• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
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  • 优先权
    • 专利摘要:
    Esters of 13,14-didehydro prostaglandins have been prepared.
    公开号:SU1301309A3
    申请号:SU823515155
    申请日:1982-11-25
    公开日:1987-03-30
    发明作者:Фаустини Франко；Вилла Витториа；Гандольфи Кармело；Ди Салле Энрико
    申请人:Фармиталиа Карло Эрба С.П.А. (Фирма)；
    IPC主号:
    专利说明:

    eleven
    The invention relates to a process for the preparation of new prostaglandin class derivatives, namely optically active or racemic ester derivatives of 13,14-didehydroprog-aglandins of the general formula
    N sh
    COO (CH2) is
    n
    С С-С-СНг (СН2Ь-В
    he
    where n is an integer from 1 to 4;
    Z is an alkyl) amino, morpho-LINO-, piperidino- or alkoxy group; m Oh, 1 or 2
    R is a saturated cycloalkyl with valuable pharmaceutical properties: luteolitic activity. The purpose of the invention is to obtain new derivatives of the class of prostaglandins, which have pharmacological advantages of one over the known structural analogues of a similar effect.
    The invention is illustrated by the following examples.
    The abbreviations THP, DMSO, THF and Et OH refer to tetrahydropyranyl, dimethylsulfoxide, tetrahydrofuran and ethyl alcohol, respectively.
    All temperatures are expressed in degrees Celsius, and the values of optical rotation are related to measurements taken at 20 ° C and at. a concentration of 1% by weight of the compound in the characteristic solvent. I
    Example 1. A solution of 5c-9 alpha, 11 alpha, 15 (k) -trioxy-16 (8) -fluoro-20-methyl-prost-5-en-13-α-acid of methyl ester (0.5 g) in 10 ml of methyl alcohol is cooled in an ice bath, and then dry watering is bubbled in this solution until saturation occurs. The reaction vessel was sealed and kept at room temperature for 24 hours, then the NH was distilled off, the NJ and the alcohol was removed. The crude product thus obtained is purified on silica gel using a mixture consisting of hexane and ethyl acetate as eluent, and as a result
    Tata get 0.45 g of pure 5c-9 alpha, 11 alpha, 15 (E) -trioxy-1b (B) - -fluoro-20-methyl-prost-5-en-13-inoic acid amide; d ,, +15,5; d 5 +60.7 (with 1 EtOH).
    Using the same procedure, the following compounds are obtained:
    5c-9 alpha, 11 alpha, 15 (h) -trioxy-1b (E) -fluoro-20-ethyl-prost-5-en-fO-13-inoic acid amide; (d) +29.6;
    5c-9 alpha, 11 alpha, 15 (K, S) -trioxy-1b (8) -fluoro-20-ethyl-simple-5-en-13-inoBoic acid amide; (d) 5 +20.8;
    5c-9 alpha, 11 alpha, 15 (c) -trioxy-16 (h) -fluoro-20-methyl-prost-5-en-13-inoic acid amide, tdlj, - +22.7; 20
    5c-9 alpha, 11 alpha, 15 (R, S) -trioxy-16 (5) -fluoro-20-methyl-simple-5-en-13-inoic acid amide, d +21,2; °
    25 5c-9 alpha, 11 alpha, 15 (8) -trioxy-16 (c) -fluoro-20-methyl-prost-5-en-13-inoic acid amide, Y +32.1;
    5c-9 alpha, 11 alpha, 15 (E) -tri30 oxn-16 (S) -fluoro-16-metsh-17,18,19, 20-tetranor-prost-5-en-13-inoic acid amide, d +27;
    5c-9 alpha, 11 alpha 15 (b) -rioxy-16 (S) -fluoro-16,20-dimethyl-prost-5-ene-13-inoic acid amide, (d)
      28.2;
    5c-9 alpha, 11 alpha, 15 (K, S) - -trioxy-16 (h) -fluoro-16-methyl-17.18, 19.20-tetranor-prost-5-en-13-one
    Q acid amide, d +30,6;
    5c-9 alpha, 11 alpha, 15 (R, S) -trioxy-16 (5) -fluoro-16.20, dimethyl-prost-5-en-13-inoic acid amide, Mp 31.3;
    5c-9 alpha, 11 alpha, 15 (n) -trioxy-16 (S) -fluoro-16-methyl-20-ethyl-simple-5-en-13-inoic acid amide, Cdl +36;
    9c-9 alpha, 11 alpha, 15 (H, S) - -trioxy-1b (3) -fluoro-18,19,20-trinor-17-cyclohexyl-prost-5-ene-13-inoic acid piperazinyl K-methylene-amide.
    Example 2. CuCl (0.017 g) is added to a solution containing 1.373 g of dicyclohexylcarbodiimide in 0.661 g of 2-ethoxyethanol cooled to 0 ° C. The resulting mixture is stirred for 1 hour at 0 ° C and then heated to room temperature
    45
    50
    55
    313013094
    temperatures and kept at this xi-ethyl ester temperature for 24 hours. This mixture is +32.6; then diluted with hexane (5 ml), 5c-9 alpha, 11 alpha, 15 (K) -trioxy-16 (S) -fluoro-19,20-dinor-18-cyc-5 loghexyl-prost-5-e- The 13-acid is filtered over silica gel and washed with hexane. The solvent is removed to obtain 1.00 g of pure dicyclohec Seal-2-ethoxyethyl urea. This product is dissolved in IO ml of tetrahydrofuran (distilled on CaClI) and then added to a solution containing 1 g of 5c-9 alpha, 1 alpha, 15 (8) -trioxy-18,19,20-trinor I7-cyclohexyl-prost-5-ene-13-inoic acid in 10 ml of anhydrous tetrahydrofuran,
    The mixture thus obtained is heated to 60 ° C and maintained at this temperature for 6 hours. The solvent is removed under vacuum, and the resulting intermediate is purified on silica gel using a mixture consisting of ethyl acetate and picloge xanum as eluent.
    5c-9 alpha, 11 alpha 15 (k) -trioxy-16 {5) -fluoro-18,19,20-trinor-17-cyclohexyl-prost-5-ene-13-inoic acid 2-ethoxyethyl complex
    The ratio of 70/30, the result is collected pure 5c-9-alpha-1 1 alpha ether, d +14,2;
    15 (5) -trioxy-18,19,20-greenor-17-cyc-5c-9 alpha, 11 alpha, 15 (R, S) - lehexyl-prost-5-ene-13-inic acid-trioxy-16 (s) -fluoro-18,19,20-trinor-17-cyclohexyl-prost-5-ene-13-α-acid of 2-ethoxyethyl
    you 2-ethoxy-ethyl ester, in the amount of 0.850 g, d +29.7;
    -trioxy-16 (s) -fluoro-18,19,20-trinor-17-cyclohexyl-prost-5-ene-13--sonic acid 2-ethoxy-ethyl
    Mg5 +97.4 (with 1 ethyl alcohol). 0 ester, 17,2;
    Using the same procedure, 5c-9 alpha, 11 alpha, 15 (E) -tripes, the following compounds are obtained: oxy-6 (3) -fluoro-18,19,20-trinor5c-9 alpha, 11 alpha, 15 (5) -trioc --17-cyclopentyl-prost-5-ene-13-inovoy
    si-20-Hop-l9-cyclohexyl-prost-5-ene-acid 2-ethoxy-ethyl complex.
