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US 7,060,722 B2Granted
Proline derivatives and use thereof as drugs
AssigneeMitsubishi Pharma Corporation
InventorsHiroshi Kitajima, Hiroshi Sakashita, Fumihiko Akahoshi, Yoshiharu Hayashi
Life of this patent
Estimating the term…
Abstract
The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.
Claims8
An L-proline derivative of the formula (I)
- wherein
- X is —NR1R2 wherein one of R1 and R2 is a hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, and the other is a hydrogen atom, alkyl, cycloalkyl or aryl,
- Y is CH2, CH—OH, S, S═O or SO2,
- Z is a hydrogen atom or a cyano, and
- of the above-mentioned groups, alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and cycloalkylalkyl each optionally have substituents,
- or a pharmaceutically acceptable salt thereof.
3 more elements
An L-proline derivative of the formula (I)
- wherein
- X is a group of the formula (III)
- wherein
- R12 is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —NR14R15, —OR16, —COR17, CO2R18, —CONR19R20 or —SO2R21 wherein R14, R15, R16, R17, R18, R19, R20 and R21 are the same or different and each is independently a hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl or haloalkyl, or R14 and R15, and R19 and R20 may be bonded to each other to form heterocycles each optionally containing 1 or 2 nitrogen atoms or oxygen atoms, said heterocycle optionally being condensed with an aromatic ring optionally having substituents, and
- R13 is a hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl,
- Y is CH2, CH—OH, S, S═O or SO2,
- Z is a hydrogen atom or a cyano, and
- of the above-mentioned groups, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and heterocycle each optionally have substituents,
- or a pharmaceutical acceptable salt thereof.
6 more elements
A compound of the formula (I-a)
- wherein
- X is —NR1R2 wherein R1 and R2 is the same or different and each is independently a hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, or may be bonded to each other to form a heterocycle optionally containing 1 or 2 nitrogen atoms or oxygen atoms, the heterocycle optionally being condensed with an aromatic ring optionally having substituents, and the heterocycle optionally being a spiro ring,
- —NR3COR4 wherein R3 and R4 are the same or different and each is independently a hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, arylalkenyl, heteroaryl or heteroarylalkyl,
- —NR5CONR6R7 or —NR5CH2CH2NR6R7 wherein R5, R6 and R7 are the same or different and each is independently a hydrogen atom, alkyl, acyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, or R6 and R7 may be bonded to each other to form a heterocycle optionally containing 1 or 2 nitrogen atoms or oxygen atoms, said heterocycle optionally being condensed with an aromatic ring optionally having substituents, or
- —NR8SO2R9 wherein R8 and R9 are the same or different and each is independently a hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl,
- Y is CH2, CH—OH, S, S═O or SO2,
- Z is a hydrogen atom or a cyano,
- R35 is —COR41, wherein R41 is a hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl or —COOR42 wherein R42 is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, and
- of the above-mentioned groups, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl and heterocycle each optionally have substituents.
6 more elements
A compound of the formula (I-b)
- wherein
- Z is a hydrogen atom or a cyano, and
- R35 is —COR41, wherein R41 is a hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, or —COOR42 wherein R42 is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, and
- of the above-mentioned groups, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl each optionally have substituents.
1 more element
Dependencies are inferred from the claim text.