Patent classifications
C07C205/59
PROCESSES AND INTERMEDIATES FOR PREPARING MCL1 INHIBITORS
The present disclosure provides methods for preparing MCL1 inhibitors or a salt thereof and related key intermediates.
PROCESS FOR THE PREPARATION OF A PDE4 INHIBITOR
The present invention relates to a process for the preparation of compounds endowed with phosphodiesterase (PDE4) inhibitory activity having formula (I). The invention also relates to the process for the isolation by crystallization of the compound (I) and to its use for the preparation of pharmaceutical compositions for inhalation in combination with suitable carriers or vehicles. The present invention also relates to solvates and crystal forms of a compound of formula (I). The synthesized product is suitable for use in pharmaceutical applications for instance in the treatment of respiratory diseases.
COMPOUNDS WITH ANTIMICROBIAL ACTIVITY
This invention relates to compounds of formula 1, 2 or 3
##STR00001##
a pharmaceutically acceptable salt, or solvate thereof, wherein X.sub.1, Y, R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are as defined herein. The compounds are antimicrobial agents that may be used to treat various bacterial and protozoal infections and disorders related to such infections. The invention also relates to pharmaceutical compositions containing the compounds and to methods of treating bacterial and protozoal infections by administering the compounds of formula 1, 2 or 3.
Process for the preparation of a PDE4 inhibitor
The present invention relates to a process for the preparation of compounds endowed with phosphodiesterase (PDE4) inhibitory activity having formula (I). The invention also relates to the process for the isolation by crystallization of the compound (I) and to its use for the preparation of pharmaceutical compositions for inhalation in combination with suitable carriers or vehicles. The present invention also relates to solvates and crystal forms of a compound of formula (I). The synthesized product is suitable for use in pharmaceutical applications for instance in the treatment of respiratory diseases.
Method for specific cleavage of C alpha-C bond and side chain of protein and peptide, and method for determining amino acid sequence
The present invention provides a method for specifically cleaving a C-C bond of a peptide backbone and/or a side chain of a protein and a peptide, and a method for determining amino acid sequences of protein and peptide. A method for specifically cleaving a C-C bond of a peptide backbone and/or a side chain bond of a protein or a peptide, comprising irradiating a protein or a peptide with laser light in the presence of at least one hydroxynitrobenzoic acid selected from the group consisting of 3-hydroxy-2-nitrobenzoic acid, 4-hydroxy-3-nitrobenzoic acid, 5-hydroxy-2-nitrobenzoic acid, 3-hydroxy-5-nitrobenzoic acid, and 4-hydroxy-2-nitrobenzoic acid. A method for determining an amino acid sequence of a protein or a peptide, comprising irradiating a protein or a peptide with laser light in the presence of the above specific hydroxynitrobenzoic acid to specifically cleave a C-C bond of a peptide backbone and/or a side chain bond, and analyzing generated fragment ions by mass spectrometry.
Method for specific cleavage of C alpha-C bond and side chain of protein and peptide, and method for determining amino acid sequence
The present invention provides a method for specifically cleaving a C-C bond of a peptide backbone and/or a side chain of a protein and a peptide, and a method for determining amino acid sequences of protein and peptide. A method for specifically cleaving a C-C bond of a peptide backbone and/or a side chain bond of a protein or a peptide, comprising irradiating a protein or a peptide with laser light in the presence of at least one hydroxynitrobenzoic acid selected from the group consisting of 3-hydroxy-2-nitrobenzoic acid, 4-hydroxy-3-nitrobenzoic acid, 5-hydroxy-2-nitrobenzoic acid, 3-hydroxy-5-nitrobenzoic acid, and 4-hydroxy-2-nitrobenzoic acid. A method for determining an amino acid sequence of a protein or a peptide, comprising irradiating a protein or a peptide with laser light in the presence of the above specific hydroxynitrobenzoic acid to specifically cleave a C-C bond of a peptide backbone and/or a side chain bond, and analyzing generated fragment ions by mass spectrometry.
Anti-tumor compound and the medical use thereof
The invention disclose a compound of formula (I), wherein, R.sub.1 is selected from H or C1-C6 hydrocarbon group, NH.sub.2, OH, O(CH.sub.2).sub.nCH.sub.3 (n=0, 1 or 2), N(CH.sub.3).sub.2, or CH.sub.2N(CH.sub.3).sub.2, R.sub.2 is selected from an amino acid ##STR00001##
or an hydroxy acid ##STR00002##
or OH (R.sub.1, R.sub.2 are not CH.sub.3 and OH at the same time), wherein X, Y are ##STR00003##
H, CH.sub.3, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2SH, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2COOH, CH.sub.2CONH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, or CH.sub.2CH.sub.2CONH.sub.2, R.sub.3-R.sub.5 are H or C1-C6 hydrocarbon group. The compound has a low toxicity, can significantly inhibit the migration and invasion of tumor cells in vitro, and can inhibit tumor metastasis in vivo in mice at low concentration, while showing notable sensitizing effect on cytotoxic anti-tumor drugs such as Paclitaxel etc. ##STR00004##
Anti-tumor compound and the medical use thereof
The invention disclose a compound of formula (I), wherein, R.sub.1 is selected from H or C1-C6 hydrocarbon group, NH.sub.2, OH, O(CH.sub.2).sub.nCH.sub.3 (n=0, 1 or 2), N(CH.sub.3).sub.2, or CH.sub.2N(CH.sub.3).sub.2, R.sub.2 is selected from an amino acid ##STR00001##
or an hydroxy acid ##STR00002##
or OH (R.sub.1, R.sub.2 are not CH.sub.3 and OH at the same time), wherein X, Y are ##STR00003##
H, CH.sub.3, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2SH, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2COOH, CH.sub.2CONH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, or CH.sub.2CH.sub.2CONH.sub.2, R.sub.3-R.sub.5 are H or C1-C6 hydrocarbon group. The compound has a low toxicity, can significantly inhibit the migration and invasion of tumor cells in vitro, and can inhibit tumor metastasis in vivo in mice at low concentration, while showing notable sensitizing effect on cytotoxic anti-tumor drugs such as Paclitaxel etc. ##STR00004##
PROCESS FOR THE PREPARATION OF A PDE4 INHIBITOR
The present invention relates to a process for the preparation of compounds endowed with phosphodiesterase (PDE4) inhibitory activity having formula (I). The invention also relates to the process for the isolation by crystallization of the compound (I) and to its use for the preparation of pharmaceutical compositions for inhalation in combination with suitable carriers or vehicles. The present invention also relates to solvates and crystal forms of a compound of formula (I). The synthesized product is suitable for use in pharmaceutical applications for instance in the treatment of respiratory diseases.
VISUAL DETECTION OF PBD INDUCED DNA CROSSLINKS
The present invention relates to the field of oncology. laboratory tools and methods, and especially anti-tumor DNA crosslinking agents. Most patients with advanced solid tumors develop resistance to chemotherapy due to the ability of cancer cells to repair or tolerate sustained DNA damages. The inventors showed that the compounds according to the present invention allow the detection and visualization of alkylated DNA damages induced by PBDs without altering their DNA crosslinking ability. This enables the study of the effect and properties of PBDs. In particular, the present invention relates new derivates of PBD molecules and their synthesis. The present invention also relates to a method for visualizing DNA crosslinking: to a method for assessing the resistance of a tumor to a crosslinking agent and to a method for identifying a molecule or treatment for improving the efficiency of a crosslinking agent.