    -13-inoic acid 2-ethoxy-ethyl 35 ether, .- +14.8; ester, Ir +21.2; 5c-9 alpha, 11 alpha, 15 (K, S) 5c-9 alpha, 11 alpha, 15 (8) -trioxy-20-nor-19-cyclopentyl-prost- 5-en-13-inoic acid 2-ethoxy-ethyl ester, and +27; 0 ester, dj 4-24;
    5c-9 alpha, And alpha, 15 (k) -trioc- 5c-9 alpha, 11 alpha, 15 (5) -tris-I6 (S) -fluoro-20-nor-19-cyclohexn1- -prost 5-ene-13-inic acid 2-ethoxyethyl ester, +28.2
    5c-9 alpha, 11 alpha, 15 (K, S) - And +38.6; -trioxy-1b (8) -fluoro-20 Gnor-19-cyclo-5c-9 alpha, II alpha, 15 (5) -trighexyl-prost-5-ene-13-inoic acid-17,18,19,20- tetranor-16-cyclo2-ethoxyethyl ester, i-pentyl-prost-5-ene-13-inoic acid
    dl +29,6; 2-ethoxy-ethnyl ester,
      +41.2;
    5c-9 alpha, 11 alpha, 15 (8) -tri- 5c-9 alpha, 1 alpha, 15 (k) -trioxy-1 9, 20-dinor-1 8-cyclohexyl-oxy-16 (3) -fluoro -17,18,19,20-tetra- -prost-5-en-13-inoic acid 2-etho- ° P 6-cyclohexyl-prost-5-en-13-ini-si-ethyl ester d it® ° acid 2-ethoxy-ethyl-type complex - +31.7; -55th ether, M +16;
    5c-9 alpha, 11 alpha, 15 (8) -tri- 5c-9 alpha, 11 alpha, 15 (K, S) oxy-19, 20-dinor-18-cyclopentyl - trioxy-16 (S) -fluoro -17,18,19,20-prost-5-nh-13-inoic acid 2 is tetranor-16-cyclohexyl-prost-5-en-trioxy-16 (S) -fluoro-18,19,20 trinor-17-cyclopentyl-prost-5-ene-13-inoic acid 2-ethoxy-ethyl complex
    hydroxy-17,18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inoic acid 2-ethoxy-ethylene ester.
    xi-ethyl ester th +32.6; 5c-9 alpha, 11 alpha, 15 (K) -tri
    hydroxy-16 (S) -fluoro-19,20-dinor-18-cyclohexyl-prost-5-ene-13-inoic acid 2 ethoxyethyl ester M, 18;
    5c-9 alpha, P alpha, 15 (R, Sj-trioxy-16 (S) -fluoro-19,20-dinor-16- -cyclohexyl-prost-5-ene-13-inoic acid 2-ethoxyethyl ester ,, +22;
    5c-9 alpha, 11 alpha, 15 (8) -trioxy-18,19,20-trinor-17-iicloheptyl--5-en-13-inoic acid 2-ethoxy-ethyl ester Id +19, 2;
    5c-9 alpha, 11 alpha 15 () -trioxy-18,19,20-trinor-17-piclopentyl-prost-5-ene-13-inoic acid 2-it-xy-ethyl ester djjj 22, 2J
    5c-9 alpha, 11 alpha 15 (k) -trioxy-16 {5) -fluoro-18,19,20-trinor-17-cyclohexyl-prost-5-ene-13-inoic acid 2-ethoxyethyl complex
    ether, d +14.2;
     5c-9 alpha, 11 alpha, 15 (R, S) -
    -trioxy-16 (s) -fluoro-18,19,20-trinor-17-cyclohexyl-prost-5-ene-13--sonic acid 2-ethoxy-ethyl
    ether, .- +14.8; 5c-9 alpha, 11 alpha, 15 (K, S) -trioxy-16 (S) -fluoro-18,19,20-trinor-17-cyclopentyl-prost-5-ene-13-inoic acid 2-ethoxy ethyl complex
     5c-9 alpha, 11 alpha, 15 (5) -tri-
    And +38.6; 5c-9 alpha, II alpha, 15 (5) -trioxy-17, 18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inoic acid 2-ethoxy-ethylene ester.
    -GZ-INOVOY acid 2-ETOXI-ETSH1OVY
    ester, +22.7;
    5c-9 alpha, 11 alpha, 15 (c) -trioxy-16 (5) -fluoro-1b-methyl-18,19,20- -trinor-17-cyclohexyl-prost-5-ene-13- Inoic acid 2-ethoxyethyl ester. Eid +34.6;
    5c-9 alpha, 11 alpha, 15 (H, S) - -trioxy-16 (S) -fluoro-16-methyl-18,19,
    5c-9 alpha, 11 alpha, 15 (h) -rioxy-18,19,20-trinor-17-cyclopentyl-prost-5-ene-13-inoic acid 2- (N, N-dimethylamino - ethyl ester;
    5c-9 alpha, 11 alpha, 15 (E) -trioxy-16 (5) - fluoro-18,19,20-trinor-17-β-cyclohexyl-simple-5-ene-13-inoic acid 2- (K, N-dimethylamino) -ethyl
    20-trinor-17-cyclohexyl-prost-5-E- O ester;
    -13-inoic acid 2-ethoxy-ethyl 5c-9 alpha, 11 alpha, 15 (R, S) ester, dip +39,2; -trioxy-16 (h) -fluoro-18, I9,20-trinor - 7-cyclohexyl-prost-5-en-13-inoic acid 2- (M-dimethylamino) ethyl 5 ester;
    5c-9 alpha, 1 alpha, 15 (E) -trioxy-1 6 (h) fluoro-1 8,19,20-trinor-1 7-β-cyclopentyl-prost-5-ene-13-inoic acid 2- (H, M-dimethylamino) -ethyl
    -en-13-inic acid 2- (W, I-dimethyl-20 ester;
    amino) ethyl ester; 5c-9 alpha, 11 alpha, 15 (R, S) 5c-9 alpha, P alpha, 15 (c) -trioxy-16 (E) -fluoro-16-methyl-18 , 19,20-trinor-17-cyclohexyl-prost-5-e-13-inoic acid 2-ethoxyethyl ester, II +46;
    5c-9 alpha, 11 alpha, 15 (5) -trioxy-20-nor-19-cyclohexyl-prost-55c-9 alpha, 11 alpha, 1b (8) -trioxy-20-Hop-l9- cyclopentyl-prost-5- -en-13-inic acid 2- (K, H-dimesh1-amino) ethyl ester;
    5c-9 alpha, 11 alpha, 15 (n) -trioxy-16 (5) -fluoro-20-nor-19-cyclohexyl-prost-5-ene-13-inoic acid 2- - (N, N-dimethylamino) ethyl ester;
    5c-9 alpha, 11 alpha, 15 (R, S) -trioc Si-16 (S) -fluoro-20-nor-19-cyc25
    -trioxy-16 (s) -fluoro-8,19,20-trinor-17-cyclopentyl-prost-5-ene-13-inoic acid 2- {K, M-dimethylamino) ethyl ester;
    5c-9 alpha, 11 alpha, 15 (5) -trioxy-17, 18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inoic acid
    2- (N, K-dimethylamino) ethyl ester;
    5c-9 alpha, 11 alpha, 15 (8) -trioxy-17,18,19,20-tetranor-16-cyclolenyl-prost-5-ene-13-inoic acid 2- (N, N-dimethylamino) ethyl ester;
