KR920004410A - 4-amino-Δ4.6-steroids and their use as 5α-reductase inhibitors - Google Patents

Abstract

No content

Description

4-amino-Δ4.5-steroids and their use as 5α-reductase inhibitors

As this is a public information case, the full text was not included.

Claims (18)

The following general formula compounds. Wherein R is hydrogen or C _1-4 alkyl; R ¹ is C _2-6 alkanoyl,-(C _1-6 alkyl) -OZ ¹ ,-(C _2-5 alkyl)-(OZ ¹ ) ₂ or -AC (O) -Y; Z ¹ is hydrogen, C _1-6 alkyl, phenyl- (C _1-4 alkyl), (Y ¹ -substitutedphenyl)-(C _1-4 alkyl), C _{1 -6} alkanoyl, benzoyl or Y ¹ -substituted benzoyl, wherein Y ¹ is methyl, halogen or methoxy; A is present or absent as alkylene of 1 to 6 carbon atoms; Y is -OH,- O (C _1-6 alkyl) or NR ³ R ⁴ ; R ³ and R ⁴ are each hydrogen, C _1-6 alkyl, C _3-6 cycloalkyl, or they are bonded- (CH ₂ ) n-( Wherein n is 4 to 6); R ² is hydrogen or methyl; R ¹ and R ² are joined to form -O-CH ₂ CH ₂ CH ₂ ...; R ⁵ is hydrogen Or methyl; X is O or (H) (H); Z is hydrogen or C _1-6 alkyl; the dashed lines in the ring each indicate that a double bond may be present, provided that 9,11-double bond Silver, X Can only be present when (H) (H), and R ² is absent if 16,17-double bond is present. A compound according to claim 1 having the following general formula. Wherein R is hydrogen or C _1-4 alkyl; R ¹ is C _2-6 alkanoyl, —CH (CH ₃ ) —CH ₂ OZ ¹ , —CH (CH ₃ ) —COO (C _1-6 Alkyl) or —C (O) —NR ³ R ⁴ ; R ² is hydrogen or methyl; R ¹ and R ² are joined to form —O—CH ₂ CH ₂ CH ₂ .. Z ¹ Are hydrogen, C _1-6 alkyl, or C _1-6 alkanoyl; R ³ and R ⁴ are each independently hydrogen, C _1-6 alkyl, C _3-6 cycloalkyl, or they are bonded-(CH ₂ ) n-, where n is 4 to 6. The compound of claim 2 having the following general formula. Wherein R is hydrogen or C _1-4 alkyl or C _1-6 alkanoyl; R ³ and R ⁴ are each independently hydrogen, C _1-6 alkyl, C _3-6 cycloalkyl, or they are bonded Form-(CH ₂ ) n-, where n is 4-6. A compound according to claim 3 having the general formula In said formula, R <^3> and R <^4> is respectively independently hydrogen and _C1-6 alkyl. The compound of claim 4, which is 4-amino-N (1,1-dimethylethyl) -3-oxoandrostar-4,6-diene-17β-carboxamide. The compound of claim 4, which is 4-amino-N, N-bis (1-methylethyl) -3-oxoandrostar-4,6-diene-17β-carboxamide. 4. The compound of claim 3, which is 4-acetamido-N- (1,1-dimethylethyl) -3-oxoandrostar-4,6-diene-17β-carboxamide. A compound according to claim 1 having the following general formula. Wherein R is hydrogen or C _1-4 alkyl, X is O or (H) (H); Z ¹ is hydrogen or C _1-6 alkyl, phenyl- (C _1-4 alkyl), (Y ¹ -substitutedphenyl)-(C _1-4 alkyl), C _1-6 alkanoyl, benzoyl or Y ¹ -substituted benzoyl, wherein Y ¹ is methyl, halogen or methoxy; each dotted line is a double bond , 9,11-double bond is present only when X is (H) (H), R ² is absent when 16,17-double bond is present. The compound of claim 8, having the general formula: Wherein R is hydrogen or C _1-4 alkyl; Z ¹ is hydrogen or C _1-6 alkanoyl 9. The compound of claim 8, which is (20S) -4-amino-21-hydroxy-20-methylpregna-4,6-dien-3-one. A method of treating a patient, comprising administering to a patient suffering from a DHT-related disease or condition an effective amount of a 5α-reductase inhibitor of a compound of the general formula: Wherein R is hydrogen or C _1-4 alkyl; R ¹ is C _2-6 alkanoyl,-(C _1-6 alkyl) -OZ ¹ ,-(C _2-5 alkyl)-(OZ ¹ ) ₂ or -AC (O) -Y; Z ¹ is hydrogen, C _1-6 alkyl, phenyl- (C _1-4 Alkyl), (Y ¹ -substitutedphenyl)-(C _1-4 alkyl), C _1-6 alkanoyl, benzoyl or Y ¹ -substituted benzoyl (Wherein Y ¹ is methyl, halogen or methoxy); A is present or absent as alkylene having 1 to 6 carbon