COMPOUND FOR TREATING GOUT, PREPARATION METHOD THEREFOR, AND USE THEREOF

Abstract

The present invention relates to a compound for treating gout, a preparation method therefor and the use thereof. The compound is as represented by formula I. Disclosed in the present invention are a method for preparing the compound and the use of the compound in the preparation of a drug for treating or preventing gout. Further disclosed in the present invention is a composition product containing the compound. The compound provided by the present invention can be used for treating inflammation and gout, and can also be used for treating cancers.

##STR00001##

Claims

1. A compound of formula I, ##STR00073## wherein, R.sub.1 is —H, (C.sub.1-C.sub.4) alkyl or —CH.sub.2—Ar; R.sub.2 is —H, (C.sub.1-C.sub.4) alkyl or —CH.sub.2—Ar; R.sub.3 is —H, —OH, halogen, —OC(═O)—(CH.sub.2)n-CH.sub.3 or —OC(═O)—Ar; n is an integer from 0 to 4; R.sub.4 is —H, —OH, —OC(═O)—(CH.sub.2)m-CH.sub.3 or —OC(═O)—Ar; m is an integer from 0 to 4; X and Y are independently selected from H, —CH.sub.3 or halogen; W is H, —CH.sub.3, or ##STR00074## and M and N are independently selected from H, (C.sub.1-C.sub.4) alkyl, —Ar (aryl), heteroaryl or benzyl; or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, a prodrug or a mixture thereof; or pharmaceutically acceptable salts or solvates or hydrates or polymorphs of the compound of formula I or its tautomer, mesomer, racemate, enantiomer, diastereomer, prodrug or a mixture thereof.

2. The compound of formula I, or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, a prodrug or a mixture thereof; or pharmaceutically acceptable salts or solvates or hydrates or polymorphs of the compound of formula I or its tautomer, mesomer, racemate, enantiomer, diastereomer, prodrug or a mixture thereof according to claim 1, wherein, R.sub.1 is —H or —CH.sub.2CH.sub.3; and/or, R.sub.2 is —H or —CH.sub.2CH.sub.3; and/or, R.sub.3 is —H, —OH, —Cl or —OAc, ##STR00075## or —CH.sub.2CH.sub.3; and/or, R.sub.4 is —H, —OH, ##STR00076## and/or, X is —H, —F or —Cl; and/or, Y is —H, —CH.sub.3, —F, or —Cl; and/or, W is —H, α-CH.sub.3, β-CH.sub.3, α-OH, β-OH, ##STR00077##

3. The compound of formula I or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, a prodrug or a mixture thereof; or pharmaceutically acceptable salts or solvates or hydrates or polymorphs of the compound of formula I or its tautomer, mesomer, racemate, enantiomer, diastereomer, prodrug or a mixture thereof according to claim 1, wherein, R.sub.1 is —H or —CH.sub.2CH.sub.3; and/or, R.sub.2 is —H or —CH.sub.2CH.sub.3; and/or, R.sub.3 is —OH or —OAc; and/or, R.sub.4 is —OH or —OAc; and/or, X is —H; and/or, Y is —H or —CH.sub.3; and/or, W is —H.

4. A compound of formula II: ##STR00078## wherein, R.sub.1, R.sub.2, R.sub.3, X, Y, M and N have the same definitions as claim 1; and preferably, M and N are independently selected from H, (C.sub.1-C.sub.4) alkyl, —Ar, heteroaryl or benzyl; or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, a prodrug or a mixture thereof or pharmaceutically acceptable salts or solvates or hydrates or polymorphs of the compound of formula II or its tautomer, mesomer, racemate, enantiomer, diastereomer, prodrug or a mixture thereof.

5. Compounds of the following structures: ##STR00079## ##STR00080## ##STR00081## or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, a prodrug or a mixture thereof; or pharmaceutically acceptable salts or solvates or hydrates or polymorphs of the compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, prodrug or a mixture thereof.

6. A method for preparing the compound of formula I, or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, a prodrug or a mixture thereof; or pharmaceutically acceptable salts or solvates or hydrates or polymorphs of the compound of formula I or its tautomer, mesomer, racemate, enantiomer, diastereomer, prodrug or a mixture thereof according to claim 1, comprising the following synthetic routes: ##STR00082## ##STR00083## wherein R.sub.1, R.sub.2, R.sub.3 R.sub.4, X, Y, W, M and N have the same definitions as claim 1; R is a linear saturated alkyl, preferably a linear saturated (C.sub.1-C.sub.12) alkyl, and more preferably a linear saturated (C.sub.1-C.sub.4) alkyl such as methyl, ethyl, n-propyl or n-butyl.

