• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    1445945 D-Homopregnenes F HOFFMANNLA ROCHE & CO AG 25 Sept 1974 [26 Sept 1973] 41707/74 Heading C2U The invention comprises #<SP>4</SP> and #<SP>1</SP>'<SP>4</SP> compounds of formulµ wherein R<SP>6</SP> is H, F, Cl, Br, Me; R<SP>91</SP> is H, F, Cl, Br; R<SP>92</SP> is Cl or Br; R<SP>110</SP> is F or Cl; R<SP>211</SP> is halo or OR; R<SP>213</SP> is halo, OH, monocarboxylic acyloxy or OR; R is a monoacyl radical of sulphuric or phosphoric acid or of a di- or tricarboxylic acid, said radical optionally being in the form of a water-soluble salt; and R<SP>17a</SP> is OH or acyloxy. Compounds I-1 and I-2 are prepared and/or interconverted by one or more reactions selected from: (a) 11#-hydroxylation (microbial or enzymatic) of corresponding 11 -unsubstituted compounds; (b) adding halogen, HOCl or HOBr across the double bond of corresponding #<SP>9</SP>(<SP>11</SP>)-compounds; (c) reacting corresponding 9#,11#-epoxides with HF, HCl or HBr; (d) 1,2- dehydrogenation (chemical or microbial); (e) 21-halogenation of corresponding 21-unsubstituted or 21-hydroxy compounds with protection of the 3-oxo group as an enamine or enaminium salt; (f) 21-esterification of 21-hydroxy, 21- halo or 21-diiodo; (g) hydrolysis of 17a- and 21-ester groups; (h) 6-halogenation of corresponding 6-unsubstituted-3-oxo-#<SP>4</SP> compounds or their enol ethers or esters; (i) 6# # 6α isomerization; (j) dehydration or dehydrohalogenation of corresponding 5α-Cl, Br, F or OH compounds; (k) 6-methylation; (1) oxidizing the double bond of corresponding #<SP>17a(20)</SP>- compounds to a hydroxyketone grouping; (m) oxidizing corresponding 3#-hydroxy-#<SP>5</SP> compounds to 3-oxo-#<SP>4</SP>. D - Homocortisone 21 - acetate # 17ahydroxy - 21 - acetoxy - D - homopregna - 4,9,(11)- diene - 3,20 - dione (XX) # 17a - hydroxy- 21 - acetoxy - D - homopregna - 1,4,9(11) - triene- 3,20 - dione (Examples 1 and 2). 11#,17α - Dihydroxy - D - homopregn - 4- ene - 3,20 - dione (XXI)# 11#,17a - dihydroxy - 21,21 - diiodo - D - homopregn - 4- ene-3,20-dione (Example 5). 17a,21 - Dihydroxy - D - homopregn - 4 - ene- 3,20 - dione # 17a - hydroxy - 21 - chloro - D- homopregn - 4 - ene - 3,20 - dione (Example 9). XX# 17a,21 - dihydroxy - D - homopregna- 4,9(11) - diene - 3,20 - dione and the 21- (hydrogen succinate) thereof (Example 10). 9α - Bromo - 11#,17a - dihydroxy - 21 - acetoxy - D - homopregn - 4 - ene - 3,20 - dione # 9,11# - epoxy - 17a - hydroxy - 21 - acetoxy - D- homo - 9# - pregn - 4 - ene - 3,20 - dione # 9,11# - epoxy - 17a,21 - dihydroxy - D - homo- 9# - pregn - 4 - ene - 3,20 - dione # 9,11#- epoxy - 17a - hydroxy - 21 - chloro - D - homo - 9# pregn-4-ene-3,20-dione (Example 11). XXI # 3 - (1 - pyrrolidinyl) - 11#,17adihydroxy - D - homopregna - 3,5 - dien - 20- one # 3 - (1 - pyrrolidinio) - 11#,17a - dihydroxy - 21 - bromo - D - homopregn - 4 - en- 20-one bromide (Example 13). 9α - Chloro - 11# - fluoro - 17a - hydroxy - 21- acetoxy - D - homopregn - 4 - ene - 3,20 - dione (XXII) # 3 - ethoxy - 9α - chloro - 11#- fluoro - 17a - hydroxy - 21 - acetoxy - D - homopregna-3,5 dien-20-one (Example 16). XXII # 3,3-ethylenedioxy-9α-chloro-11#- fluoro - 17a - hydroxy - 21 - acetoxy - D - homopregn - 5 - en - 20 - one # 3,3 - ethylenedioxy- 5α,6#,9α - trichloro - 11# - -fluoro - 17a - hydroxy 21 - acetoxy - D - homopregnan - 20 - one # 5α,6#,9α - trichloro - 11# -fluoro - 17a - hydroxy- 21 - acetoxy - D - homopregnane - 3,20 - dione (Example 18). 