The present invention relates to novel heterocyclicalkyl derivatives having histone deacetylase (HDAC) inhibitory activity, optical isomers thereof or pharmaceutically acceptable salts thereof, the use thereof for the preparation of medicaments, pharmaceutical compositions containing the same, a method for treating diseases using the composition, and methods for preparing the novel heterocyclicalkyl derivatives. The novel heterocyclicalkyl derivatives according to the present invention are selective histone deacetylase (HDAC) inhibitors, and may be effectively used for the treatment of histone deacetylase-mediated diseases, such as cell proliferative diseases, inflammatory diseases, autosomal dominant diseases, genetic metabolic diseases, autoimmune diseases, acute/chronic neurological disease, hypertrophy, heart failure, ocular diseases, or neurodegenerative diseases.

The present invention relates to novel heterocyclicalkyl derivatives having histone deacetylase (HDAC) inhibitory activity, optical isomers thereof or pharmaceutically acceptable salts thereof, the use thereof for the preparation of medicaments, pharmaceutical compositions containing the same, a method for treating diseases using the composition, and methods for preparing the novel heterocyclicalkyl derivatives. The novel heterocyclicalkyl derivatives according to the present invention are selective histone deacetylase (HDAC) inhibitors, and may be effectively used for the treatment of histone deacetylase-mediated diseases, such as cell proliferative diseases, inflammatory diseases, autosomal dominant diseases, genetic metabolic diseases, autoimmune diseases, acute/chronic neurological disease, hypertrophy, heart failure, ocular diseases, or neurodegenerative diseases.

The present invention discloses a hypocrellin derivative substituted both in a pen-position and in a 2-position by an amino, and a preparation method and use thereof. A general structural formula of the derivative is as represented by formulas I-a to I-d: ##STR00001## The hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino prepared in the present invention has a maximum absorption wavelength of 600-650 nm and a molar extinction coefficient reaching about 20000-40000 M.sup.−1cm.sup.−1. Compared with unmodified hypocrellin or hypocrellin having only a 2-position modified, an absorption spectrum of the derivative is significantly red-shifted and the molar extinction coefficient is greatly improved, and the derivative can efficiently produce reactive oxygen species such as singlet oxygen in a photosensitive condition. In the same condition, the hypocrellin derivative substituted both in a pen-position and in a 2-position by an amino involved in the present invention, when used as a photosensitizer, has a stronger ability to photo-dynamically inactivate tumor cells than the first and second generation commercial photosensitizers.

The present invention discloses a hypocrellin derivative substituted both in a pen-position and in a 2-position by an amino, and a preparation method and use thereof. A general structural formula of the derivative is as represented by formulas I-a to I-d: ##STR00001## The hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino prepared in the present invention has a maximum absorption wavelength of 600-650 nm and a molar extinction coefficient reaching about 20000-40000 M.sup.−1cm.sup.−1. Compared with unmodified hypocrellin or hypocrellin having only a 2-position modified, an absorption spectrum of the derivative is significantly red-shifted and the molar extinction coefficient is greatly improved, and the derivative can efficiently produce reactive oxygen species such as singlet oxygen in a photosensitive condition. In the same condition, the hypocrellin derivative substituted both in a pen-position and in a 2-position by an amino involved in the present invention, when used as a photosensitizer, has a stronger ability to photo-dynamically inactivate tumor cells than the first and second generation commercial photosensitizers.

The present invention provides a compound represented by formula (I) [wherein L represents an oxygen atom or CH.sub.2, E represents a C2-C10 chain hydrocarbon group or the like, R.sup.1 represents a C1-C3 chain hydrocarbon group or the like, R.sup.2 represents a C1-C3 chain hydrocarbon group or the like, and n is 0, 1, 2 or 3.] or its N oxide or agriculturally acceptable salt, which is a compound that have excellent pests controlling effects.

##STR00001##

This invention relates to compounds that are agonists of the muscarinic M.sub.1 receptor or M.sub.1 and M.sub.4 receptors and which are useful in the treatment of muscarinic M.sub.1 or M.sub.1/M.sub.4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula

##STR00001##

wherein Q.sup.4, Q.sup.5, R.sup.5, p, V, Q.sup.1, Q.sup.2, X.sup.1, X.sup.2 and W are defined herein.

This invention relates to compounds that are agonists of the muscarinic M.sub.1 receptor or M.sub.1 and M.sub.4 receptors and which are useful in the treatment of muscarinic M.sub.1 or M.sub.1/M.sub.4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula

##STR00001##

wherein Q.sup.4, Q.sup.5, R.sup.5, p, V, Q.sup.1, Q.sup.2, X.sup.1, X.sup.2 and W are defined herein.

A composition and method of treatment of neuromuscular, neuromuscular degenerative, neurodegenerative, autoimmune, developmental, traumatic, hearing loss related, and/or metabolic diseases, including spinal muscular atrophy (SMA) syndrome (SMA1, SMA2, SMA3, and SMA4, also called Type I, II, III and IV), traumatic brain injury (TBI), concussion, keratoconjunctivitis sicca (Dry Eye Disease), glaucoma, Sjogren's syndrome, rheumatoid arthritis, post-LASIK surgery, anti-depressants use, Wolfram Syndrome, and Wolcott-Rallison syndrome. The composition is selected from the group consisting of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, bipartite 2,3-dinitrophenol, 2,4-dinitrophenol, 2,5-dinitrophenol, 2,6-dinitrophenol, 3,4-dinitrophenol, or 3,5-dinitrophenol (2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP) prodrugs; Gemini prodrugs, bioprecursor molecules, and combinations thereof. A dose of the composition for treatment of neurodegenerative diseases may be from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment. A dose of the composition for treatment of metabolic diseases may be from about 1 mg/70 kg of body weight to about 100 mg/70 kg of body weight of the patient in need of treatment, and a maximum dose per day is about 200 mg/70 kg of body weight of the patient in need of treatment.

This compound, which absorbs long-wavelength active energy rays and generates with high-efficiency radicals and strong bases, and which has excellent reaction efficiency in a base generating chain reaction, is represented by formula (1), where, in formula (1), R.sub.1, R.sub.2, R.sub.3, R.sub.5 and R.sub.6 independently represent a hydroxy group, an alkoxy group, or an organic group other than those substituents, the R.sub.4's independently represent an organic group including a thioether bond, and ‘A’ represents a substituent represented by formula (1-1) or (1-2), where, in formula (1-1), R.sub.7 and R.sub.8 independently represent a hydrogen atom, an alkyl group or a heterocyclic group, and where, in formula (1-2), R.sub.9 and R.sub.10 independently represent an amino group or a substituted amino group. A photopolymerization initiator can include said compound; and a photosensitive resin composition can include said photopolymerization initiator. ##STR00001##

This compound, which absorbs long-wavelength active energy rays and generates with high-efficiency radicals and strong bases, and which has excellent reaction efficiency in a base generating chain reaction, is represented by formula (1), where, in formula (1), R.sub.1, R.sub.2, R.sub.3, R.sub.5 and R.sub.6 independently represent a hydroxy group, an alkoxy group, or an organic group other than those substituents, the R.sub.4's independently represent an organic group including a thioether bond, and ‘A’ represents a substituent represented by formula (1-1) or (1-2), where, in formula (1-1), R.sub.7 and R.sub.8 independently represent a hydrogen atom, an alkyl group or a heterocyclic group, and where, in formula (1-2), R.sub.9 and R.sub.10 independently represent an amino group or a substituted amino group. A photopolymerization initiator can include said compound; and a photosensitive resin composition can include said photopolymerization initiator. ##STR00001##