    5c-9 alpha, 11 alpha, 15 (E) -tri-OXI-6 (s) -fluoro-17,18,19,20-tetra-nor-16-cyclohexyl-prost-5-ene-13--in acids 2- (K, K-dimesch1amino) logex-prost-5-ene-13-inoic acid 2 -. (N, N-dimetylamino) -ethyl ester;
    5c-9 alpha, 11 alpha, 15 (8) -trioxy-19,20-dinor-18-cyclohexyl-prost--5-en-13-inoic acid 2- (k, k-dimethylamino) - ethyl ester;
    5c-9 alpha, P alpha, 15 (3) -tri-ethyl ester; hydroxy-19,20-dinor-18-cyclopentyl-5c-9 alpha, 11 alpha, 15 (H, S) -prost-5-ene-13-inoic acid 2- (N, N- -dimethylamino) -ethyl complex ether;
    5c-9 alpha, 11 alpha 15 (n) -trioxy-16 (8) -fluoro-19,2a-dinor-18-islomino) ethyl ester; hexyl-prost-5-en-13-inic acid 5c-9 alpha, 11 alpha, 15 (K) -tri- 2- (M, K-dimesh1amino) -ethyl complex oxy-16 (3) -fluoro-1b- methyl-18.1 9,20-ether-trinor-17-cyclohexyl-prost-5-en5c-9 alpha, 11 alpha, 15 (K, S) -13-inoic acid 2- (N, N-dimethylamine- -trioxy-16 (h) -fluoro-19,20 dinor-18- -50 but) -til complex ester; -cyclohexyl-prost-5-en-13-inoic acid 2- (N, N-dimethylamino) ethyl ester;
    -trioxy-16 (3) -fluoro-17,18,19,20- -tetranor-16-cyclohexyl-prost-5-ene-13-inoic acid 2- {N, N-dimethyl5c-9 alpha, 11 alpha , 15 (R, S) - -trioxy-16 (s) -fluoro-16-methyl-18,19, 20-trinor-17-iiclohexyl-prost-5-e-5c-9 alpha, 11 alpha, 15 ( 5) -tri- 55 13-inic acid 2- (N, N-dimethyl O L 1l - amino) ethyl ester;
    5c-9 alpha, P alpha, 15 (H) -trioxy-18, 19,20-trinor-17-cyclohexyl- -prost-5-en-13-inoic acid 2- (N, N-dimethylamino) -ethyl complex ether;
    oxy-16 (R) -fluoro-6-methyl-18,19,20- -trinor-17-cyclohexyl-prost-5-ene-135c-9 alpha, 11 alpha, 15 (h) -trioxi- 18,19,20-trinor-17-cyclopentyl-propro-5-ene-13-inoic acid 2- (N, N-dimethylamino) ethyl ester;
    5c-9 alpha, 11 alpha, 15 (E) -trioxy-16 (5) - fluoro-18,19,20-trinor-17-β-cyclohexyl-simple-5-ene-13-inoic acid 2- (K, N-dimethylamino) -ethyl
    5c-9 alpha, 11 alpha, 15 (R, S)
    -trioxy-16 (s) -fluoro-8,19,20-trinor-17-cyclopentyl-prost-5-ene-13-inoic acid 2- {K, M-dimethylamino) ethyl ester;
    5c-9 alpha, 11 alpha, 15 (5) -trioxy-17, 18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inoic acid
    2- (N, K-dimethylamino) ethyl ester;
    5c-9 alpha, 11 alpha, 15 (8) -trioxy-17,18,19,20-tetranor-16-cyclolenyl-prost-5-ene-13-inoic acid 2- (N, N-dimethylamino) ethyl ester;
    5c-9 alpha, 11 alpha, 15 (E) -tri-OXI-6 (s) -fluoro-17,18,19,20-tetra-nor-16-cyclohexyl-prost-5-ene-13--in acids 2- (K, K-dimesh1amino) -ethyl ester; 5c-9 alpha, 11 alpha, 15 (H, S) -trioxy-16 (3) -fluoro-17,18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inoic acid 2- {N, N-dimethyloxy-16 (R) -fluoro-6-methyl-18,19,20- -trinor-17-cyclohexyl-prost-5-en-13-inoic acid 2- (N, K- dimethylamino-ethyl ester;
    5c-9 alpha, 11 alpha, 5 (8) -rioxy-18,19,20-trinor-17-cyclohexyl-5-en-13-inoic acid 2- (piperidino) -ethyl ester, +22.7 (with 1 ethyl alcohol);
    5c-9-oxo-11 alpha, 15 (B) -dioxy--16 (R) -fluoro-16-methyl-18-19,20-triphor-17-cyclohexyl-prost-5-en-13- Inoic acid 2- (N, N-dimethylamino) ethyl ester, -51.3;
    5c-9 alpha, P alpha, 15 (8) -trioxy-20-Hop-l9-cyclohexyl) prost-5-en-13-inoic acid 2-morpholino ethyl ester, 20.1
    5c-9 alpha, P alpha, 15 (8) -trioxy-20-nor-19-cyclopentyl-prost-5-en-1 3-inoic acid 2-mol 1 folominoethyl ester, +26, four
    5c-9 alpha, 11 alpha, 15 (k) -tri-OXI-b (h) -fluoro-20-nor-19-cyclohexyl-prost-5-ene-13-inoic acid 2- morpholino ethyl ester, Mp +29,5;
    .5c-9 alpha, 11 alpha, 15 (K, S) -trioxy-16 (S) -fluoro-20-nor-19-cyclohexyl-prost-5-ene-13-inoic acid 2-morpholino ethyl ester dl +26,2;
    5c-9 alpha, P alpha, 15 (8) -trioxy-19,20-dinor-18-cyclohexnl-simple-5-ene-13-inoic acid 2-morpholino-ethyl ester, dlp +30, 7;
    5c-9 alpha, P alpha, 15 (5) -trioxy-19,20-dinor-18-cyclopentyl-prost-5-ene-13-inoic acid 2-morpholino-ethyl ester, Ldjp +33, 2;
    5c-9 alpha, P alpha, 15 (n) -trioxy-16 (S) -fluoro-19,20-dinor-18-cyclohexyl-prost-5-ene-13-inoic acid 2-morpholino- ethyl ester, +18.7;
    5c-9 alpha, P alpha, 15 (R, S) - -trioxy-16 (h) -fluoro-19,20-dinor-1 8- -cyclohexyl-prost-5-ene-13-inoic acid 2-morpholino - ethyl ester, Shd +20;
    5c-9 alpha, P alpha, 15 (3) -trioxy-18,19,20-trinor-17-cyclohexyl- -prost-5-ene-13-inoic acid 2-morpholino ethyl ester, Schr 17.6 ;
    5c-9 alpha, 11 alpha, 15 (8) -rioxy-18, I9,20-trinor-17-cyclopentyl-prost-5-e-3-inoic acid 2-mor
    five
    0
    five
    0
    five
    0
    five
    0
    five
    folino ethyl ester, djp +19.6;
    5c-9 alpha, 11 alpha, 15 {k) -trioc- (S) -fluoro-18,19,20-trinor-17-β-cyclohexyl-prost-5-ene-13-inoic acid 2-morpholino-ethyl complex ether ,, d +13,1;
    5c-9 alpha, 11 alpha, 5 (P, S) -trioxy-16 (S) -fluoro-18,19,20-trinor-17-cyclohexyl-5-ene-13-inoic acid 2-MORFOLIN- ETSh1OVYY ester, +26.3 (with 1, EtOH).