3# - Hydroxy - 11# - acetoxy - 17,20 - epoxy- 21 - norpregn - 5 - ene (XXIII) # 3#,17#- dihydroxy - 11# - acetoxy - 17# - (aminomethyl)- androst - 5 - ene # 3# - hydroxy - 11# - acetoxy- D - homoandrost - 5 - en - 17a - one # 3#,11#- dihydroxy - D - homoandrost - 5 - en - 17a - one #ethyl 3#,11# - dihydroxy - D - homopregna- 5,17a(20) - dien - 21 - oate # 3#,11#,21- trihydroxy - D - homopregna - 5,17a(20) - diene # 3#,11# - dihydroxy - 21 - (triphenylmethoxy). D - homopregna - 5,17a(20) - diene # 11#- hydroxy - 21 - (triphenylmethoxy) - D - homopregna - 4,17α(20) - dien - 3 - one # 11#,21- dihydroxy - D - homopregna - 4,17a(20) - dien- 3 - one # 11# - hydroxy - 21 - chloro - D- homopregna - 4,17a(20) - dien - 3 - one (Example 19). 3#,11# - Dihydroxy - D - homopregna- 5,17a(20) - diene # 3#,11#,17a - trihydroxy- D - homopregn - 5 - en - 20 - one# 3#,11#,17a trihydroxy - 21,21 - diiodo - D - homopregn - 5- en - 20 - one # 3#,11#,17a - trihydroxy - 21- acetoxy - D - homopregn - 5 - en - 20 - one # 3#,11#,17α,21 - tetrahydroxy - D - homopregn- 5 - en - 20 - one # 3#,11#,17a - trihydroxy - 21- chloro - D - homopregn - 5 - en - 20 - one (Example 20). The preparation of XXI (Example 13), XXIII (Example 19) and 9α - fluoro - D - homoprednisolone (Example 7) is as described in Specification 1,365,469. Antiinflammatory compositions for oral, parenteral, rectal and topical administration comprise a compound (I-1) or (I-2) and a carrier. Reference has been directed by the Comptroller to Specification 1,365,469.
    公开号:SU867316A3
    申请号:SU752145938
    申请日:1975-06-20
    公开日:1981-09-23
    发明作者:Алиг Лео；Фюрст Андор；Мюллер Марсель
    申请人:Ф.Гоффманн-Ля Рош И Ко Аг (Фирма)；
    IPC主号:
    专利说明:

    Union of Soviet
    Socialist
    Republics
    DESCRIPTION
    Inventions
    TO THE PATENT
    (72) Authors of the invention (71) Applicant
    (..) 867316 (61) Additional to the patent - (22) Declared 06/20/75 (21) 2063139 /
    2145938 / 23-04 (23) Priority 25.09.74 (32) 26.09.73 (31) 13764/73 (33) Switzerland
    Published 2 3.0 9.81 £ Bulletin No. 35
    Date of publication of the description 09/23/81
    Aliens f
    Leo Alig, Andor Fürst and Marcel Mülle (Switzerland) T
    Foreign company 1 'F. Hoffmann-La Roche and Co., (Switzerland) (54) METHOD FOR PRODUCING D-HOMOSTEROIDS (51) M. Cl. 3
    S 07 a 63/00 //
    A 61 K 31/56 (53) UDC 547.689.
    .6.07 (088.8)
    A method for producing D-homosteroids of the general formula
    where R 11 is an oxy group, fluoro or chloro;
    - hydrogen or fluorine, if R 4 ” 1 is an oxy group, and chlorine, if R ll is fluorine or chlorine;
    R ^ 1 - halogen, sulfate, phosphate residue or residue of x-di and tricarboxylic acids,. if R is an oxy group or a halogen or an acyloxy group, if 4 '* is fluoro or chloro; hydroxy or acyloxy group, 35 possessing pharmacological activity.
    A known method of obtaining a steroid of the formula 30
    consisting in the fact that the compound of the formula
    dehydrogenated with selenium dioxide in alcohol [1].
    Using the known reaction allows you to get new D-homosteroids of General formula (1) with hormonal activity.
    The purpose of the invention is ’expanding the range of D-homosteroids of the general formula (1) with pharmacological activity.