7. A method for preparing the compound of formula II, or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, a prodrug or a mixture thereof; or pharmaceutically acceptable salts or solvates or hydrates or polymorphs of the compound of formula II or its tautomer, mesomer, racemate, enantiomer, diastereomer, prodrug or a mixture thereof according to claim 4, comprising the following synthetic routes: ##STR00084## wherein preferably, M and N are independently selected from H, (C.sub.1-C.sub.4) alkyl, —Ar, heteroaryl or benzyl.

8. (canceled)

9. A combination product for treating or preventing gout or inflammation or cancer (or tumor), wherein the combination product comprises one or more of the compound or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, a prodrug or a mixture thereof; or pharmaceutically acceptable salts or solvates or hydrates or polymorphs of the compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, prodrug or a mixture thereof according to preferably further comprises a pharmaceutically acceptable auxiliary material; and/or the combination product is a kit.

10. A method for treating or preventing gout or inflammation or cancer, comprising: administering to a subject or patient in need thereof, orally or non-orally, an effective amount of the compound or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, a prodrug or a mixture thereof; or pharmaceutically acceptable salts or solvates or hydrates or polymorphs of the compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, prodrug or a mixture thereof according to claim 1; wherein the gout is preferably a gout in the acute stage; the inflammation is preferably an inflammation associated with regulating any one or more of the expressions of glucocorticoid receptor GRa, glucocorticoid receptor GRb, proinflammatory factor TNF-α, and inflammatory protective factor IL-10 in the inflammatory response pathway; the cancer is preferably any one or more of human lung adenocarcinoma, human acute lymphoblastic leukemia, human B cell lymphoma, human breast carcinoma, human malignant glioblastoma, human live cancer, human cervical cancer, human non-small cell lung cancer, human osteosarcoma, human colon cancer, human osteoblastic sarcoma, and human Burkitt's lymphoma.

11. A method for treating or preventing gout or inflammation or cancer, comprising: administering to a subject or patient in need thereof, orally or non-orally, an effective amount of the combination product according to claim 9; wherein the gout is preferably a gout in the acute stage; the inflammation is preferably an inflammation associated with regulating any one or more of the expressions of glucocorticoid receptor GRa, glucocorticoid receptor GRb, proinflammatory factor TNF-α, and inflammatory protective factor IL-10 in the inflammatory response pathway; the cancer is preferably any one or more of human lung adenocarcinoma, human acute lymphoblastic leukemia, human B cell lymphoma, human breast carcinoma, human malignant glioblastoma, human live cancer, human cervical cancer, human non-small cell lung cancer, human osteosarcoma, human colon cancer, human osteoblastic sarcoma, and human Burkitt's lymphoma.

Description

SPECIFIC MODES FOR CARRYING OUT THE EMBODIMENTS

[0087] The present invention is described in further detail below in conjunction with specific Examples, but is not intended to limit the scope of the present invention.

[0088] The raw material can all available from open commercial sources unless otherwise specified.

Example 1

(6S,8S, 9S, 10R, 11S, 13S, 14S, 17R)-11,17-dihydroxy-17-((E)-2-hydroxy-1-(hydroxyimino)ethyl)-6,10,13-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentane[α]phenanthrene-3-one oxime

[0089] ##STR00055##

[0090] To a solution of methylprednisolone a (500 mg, 1.0 eq) in methanol at room temperature was added sodium acetate (370 mg, 2.5 eq), and hydroxylamine hydrochloride (203 mg, 2.2 eq) was added in batches, to react at room temperature for 6 h. After TLC monitoring the reaction was completed, the solvent was spun dry in vacuo. The resultant was purified under EA and PE gradients using a Biotage Isolera automated column chromatograph, and then dried under reduced pressure. Z/E-1 (510 mg, 95%) was obtained as an off-white solid. The resultant was then further purified by RPHPLC under a gradient of MeOH and H.sub.2O, and dried under reduced pressure to give pure compound 3(Z)-1 (200 mg) and compound 3(E)-1 (248 mg).

[0091] Compound 3(Z)-1: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.629 (m, 1H), 0.870-0.835 (m, 4H), 1.051-1.035 (d, 3H), 1.254-1.119 (m, 1H), 1.323 (s, 3H), 1.436-1.354 (m, 1H), 1.604-1.590 (m, 2H), 1.758-1.714 (m, 2H), 1.995-1.969 (m, 2H), 2.636-2.536 (m, 1H), 2.734 (m, 1H), 4.164-4.132 (m, 1H), 4.274-4.225 (m, 2H), 4.406-4.397 (m, 1H), 4.589-4.560 (m, 1H), 4.807 (s, 1H), 6.116-6.087 (m, 1H), 6.354-6.329 (d, 1H), 6.446 (s, 1H), 10.576 (s, 1H), 10.796 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.24, 18.62, 23.45, 23.60, 31.71, 32.73, 32.83, 39.96, 43.51, 43.67, 47.07, 50.90, 55.74, 56.94, 67.76, 85.67, 104.83, 121.59, 141.73, 148.76, 159.72, 161.47; Calculated value 405.3, Experimental value 405.2 for LRMS(ES+)[C.sub.22H.sub.32N.sub.2O.sub.5+H].

