4770-30-3

Usage

General Description

2-(dimethylamino)-1H-isoindole-1,3(2H)-dione, also known as thalidomide, is a pharmaceutical drug and a synthetic derivative of glutamic acid. It was originally developed as a sedative and an antiemetic, but was later withdrawn from the market due to its severe teratogenic effects, causing birth defects in babies when taken by pregnant women. Despite its controversial history, thalidomide has found new uses in modern medicine, particularly as a treatment for leprosy and certain types of cancer. It works by inhibiting the production of tumor necrosis factor-alpha and other inflammatory cytokines, as well as by disrupting the formation of new blood vessels that feed tumors. Thalidomide is also being studied for potential applications in various autoimmune and inflammatory diseases.

Upstream product

• 85-44-9 phthalic anhydride 
• 55484-54-3 N,N-dimethylhydrazine dihydrochloride 
• 57-14-7 N,N-Dimethylhydrazine 

Downstream Products

• 28352-78-5 2-(Dimethylamino)-3-hydroxy-3-phenyl-2,3-dihydroisoindol-1-one 
• 835-18-7 3-phenyl-2,3-dihydro-isoindol-1-one 
• 149549-11-1 4-(4-methylthiophen-2-yl)-phthalazin-1(2H)-one 
• 945595-80-2 AMG 900 
• 1372642-13-1 3-benzyl-2-(dimethylamino)-3-hydroxyisoindolin-1-one 
• 1372642-15-3 3-cyclohexyl-2-(dimethylamino)-3-hydroxyisoindolin-1-one 

Relevant academic research and scientific papers

CRYSTALLINE FORMS OF N-(4-((3-(2-AMINO-4-PYRIMIDINYL) - 2-PYRIDINYL)OXY)PHENYL)-4-(4-METHYL-2-THIENYL)-1 -PHTHALAZINAMINE PHARMACEUTICALLY ACCEPTABLE SALTS AND USES THEREOF

The present invention relates to crystalline forms and co-crystal forms of pharmaceutically acceptable salts of the compound, N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinamine (AMG 900, and pharmaceutical compositions comprising said crystalline and co-crystal forms thereof. The invention further provides uses of the crystalline foms and compositions, to treat cancer, including various types of solid tumors and hematologic cancer including myeloma and leukemia.

Aurora Kinase Modulators and Method of Use

The present invention relates to chemical compounds having a general formula I wherein A1-8, D′, L1, L2, R1, R6-8 and n are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinases. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.

Synthesis of 4-substituted chlorophthalazines, dihydrobenzoazepinediones, 2-pyrazolylbenzoic acid, and 2-pyrazolylbenzohydrazide via 3-substituted 3-hydroxyisoindolin-1-ones

Figure Persented: Herein we describe a general three-step synthesis of 4-substituted chlorophthalazines in good overall yields. In the key step, N,N-dimethylaminophthalimide (8a) directs the selective monoaddition of alkyl, aryl, and heteroaryl organometallic reagents to afford 3-substituted 3-hydroxyisoindolinones 9b, 9i-9am. Many of these hydroxyisoindolinones are converted to chlorophthalazines 1b-1v via reaction with hydrazine, followed by chlorination with POCl3. We have also discovered two novel transformations of 3-vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic reagents to N,N-dimethylaminophthalimide (8a) provided dihydrobenzoazepinediones 15a-15c via the proposed ring expansion of 3-vinyl-3-hydroxyisoindolinone intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and substituted hydrazines to afford 2-pyrazolyl benzoic acids 16a-16d and 2-pyrazolyl benzohydrazides 17a-17g rather than the expected alkynyl phthalazinones.

HETEROCYCLIC DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE THEREOF

The present invention relates to novel quinoxaline, quinazoline and phthalazine derivatives as well as multimeric derivatives, methods for their preparation, pharmaceutical compositions including such compounds, and methods of using these compounds for the treatment and prevention of brain damage resulting from brain injury, especially secondary brain damage due to traumatic brain injury (TBI). The compounds of the invention are also useful in treating and preventing neurodegenerative diseases.

AURORA KINASE MODULATORS AND METHOD OF USE

The present invention relates to chemical compounds having a general formula (I) wherein A1-5 and 7-8, D', L1, L2, R1, R3, R6-8, n and o are defined herein, and synthetic intermediates, which are capable of modulating the activity of Aurora kinase proteins and, thereby, influencing various disease states and conditions related to the activities of Aurora kinases. For example, the compounds are capable of influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.

HETEROCYCLIC DERIVATIVES BINDING TO THE PERIPHERAL-TYPE BENZODIAZEPINE RECEPTOR (PBR)

The present invention relates to novel quinoxaline, quinazoline and phthalazine derivatives as well as multimeric derivatives, methods for their preparation, pharmaceutical compositions including such compounds, and methods of using these compounds for the treatment and prevention of brain damage resulting from brain injury, especially secondary brain damage due to traumatic brain injury (TBI). The compounds of the invention are also useful in treating and preventing neurodegenerative diseases.

Synthesis of 3-alkyl-1-isoindolinones by alkylation of a benzotriazolyl substituted N-dimethylamino-phthalimidine

A convenient and versatile synthesis of 3-alkyl-2,3-dihydro-1H-isoindol-1-ones (isoindolinones) based upon sequential metalation, alkylation alpha to nitrogen and C,N-deprotection from 3-benzotriazolyl-2-dimethylamino-phthalimidine is described.