The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure: ##STR00001##
wherein
A is an aryl or heteroaryl, each with or without subsutitution; and
R.sub.1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), NH-(alkyl), N(alkyl).sub.2, NH-(alkenyl), NH-(alkynyl)NH-(aryl), NH-(heteroaryl), O-(alkyl), O-(alkenyl), O-(alkynyl), O-(aryl), O-(heteroaryl), S-(alkyl), S-(alkenyl), S-(alkynyl), S-(aryl), or S-(heteroaryl),
comprising:
(a) reacting a compound having the structure: ##STR00002##
with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: ##STR00003##
and
(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: ##STR00004##

The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure: ##STR00001##
wherein
A is an aryl or heteroaryl, each with or without subsutitution; and
R.sub.1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), NH-(alkyl), N(alkyl).sub.2, NH-(alkenyl), NH-(alkynyl)NH-(aryl), NH-(heteroaryl), O-(alkyl), O-(alkenyl), O-(alkynyl), O-(aryl), O-(heteroaryl), S-(alkyl), S-(alkenyl), S-(alkynyl), S-(aryl), or S-(heteroaryl),
comprising:
(a) reacting a compound having the structure: ##STR00002##
with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: ##STR00003##
and
(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: ##STR00004##

The present invention provides a compound represented by general formula I or a pharmaceutical acceptable salt thereof, the preparation method therefor and the use thereof in preparing a medicine for treating a neurological disease, such as epilepsy, convulsion, neuropathic pain, acute ischemic stroke, and a neurodegenerative disease. The compound according to present invention has a better absorption in brain tissue when compared with RTG. In addition, the compound provided by present invention has not only a greatly enhanced efficacy, but also a neurotoxicity greatly lower than that of RTG, and thus possesses a wider safety window. ##STR00001##

The present invention provides a compound represented by general formula I or a pharmaceutical acceptable salt thereof, the preparation method therefor and the use thereof in preparing a medicine for treating a neurological disease, such as epilepsy, convulsion, neuropathic pain, acute ischemic stroke, and a neurodegenerative disease. The compound according to present invention has a better absorption in brain tissue when compared with RTG. In addition, the compound provided by present invention has not only a greatly enhanced efficacy, but also a neurotoxicity greatly lower than that of RTG, and thus possesses a wider safety window. ##STR00001##

Compounds of formula (I):

##STR00001##

where

##STR00002##

n, R.sup.1, R.sup.4a, R.sup.4b, R.sup.5, R.sup.7 and R.sup.8 are defined herein, or pharmaceutically acceptable salts thereof, are described herein. The disclosed compounds have activity as SHIP1 modulators, and thus may be used to treat any of a variety of diseases, disorders or conditions that would benefit from SHIP1 modulation. Compositions comprising a compound of formula (I) in combination with a pharmaceutically acceptable carrier or diluent are also disclosed, as are methods of SHIP1 modulation by administration of such compounds to an animal in need thereof.

The present invention provides a compound represented by general formula I or a pharmaceutical acceptable salt thereof, the preparation method therefor and the use thereof in preparing a medicine for treating a neurological disease, such as epilepsy, convulsion, neuropathic pain, acute ischemic stroke, and a neurodegenerative disease. The compound according to present invention has a better absorption in brain tissue when compared with RTG. In addition, the compound provided by present invention has not only a greatly enhanced efficacy, but also a neurotoxicity greatly lower than that of RTG, and thus possesses a wider safety window.

##STR00001##

The present invention provides a compound represented by general formula I or a pharmaceutical acceptable salt thereof, the preparation method therefor and the use thereof in preparing a medicine for treating a neurological disease, such as epilepsy, convulsion, neuropathic pain, acute ischemic stroke, and a neurodegenerative disease. The compound according to present invention has a better absorption in brain tissue when compared with RTG. In addition, the compound provided by present invention has not only a greatly enhanced efficacy, but also a neurotoxicity greatly lower than that of RTG, and thus possesses a wider safety window.

##STR00001##

Compounds of formula (I): ##STR00001##
where ##STR00002##
n, R.sup.1, R.sup.4a, R.sup.4b, R.sup.5, R.sup.7 and R.sup.8 are defined herein, or pharmaceutically acceptable salts thereof, are described herein. The disclosed compounds have activity as SHIP1 modulators, and thus may be used to treat any of a variety of diseases, disorders or conditions that would benefit from SHIP1 modulation. Compositions comprising a compound of formula (I) in combination with a pharmaceutically acceptable carrier or diluent are also disclosed, as are methods of SHIP1 modulation by administration of such compounds to an animal in need thereof.

The present invention relates to the design, synthesis, and biological study of multi-targeted Ubenimex pro-drug derivative. More particularly, provided in the present invention is a compound as shown by general structural formula (I) (wherein the definition of R is shown in the description). The derivative is a multi-targeted compound obtained by binding an aminopeptidase (APN/CD13) inhibitor, Ubenimex, with some anti-tumor drugs already on the market through an ester bond or amide bond, and is suitable for use as an anti-tumor drug for the treating various malignant tumors, and is especially suitable for treating various solid tumors. ##STR00001##

The present invention relates to the design, synthesis, and biological study of multi-targeted Ubenimex pro-drug derivative. More particularly, provided in the present invention is a compound as shown by general structural formula (I) (wherein the definition of R is shown in the description). The derivative is a multi-targeted compound obtained by binding an aminopeptidase (APN/CD13) inhibitor, Ubenimex, with some anti-tumor drugs already on the market through an ester bond or amide bond, and is suitable for use as an anti-tumor drug for the treating various malignant tumors, and is especially suitable for treating various solid tumors. ##STR00001##