Described are improved linking agents that are useful for facilitating the attachment of targeting groups, pharmacokinetic (PK) enhancers or modifiers, or other delivery agents to oligonucleotides. The described linking agents may exhibit improved reaction yields, stability, and biological activity, particularly when used in connection with oligonucleotide-based compounds, such as RNA interference (RNAi) agents.

Described are improved linking agents that are useful for facilitating the attachment of targeting groups, pharmacokinetic (PK) enhancers or modifiers, or other delivery agents to oligonucleotides. The described linking agents may exhibit improved reaction yields, stability, and biological activity, particularly when used in connection with oligonucleotide-based compounds, such as RNA interference (RNAi) agents.

A resist composition comprising a sulfonium salt of a carboxylic acid having a nitro-substituted benzene ring is provided. The carboxylic acid is free of iodine and bromine, and when the benzene ring is fluorinated, the number of fluorine atoms is up to 3. The resist composition offers a high sensitivity, reduced LWR and improved CDU independent of whether it is of positive or negative tone.

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.

The present invention provides a method for specifically cleaving a Cα-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 Cα-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 Cα-C bond of a peptide backbone and/or a side chain bond, and analyzing generated fragment ions by mass spectrometry.

The present invention provides a method for specifically cleaving a Cα-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 Cα-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 Cα-C bond of a peptide backbone and/or a side chain bond, and analyzing generated fragment ions by mass spectrometry.

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.

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##

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##

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.