    5c-9 alpha, P alpha, 15 (E) -trioxy-16 (S) -fluoro-18,19,20-trinor-17-β-cyclopentyl-prost-5-ene-18-inoic acid 2-morpholino - ethyl ester, din +13.9;
    5c-9 alpha, And alpha, 15 (R, S) - -trioxy-16 (S) -fluoro-18,19,20-trinor-17-cyclopentyl-prost-5-ene-13-inoic acid 2- morpholino ethyl ester, +21.7;
    5c-9 alpha, P alpha, 15 (8) -trioxy-17,18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inoic acid 2-morpholium ethyl ester , +37.9;
    5c-9 alpha, 11 alpha, 15 (5) -trioxy-17,18,19,20-tetranor-16-cyclopentyl-prost-5-ene-13-inoic acid 2- - morpholino-ethyl complex Ether, Id +42.2;
    5c-9 alpha, P alpha, 15 (K) -trioxy-1b (8) -fluoro-17,18,19,20-tetra-nor-16-cyclohexch1-prost-5-ene-13-inoic acid 2-morpholino ethyl ester, d JJ 14.1;
    5c-9 alpha, P alpha, 15 (H, S) -trioxy-16 (R) -fluoro-17,18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inov acids 2-morpholino ethyl ester, d3p +20,5;
    5c-9 alpha, P alpha, 15 (H) -trioxy-1 6 (B) -fluoro-1 6-methyl-1 8, 19,20- -trinor-17-cyclohexyl-prost-5-en-13 -anoic acid 2-morpholino ethyl ester, d3j3 +33.1;
    5c-9 alpha, n alpha, 15 (n, s) -trioxy-16 (h) -fluoro-16, methyl--18,19,20-trinor-13-cyclohexyl- -prost-5-en- 3 α-acid acid 2-morpholino ethyl ester. I- +37.6;
    5c-9 alpha, 11 alpha, 15 (n) -trioxy-16 (B) -fluoro-16-methyl-18,19,20-trinor-G7-cyclohexyl-prost-5-en-13- inoic acid 2-msrfolino-ethyl ester, Id +44.4;
    5c-9 oxo-11 alpha, 1 5 (S) -dihydp oxy-ci-l 8,1 9,20-trinor-17-cyclohexyl-prost-5-en-13-inoic acid 2- (N, N -dimethylamino) ethyl-amide, s-Zr -2.7 (c 1, EtOH);
    5c-9-oxo-11 alpha, 15 (5) -dioxy-20-nor-19-cyclohexyl-prost-5-ene-13-inoic acid 2-ethoxy-ethyl ester, oil p -31.2 ;
    5c-9-oxo-11-alpha, 15 (8) -dioxy-20-Hop-l9-cyclopentyl-prost-5-ene-13-inoic acid 2-ethoxy-ethyl ester, D -32, one;
    5c-9-oxo-11 alpha, 15 (c) -dioxy- -16 (h) -fluoro-20-nor-19-icyclohexyl- -prost-5-ene-13-inoic acid 2-ethoxy-ethylic complex Ether, Ir -29,6
    5C-9-OXO-1 1 alpha, 15 (P., 3) -dioxy-1b (3) -fluoro-20-nor-19-cyclohexyl-prost-5-ene-13-inoic acid 2 - ethoxy-ethyl ester, o4.1d -33,5;
    5c-9-oxo-P alpha, 15 (8) -dioxy--19,20-dinor-18-cyclohexyl-space-5-en-l 3-inic acid 2-ethoxy-ethyl ester, b (- 1 p -32.1;
    5c-9-oxo-11 alpha, 15 (8) -dioxy-19,20-dinor-18-cyclopentyl-prost-5-en-13-inoic acid 2-ethoxy-ethyl-vi ester, otlp -37 ,eight;
    5C-9-OXO-11 alpha, 15 (k) -dioxy-16 (8) -fluoro-19,20-dinor-18-cyclohexyl-prost-5-ene-13-inoic acid 2-ethoxy ethyl ester, Hj, -34.9;
    5C-9-OXO-11 alpha, 15 (R, 3) -dioxy-16 (S) -fluoro-19,20-dinor-18-cyclohexyl-prost-5-ene-13-inoic acid 2 - ethoxy-eth11 ester, WD -33,8;
    5c-9-oxo-11 alpha, 15 (8) -dioxy--18,19,20-trinor-17-cyclohexch1- -prost-5-ene-13-inoic acid 2-it-xy - ethyl ester, with ,, -38.7;
    5c-9-oxo-1I alpha, 15 (8) -dioxy-18,19,20-trinor-17-cyclopentyl-prost-5-e-3-inoic acid 2-ethoxyethyl ester, Mp -40,
    5C-9-OXO-P alpha, 15 (H) -dioxy-16 (3) -fluoro-18 19,20-trinor-17-cyclohexyl-prost-5-ene-13-inoic acid 2-ethoxy ethyl ester, Wj, -18.2;
    5c-9-oxo-11 alpha, 15 {E, 8) -dioxy-16 (8) -fluoro-18,19,20-trinor-17-cyclohexyl-prost-5-en-13-inova
    acids 2-ethoxyethyl ester, -27,7;
    5c-9-oxo-11 alpha, 15 (E) -dioxy- (8) -fluoro-18,19,20-trinor-17-cyclopentyl-prost-5-ene-13-inoic acid 2-ethoxyethyl ester , o (.j, -31, 6;
    5c-9-oxo-1 1 alpha, 15 (P ,, 8) -dioxy-16 (8) -fluoro-18,19,20-trinor-17-cyclopentyl-prost-5-en-13- Inoic acid 2-ethoxyethyl ester Wn -29,7;
    5c-9-oxo-11 alpha, 15 (8) -dioxy-l 7, 1 8, 1 9, 20-tetranor-16-iiclohexyl-prost-5-ene-13-inoic acid 2-ethoxyethyl ester, -3J3 -41.2
    5c-9-oxo-11 alpha, 15 (8) -dioxy, 19,20-tetranor-16-cyclopentyl-prost-5-ene-13-inoic acid 2-ethoxy-ethyl ester, -48,6 ;
    5c-9-oxo-11 alpha, 15 (E) -dioxy--16 (8).-Fluoro-17, 18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inoic acid 2-ethoxy-ethyl ester, Mr-21, 7;
    5C-9-OXO-P alpha, 15 (BRO-Dioxy-16 (8) -fluoro-17,18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inoic acid 2 ethoxy ethyl ester, WJ, -20.2;
    5C-9-OXO-11 alpha, 15 (P) -dioxy--16 (8) -fluoro-I6-methyl-18,19,20-tri-nor-17-cyclohexyl-prost-5-en-13- inoic acid 2-ethoxy ethyl ester,) 48.5;
    5c-9-oxo-11 alpha, 15 (K8) -dioxy-16 (E) -fluoro-16-methyl-18,19,20-tri-nor-17-cyclohexyl-prost-5-en-13 -anoic acid 2-ETOXY-ETSH1OVY ester, o4, WE 5,5;
    5c-9-oxo-11 alpha, 15 (K) -dioxy--16 (R) -fluoro-16-methyl-18,19,20-trinor-1 7-cyclohexyl-prost-5-en-13 - - inoic acid 2-ethoxyethyl ester, 56.3;
    5C-9-OXO-P alpha, 15 (8) -dihydro-20-nor-19-cyclohexyl-prost-5-ene-13-inoic acid 2-piperidinoethyl ester, vol) d -30.7;
    5c-9-oxo-11 alpha, 15 (8) -dioxy-20-nor-19-cyclopentyl-prost-5-ene-13-inoic acid 2-piperidinoethyl ester, -29.8 ;
    5c-9-ocean-11 alpha, 15 (B) -dioxy- -1b (8) -fluoro-20-nor-19-cyclohexyl- -prost-5-ene-13-inoic acid 2-piperidino ethyl ester ,
    WD -30 J;
    5c-9-oxo-11 alpha, 15 (K8) -dioxy-16 (8) -fluoro-20-nor-19 -cyclohexyl-prost-5-ene-13-inoic acid 2- piperidino- ethyl ester, W -31,5;
    5c-9-oxo-11 alpha, 15 (s) -dioxy- 1 9, 20-dinor-1 8-1, iclohexyl-prost-5-en-13-inoic acid 2-piperidino ethyl ester -30.2;
    5c-9-oxo-11 alpha, 15 (8) -dioxy-19,20-dinor-18-cyclopentyl-prost-, -5-ene-13-inoic acid 2-piperidino ethyl ethyl ester, o.r -32,5;
    5c-9-oxo-11 alpha, 15 (E) -dioxy--16 (h) -fluoro-19,20-dinor-18-cyclohec sil-prost-5-ene-13-inoic acid 2- piperidino- ethyl ester, MD -31,7;
    5c-9-oxo-P alpha, 15 (CG) -dioxy-16 (5) -fluoro-19,20-dinor-18-cyclohec sil-simple-5-en-13-inoic acid 2- piperidinoethyl ester, Mr -32,5;
    5c-9-oxo-11 alpha, 15 (s) -dioxy-l 8, 1 9,20-trinor-17-cyclohexyl- -prost-5-ene-13-inoic acid 2-peridino-ethyl complex Ether, WE -32.9;
    5c-9-oxo-1g alpha, 15 (h) -dioxy-18,19,20-trinor-17-cyclopentyl-prost-5-e-3-inoic acid 2-pyperidinoethyl ester, Wo -35.2;
    5c-9-oxo-11 alpha, 15 (E) -dioxy--1b (8) -fluoro-18,19,20-trinor-17-cyclohexyl-prost-5-ene-13-inoic acid 2- piperidino ethyl ester, oclp -20,1;
