Antiviral pyrrolopyridine derivatives and method for preparing the same
Inventors
Son, Jong Chan • Kim, Bong Jin • Kim, Jae Hak • Lee, Ill Young • YUN, Chang Soo • Lee, Sang Ho • Lee, Chong Kgo
Assignees
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Publication Number
US-9499537-B2
Publication Date
2016-11-22
Expiration Date
Abstract
The present invention relates to a pyrrolopyridine derivative represented by the Chemical Formula I, and a racemate or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and relates to an antiviral composition including the same as an active ingredient. The compound of the Chemical Formula I has excellent antiviral activity and selectivity for wild type and resistant HIV-1, and thereby is useful as a therapeutic agent for acquired immune deficiency syndrome (AIDS).
Core Innovation
The patent describes compounds represented by Chemical Formula I, including racemates, stereoisomers, and pharmaceutically acceptable salts. The compounds are defined by structural constraints on R2 being tert-butoxy, R6 being hydrogen or —(CH2)n—R7, R7 being hydrogen or selected functional groups and heteroaryl or cycloalkyl options, and n being an integer of 1 to 5.
The patent further characterizes compounds represented by Chemical Formula II or IV, where R2 is tert-butoxy, R6 is hydrogen or —(CH2)n—R7, R7 follows the same substituent definitions, n is an integer of 1 to 5, and R8 is C1-6 alkyl. In this structure framework, the allowed substituents include phenyl, pyridinyl, pyrimidinyl, dioxoisoindolinyl, oxazolyl, furanyl, thiophenyl, pyrrolidinyl, 2-oxopyrrolidinyl, pyrazolyl, and thiazolyl with defined substitution limits.
The patent also includes a method for preparing a compound represented by Chemical Formula I. The method includes preparing Chemical Formula IV by reacting a compound represented by Chemical Formula II with a compound represented by Chemical Formula III, followed by hydrolyzing Chemical Formula IV, with X as halogen, methanesulfonyl, p-toluenesulfonyl, or trifluoromethanesulfonyl.
Claims Coverage
The independent claim coverage includes Chemical Formula I compounds, Chemical Formula II or IV compounds, and a two-step method to prepare Chemical Formula I. Across these independent claims, the inventive features are the defined chemical scaffold with substituent constraints and the defined preparation sequence forming Chemical Formula IV followed by hydrolysis.
Chemical formula I compound scope
A compound represented by Chemical Formula I, a racemate or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R2 is tert-butoxy; R6 is hydrogen or —(CH2)n—R7; R7 is hydrogen or specified groups selected from halogen, hydroxy, amino, cyano, trifluoromethyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, carbamoyl, CONH(C1-3 alkyl), CON(C1-3 alkyl)2, COOH, C3-6 cycloalkyl, phenyl, pyridinyl, pyrimidinyl, dioxoisoindolinyl, oxazolyl, furanyl, thiophenyl, pyrrolidinyl, 2-oxopyrrolidinyl, pyrazolyl, and thiazolyl options, with n being an integer of 1 to 5.
Chemical formula II or IV compound scope
A compound represented by Chemical Formula II or IV, wherein R2 is tert-butoxy; R6 is hydrogen or —(CH2)n—R7; R7 is hydrogen or specified groups selected from halogen, hydroxy, amino, cyano, trifluoromethyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, carbamoyl, CONH(C1-3 alkyl), CON(C1-3 alkyl)2, COOH, C3-6 cycloalkyl, phenyl, pyridinyl, pyrimidinyl, dioxoisoindolinyl, oxazolyl, furanyl, thiophenyl, pyrrolidinyl, 2-oxopyrrolidinyl, pyrazolyl, and thiazolyl options, with n being an integer of 1 to 5 and R8 being C1-6 alkyl.
Two-step preparation to chemical formula I
A method for preparing a compound represented by Chemical Formula I comprising preparing a compound represented by Chemical Formula IV by reacting a compound represented by Chemical Formula II with a compound represented by Chemical Formula III, and hydrolyzing the compound represented by Chemical Formula IV, wherein R2 is tert-butoxy; R6 is hydrogen or —(CH2)n—R7; R7 is specified; n is an integer of 1 to 5; R8 is C1-6 alkyl; and X is halogen, methanesulfonyl, p-toluenesulfonyl or trifluoromethanesulfonyl.
Overall, the independent claims cover compounds of Chemical Formula I with defined substituent categories and n being 1 to 5, compounds of Chemical Formula II or IV with R8 as C1-6 alkyl, and a two-step method in which Chemical Formula IV is formed by reacting Chemical Formula II with Chemical Formula III and then converted to Chemical Formula I via hydrolysis, with specified definitions for the substituent parameters and X.
Stated Advantages
High selectivity and antiviral activity against HIV-1.
Low cytotoxicity.
Utility for treating AIDS.
Documented Applications
Antiviral use against HIV-1, including treatment of acquired immune deficiency syndrome (AIDS).
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