atoms; and Y is -OH, -O (C _1-6 alkyl) or NR ³ R ⁴ ; R ³ and R ⁴ are each hydrogen, C _1-6 alkyl, C _3-6 cycloalkyl, or they are bonded to form — (CH ₂ ) n — where n is 4 to 6; R ² is hydrogen or methyl; R ¹ and R ² are joined to form —O—CH ₂ CH ₂ CH ₂ ...; R ⁵ is hydrogen or methyl; X is O or (H) ( H); Z is hydrogen or C _1-6 alkyl; the dashed lines in the ring each indicate that a double bond may be present, provided that 9,11-double bonds are only when X is (H) (H) Can be present and when there is a 16,17-double bond there is no R ² . The method of claim 11, comprising administering a compound of the general formula: Wherein R is hydrogen or C _1-4 alkyl; R ³ and R ⁴ are each independently hydrogen, C _1-6 alkyl, C _3-6 cycloalkyl, or they are combined-(CH ₂ ) n Form (where n is 4 to 6). The method of claim 12, comprising administering 4-amino-N- (1,1-dimethylethyl) -3-oxoandrostar-4,6-diene-17β-carboxamide. A method of treating a patient, comprising administering to the patient in need of benign prostatic hypertrophy treatment an effective amount of a 5α-reductase inhibitor of a compound of the general formula: Wherein R is hydrogen or C _1-4 alkyl; R ¹ is C _2-6 alkanoyl,-(C _1-6 alkyl) -OZ ¹ ,-(C _2-5 alkyl)-(OZ ¹ ) ₂ or -AC (O) -Y; Z ¹ is hydrogen, C _1-6 alkyl, phenyl- (C _1-4 alkyl), (Y ¹ -substitutedphenyl)-(C _1-4 alkyl), C _{1 -6} alkanoyl, benzoyl or Y ¹ -substituted benzoyl, wherein Y ¹ is methyl, halogen or methoxy; A is present or absent as alkylene of 1 to 6 carbon atoms; Y is -OH,- 0 (C _1-6 alkyl) or NR ³ R ⁴ ; R ³ and R ⁴ are each hydrogen, C _1-6 alkyl, C _3-6 cycloalkyl, or they are bonded- (CH ₂ ) n-( Wherein n is 4 to 6); R ² is hydrogen or methyl; R ¹ and R ² are joined to form -O-CH ₂ CH ₂ CH ₂ ...; R ⁵ is hydrogen Or methyl; X is O or (H) (H); Z is hydrogen or C _1-6 alkyl; the dashed lines in the ring each indicate that a double bond may be present, provided that 9,11-double bond Silver, X Can only be present when (H) (H), and R ² is absent if 16,17-double bond is present. 15. The method of claim 14, wherein the compound administered is (20S) -4-amino-21-hydroxy-20-methylpregna-4,6-dien-3-one. A process for preparing a compound of formula (I), consisting of reacting a compound of formula (II) with NaN _{3 in} an inert solvent at 100 ° in the presence of sulfuric acid. Wherein R ¹ is C _2-6 alkanoyl,-(C _1-6 alkyl) -OZ ¹ ,-(C _2-5 alkyl)-(OZ ¹ ) ₂ or -AC (O) -Y; Z ¹ is hydrogen, C _1-6 alkyl, phenyl- (C _1-4 alkyl), (Y ¹ -substitutedphenyl)-(C _1-4 alkyl), C _1-6 alkanoyl, benzoyl or Y ¹ -substituted benzoyl Wherein Y ¹ is methyl, halogen or methoxy; A is present or absent as alkylene having 1 to 6 carbon atoms; Y is -OH, -0 (C _1-6 alkyl) or NR ³ R ⁴ ; R 2 is hydrogen, or R ¹ and R ² are joined to form —O—CH ₂ CH ₂ CH ₂ .. R ³ and R ⁴ are each independently hydrogen, C _1-6 alkyl, C _3-6 cycloalkyl, or they are combined to form — (CH ₂ ) n — where n is 4 to 6; R ⁵ is hydrogen or methyl; X is O or (H) (H Z is hydrogen or C _1-6 alkyl; the dashed lines in the ring each indicate that a double bond may be present, provided that 9,11-double bonds only exist when X is (H) (H) Can , R ² is not present when 16,17- double bond is present. 18-Amino-N- (according to claim 16, consisting of reacting N- (1,1-dimethylethyl) -4,5-epoxy-3-oxoandrostar-17β-carboxamide with NaN _3. Process for the preparation of 1,1-dimethylethyl) -3-oxoandrostar-4,6-diene-17β-carboxamide. The (20S) -4-amino-21-hydroxy of claim 16, consisting of reacting (20S) -4,5-epoxy-21-hydroxy-20-methylpregnan-3one with NaN _3. Method for preparing -20-methylpregnan-4,6-diene-3one. ※ Note: The disclosure is based on the initial application.