    5c-9-oxo-11 alpha, 15 (R, S) -dioxy-ci-l 6 {3) -fluoro-1 8, 1 9, 20-trinor-1 7-cyclohexyl-prost-5-e- 13-inoic acid 2-piperidino ethyl ester, “. -22.5;
    5c-9-oxo-11 alpha, 15 (E) -dioxy-16 (S) -fluoro-18,19,20-trinor-17-cyclopentyl-prost-5-ene-13-inoic acid 2- piperidino ethyl ester, otlj, -30.2;
    5c-9-oxo-11 alpha, 15 (B, 5) -dio si-16 (5) -fluoro-18,19,20-trinor-17-cyclopentyl-prost-5-en-13-in-ki - en-13-inic acid 2-morpholino acid 2-piperidino ethyl ester-ethyl ester, Go -1) -35.8;
    ether, -27.5; 3c-B-ca co-11-alpha, 15 (K) -dioxy5c-9-oxo-11 alpha, 15 (B) -dioxy - 16 (S) -ftopo-19,20 -dinop-18-cyclogek-l 7, 1 8, 1 9,20-tetranor-1 6-cyclohexylsyl-prost-5-en-13-inoic acid 2

    ten
    301309 12
    -prost-5-ene-13-inic acid 2-piperidino ethyl ester, MD, 7;
    5c-9-oxo-11 alpha, 15 (b) -dioxy-5 -17,18,19,20-tetranor-16-cyclopentsh-1 -gfost-5-en-13-inoic acid 2-piperidino-zthyl ester, og..ts -45,5;
    5c-9-oxo-11 alpha, 15 (H) -dioxy- -16 (S) -fluoro-17,18,19,20-tetranol-16-cyclohexyl-prost-5-ene-13-inoic acid 2 -piperidino-ethyl ester, s.31, -20;
    5c-9-oxo-11 alpha, 15 {B, 8) -di-J5 hydroxy-16 (S) -fluoro-17,18,19,20-tetra-nor-16-cyclohexnl-prost-5-e- 13-inoic acid 2-piperidino ethyl
    ester, M D -
    5C-9-OXO-P alpha, 15 (E) -dioxy-20 -16 (S) -fluoro-16-metsh-18,19,20-trinor-17-cyclohexyl-prost-5-en-13- Inoic acid 2 piperidino ethyl ester, Mj, -42.9;
    5C-9-OXO-11 alpha, 15 {B, 3) -dioxy-16 (S) -fluoro-16-methyl-18,19,20-trinor-17-cyclshexyl-prost-5- en-13-inic acid 2-piperidino ethyl ester, o (, 1p -55.6;
    5c-9-oxo-11 alpha, 15 (5) -dioxy-20-nor-19-cshslohexyl-prost-5-ene-13-inoic acid 2-morpholinoethyl ester, -30,7 ;
    5c-9-oxo-P alpha, 15 (B) -dioxy-20-nor-19-cyclopentyl-prost-5-ene-13-inoic acid 2-morpholino-ethyl S. POSTER ester, H. Sn - -31;
    5C-9-OXO-11 alpha, 15 (E) -dioxy-16 (S) -fluoro-20-nor-19-cyclohexyl- -prost-5-ene-13-inoic acid 2-morpholino-ethyl ester.Md -28.9;
    thirty
    35
    40
    5C-9-OXO-11 alpha, 15 (B, 8) -dioxy-16 (S) -fluoro-20-nor-19-cyclohexyl-PEOC-5-en-13-inoic acid 2- - morpholino ethyl ester, M -32.9;
    5c-9-oxo-11 alpha, 15 (5) -dioxy--19,20-dinor-18-cyclohexyl-prost-5-en-13-inoic acid of 2-morFolino-e-onyl ester, Go -1o -31.9;
    5C-9-OXO-11-alpha, 15 (B) -dioxy--19,20-dinor-18-cyclopentyl-prost-5131301309I
    -morpholino-ethyl ester, 5c-9-oxo-11 alpha, 15 (K) -dioxy- ID -33,7; -1 b (5) -fluoro-16-methyl-18,1 9,20-tri5s -9-oxo-11-alpha, 15 (R, B) -DI-nor-17-cyclohexyl-prost-5-ene-1 3-ino-hydroxy-1b (8) -fluoro-1 9, 20-dinor -1 8-cyclic acid 2-morpholino-ethyl. logexyl-prost-5-en-13-inoic acid-5 ester, s (. p -A9,2;
    5c-9-oxo-11 alpha, 15 (K, 8) -dioxy-16 (5) -fluoro-16-methyl-18,19,20- -trinor-17-cyclohexyl-prost-5-ene- -1 3-inic acid 2-morino-ethites 2-morpholino ethyl ester, 1-30.6;
    5c-9-oxo-11 alpha 15 (h) -dioxy--18.1 9,20-trinor-17-cyclohexyl-prost-5-ene-13-inoic acid 2-morto-O ester, o ( ., p -46;
    Folino ethyl ester, S1d 5c-9-oxo-11 alpha, 15 (E) -dioxy-36, 2; -16 (5) -fluoro-16-methyl-18,19,20-trinor-17-cyclohexyl -prost-5-ene-13-inic acid 2-morpholino-ethyl
    5c-9-oxo-11 alpha, 15 (5) -dioxy-18,19,20-trinor-17-cyclopentyl-prost-5-en-13-inoic acid 2-mor-15 ester, about -49 ,eight;
    Folino ethyl ester, O1. 5c-9-oxo-11 alpha, 15 (8) -dioxy-20-nor-19-cyclohexyl-prost-5-ene-13-inoic acid 2- (and, M-dimethylamino) ethyl ester, o.1 .
    -cyclohexyl-prost-5-en-13-inoic acid 2-morpholino-ethyl complex
    ether, s, -26,6; I
    5c-9-oxc-11 alpha, 15 (B) -dioxy-39.1;
    5c-9-oxo-11 alpha, 15 (E) -dioxy--16 (5) -fluoro-18,19,20-TRINOR-17-cyclohexyl-prost-5-ene-13-inoic acid 20 -32.4;
    you are a 2-morpholino-ethyl ester, 5c-9-oxo-11 alpha, 15 (3) -dioxy-) -21.1; -20-nor-1 9-cyclopentyl-prost-5-en5c-9-oxo -11-alpha, 15 (K, 3) -di- -13-inoic acid 2- (K, K-dimethyl-oxy-1 6 (8) -fluoro-18.1 9,20-triHor-1 7- amino) ethyl ester, (A. p
    25 -33.3;
    5c-9-oxo-11 alpha, 15 (k) -dioxy--16 (S) -fluoro-20-nor-19-cyclohexyl- -prost-5-ene-1 3-inoic acid 2- (N, N - -dimethylamino) -ethyl ester,
    -16 (5) -fluoro-18,19,20-trinor-17-cyclo-SO oi-l d -31.6; lopentyl-prost-5-en-13-inoic acid-5c-9-oxo-11 alpha, 15 (c, 3) -dioxy 2-morpholino-ethyl ester, si-1b (5) -fluoro-20 -nor-19-cyclohexyl- (- -30,2 ;. -prost-5-ene-13-inoic acid 2- (N, N5c-9-oxo-11 alpha, l5 (R, 5) -diox - dimethylamino) ethyl ester, si-16 (3) -fluoro-18.1 9,20-trinor-17-35 M -32.1;
    5C-9-OXO-11 alpha, 15 (5) -dioxy--19,20-dinor-18-cyclohexyl-prost-5-. -en-13-inoic acid 2- (S, I-dimethyl-amino) -ethyl ester, Ir-31;
    5C-9-OXO-P alpha, 15 (3) -dioxy-19,20-dinor-18-cyclopentyl-prost-5-en-13-inoic acid 2- (N, N-dimethylamino) -ethyl complex ether, bi- .J3
     -36.5;
    5C-9-OXO-11 alpha, 15 (E) -dioxy-cyclopentyl-prost-5-ene-13-inoic acid 2-morpholino ethyl ester, -25.9;
    5c-9-oxo-11 alpha, 15 (8) -dioxy-17,18,19,20-tetranor-16-cyclohexyl-40-simple-5-ene-13-inoic acid 2-morpholino ethyl ester , o (, d -40.2;
    5c-9-oxo-11 alpha, 15 (3) -dioxy-17,18,19,20-tetranor-16-cyclopentyl-45-simple-5-ene-13-inoic acid 2-morpholino ethyl ester , Ir -45;
    -16 (S) -fluoro-19,20-dinor-18-cyclohexyl-prost-5-ene-13-inoic acid 2- - (And, and-dimethylamino) -ethyl complex
    5c-9-oxo-11 alpha, 15 (E) -dioxy-16 (S) -fluoro-19,20-dinor-18-cyclohexyl-prost-5-en-13-inoic acid 2- - (And , And-dimethylamino) -ethyl complex
    50 ether, 1 „-30,7;
    -16 (8) -fluoro-17,18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inova 5c-9-oxo-11 alpha, 15 (K, 3) -di- Acids 2-morpholino ethyl oxy-1b (B) -fluoro-19,20-dinor-18-cyc-ester-LO (. -20.1; logexyl-prost-5-ene-13-inicic acid 5C-9-OXO) -1I alpha, 15 (R, 5) -dioxy-2y (K, K-dimethylamino) ethyl ethyl-1b (8) -fluoro-17,18,19,20-tetranor-16-cyclohexyl simple-5-ene-15-inic acid 2-morpholino-ethyl complex EFIR.MP -20,7;
      7
    DIFFICULT Ether, "/. P -31.9;
    5c-9-oxo-11 alpha, 15 (5) -dioxy- -18,19,20-trinor-17-cyclohexyl- -prost-5-ene-13-inoic acid 2- (N, N-20-nor -19-cyclohexyl-prost-13-inic acid 2- (and, M-dime
    but) -ethyl ester, o.1.
