KR910009724A - Aromatic Steroid 5-α-Reductase Inhibitor - Google Patents

Abstract

No content

Description

Aromatic Steroid 5-α-Reductase Inhibitor

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

Claims (15)

A compound of formula (I) or a pharmaceutically acceptable salt thereof; Has an optional double bond indicated by the above formula, B, C and D ring broken lines, provided that, C ring B ring C ₈ -C ₉ does not have a double bond when you have a double bond, ring D ³ is R 2 or two substituents Does not have a C ₁₆ -C ₁₇ double bond when represents a substituent; X ¹ , X ² and X ³ are H, Cl, F, Br, I, CF ₃ , or C _1-6 alkyl, OH, C _1-6 alkoxy, CN, NO ₂ , N (R ¹ ) ₂ , CHO Or any accessible combination of CO ₂ R ¹ , A is oxygen or sulfur, n is 0 or 1 and R ¹ is each independently H or C _1-6 alkyl; R ³ represents (1) α-hydrogen, α-hydroxyl or α-acetoxy and / or (a) [Wherein W is a bond or C _1-12 alkyl, R ⁴ is (i) hydrogen, (ii) hydroxyl, (iii) C _1-8 alkyl, (iii) hydroxy C _1-8 alkyl, ) C _1-8 alkoxy, (i) NR ⁵ R ⁶ wherein R ⁵ and R ⁶ are each independently selected from hydrogen, C _1-8 alkyl, C _3-6 cycloalkyl and phenyl, or R ⁵ and R ⁶ represents a 5-6 membered saturated ring containing one or less other heteroatoms selected from oxygen and nitrogen together with the nitrogen to which they are attached, or (iii) OR ⁷ where R ⁷ is an alkali metal, C _1-18 alkyl or benzyl)], or (b) β-Aik-OR ⁸ wherein Aik is C _1-12 alkyl, R ⁸ is (ⅰ) phenyl C _1-8 alkylcarbonyl, ( Ii) C _5-10 cycloalkylcarbonyl, (iii) benzoyl, (iii) C _1-8 alkoxycarbonyl, (iii) amino, or C _{1-8 alkylsubstituted} amino or carbonyl, or (iii) C _1-8 alkyl; (2) = CH-W-CO-R ⁴ or = CH-W-OR ⁸ , wherein W is a bond or C _1-12 alkyl, R ⁴ and R ⁸ have the same meaning as described above, and R ⁸ is Also C _1-20 alkylcarbonyl); (3) (Where the bond of the dotted line replaces 17-α-hydrogen); (4) α-hydrogen and β-NHCOR ⁹ (wherein R ⁹ is C _1-12 alkyl) or α-NR ⁵ R ⁶ , wherein R ⁵ and R ⁶ are as defined above, or (5) α-hydrogen and β-cyano; (6) α-hydrogen and β-tetrazolyl or (7) keto. The compound of claim 1 or a pharmaceutically acceptable salt thereof: Wherein X ⁴ , X ⁵ and X ⁶ are independently hydrogen, halo or C _1-8 alkyl; R ¹ is hydrogen or C _1-8 alkyl; R ¹³ is (a) CH (CH ₃ ) CH ₂ OR ¹ or (b) CONR ¹ R ¹ . The compound of claim 2, wherein the R ¹ substituent in the 3-position is hydrogen. The 17β- (N, N-diisopropyl carboxamide) -estr-1,3,5 (10) -triene-3-carboxylic acid or salt thereof. The 17β- (N-tert-butylcarboxamide) -estr-1,3,5 (10) -triene-3-carboxylic acid or salt thereof according to claim 3. The method of claim 1, wherein the 17β- (N, N-diisopropyl carboxamide) -2-methyl-estr-1,3,5 (10) -triene-3-carboxylic acid or salt thereof, 17β- ( N, N-diisopropyl carboxamide) -4-methyl-estr-1,3,5 (10) -triene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carbox) Amide) -2-chloro-estr-1,3,5 (10) -triene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carboxamide) -4-chloro-estr -1,3,5 (10) -triene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carboxamide) -estr-1,3,5 (10), 16-tetra En-3-carboxylic acids or salts thereof. 