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US 6,187,809 B1Granted
Tricyclic compounds and drug compositions containing the same
AssigneeAsahi Kasei Kogyo Kabushiki Kaisha
InventorsShiro Miyoshi, Kohei Ogawa
Life of this patent
Estimating the term…
Abstract
Compounds having a β-3 adrenaline receptor agonist and are useful as drugs for the treatment and prevention of diabetes, obesity, hyperlipemia, etc., represented by a general formula (I) and salts thereof, and a process for producing these, and their intermediates, wherein R represents hydrogen or methyl; R1 represents hydrogen, halogen, hydroxy, benzyloxy, amino, or hydroxymethyl; R2 represents hydrogen, hydroxymethyl, NHR3, SO2NR4R4, or nitro; R6 represents hydrogen or lower alkyl; and X represents nitrogen, R9 represents hydrogen, one of R7 and R8 represent hydrogen, and the other thereof represents hydrogen, amino, acetylamino, or hydroxy.
Claims16
A compound represented by the general formula (I) or a salt thereof:
- in which R represents hydrogen atom or methyl, R1 stands for hydrogen atom, halogen atom, hydroxy, benzyloxy, amino or hydroxymethyl, R2 stands for hydrogen atom, hydroxymethyl, NHR3, SO4NR4R4′ stand for hydrogen atom, methyl, SO2R5, formyl or CONHR6′, with R5 being lower alkyl, benzyl or NR4R4′ and R6′ being hydrogen atom or lower alkyl, and R4 and R4′ may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzyl, R6 represents hydrogen atom or lower alkyl, X is oxygen atom or sulfur atom, R9 stands for hydrogen atom and either one of R7 and R8 is hydrogen atom, and the other one is hydrogen atom, amino, acetyl amino or hydroxy, and *1 indicate an asymmetric carbon atom and *2 indicates that the carbon atom is asymmetric provided that R6 is lower alkyl.
A method for producing a compound represented by the general formula (I)
- in which R represents hydrogen atom, R1 stands for hydrogen atom, halogen atom, hydroxy, benzyloxy, amino or hydroxymethyl, R2 stands for hydrogen atom, hydroxymethyl, NHR3, SO2NR4R4′ or nitro, wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6′, with R5 being lower alkyl, benzyl or NR4 and R4′ being hydrogen atom or lower alkyl, and R4 and R4′ may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzyl, R6 represents hydrogen atom or lower alkyl, X is oxygen atom or sulfur atom, R9 stands for hydrogen atom and either one of R7 and R8 is hydrogen atom and the other one is hydrogen atom, amino, acetylamino or hydroxy, and *1 indicates an asymmetric carbon atom and *2 indicates that the carbon atom is asymmetric provided that R6 is lower alkyl, comprising the step of reacting a compound represented by general formula (II)
- in which R1 represent hydrogen atom, halogen atom, a protected hydroxyl group protected by a protecting group A, a protected amino group protected by acetyl group or a protected hydroxymethyl group protected by acetyl group, R2′ stands for hydrogen atom, for a protected hydroxymethyl group in which the hydroxyl group is protected by a protecting group A″′ for NHR3′, for SO2NR4R4′ or for nitro, wherein R3′ represents a protecting group for the amino group, methyl, SO2R5, formyl or CONHR6′, with R5 being lower alkyl, benzyl or NR4R4′ and R6′ being hydrogen atom or lower alkyl, R4 and R4′ may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzyl, R6 denotes hydrogen atom or lower alkyl, A′ represents a protecting group for the hydroxyl group, B is bromine atom or iodine atom and *1 indicates an asymmetric carbon atom with a compound represented by the general formula (III)
- in which Y represents hydrogen atom, R6 is hydrogen atom or lower alkyl, X is oxygen atom or sulfur atom, R9′ is hydrogen atom and either one of R7′ and R8′ is hydrogen atom and the other one is hydrogen atom, acetylamino or a protected hydroxyl group protected by A protecting group A″, and *2 indicates that the carbon atom is asymmetric provided that R6 is lower alkyl,
- wherein the protecting groups A, A′, A″, and A″′ as well as the protecting group for the amino group in R3′ and the protecting acetyl group in R1′ are eliminated for protection with the proviso that the protecting group A is not eliminated if A is benzyl and R1 is benzyloxy.
1 more element
A compound represented by the general formula (III)
- in which Y represents hydrogen atom or a protecting group for the amino group, R6 is hydrogen atom or lower alkyl, X is oxygen atom or sulfur atom, R3′ is hydrogen atom and either one of R7′ and R8′ is hydrogen atom and the other one is hydrogen atom, acetylamino or a protected hydroxyl group protected by a protecting group A″, and *2 indicates that the carbon atom is asymmetric provided that R6 is lower alkyl.
A compound represented by the general formula (IV)
- in which R1′ reprsents hydrogen atom, halogen atom, a protected hydroxyl group protected by a protecting group A, a protected amino group protected by acetyl group or a protected hydroxymethyl group in which the hydroxyl group is protected by acetyl group, R6 stands for hydrogen atom or lower alkyl, Y′ is hydrogen atom or a proctecting group for the amino group, X is oxygen atom or sulfur atom, R9′ is hydrogen atom and either one of R7′ and R8′ is hydrogen atom and the other one is acetylamino or a protected hydroxyl group protected by a protecting group A″, A′ represents a protecting group for the hydroxyl group, *1 indicates an asymmetric carbon atom and *2 indicates that the carbon atom is asymmetric provided that R6 lower alkyl.
Dependencies are inferred from the claim text.