     -32.4;
    -16 (S) -fluoro-19,20-dinor-18-cyclohexyl-prost-5-ene-13-inoic acid 2- - (And, and-dimethylamino) -ethyl complex
    air, 1 „-30,7;
    5c-9-oxo-11 alpha, 15 (K, 3) -dioxy-1b (B) -fluoro-19,20-dinor-18-cyclohexyl-prost-5-ene-13-inoic acid 2 - (K, K-dimethylamino) -ethyl
      7
    DIFFICULT Ether, "/. P -31.9;
    5c-9-oxo-11 alpha, 15 (5) -dioxy- -18,19,20-trinor-17-cyclohexyl- -prost-5-ene-13-inoic acid 2- (N, N +3.5 (from 1
    15130130916
    dimethylamino) ethyl ester, 5c-9-oxp-15 (8) -oxy-16 (n) -Ltoro oilp -42,5; , -20-ethyl-simple-5,1 O-dien-13-in
    5c-9-oxo-P alpha, 15 (8) -dioxy-acid amide N1
    -18,19,20-trinor-17-cyclopentyl ethyl alcohol);
    -prost-5-ei-13-inic acid 2- (N, N-5-dimethylamino) -ethyl ester, We -48.9;
    5c-9-oxo-P alpha, 15 (P) -dioxy--16 (S) -fluoro-18,19,20-trinor-17-cyc10
    logexyl-prost-5-en-13-inic acid 2- (I, K-dimethylamino) -ethyl ester, 1-3-3p 27,2j
    5C-9-OXO-11 alpha, 15 (K, 8) -dioxy-16 (S) -fluoro-18,19,20-trinor5s-9-oxo-15 (5) -oxy-20-nor- 19-α-cyclohexyl-prosta-5-10-diene-13-α-acid-2-ethoxyethyl ester, 2.8;
    5c-0-oxo-15 (K) -oxy-20-nor-19-β-cyclopentyl-simple-5,10-diene-13-α-acid-2-ethoxy-ethyl ester, oil J3 +11, fj;
    5c-9-oxo-15 (P) -oxy-16 (8) -fluoro-20-nor-19-cyclohexyl7Prosta-5,10-17-iiklohexyl-prost-5-en-13-inovoy 15 -di- 13-inoic acid 2-ethoxy-acid 2- (I, K-dimethylamino) -ethyl-ethyl ester, o (, 1.p, + 6.7; new ester, -29.2;
    5c-9-oxo-11 alpha, 15 (E) -dioxy5c-9-oxo-15 {K, 8) -oxy-16 (8) - -fluoro-20-nor-19-cyclohexyl-prosta-5, 10-diene-13-inoic acid 2-ethoclopentyl-prost-5-ene-13-inoic acid-20-ethyl ethyl ester,) 5.8; you are 2- (W, K-dimethylamino) -ethyl 5c-9-oxo-15 (S) -oxy-19.2P-dinor-18-cyclohexyl-simple-5, 1O-diene-13--anoic acid 2-ethoxy ethyl ester "ilc +2,2;
    -17-cyclopentyl-prost-5-en-1 3-inova 5c-9-oxo-16 (8) -oxy-19,20-dinor-acid 2- (K, M-dimethylamino) -ethyl - 18- cyclopentyl-simple-5,10-diene-13-inoic acid 2-ethoxyethyl ester to -l D +3.2;
    5c-9-oxo-1 5 {B) -oxy-1b (8) -fluoro-30 -19,20-dinor-18-cyclohexyl-prosta-5,1 O-diene-13-inoic acid 2-ethoc - b-ethyl ester, bb11, 16,2j
    5c-9-oxo-11 alpha, 15 (8) -dioxy-5c-9-oxo-15 (B, 8) -oxy-16 (n) -17, 18,19,20-tetranor-16-cyclopentyl -fluoro-20-nor-19-cyclohexn1-prosta-propro-5-ene-13-inoic acid 2-35 -5,10-diene-13-inovsy acid 2-ethok- (AND, ET-dimethylamino) - ethyl complex-ethyl ester,, 6,
    ny ether, yild -50,2; 5c-9-oxo-1 5 (8) -oxy-18.1 9,20-tri5c-9-oxo-11 alpha, 15 (E) -dioxy-nor-17- cyclohexyl-pro-cta-5,10-diene-lb (8) -fluoro-17,18,19,20-tetranor-13-inoic acid 2-ethoxyethyl-16-cshslohexyl-prost-5-en -13-inovoy 40 ester, 2.4; Acids of 2- (M, M-dimesh1amino) -ethyl 5c-9-oxo-15 (8) -oxy-18,19,20-tri-16 (8) -fluoro-18,19,20-trinor-17-cyclic complex ether, l1r -30,7;
    5c-9-oxo-11 alpha, 15 (R, B) -dioxy-1b (8) -fluoro-18,19,20-trinory ester, oil.р -25,2;
    5c-9-oxo-11 alpha, 15 (8) -dioxy-17,18,19-20-tetranor-6-cyclohexyl-prost-5-en-13-inoic acid 2- - (N, 1T -methylamino) ethyl ester, s, 1d -40,8;
    ester, og -19,6;
    5c-9-oxo-11 alpha, 15 (E, 8) -dioxy-16 (8) -fluoro-17,18,19,20-tetranor-16-cyclohexn1-prost-5-en-13- Inoic 45 acid 2- (P, H-dimethylamino) -ethyl ester, oi.jj -22,2;
    5c-9-oxo-11 alpha, 15 (E) -dioxy--1b (8) -fluoro-16-methyl-18,19,20-tri-nor-17-cyclohexyl-prost-5-en-13- 2- (K, 1 (1-dimethylamino) -ethyl ester of the acid, (1b1 39.7;
    5C-9-OXO-11 alpha, 15 (R, 8) -dn-oxy-16 (8) -fluoro-16-methyl-18,19,20- 55-trinor-17-cyclohexyl-prost-5-ene - -13-inoic acid 2- (N, N-dimethyl-amino) -ethyl ester, () G1 -40.9;
    nor-cyclopentyl-simple-5,1O-diene-13- -anoic acid 2-ethoxy ethyl ester, yd + 2.9;
    5c-9-oxo-15 (R) -oxy-16 (8) -fluors-18,19,20-trinor-17-cyclohexn-1-simple-5,1O-diene-13-inoic acid 2-ethoxy ethyl ester, Mj, +2.9;
    5c-9-OKCo-15 (R, 5) -oxy-16 (8) -fluoro-18,19,20-trinor-17-cyclohexyl-simple-5,10-diene-13-inoic acid 2 - ethoxy-ethyl ester,
    WB +9.9;
    5c-9-hydroxy-15 (K) -oxy-16 (5) -fluoro-18,19,20-trinor-17-cyclopentyl-simple-5, IO-diene-13-inoic acid 2-et - hydroxyethyl ester, OH | d +12.1;
     +3.5 (from 1
    -diene-13-new
    ethanol);
    5c-9-oxo-15 (5) -oxy-20-nor-19-β-cyclohexyl-simple-5-10-diene-13-α-acid-2-ethoxyethyl ester, 2.8;
    5c-0-oxo-15 (K) -oxy-20-nor-19-β-cyclopentyl-simple-5,10-diene-13-α-acid-2-ethoxy-ethyl ester, oil J3 +11, fj;
    5c-9-oxo-15 (P) -oxy-16 (8) -fluoro-20-nor-19-cyclohexyl7Prosta-5,10nor-cyclopentyl-simple-5, 1O-diene-13--incoic acid 2-ethoxy - ethyl ester, s1d +2,9;
    5c-9-oxo-15 (R) -oxy-16 (8) -fluors-18,19,20-trinor-17-cyclohexn-1-simple-5,1O-diene-13-inoic acid 2-ethoxy ethyl ester, Mj, +2.9;
    5c-9-OKCo-15 (R, 5) -oxy-16 (8) -fluoro-18,19,20-trinor-17-cyclohexyl-simple-5,10-diene-13-inoic acid 2 - ethoxy-ethyl ester,
    WB +9.9;
    5c-9-hydroxy-15 (K) -oxy-16 (5) -fluoro-18,19,20-trinor-17-cyclopentyl-simple-5, IO-diene-13-inoic acid 2-et - hydroxyethyl ester, OH | D +12.1
    171301309
    5c-9-OKCo-15 (R, 5) -oxy-16 (3) -fluoro-po-18,19,20-trinor-17-cyclopentyl-simple-5,1 O-diene-13-inoic acid 2 - ethoxy-ethyl ester.
