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US 2002/0002163 A1Published application
1,4-benzodiazepinones and their uses as CCK antagonists
AssigneeFujisawa Pharmaceutical Co., Ltd.
InventorsYoshinari Sato, Seiichiro Tabuchi, Hitoshi Mitsui, Ikuyo Katsumi, Naoko Yamamoto
Life of this patent
Estimating the term…
Abstract
Benzodiazepine derivatives of the formula: 1 wherein R1 is heterocyclic(lower)alkyl which may have one or more suitable substituent(s), etc., R2 is lower alkyl, etc., R3 is indolyl, etc., R4 is hydrogen, etc., or a pharmaceutically acceptable salt thereof, which are useful as a medicament.
Claims11
A Compound of the formula:
- 24
- [Wherein
- R1 is
- (1) lower alkyl;
- (2) hydroxy(lower)alkyl;
- (3) protected hydroxy(lower)alkyl;
- (4) heterocyclic(lower)alkyl which may have one or more suitable substituent(s);
- (5) aryl(lower)alkyl which may have one or more suitable substituent(s)],
- (6) carboxy(lower)alkyl;
- (7) protected carboxy(lower)alkyl;
- or
- (8)
- 25
- [wherein
- A is lower alkylene and
- R5 is
- (a) lower alkyl,
- (b) C3-C8 cycloalkyl,
- (c) adamantyl,
- (d) aryl which may have one or more suitable substituent(s),
- (e) amino which may have one or two suitable substituent(s)
- (f) azabicyclo[3.2.2]nonyl, or
- (g) saturated heteromonocyclic group containing at least one nitrogen atom, which may have one or more suitable substituent(s)],
- R2 is
- (1) lower alkyl,
- (2) C3-C8 cycloalkyl,
- (3) lower alkoxy(lower)alkyl,
- (4) C3-C8 cycloalkyl(lower)alkyl,
- (5) N,N-di(lower)alkylamino(lower)alkyl,
- (6) lower alkylpiperazinyl(lower)alkyl,
- (7) lower alkylthio(lower)alkyl,
- (8) hydroxy(lower)alkyl,
- (9) protected hydroxy(lower)alkyl,
- (10) azabicyclo[3.2.2]nonyl(lower)alkyl,
- (11) ary] which may have one or more suitable substituent(s),
- (12) cyano,
- (13) lower alkanoyl,
- (14) carboxy(lower)alkenyl, or
- (15) protected carboxy(lower)alkenyl,
- R3 is indolyl or —NH-R6, and
- R4 is
- (1) hydrogen,
- (2) lower alkyl,
- (3) halogen, or
- (4) di(lower)alkylamino,
- with proviso that when R4 is hydrogen, then R2 is lower alkyl or C3-C8 cycloalkyl(lower)alkyl,
- or a pharmaceutically acceptable salt thereof.
44 more elements
A process for preparing a compound of the formula;
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- Wherein
- R1 is
- (1) lower alkyl;
- (2) hydroxy(lower)alkyl;
- (3) protected hydroxy(lower)alkyl;
- (4) heterocyclic(lower)alky which may have one or more suitable substituent(s);
- (5) aryl(lower)alkyl which may have one or more suitable substituent(s);
- (6) carboxy(lower)alkyl;
- (7) protected carboxy(lower)alkyl;
- or
- (8)
- 32
- [wherein
- A is lower alkylene and
- R5 is
- (a) lower alkyl,
- (b) C3-C8 cycloalkyl,
- (c) adamantyl,
- (d) aryl which may have one or more suitable substituent(s),
- (e) amino which may have one or two suitable substituent(s),
- (f) azabicyclo[3.2.2]nonyl, or
- (g) saturated heteromonocyclic group containing at least one nitrogen atom, which may have one or more suitable substituent(s)],
- R2 is
- (1) lower alkyl,
- (2) C3-C8 cycloalkyl,
- (3) lower alkoxy(lower)alkyl,
- (4) C3-C8 cycloalkyl(lower)alkyl,
- (5) N,N-di(lower)alkylamino(lower)alkyl,
- (6) lower alkylpiperazinyl(lower)alkyl,
- (7) lower alkylthio(lower)alkyl,
- (8) hydroxy(lower)alkyl,
- (9) protected hydroxy(lower)alkyl,
- (10) azabicyclo[3.2.2]nonyl(lower)alkyl,
- (11) aryl which may have one or more suitable substituent(s),
- (12) cyano,
- (13) lower alkanoyl,
- (14) carboxy(lower)alkenyl, or
- (15) esterified carboxy(lower)alkenyl,
- R3 is indolyl or —NH-R6, and substituent(s), or
- R4 is
- (1) hydrogen,
- (2) lower alkyl,
- (3) halogen, or
- (4) di(lower)alkylamino,
- with proviso that when R4 is hydrogen, then R2 is lower alkyl or C3-C8 cycloalkyl(lower)alkyl, or a salt thereof, which comprises,
- (1) reacting a compound of the formula (II):
- 33
- wherein R1, R2 and R4 are each as defined above, or its reactive derivatives at the amino group or a salt thereof with a compound of the formula (III):
- 34
- wherein R3 is each as defined above, or its reactive derivative or a salt thereof to give a compound of the formula (I):
- 35
- wherein R1, R2, R3 and R4 are each as defined above, or a salt thereof,
- (2) reacting a compound of the formula (IV):
- 36
- wherein R2, R3, and R4 are each as defined above, or a salt thereof with a compound of the formula (V):
- X-R1 (V)
- wherein R1 is as defined above, X is halogen,or a salt thereof to give a compound of the formula (I):
- 37
- wherein R1, R2, R3 and R4 are each as defined above, or a salt thereof,
- (3) reacting a compound of the formula (VI):
- 38
- wherein R2, R3, R4 and A are each as defined above, or its reactive derivative at the carboxy group or a salt thereof with a compound of the formula (VII):
- 39
- wherein
- 40
- is saturated heteromonocyclic group containing at least one nitrogen atom, which may have one or more suitable substituent(s) or its reactive derivative at the imino group or salt thereof to give a compound of the formula (Ia):
- 41
- wherein R2, R3, R4, A and
- 42
- are each as defined above, or a salt thereof, or
- (4) reacting a compound of the formula (VI):
- 43
- wherein R2, R3, R4 and A are each as defined above, or its reactive derivative at the carboxy group or a salt thereof with a compound of the formula (VIII):
- 44
- wherein R7 is hydrogen, lower alkyl, or hydroxy(lower)alkyl, R8 is lower alkyl, hydroxy(lower)alkyl, aryl(lower)alkyl or pyridyl, or its reactive derivative at the imino group or a salt thereof to give a compound of the formula (Ib):
- 45
- wherein R2, R3, R4, R7, R8 and A are each as defined above, or a salt thereof.
75 more elements
Dependencies are inferred from the claim text.