[0092] Compound 3(E)-1: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.632-0.612 (m, 1H), 0.875-0.832 (m, 4H), 1.032-1.021 (d, 3H), 1.254-1.119 (m, 1H), 1.324 (s, 3H), 1.368-1.354 (m, 1H), 1.607-1.595 (m, 2H), 1.760-1.709 (m, 2H), 2.004-1.943 (m, 2H), 2.511 (m, 1H), 2.731 (m, 1H), 4.157-4.127 (m, 1H), 4.266-4.233 (m, 2H), 4.408-4.402 (m, 1H), 4.592-4.572 (m, 1H), 4.809 (s, 1H), 5.708 (s, 1H), 6.519-6.501 (d, 1H), 6.779-6.759 (m, 1H), 10.522 (s, 1H), 10.793 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.23, 18.57, 23.31, 23.48, 31.74, 32.64, 32.83, 39.95, 43.42, 43.62, 47.03, 50.92, 55.76, 56.69, 67.70, 85.71, 112.20, 113.75, 145.96, 149.06, 156.86, 159.72; Calculated value 405.3, Experimental value 405.2 for LRMS(ES+)[C.sub.22H.sub.32N.sub.2O.sub.5+H].

Example 2

(2E)-2-((6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-3-(hydroxyimino)-6,10,13-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentane[α]phenanthrene-17-yl)-2-(hydroxyimino)ethyl acetate

[0093] ##STR00056##

[0094] Compound 2 was prepared according to the methods shown in Synthesis Routes I and II in the general synthetic methods above using appropriate starting materials and separated to give 3(Z)-2 and 3(E)-2.

[0095] Compound 3(Z)-2: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.630 (m, 1H), 0.863-0.835 (m, 4H), 1.044-1.032 (d, 3H), 1.255-1.122 (m, 1H), 1.325 (s, 3H), 1.366-1.352 (m, 1H), 1.603-1.590 (m, 2H), 1.758-1.712 (m, 2H), 1.998-1.953 (m, 2H), 2.632 (m, 1H), 2.688 (s, 3H), 2.733 (m, 1H), 4.166-4.142 (m, 1H), 4.259-4.227 (m, 2H), 4.405-4.386 (m, 1H), 4.806 (s, 1H), 6.113-6.078 (m, 1H), 6.345-6.327 (d, 1H), 6.452 (s, 1H), 10.574 (s, 1H), 10.793 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.22, 18.56, 22.93, 23.39, 23.60, 31.72, 32.69, 32.81, 39.94, 43.52, 43.66, 47.07, 50.92, 55.75, 56.92, 67.74, 85.65, 104.81, 121.60, 141.71, 148.78, 159.73, 161.47, 168.91; Calculated value 447.3 Experimental value 447.2 for LRMS(ES+)[C.sub.24H.sub.34N.sub.2O.sub.6+H].

[0096] Compound 3(E)-2: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.628 (m, 1H), 0.865-0.840 (m, 4H), 1.038-1.025 (d, 3H), 1.252-1.120 (m, 1H), 1.327 (s, 3H), 1.368-1.353 (m, 1H), 1.605-1.596 (m, 2H), 1.761-1.718 (m, 2H), 2.002-1.956 (m, 2H), 2.598 (m, 1H), 2.730 (m, 4H), 4.157-4.127 (m, 1H), 4.263-4.237 (m, 2H), 4.404-4.400 (m, 1H), 4.807 (s, 1H), 5.705 (s, 1H), 6.518-6.502 (d, 1H), 6.781-6.758 (m, 1H), 10.524 (s, 1H), 10.781 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.25, 18.55, 22.88, 23.35, 23.49, 31.72, 32.63, 32.82, 39.95, 43.54, 43.61, 47.04, 50.92, 55.75, 56.70, 67.72, 85.70, 112.22, 113.74, 145.93, 149.07, 156.86, 159.73, 168.95; Calculated value 447.3 Experimental value 447.2 for LRMS(ES+)[C.sub.24H.sub.34N.sub.2O.sub.6+H].

Example 3

(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-((E)-2-hydroxy (hydroxyimino)ethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentane[α]phenanthrene-3-one oxime

[0097] ##STR00057##

[0098] Compound 3 was prepared according to the method shown in Synthesis Route I in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-3 and (3E)-3.

