66336-42-3

Usage

Uses

Used in Pharmaceutical Industry:
8-Methyl-1,4-dioxaspiro[4,5]decan-8-ol is used as a key intermediate in the preparation of pyrrolopyridine derivatives and related compounds. These compounds act as BCL-2 inhibitors, which are important for the development of drugs to treat neoplastic, autoimmune, or neurodegenerative diseases. By inhibiting BCL-2, these drugs can help regulate cell death and potentially provide therapeutic benefits for patients suffering from these conditions.

Upstream product

• 4746-97-8 cyclohexanedione monoethylene ketal 
• 917-54-4 methyllithium 
• 917-64-6 methyl magnesium iodide 
• 75-16-1 methylmagnesium bromide 
• 74-88-4 methyl iodide 
• 676-58-4 methylmagnesium chloride 
• 100-58-3 phenylmagnesium bromide 
• 74-83-9 methyl bromide 

Downstream Products

• 17429-02-6 4-hydroxy-4-methylcyclohexanone 
• 124899-25-8 (1s,4s)-1-methylcyclohexane-1,4-diol 
• 341534-97-2 trans-4-Hydroxy-4-methylcyclohexyl acetate 
• 341535-05-5 trans-(4-Hydroxy-4-methylcyclohexyl)methyl acetate 
• 341535-11-3 cis-(4-Hydroxy-4-methylcyclohexyl)methyl acetate 
• 23438-15-5 4-methoxy-4-methylcyclohexan-1-one 
• 224447-17-0 4-Benzyloxy-4-methylcyclohexanone 

Relevant academic research and scientific papers

Assembly of tricyclic compounds that include the spiro[4.4]nonane subunit

Spiroannulation of ketals derived from unsaturated cyclohexenone derivatives by the Lewis acid-catalyzed reaction of l,2-bis((trimethylsilyl)oxy)cyclobutene 5 led to spiro[4.5]decene-diones 9 and 30. These were transformed into spiro[4.4]nonene derivatives 25 and 35/36 via similar sequences involving ozonolysis and aldol ring reclosure. Reduction of an annular double bond allowed facile closure of a third ring, also by an aldol reaction. This work led to a single oxygenated angular triquinane 28 from 9, and to the tricyclo[6.2.1.01,5]undecane derivative 41 from 30. An oxatricyclo[5.3.1.01,5]undecane derivative 19 was also obtained from 9.

1H-PYRROLO[2,3-B]PYRIDINE DERIVATIVES AS BCL-2 INHIBITORS FOR THE TREATMENT OF NEOPLASTIC AND AUTOIMMUNE DISEASES

The present invention relates to lH-pyrrolo[2,3-b]pyridine derivatives and related compounds as BCL-2 inhibitors for treating neoplastic, autoimmune or neurodegenerative diseases. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 162 to 233; examples 1 to 8; table; compound examples cpd-1 to cpd-135; biological examples 1 to 4).

Application of Transaminases in a Disperse System for the Bioamination of Hydrophobic Substrates

The challenging bioamination of hydrophobic substrates has been attained through the employment of a disperse system consisting of a combination of a low polarity solvent (e. g. isooctane or methyl-tert-butylether), a non-ionic surfactant and a minimal amount of water. In these conditions, amine transaminases (ATA) were shown to efficiently carry out the reductive amination of variously substituted cyclohexanones, providing good conversions often coupled with a superior stereoselectivity if compared with the corresponding chemical reductive amination. An array of synthetically useful 4-substituted aminocyclohexanes was consequentially synthesized through biocatalysis, analyzed and stereochemically characterized. (Figure presented.).

Synthesis and evaluation of 1,1,7,7-tetramethyl-9-azajulolidine (TMAJ) as a highly active derivative of N,N-dimethylaminopyridine

1,1,7,7-Tetramethyl-9-azajulolidine (TMAJ), which theoretical studies have suggested as a highly active DMAP analog, was synthesized for the first time. The catalytic activity of TMAJ was confirmed by the acetylation reactions of various tert-alcohols. TMAJ showed much higher catalytic activity than DMAP and one of the highest activity levels among the conventional DMAP analogs. These experimental results were in good agreement with the previous theoretical studies.

Design and Optimization Leading to an Orally Active TTK Protein Kinase Inhibitor with Robust Single Agent Efficacy

Triple negative breast cancer (TNBC) is an aggressive disease with high relapse rates and few treatment options. Outlined in previous publications, we identified a series of potent, dual TTK/CLK2 inhibitors with strong efficacy in TNBC xenograft models. P

Bcl-2 INHIBITORS

Disclosed herein is a compound of Formula (I) for inhibiting Bcl-2 and treating disease associated with undesirable bcl-2 activity (Bcl-2 related diseases), a method of using the compounds disclosed herein for treating dysregulated apoptotic diseases including cancers and treating autoimmune disease, and a pharmaceutical composition comprising the same.

Deoxygenative Borylation of Secondary and Tertiary Alcohols

Two different approaches for the deoxygenative radical borylation of secondary and tertiary alcohols are presented. These transformations either proceed through a metal-free silyl-radical-mediated pathway or utilize visible-light photoredox catalysis. Readily available xanthates or methyl oxalates are used as radical precursors. The reactions show broad substrate scope and high functional-group tolerance, and are conducted under mild and practical conditions.

The Discovery of a Dual TTK Protein Kinase/CDC2-Like Kinase (CLK2) Inhibitor for the Treatment of Triple Negative Breast Cancer Initiated from a Phenotypic Screen

Triple negative breast cancer (TNBC) remains a serious unmet medical need with discouragingly high relapse rates. We report here the synthesis and structure-activity relationship (SAR) of a novel series of 2,4,5-trisubstituted-7H-pyrrolo[2,3-d]pyrimidines with potent activity against TNBC tumor cell lines. These compounds were discovered from a TNBC phenotypic screen and possess a unique dual inhibition profile targeting TTK (mitotic exit) and CLK2 (mRNA splicing). Design and optimization, driven with a TNBC tumor cell assay, identified potent and selective compounds with favorable in vitro and in vivo activity profiles and good iv PK properties. This cell-based driven SAR produced compounds with strong single agent in vivo efficacy in multiple TNBC xenograft models without significant body weight loss. These data supported the nomination of CC-671 into IND-enabling studies as a single agent TNBC therapy.

COMPOUNDS USEFUL AS KINASE INHIBITORS

This invention relates to novel compounds. The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK).The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.

PYRAZOLOPYRIMIDINE DERIVATIVES AS BTK INHIBITORS FOR THE TREATMENT OF CANCER

This invention relates to novel compounds. The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK). The invention also contemplates the use of t