Method of increasing neutrophil production using optically-pure (R)-2,3-benzodiazepines
AssigneeVela Pharmaceuticals, Inc.
InventorsHerbert W. Harris, Robert F. Kucharik
Life of this patent
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Abstract
Compounds according to formula I: 1 wherein R1, R2, R3, R4, R5 and n are as defined herein, are administered to increase neutrophil levels in mammels.
Claims20
A method of increasing the absolute neutrophil count in an individual, comprising administering to said individual an effective amount of at least one compound of formula I:
- 12
- wherein:
- R1 is —(C1-C7)hydrocarbyl or —(C2-C6)heteroalkyl;
- R2 is selected from the group consisting of —H, and —(C1-C7)hydrocarbyl;
- wherein R1 and R2 may combine to form a carbocyclic or heterocyclic 5- or 6-membered ring;
- R3 is independently selected from the group consisting of —O(C1-C6)alkyl, —OH, —O-acyl, —SH, —S(C1-C3)alkyl, —NH2, —NH(C1-C6)alkyl, —N((C1-C6)alkyl)2, —NH-acyl, —NO2 and halogen;
- n is 1, 2 or 3;
- R4 and R5 are independently selected from the group consisting of —O(C1-C6)alkyl, —OH, O-acyl, —SH, —S(C1-C3)alkyl, —NH2, NH-acyl and halogen;
- wherein, R4 and R5 may combine to form a 5, 6 or 7-membered heterocyclic ring;
- and
- wherein, compounds according to formula I are (R)-enantiomers substantially free of the corresponding (S)-enantiomers, with respect to the absolute conformation at the 5-position of the benzodiazepine ring;
- or a pharmaceutically-acceptable salt of such a compound.
A method of treating an individual afflicted with neutropenia, comprising administering to said individual an effective amount of at least one compound of formula I:
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- wherein:
- R1 is —(C1-C7)hydrocarbyl or —(C2-C6)heteroalkyl;
- R1 is selected from the group consisting of —H, and —(C1-C7)hydrocarbyl;
- wherein R1 and R2 may combine to form a carbocyclic or heterocyclic 5- or 6-membered ring;
- R3 is independently selected from the group consisting of —O(C1-C6)alkyl, —OH, —O-acyl, —SH, —S(C1-C3)alkyl, —NH2, —NH(C1-C6)alkyl, —N((C1-C6)alkyl)2, —NH-acyl, —NO2 and halogen;
- n is 1, 2 or 3;
- R4 and R5 are independently selected from the group consisting of —O(C1-C6)alkyl, —OH, O-acyl, —SH, —S(C1-C3)alkyl, —NH2, NH-acyl and halogen;
- wherein, R4 and R5 may combine to form a 5, 6 or 7-membered heterocyclic ring;
- wherein, compounds according to formula I are (R)-enantiomers substantially free of the corresponding (S)-enantiomers, with respect to the absolute conformation at the 5-position of the benzodiazepine ring;
- or a pharmaceutically-acceptable salt of such a compound.
A method of preventing neutropenia in an individual who is at risk of developing neutropenia, said method comprising administering to said individual an effective amount of at least one compound of formula I:
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- wherein:
- R1 is —(C1-C7)hydrocarbyl or —(C2-C6)heteroalkyl;
- R2 is selected from the group consisting of —H, and —(C1-C7)hydrocarbyl;
- wherein R1 and R2 may combine to form a carbocyclic or heterocyclic 5- or 6-membered ring;
- R3 is independently selected from the group consisting of —O(C1-C6)alkyl, —OH, —O-acyl, —SH, —S(C1-C3)alkyl, —NH2, —NH(C1-C6)alkyl, —N((C1-C6)alkyl)2, —NH-acyl, —NO2 and halogen;
- n is 1, 2 or 3;
- R4 and R5 are independently selected from the group consisting of —O(C1-C6)alkyl, —OH, O-acyl, —SH, —S(C1-C3)alkyl, —NH2, NH-acyl and halogen;
- wherein, R4 and R5 may combine to form a 5, 6 or 7-membered heterocyclic ring;
- and
- wherein, compounds according to formula I are (R)-enantiomers substantially free of the corresponding (S)-enantiomers, with respect to the absolute conformation at the 5-position of the benzodiazepine ring;
- or a pharmaceutically-acceptable salt of such a compound.
Dependencies are inferred from the claim text.