[0099] Compound 3(Z)-3: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.630 (m, 1H), 0.869-0.834 (m, 4H), 1.253-1.120 (m, 1H), 1.325 (s, 3H), 1.368-1.352 (m, 1H), 1.601-1.592 (m, 2H), 1.756-1.713 (m, 2H), 1.998-1.971 (m, 2H), 2.602-2.523 (m, 2H), 2.735 (m, 1H), 4.162-4.131 (m, 1H), 4.273-4.224 (m, 2H), 4.402-4.394 (m, 1H), 4.591-4.557 (m, 1H), 4.806 (s, 1H), 6.114-6.085 (m, 1H), 6.352-6.327 (d, 1H), 6.448 (s, 1H), 10.573 (s, 1H), 10.798 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.23, 23.47, 23.58, 31.73, 32.49, 32.84, 39.93, 43.58, 43.67, 47.06, 50.92, 55.75, 56.94, 67.77, 85.65, 104.82, 121.60, 141.72, 148.76, 159.73, 161.49; Calculated value 391.3 Experimental value 391.2 for LRMS(ES+)[C.sub.21H.sub.30N.sub.2O.sub.5+H].

[0100] Compound 3(E)-3: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.627 (m, 1H), 0.872-0.835 (m, 4H), 1.250-1.122 (m, 1H), 1.323 (s, 3H), 1.364-1.357 (m, 1H), 1.606-1.598 (m, 2H), 1.768-1.709 (m, 2H), 2.001-1.939 (m, 2H), 2.589-2.478 (m, 2H), 2.732 (m, 1H), 4.153-4.125 (m, 1H), 4.263-4.231 (m, 2H), 4.409-4.404 (m, 1H), 4.590-4.574 (m, 1H), 4.810 (s, 1H), 5.707 (s, 1H), 6.518-6.502 (d, 1H), 6.779-6.762 (m, 1H), 10.524 (s, 1H), 10.796 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.24, 23.34, 23.47, 31.75, 32.47, 32.86, 39.94, 43.53, 43.64, 47.02, 50.94, 55.73, 56.69, 67.68, 85.72, 112.23, 113.74, 145.95, 149.06, 156.83, 159.74; Calculated value 391.3 Experimental value 391.2 for LRMS(ES+)[C.sub.21H.sub.30N.sub.2O.sub.5+H].

Example 4

(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-((E)-2-hydroxy-1-(hydroxyimino)ethyl)-6,10,13-trimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetrahydro-3H-cyclopentane[α]phenanthrene-3-one oxime

[0101] ##STR00058##

[0102] Compound 4 was prepared according to the methods shown in Synthesis Route I in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-4 and (3E)-4.

[0103] Compound 3(Z)-4: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.635 (m, 1H), 0.868-0.837 (m, 4H), 1.053-1.032 (d, 3H), 1.085-1.089 (m, 1H), 1.156-1.127 (m, 1H), 1.284-1.277 (m, 1H), 1.323 (s, 3H), 1.371-1.352 (m, 1H), 1.603-1.585 (m, 2H), 1.759-1.713 (m, 2H), 1.996-1.965 (m, 2H), 2.636-2.534 (m, 1H), 2.738 (m, 1H), 2.979-2.965 (m, 2H), 4.166-4.135 (m, 1H), 4.273-4.226 (m, 2H), 4.405-4.399 (m, 1H), 4.588-4.561 (m, 1H), 4.809 (s, 1H), 6.407 (s, 1H), 10.127 (s, 1H), 10.791 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.22, 18.65, 23.47, 23.61, 30.82, 31.71, 32.74, 32.84, 38.75, 39.95, 43.52, 43.68, 47.05, 50.92, 55.73, 56.96, 67.73, 85.65, 101.52, 148.59, 159.71, 162.47; Calculated value 407.3 Experimental value 407.2 for LRMS(ES+)[C.sub.22H.sub.32N.sub.2O.sub.5+H].

[0104] Compound 3(E)-4: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.623 (m, 1H), 0.873-0.834 (m, 4H), 1.035-1.026 (d, 3H), 1.089-1.082 (m, 1H), 1.156-1.117 (m, 1H), 1.282-1.274 (m, 1H), 1.325 (s, 3H), 1.367-1.358 (m, 1H), 1.609-1.597 (m, 2H), 1.759-1.708 (m, 2H), 2.001-1.945 (m, 2H), 2.514 (m, 1H), 2.733 (m, 1H), 3.124-3.037 (m, 2H), 4.154-4.123 (m, 1H), 4.268-4.232 (m, 2H), 4.406-4.401 (m, 1H), 4.590-4.575 (m, 1H), 4.811 (s, 1H), 5.701 (s, 1H), 10.124 (s, 1H), 10.791 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.23, 18.56, 23.33, 23.47, 30.21, 31.78, 32.02, 32.84, 39.07, 39.93, 43.44, 43.65, 47.01, 50.93, 55.74, 56.69, 67.70, 85.71, 113.21, 149.03, 157.86, 159.74; Calculated value 407.3 Experimental value 407.2 for LRMS(ES+)[C.sub.22H.sub.32N.sub.2O.sub.5+H].