17β- (N-tert-butyl carboxamide) -estr-1,3,5 (10), 16-tetraene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carbox) Amide) -estr-1,3,5 (10), 6-tetraene-3-carboxylic acid or salts thereof. The ring of claim 1 wherein the B, C and D rings contain no double bonds, n is 1, A is 0, X ¹ , X ² and X ³ are hydrogen, and R ³ is β-CH (CH ₃ ) CH ₂ OR ¹ or β-CONR ¹ R ¹ . The method according to claim 7, wherein 17β- (N, N-diisopropyl carboxamide) -estr-1,3,5 (10) -triene-3-acetic acid or a pharmaceutically acceptable salt thereof and 17β- (Nt-butylcarbox amide) -estr-1,3,5 (10) -triene-3-acetic acid or a pharmaceutically acceptable salt thereof. A pharmaceutical composition containing a suitable pharmaceutical carrier and the compound of claim 1. The compound of claim 9, wherein the compound is 17β- (N-tert-butylcarboxamide) -estr-1,3,5 (10) -triene-3-carboxylic acid or salt thereof, 17β- (N, N -Diisopropyl carboxamide) -estre-1,3,5 (10) -triene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carboxamide) -2-methyl- Estre-1,3,5 (10) -triene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carboxamide) -4-methyl-estre-1,3,5 ( 10) -triene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carboxamide) -2-chloro-estr-1,3,5 (10) -triene-3-carboxylic acid Or salts thereof, 17β- (N, N-diisopropyl carboxamide) -4-chloro-estr-1,3,5 (10) -triene-3-carboxylic acid or salts thereof, 17β- (N, N-diisopropyl carboxamide) -ester-1,3,5 (10), 16-tetraene-3-carboxylic acid or salt thereof, 17β- (N-tert-butylcarboxamide) -ester -1,3,5 (10), 16-tetraene-3-carboxylic acid or salt thereof, 1 7β- (N, N-diisopropylcarboxamide) -estr-1,3,5 (10), 6,8-pentaene-3-carboxylic acid or salt thereof, 17β- (NN-diisopropyl car Voxamide) -estr-1,3,5 (10), 6-tetraene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carboxamide) -estr-1,3, 5 (10) -triene-3-acetic acid or a salt thereof, 17β- (Nt-butylcarbox amide) -estr-1,3,5 (10) -triene-3-acetic acid or an acceptable salt thereof A composition selected from the group consisting of. A method of inhibiting steroid 5-α-reductase activity in a patient, characterized by administering an effective amount of the compound of claim 1 to the patient. 12. The compound of claim 11, wherein the compound is 17β- (N-tert-butylcarboxamide) -estr-1,3,5 (10) -triene-3-carboxylic acid or salt thereof, 17β- (N, N -Diisopropyl carboxamide) -estre-1,3,5 (10) -triene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carboxamide) -2-methyl- Estre-1,3,5 (10) -triene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carboxamide) -4-methyl-estre-1,3,5 ( 10) -triene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carboxamide) -2-chloro-estr-1,3,5 (10) -triene-3-carboxylic acid Or salts thereof, 17β- (N, N-diisopropyl carboxamide) -4-chloro-estr-1,3,5 (10) -triene-3-carboxylic acid or salts thereof, 17β- (N, N-diisopropyl carboxamide) -ester-1,3,5 (10), 16-tetraene-3-carboxylic acid or salt thereof, 17β- (N-tert-butyl carboxamide) -ester -1,3,5 (10), 