    18
    Wj, + 7.7;
    The semi-product is purified on silica gel using a mixture consisting of ethyl acetate and cyclohexane in the ratio of 50:50 as eluent, which made it possible to obtain 0.295 g of pure 5c-9-alpha, II alpha, 15 (3) -trioxy-18 , 19,20-trinor-17-cyclohexyl-prost-5-en-) 3-inoic acid, 2- (piperidine) -ethyl ester 5C-9-OXO-15 (8) -oxy-17,18, 19,20-β-tetranor-16-cyclohexyl-simple-5,10- -diene-13-inoic acid 2-ethoxy 1-ethyl ester, +6.2;
    5c-9-oxo-15 (5) -oxy-17,18,19,20- Ora 9-acetate, ci +86,2 (ethyl-α-tetranor-16-cyclopentyl-simple 5,10-alcohol ). Using the same -diene-13-inoic acid 2-ethoxyethyl ester, (Y, 3jj 5.8;
    5C-9-OXO-15 (K) -oxy-16 (8) -fluoro-17,18,19,20-tetranor-1 6-cyclohexyl-5-simple-5,10-diene-13-in acids 2-ethoxyethyl ester, Wj, +2.9;
    5c-9-OKCo-15 (R, 8) -oxy-16 (5) -fluoro-17, I8,19,20-tetranor-16-cyclohex- 20 final 9 acetate derivatives in its simplest-simple 5,1O-diene-13-inovy acidic form: lots of 2-ETOXYETCH1 ester, MB +5.1.
    method, derivatives of 9-acetate-2- -ethoxy-ethyl ester-11,15-bis-THF-ester, 2-piperidino ethyl ester 11, I5-bis-THF ester, 2-morpholino ethyl ether, 1I, 15 -bis-THF-ester and 2 (K, N-dimethylamino) ethyl ester 11, 5-bis-THF-ester, receive the following acids with 11 alpha and 15 hydroxy groups
    5c-9 alpha, 11 alpha, 15 (5) -rioxy-20-nor-19-cyclohexyl-prost-5-en5c-9 alpha, 11 and si-20-nor-19-cyclograph
    Froze 5c-9 alpha, 11 al-1z-inic acid; , 15 (5) -trioxy-18,19,20-trinor-5c-9 alpha, 11a
    thirty
    F
    -17-cyclohexyl-prost-5-en-13-inoic acid 2- (piperidino) ethyl ester 11,15-bis-tetrahydropyryl-ether (0.720 g) is dissolved in 10 ml of anhydrous carbon tetrachloride and 0 , 5 ml of pyridine, and then 0.1 ml of acetyl chloride is added dropwise to this solution.
    35
    The solution thus obtained is stirred for about 2 hours at room temperature and then neutralized with a 10% solution of NaH, j, P04 and then extracted with ethyl ether.
    si-20-nor-19-cyclop-13-inic acid;
    5c-9 alpha, 11a oxy-16- (8) -fluoro-2 syl-prost-5-en-13th
    5c-9 alpha, 11a -trioxy-16 (8) -fluorohexyl-prost-5-en-1
    5c-9 alpha, 11 a b-19,20-dinor-18-c-5-en-13-inov kis
    5c-9 alpha, 1 and Si-19,20-dinor-18-ts -5-en-13-inova acid
    5c-9 alpha, 11a b-16 (8) -fluoro-19,2 hexyl-prost-5-en-1
    5c-9 alpha, 11 alpha, 15 (K) -rioxy-16 (8) -fluoro-19,20-dinor-18-cyclohexyl-prost-5-ene-13-inovaic acid;
    5c-9 alpha, 11 alpha, -15 (R, 8) Next, the solvent is separated and the resulting intermediate is obtained: 5c-9 alpha, 11 alpha, 5 Trioxy-6 (8) -topopo-19,20-dinop- 18- l 5 (8) -trioxy-18,19,20-trinor-17-cyc-β-cyclohexyl-prost-5-en-13-inova levexyl-prost-5-en-13-inoic acid 2- (piperidino -ethyl ether 11,15-bis-tetrahydropyryl-ether-ether 9 acetate, which is dissolved in a mixture of 10 MP of acetone and 10 ml of one-normal oxalic acid, and the resulting mixture is stirred for 6 hours at .55 hydroxy-16 (8) -fluoro-18,19,20-trinor-17. Further reaction solution was diluted -cyclohexyl-simple-5-ene-13-ins L with 10 ml of water. Acetone is separated by bottom-acid;
    The mixture and the remaining mixture, extra-5c-9 alpha, 11 alpha, 15 (R, S), are washed with ethyl ether. -trioxy-16 (8) -fluoro-18,19,20-trinoric acid;
    5c-9 alpha, P alpha, 15 (8) -rioxy-18,19,20-trinor-17-cyclohexyl-5Q-simple-5-ene-13-inic acid;
    5c-9 alpha, 11 alpha, 15 (5) -rioxy-18,19,20-trinor-17-cyclopentyl-prost-5-ene-inoic acid;
    5c-9 alpha, 11 alpha, 15 (R) -TpH18
    The semi-product is purified on silica gel using a mixture consisting of ethyl acetate and cyclohexane in the ratio of 50:50 as eluent, which made it possible to obtain 0.295 g of pure 5c-9-alpha, II alpha, 15 (3) -trioxy-18 , 19,20-trinor-17-cyclohexyl-prost-5-en-) 3-inoic acid 2- (piperidine) ethyl ester of 9-acetate, ci +86,2 (ethyl alcohol). Using a similar
    pa of 9-acetate, ci +86.2 (ethyl alcohol). Using a similar
    the final 9 acetate derivatives in free form:
    method, derivatives of 9-acetate-2- -ethoxy-ethyl ester-11,15-bis-THF-ester, 2-piperidino ethyl ester 11, I5-bis-THF ester, 2-morpholino ethyl ether, 1I, 15 -bis-THF-ester and 2 (K, N-dimethylamino) ethyl ester 11, 5-bis-THF-ester, receive the following acids with 11 alpha and 15 hydroxy groups
    the final 9 acetate derivatives in free form:
    5c-9 alpha, 11 alpha, 15 (5) -rioxy-20-nor-19-cyclohexyl-prost-5-ene 1z-inic acid; 5c-9 alpha, 11 a
    1z-inic acid; 5c-9 alpha, 11 a
    alpha, 15 (8) -trioxy-20-nor-19-cyclopents-1-simple-5-ene-13-inoic acid;
    5c-9 alpha, 11 alpha, 15 (K) -trioxy-16- (8) -fluoro-20-nor-19-cyclohexyl-prost-5-ene-13-inic acid;
    5c-9 alpha, 11 alpha, 15 (R, 8) -trioxy-16 (8) -fluoro-20-nor-19-cyclohexyl-prost-5-ene-13-inoic acid,
    5c-9 alpha, 11 alpha, 15 (8) -rioxy-19,20-dinor-18-cyclohexyl-prost-5-ene-13-inoic acid;
    5c-9 alpha, 1 alpha, 15 (K) -trioxy-19,20-dinor-18-cyclohexyl-prost-5-ene-13-inoic acid;
    5c-9 alpha, 11 alpha, 15 (K) -rioxy-16 (8) -fluoro-19,20-dinor-18-cyclohexyl-prost-5-ene-13-inovaic acid;
    5c-9 alpha, 11 alpha, -15 (R, 8) Trioxy-6 (8) -topo-19,20-dinop-18-β-cyclohexyl-prost-5-ene-13-inov oxy-16 (8) -fluoro-18,19,20-trinor-17 Trioxy-6 (8) -fopo-19,20-dinop-18-cyclohexyl-prost-5-ene-13-in-oxy-16 (8) -fluoro- 18,19,20-trinor-17 acid;
    5c-9 alpha, P alpha, 15 (8) -rioxy-18,19,20-trinor-17-cyclohexyl-simple-5-ene-13-inovic acid;
    5c-9 alpha, 11 alpha, 15 (5) -rioxy-18,19,20-trinor-17-cyclopentyl-prost-5-ene-inoic acid;
    5c-9 alpha, 11 alpha, 15 (R) -TpH
    -17-cyclohexyl-prost-5-en-13-inic acid;
    5c-9 alpha, 11 alpha, 15 (K) -trioxy-16 (S) -fluoro-18,19,20-trinor-cyclopentyl-prost-5-ene-13-inova acid;