Example 5

(2E)-2-((8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-3-(hydroxyimino)-10,13-dimethyl-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetrahydro-1H-cyclopentane[α]phenanthro yl)-2-(hydroxyimino)ethyl acetate

[0105] ##STR00059##

[0106] Compound 5 was prepared according to the methods shown in Synthesis Routes I and II in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-5 and (3E)-5.

[0107] Compound 3(Z)-5: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.631 (m, 1H), 0.868-0.837 (m, 4H), 1.085-1.089 (m, 1H), 1.156-1.127 (m, 1H), 1.284-1.277 (m, 1H), 1.323 (s, 3H), 1.371-1.352 (m, 1H), 1.603-1.585 (m, 2H), 1.759-1.713 (m, 2H), 1.996-1.965 (m, 2H), 2.602-2.523 (m, 2H), 2.688 (s, 3H), 2.738 (m, 1H), 2.979-2.965 (m, 2H), 4.166-4.135 (m, 1H), 4.273-4.226 (m, 2H), 4.405-4.399 (m, 1H), 4.809 (s, 1H), 6.407 (s, 1H), 10.127 (s, 1H), 10.791 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.22, 22.93, 23.47, 23.61, 30.82, 31.71, 32.48, 32.84, 38.75, 39.95, 43.52, 43.68, 47.05, 50.92, 55.73, 56.96, 67.73, 85.65, 101.52, 148.59, 159.71, 162.47, 168.91; Calculated value 435.3 Experimental value 435.2 for LRMS(ES+)[C.sub.23H.sub.34N.sub.2O.sub.6+H].

[0108] Compound 3(E)-5: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.624 (m, 1H), 0.872-0.835 (m, 4H), 1.091-1.078 (m, 1H), 1.154-1.116 (m, 1H), 1.283-1.275 (m, 1H), 1.324 (s, 3H), 1.366-1.359 (m, 1H), 1.610-1.595 (m, 2H), 1.754-1.706 (m, 2H), 2.002-1.945 (m, 2H), 2.603-2.522 (m, 2H), 2.687 (s, 3H), 2.735 (m, 1H), 3.126-3.034 (m, 2H), 4.155-4.124 (m, 1H), 4.267-4.231 (m, 2H), 4.408-4.403 (m, 1H), 4.813 (s, 1H), 5.704 (s, 1H), 10.127 (s, 1H), 10.793 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.23, 22.88, 23.33, 23.47, 30.21, 31.78, 32.02, 32.44, 39.06, 39.94, 43.45, 43.66, 47.02, 50.94, 55.73, 56.68, 67.71, 85.72, 113.23, 149.07, 157.88, 159.75, 168.95; Calculated value 435.3 Experimental value 435.2 for LRMS(ES+)[C.sub.23H.sub.34N.sub.2O.sub.6+H].

Example 6

(8S,9S,10R,11S,13S,14S,16S,17R)-11,17-dihydroxy-17-((E)-2-hydroxy-1-(hydroxyimino)ethyl)-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentane[α]phenanthrene-3-one oxime

[0109] ##STR00060##

[0110] Compound 6 was prepared according to the methods shown in Synthesis Routes I and II in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-6 and (3E)-6.

[0111] Compound 3(Z)-6: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.630 (m, 1H), 0.870-0.832 (m, 7H), 1.252-1.123 (m, 1H), 1.324 (s, 3H), 1.602-1.593 (m, 2H), 1.755-1.716 (m, 3H), 2.001-1.974 (m, 2H), 2.605-2.526 (m, 2H), 4.162-4.135 (m, 1H), 4.272-4.228 (m, 2H), 4.403-4.397 (m, 1H), 4.587-4.561 (m, 1H), 4.806 (s, 1H), 6.112-6.084 (m, 1H), 6.353-6.328 (d, 1H), 6.451 (s, 1H), 10.569 (s, 1H), 10.793 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 17.28, 18.22, 23.57, 27.38, 31.74, 32.45, 38.89, 39.93, 43.66, 43.57, 47.07, 50.90, 55.74, 56.94, 67.76, 88.93, 104.84, 121.63, 141.70, 148.75, 159.70, 161.39; Calculated value 405.43 Experimental value 405.3 for LRMS(ES+)[C.sub.22H.sub.32N.sub.2O.sub.5+H].