16-tetraene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carboxamide) -estr-1,3,5 (10), 6,8-pentaene-3-carboxylic acid or salt thereof, 17β- (NN-diisopropyl car Voxamide) -estr-1,3,5 (10), 6-tetraene-3-carboxylic acid or salt thereof, 17β- (N, N-diisopropyl carboxamide) -estr-1,3, 5 (10) -triene-3-acetic acid or a salt thereof, 17β- (Nt-butylcarbox amide) -estr-1,3,5 (10) -triene-3-acetic acid or an acceptable salt thereof The method selected from the group consisting of. A method of reducing prostate size in a patient, characterized by administering an effective amount of the compound of claim 1 to the patient. A compound of the general formula Has an optional double bond indicated by the above formula, B, C and D ring broken lines, provided that, C ring B ring C ₈ -C ₉ does not have a double bond when you have a double bond, ring D ³ is R 2 or two substituents Does not have a C ₁₆ -C ₁₇ double bond when represents a substituent; X ¹ , X ² and X ³ are H, Cl, F, Br, I, CF ₃ , or C _1-6 alkyl, OH, C _1-6 alkoxy, CN, NO ₂ , N (R ¹ ) ₂ , CHO , Or any accessible combination of CO ₂ R ¹ , wherein each R ¹ is independently H or C _1-6 alkyl; R ³ represents (1) α-hydrogen, α-hydroxyl or α-acetoxy and / or (a) [Wherein W is a bond or C _1-12 alkyl, R ⁴ is (i) hydrogen, (ii) hydroxyl, (iii) C _1-8 alkyl, (iii) hydroxy C _1-8 alkyl, ) C _1-8 alkoxy, (i) NR ⁵ R ⁶ wherein R ⁵ and R ⁶ are each independently selected from hydrogen, C _1-8 alkyl, C _3-6 cycloalkyl and phenyl, or R ⁵ and R ⁶ represents a 5-6 membered saturated ring containing one or less other heteroatoms selected from oxygen and nitrogen together with the nitrogen to which they are attached, or (iii) OR ⁷ where R ⁷ is an alkali metal, C _1-18 alkyl or benzyl)], or (b) β-Aik-OR ⁸ wherein Aik is C _1-12 alkyl, R ⁸ is (ⅰ) phenyl C _1-8 alkylcarbonyl, ( Ii) C _5-10 cycloalkylcarbonyl, (iii) benzoyl, (iii) C _1-8 alkoxycarbonyl, (iii) amino, or C _{1-8 alkylsubstituted} amino or carbonyl, or (iii) C _1-8 alkyl; (2) = CH-W-CO-R ⁴ or = CH-W-OR ⁸ , wherein W is a bond or C _1-12 alkyl, R ⁴ and R ⁸ have the same meaning as described above, and R ⁸ is Also C _1-20 alkylcarbonyl); (3) (Where the bond of the dotted line replaces 17-α-hydrogen); (4) α-hydrogen and β-NHCOR ⁹ (wherein R ⁹ is C _1-12 alkyl) or α-NR ⁵ R ⁶ , wherein R ⁵ and R ⁶ are as defined above, or (5) α-hydrogen and β-cyano; (6) α-hydrogen and β-tetrazolyl or (7) keto, provided that R ³ is not keto when X ¹ , X ² and X ³ are hydrogen. 16- (N, N-diisopropyl carboxamide) -3- (trifluoromethylsulfonate) -estr-1,3,5 (10), 16-tetraene, 17- (N, tert-butylcarbuksamide) -3- (trifluoromethylsulfonate) -estr-1,3,5 (10), 16-tetraene, 17- (N, N-diisopropyl Carboxamide) -3- (trifluoromethylsulfonate) -estr-1,3,5 (10), 6,8-pentaene, 17- (N, N-diisopropyl carboxamide) -3 -(Trifluoromethylsulfonate) -2-methyl-estr-1,3,5 (10) -triene, 17- (N, N-diisopropyl carboxamide) -3- (trifluoromethylsulfo Nate) -4-methyl-estr-1,3,5 (10) -triene, or 17- (N, N-diisopropyl carboxamide) -3- (trifluoro methylsulfonate) -ester -1,3,5 (10) .6-tetraene. ※ Note: The disclosure is based on the initial application.