcriptional activity, which was comparable to those of 1α,25-dihydroxyvitamin D3 and YR301. The crystal structure of the complex formed between YR335 and the VDR ligand-binding domain was solved, which revealed that YR335 formed H-bonds with the six amino acid residues mentioned above.

BENZOXAZOLE DERIVATIVES

It is intended to provide a benzoxazole derivative or a pharmaceutically acceptable salt or solvate thereof which is useful in the early diagnosis of a conformation disease; a composition or a kit containing the same for diagnosing a conformation disease; a medical composition for ttreating and/or preventing a conformation disease; and so on.