[0112] Compound 3(E)-6: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.629 (m, 1H), 0.872-0.8345 (m, 7H), 1.251-1.123 (m, 1H), 1.325 (s, 3H), 1.604-1.596 (m, 2H), 1.765-1.711 (m, 3H), 2.001-1.969 (m, 2H), 2.593-2.481 (m, 2H), 4.152-4.137 (m, 1H), 4.269-4.233 (m, 2H), 4.405-4.402 (m, 1H), 4.590-4.574 (m, 1H), 4.810 (s, 1H), 5.702 (s, 1H), 6.513-6.501 (d, 1H), 6.776-6.761 (m, 1H), 10.523 (s, 1H), 10.794 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 17.27, 18.23, 23.34, 27.38, 31.76, 32.47, 38.85, 39.94, 43.56, 43.64, 47.03, 50.93, 55.74, 56.67, 67.69, 88.98, 112.24, 113.72, 145.95, 149.07, 156.85, 159.78; Calculated value 405.43 Experimental value 405.3 for LRMS(ES+)[C.sub.22H.sub.32N.sub.2O.sub.5+H].

Example 7

(6aS,6bR,7S,8aS,8bR,11aR,12aS,12bS)-6b-fluoro-7-hydroxy-8b-((E)-2-hydroxy (hydroxyimino)ethyl)-6a,8a,10,10-tetramethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecyl-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxan-4-one oxime

[0113] ##STR00061##

[0114] Compound 7 was prepared according to the methods shown in Synthesis Routes I and III in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-7 and (3E)-7.

[0115] Compound 3 (Z)-7: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.731 (m, 1H), 0.877-0.852 (m, 4H), 1.233 (s, 6H), 1.287-1.198 (m, 1H), 1.347 (s, 3H), 1.611-1.597 (m, 1H), 1.783-1.774 (m, 2H), 1.998-1.972 (m, 2H), 2.798 (m, 2H), 3.986 (m, 1H), 4.174-4.163 (m, 1H), 4.285-4.273 (m, 2H), 4.411-4.402 (m, 1H), 4.587-4.559 (m, 1H), 6.118-6.097 (m, 1H), 6.361-6.333 (d, 1H), 6.442 (s, 1H), 10.574 (s, 1H), 10.799 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.34, 23.62, 26.57, 33.86, 33.92, 34.37, 39.94, 43.51, 43.69, 47.08, 50.92, 55.76, 70.83, 83.49, 96.91, 100.24, 104.82, 121.62, 123.13, 141.72, 148.75, 159.73, 161.49; Calculated value 465.3 Experimental value 465.2 for LRMS(ES+)[C.sub.23H.sub.33F.sub.2N.sub.2O.sub.6+H].

[0116] Compound 3 (E)-7: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.728 (m, 1H), 0.874-0.833 (m, 4H), 1.234 (s, 6H), 1.256-1.121 (m, 1H), 1.326 (s, 3H), 1.609-1.593 (m, 1H), 1.762-1.723 (m, 2H), 2.003-1.965 (m, 2H), 2.788 (m, 2H), 3.979 (m, 1H), 4.154-4.123 (m, 1H), 4.269-4.253 (m, 2H), 4.407-4.403 (m, 1H), 4.591-4.570 (m, 1H), 5.706 (s, 1H), 6.513-6.504 (d, 1H), 6.779-6.759 (m, 1H), 10.522 (s, 1H), 10.793 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.33, 23.64, 26.56, 33.85, 33.94, 34.38, 39.93, 43.47, 43.64, 47.03, 50.93, 55.75, 70.82, 83.56, 96.94, 100.23, 112.25, 113.72, 121.63, 145.97, 149.09, 156.88, 159.74; Calculated value 465.3 Experimental value 465.2 for LRMS(ES+)[C.sub.23H.sub.33F.sub.2N.sub.2O.sub.6+H].

Example 8

(2S,6aS,6bR,7S,8aS,8bR,11aR,12aS,12bS)-2,6b-difluoro-7-hydroxy-8b-((E)-2-hydroxy-1-(hydroxyimino)ethyl)-6a,8a,10,10-tetramethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one oxime

[0117] ##STR00062##

[0118] Compound 8 was prepared according to the methods shown in Synthesis Routes I and III in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-8 and (3E)-8.