    The proposed method for the preparation of © -homosteroids of the general formula (1) is 867316 in that the B -homosteroids of the general formula • i
    values, they are dehydrated in poses (1) and (2) with the help of dioxide, the research institutes usually in an alcohol solution in the presence of lower aliphatic carboxylic acid, followed by isolation of the target product.
    Example 1. 470 mg 21-acetoxy-94., 110-dichloro-17s (-oxy-1> -homopregn-4-en-3, 20-dione and 250 mg of selenium dioxide in 20 ml of tert-butanol and 0.2 ml glacial acetic acid is boiled for 24 hours under argon atmosphere. The reaction mixture is filtered and evaporated. The resulting oil is dissolved in ethyl acetate and washed with sodium hydrogen carbonate solution, water, ice-cold ammonium sulfide solution, diluted with ammonia, water, diluted with hydrochloric acid and water, then dried with sodium sulfate. and evaporated, chromatography on silica gel gives 21-acetoxy-9c1,110-dichloro-17a-hydroxy-E-hom opregna-1,4-diene-3,20-dion, melting point T mp 222-224 ° G; UV spectrum! £ 137 15300; Gci] d + 142 ° (C = 0.1% in dioxane).
    The starting material was prepared by chlorination of 21-acetoxy-170-hydroxy-B-homopregn-4,9 (11) -diene-3,20-dione in a known manner.
    Example 2 ‘. 410 mg of 17a-butyroxy-21-chloro-9 <1.-fluoro-110Chsi-B ~ gOmopregn-4-ene-3,20-dione is dehydrogenated with selenium dioxide in tert-butanol in the same way as described in Example 40 (1); in the presence of acetic acid: 45 acid, at position 1,2 in 17ya-butyroxy-21-hlp-94.-fluoro-110-hydroxy-1> homopregna-1,4-diene-3, 20-dione. Yield 49%.
    Example 3. Similarly to the method described in example (1), 450 mg of 110, 17s |, 21-trioxy ~ C-homopregn-4-en-3-on-21-hemisuccinate are dehydrated with dioxide, selenium in rub rubbut-butanol in the presence of acetic acid , at position 1.2 in 1.1p>, 17ct, 21-trioxy-B-homopregna-1, 4-diene-Z-one-21-hemi succinate. Mp 211-213 ° C; [el] p + 116 °. , (C - 0.1 in dioxane), yield 42%.
    Example 4. 'Similar to the method described in example (1), 450 mg of 9s1-fluoro-110, 17a, 21-trioxy-P-homopregn-4-en-Z-one-21-hemisuccinate de' is hydrogenated with selenium dioxide in tert-butanol in the presence of acetic acid VISNIPI Order 8119/85 £
    sweats, at position 1.2 in 94, fluoro7110, 17q, 21-trioxy-1) -homopregna -1,4-diene-3-one-21-hemi succinate. T t 186-187 ° C; 1X3i + 870 ° (C = 0.1 in • dioxane), Yield 47.5%.
    Example 5. Analogously to example (1) of, 21-chloro-11 (L-hydroxy-17 "-va / 1eroyloxy-B-homopregn-4-en-3, 20-dione: 21-chloro-110-hydroxy- is obtained 17a-valeroloxy-P-homopregna-1,4-diene-Z, 20-dione, mp 241-242 ° C; + 34 ° (c = 0.1% in dioxane), UV spectrum: € 140.14600.
    Example 6. 200 mg 3 ml of butyric acid in argon atmosphere for 20 hours. The reaction mixture is Worked up as described in f example (1) and the product is chromatographed on silica gel to give 174, 21-5is- (butyryloxy) -9-chloro-110-fluoro-B- homopregna-1,4-diene-Z, 20-dione, mp 154-155 ° C; [dJij- 58 ° (C = 0.1% in dioxane); UV spectrum: £ M5 15,400.
    权利要求:
    Claims (1)
    [1]
    Claim
    The method of obtaining i-homosteroids where, th on aphids about
    D-homost eroid hydroxy group, fluorine or chlorine; hydrogen or fluorine, if Rti is an oxy group, and chlorine, if Y is fluorine or chlorine; halogen, sulfate, phosphate residue or a residue of di- and tricarboxylic acid, if R 41 is an oxy group or a halogen, or an acyloxy group, if 44 is a fluorine or chlorine; hydroxy or acyloxy group
    I’m with the fact that the general formula
    SUCK / 2 '
    - and ™. where the dehydrogenated in position (1) and (2) with selenium dioxide, followed by isolation of the target product
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