    5c-9 alpha, P alpha, 15 (R, S) - -triksi-16 (5) -fluoro-18,19,20-triprin-17-cyclopentyl-prost-5-en-13--nic acid ;
    5c-9 alpha, 11 alpha, 15 (5) -trioxy-17,18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inic acid;
    5c-9 alpha, 11 alpha, 15 (8) -trioxy-17,18,19,20-tetranor-16-cyclopentyl-prost-5-ene-3-inic acid;
    5c-9 alpha, P alpha, 15 (K) -trioc Si-16 (5) -fluoro-17,18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inovaic acid;
    5c-9 alpha, 11 alpha, 15 (R, S) -trioxy-16 (S) -fluoro-17,18,19,20-tetranor-16-cyclohexyl-prost-5-ene-13-inova acid;
    5c-9 alpha, 11 alpha, 15 (K) -trioxy-16 (5) -fluoro-1b-methyl-18,19,20- -trinor-17-cyclohexyl-prost-5-ene-13- inova acid;
    5c-9 alpha, 11 alpha, 15 (R, S) - -trioxy-16 (5) -fluoro-16-methyl-18,19, 20-trinor-17-cyclohexyl-prost-5-en-13- inova acid;
    5c-9 alpha, 11 alpha, 15 (K) -trioxy-16 (R) -fluoro-16-methyl-18,19,20-trinor-17-cyclohexyl-prost-5-ene-13- acid acid
    An example. To a solution of 5c-9 alpha, 11 alpha, 15 (R, 5) -trioxy-16 (5) -fluoro-18,19,20-trinor-17-cyclohexane-prost-5-en-13-inova piperazinyl-K-methylene acid amide (0.2 g in 95% ethyl alcohol (5 ml) is added to a stoichiometric amount of one-normal hydrochloric acid. The solvent is evaporated to a dry product of 5 sec-9 alpha, 1G alpha, 15 (R, 8) -trioxy-16 (8) -fluoro-18,19,20-trinor-17-cyclohexyl-prost-5-ene-13-inoic acid piperazinyl N-methyl-amidhydrochloride in the form of white crystals, +23.7 (ethyl alcohol).
    The proposed compounds are either administered by intravenous infusion at a dosage of 0.01-0.05 mg (kg live weight) / min before the end of the operation, or through the mouth by injecting a single dose

    or several doses, and in an amount of from 0.05 mg to about 5 mg in a single dose. Further, the compounds, and in particular, the 9 alpha-oxia derivatives, are also o (luteolytic (spasmolytic) activity) and are more potent, especially when administered parenterally, compared to the well-known compounds mentioned above. Luteolithic the activity of the four compounds of the invention (AD) was compared with a known compound of a similar structure (
    A) 5c-9o6, 1 I oi-, 15 (8) -trioxy-18,19,20-trinor-17-cyclohexyl-propro-5-ene-13-inoic acid-2-ethoxy-ethyl ester ;
    B) 5c-9oi ,, 1 1 vol, 15 (5) -trihydroxy-18,19,20-trinor-17-cyclohexyl- -prost-5-ene-13-inoic acid 2-piperidine-ethyl ether;
    C) 5c-9o ,, 1Y, 15 (5) -hydrihydroxy-18,19,20-trinor-1 7-cyclohexyl-pure-5-ene-13-inoic acid 2-morpholino ethyl ester;
    D) 5c-9 oi, Pob, 15 (5) -hydrihydroxy-18,19,20-trinor-17-cyclohexyl-propro-5-en-13-inoic acid 2- (N, N-dimethylaminoethyl ester ;
    E) 5c-9 alpha, 11 alpha, 15 (5) - -trioxy-18,19,20-trinor-17-cyclohexylprost-5-ene-13-inoic acid
    methyl ester (US Patent No. 4,035,415).
    The results are shown in the following table.
    ED luteolytic activity is alive. weights
    about
    g / kg
    A B C D
    E
    5 6 6 5 9

    The advantages of the compounds of the invention can be seen from the above table.
    Thus, the proposed compounds can be used to control fertility and are characterized by significantly reduced ability21
    to smooth muscle stimulation, there are no side effects typical of natural prostaglandins that cause vomiting and diarrhea.
    The toxicity of the compounds of this invention was determined on oral routes.
    The results indicate that compounds A-D LD 3 g / kg live weight.
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of obtaining optically active or racemic ester derivatives of 13,14-didehydroprostaglandia of general formula 1
    H he
    h
    COO (CH2) n- Z
    ft in he
    0130922
    where n is an integer from 1 to 4;
    Z is di (C, -C4-alkyl) amino, morpho-LINO-, piperidino or C, -alkoxy; 5m - O, 1 or 2;
    R is the preferred C-C-cycloalkyl, consisting in the fact that the optically active or racemic compound of the formula
     ABOUT N. HE
    soon
    )five
    CHC-C-CH2- (CH) m-R OH
    where m and R have the indicated meanings, are reacted with a compound of the formula
    BUT - (CH, j) -Z,
    where p and Z have the indicated meanings, in the presence of a condensing agent in an inert solvent at a temperature from room temperature to reflux temperature.
    Compiled by And, Fedoseeva Editor A. Dolinich Tehred V. Kadar Proofreader M. Demchik
    . Order 1163/58 Circulation 372Subscription
    VNIIPI USSR State Committee
    for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., 4/5
    Production and printing company, Uzhgorod, st. Project, 4
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    同族专利:
    公开号 | 公开日
    FR2517302B1|1984-12-14|
    IT8224327D0|1982-11-19|
    SE8206731D0|1982-11-25|
    IE54347B1|1989-08-30|
    AU552847B2|1986-06-26|
    IL67103A|1986-11-30|
    SE454588B|1988-05-16|
    DE3241399C2|1990-10-31|
    ATA421482A|1990-12-15|
    IT1153080B|1987-01-14|
    GB2111986B|1985-05-15|
    CH656877A5|1986-07-31|
    IL67103D0|1983-02-23|
    US4543353A|1985-09-24|
    JPS58103356A|1983-06-20|
    CA1237718A|1988-06-07|
    AT392964B|1991-07-25|
    BE895137A|1983-05-25|
    FI77442C|1989-03-10|
    NL8204611A|1983-06-16|
    FR2517302A1|1983-06-03|
    GB2111986A|1983-07-13|
    SU1321372A3|1987-06-30|
    FI824017A0|1982-11-23|
    JPH0369899B2|1991-11-05|
    DE3241399A1|1983-06-01|
    AU8979782A|1983-06-02|
    FI824017L|1983-05-28|
    SE8206731L|1983-05-28|
    FI77442B|1988-11-30|
    IE822568L|1983-05-27|
    ZA827825B|1983-08-31|
    DK528982A|1983-05-28|
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    法律状态:
    优先权:
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    GB8135799|1981-11-27|
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