[0119] Compound 3(Z)-8: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.702 (m, 1H), 0.876-0.853 (m, 4H), 1.235 (s, 6H), 1.258-1.121 (m, 1H), 1.331 (s, 3H), 1.613-1.598 (m, 1H), 1.782-1.775 (m, 2H), 1.871-1.859 (m, 1H), 1.998-1.972 (m, 1H), 3.983 (m, 1H), 4.093-4.087 (m, 1H), 4.172-4.165 (m, 1H), 4.289-4.276 (m, 2H), 4.404 (m, 1H), 4.583-4.563 (m, 1H), 6.124-6.102 (m, 1H), 6.364-6.341 (d, 1H), 6.573 (s, 1H), 10.576 (s, 1H), 10.801 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.35, 23.64, 26.58, 33.87, 34.38, 39.97, 43.59, 43.73, 47.11, 50.94, 55.75, 70.85, 83.47, 88.87, 96.94, 100.25, 104.83, 121.60, 123.14, 141.73, 148.76, 159.72, 161.03; Calculated value 483.2 Experimental value 483.3 for LRMS(ES+)[C.sub.24H.sub.32F.sub.2N.sub.2O.sub.6+H].

[0120] Compound 3(E)-8: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.703 (m, 1H), 0.874-0.851 (m, 4H), 1.234 (s, 6H), 1.256-1.124 (m, 1H), 1.328 (s, 3H), 1.610-1.595 (m, 1H), 1.771-1.765 (m, 2H), 1.872-1.861 (m, 1H), 2.002-1.974 (m, 1H), 3.977 (m, 1H), 4.091-4.085 (m, 1H), 4.152-4.126 (m, 1H), 4.271-4.254 (m, 2H), 4.406 (m, 1H), 4.587-4.569 (m, 1H), 5.784 (s, 1H), 6.521-6.510 (d, 1H), 6.775-6.761 (m, 1H), 10.523 (s, 1H), 10.789 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 18.34, 23.65, 26.57, 33.86, 34.37, 39.95, 43.58, 43.75, 47.08, 50.95, 55.76, 70.83, 83.54, 96.96, 100.24, 112.24, 113.75, 121.62, 145.96, 149.11, 156.87, 159.72; Calculated value 483.2 Experimental value 483.3 for LRMS(ES+)[C.sub.24H.sub.32F.sub.2N.sub.2O.sub.6+H].

Example 9

(6S,8S,9S,10R,11S,13S,14S,17R,E)-17-((E)-1-(ethoxysimino)-2-hydroxyethyl)-11,17-dihydroxy-6,10,13-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentane[α]phenanthrene-3-ketoO-ethyl oxime

[0121] ##STR00063##

[0122] Compound 9 was prepared according to the methods shown in Synthesis Routes I and IV in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-9 and (3E)-9.

[0123] Compound 3 (Z)-9: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.629 (m, 1H), 0.870-0.835 (m, 4H), 0.987-0.975 (m, 6H), 1.051-1.035 (d, 3H), 1.254-1.119 (m, 1H), 1.323 (s, 3H), 1.396-1.354 (m, 1H), 1.604-1.590 (m, 2H), 1.758-1.714 (m, 2H), 1.995-1.969 (m, 2H), 2.636-2.536 (m, 1H), 2.734 (m, 1H), 3.882-3.754 (m, 4H), 4.164-4.132 (m, 1H), 4.274-4.225 (m, 2H), 4.406-4.397 (m, 1H), 4.589-4.560 (m, 1H), 4.807 (s, 1H), 6.116-6.087 (m, 1H), 6.354-6.329 (d, 1H), 6.446 (s, 1H),; .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 13.9, 18.26, 18.64, 23.47, 23.62, 31.73, 32.75, 32.84, 39.93, 43.52, 43.66, 47.09, 50.95, 55.79, 56.97, 66.93, 67.02, 67.75, 85.69, 104.84, 121.61, 141.76, 148.73, 159.74, 161.48; Calculated value 461.3 Experimental value 461.4 for LRMS(ES+)[C.sub.26H.sub.40N.sub.2O.sub.5+H].

[0124] Compound 3 (E)-9: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.631-0.624 (m, 1H), 0.873-0.835 (m, 4H), 0.985-0.974 (m, 6H), 1.035-1.028 (d, 3H), 1.253-1.121 (m, 1H), 1.326 (s, 3H), 1.365-1.351 (m, 1H), 1.604-1.592 (m, 2H), 1.760-1.713 (m, 2H), 2.002-1.954 (m, 2H), 2.516 (m, 1H), 2.735 (m, 1H), 3.796-3.728 (m, 4H), 4.157-4.128 (m, 1H), 4.269-4.235 (m, 2H), 4.407-4.401 (m, 1H), 4.590-4.571 (m, 1H), 4.804 (s, 1H), 5.702 (s, 1H), 6.517-6.506 (d, 1H), 6.801-6.762 (m, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 14.01, 18.24, 18.58, 23.33, 23.49, 31.75, 32.66, 32.83, 39.96, 43.41, 43.64, 47.02, 50.93, 55.85, 56.70, 67.72, 85.73, 112.21, 113.76, 145.94, 149.07, 156.83, 159.74; Calculated value 461.3 Experimental value 461.4 for LRMS(ES+)[C.sub.26H.sub.40N.sub.2O.sub.5+H].

Example 10

(8S,9S,10R,11S,13S,14S,16R,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentane[α]phenanthrene one

[0125] ##STR00064##

[0126] Compound 10 was prepared according to the methods shown in Synthesis Route I in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-10 and (3E)-10.

[0127] Compound 3 (Z)-10: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.630 (m, 1H), 0.870-0.832 (m, 4H), 0.989-0.975 (s, 3H), 1.254-1.126 (m, 1H), 1.327 (s, 3H), 1.602-1.593 (m, 2H), 1.755-1.716 (m, 3H), 1.896-1.874 (m, 1H), 2.003-1.977 (m, 2H), 2.606-2.528 (m, 2H), 4.163-4.142 (m, 1H), 4.273-4.231 (m, 2H), 4.405-4.396 (m, 1H), 4.591-4.575 (m, 1H), 6.113-6.087 (m, 1H), 6.354-6.329 (m, 1H), 6.453 (s, 1H), 10.567 (s, 1H), 10.797 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 17.21, 18.32, 23.51, 31.42, 31.96, 38.95, 39.71, 40.03, 42.97, 43.92, 45.88, 49.73, 56.81, 56.89, 67.76, 85.67, 104.83, 121.59, 141.73, 148.76, 159.72, 161.47; Calculated value 389.3 Experimental value 389.2 for LRMS(ES+)[C.sub.22H.sub.32N.sub.2O.sub.4+H].

[0128] Compound 3 (E)-10: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.628 (m, 1H), 0.873-0.834 (m, 4H), 0.988-0.976 (s, 3H), 1.253-1.121 (m, 1H), 1.327 (s, 3H), 1.606-1.594 (m, 2H), 1.764-1.712 (m, 3H), 1.894-1.873 (m, 1H), 1.998-1.962 (m, 2H), 2.597-2.485 (m, 2H), 4.155-4.134 (m, 1H), 4.267-4.231 (m, 2H), 4.408-4.403 (m, 1H), 4.588-4.572 (m, 1H), 5.704 (s, 1H), 6.511-6.503 (d, 1H), 6.778-6.764 (m, 1H), 10.522 (s, 1H), 10.793 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 17.25, 18.26, 23.37, 31.39, 31.87, 38.93, 39.69, 40.01, 42.92, 43.89, 45.86, 49.71, 56.76, 56.85, 67.70, 85.64, 112.19, 113.78, 145.94, 149.11, 156.87, 159.82; Calculated value 389.3 Experimental value 389.2 for LRMS(ES+)[C.sub.22H.sub.32N.sub.2O.sub.4+H].

Example 11

(2E)-2-(ethoxysilane)-2-((8S,9S,10R,11S,13S,14S,16R,17R)-3-(ethoxysilane)-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentanone[α]phenanthrene-17-yl)ethyl acetate

[0129] ##STR00065##

[0130] Compound 11 was prepared according to the methods shown in Synthesis Routes I and IV in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-11 and (3E)-11.

[0131] Compound 3(Z)-11: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.641 (m, 1H), 0.877-0.841 (m, 4H), 0.992-0.975 (s, 9H), 1.254-1.126 (m, 1H), 1.327 (s, 3H), 1.602-1.593 (m, 2H), 1.755-1.716 (m, 3H), 2.003-1.977 (m, 2H), 2.606-2.528 (m, 2H), 2.688 (s, 3H), 3.882-3.754 (m, 4H), 4.163-4.142 (m, 1H), 4.273-4.231 (m, 2H), 4.405-4.396 (m, 1H), 4.806 (s, 1H), 6.113-6.087 (m, 1H), 6.354-6.329 (m, 1H), 6.453 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 13.56, 17.21, 18.33, 23.53, 30.35, 31.63, 32.58, 36.83, 39.98, 42.36, 43.62, 46.11, 50.83, 56.89, 56.93, 67.74, 69.81, 69.84 88.87, 104.85, 121.54, 141.76, 148.74, 159.71, 161.45, 169.88; Calculated value 503.3 Experimental value 503.2 for LRMS(ES+)[C.sub.28H.sub.42N.sub.2O.sub.6+H].

[0132] Compound 3(E)-11: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.633 (m, 1H), 0.875-0.837 (m, 4H), 0.987-0.979 (s, 9H), 1.2543-1.120 (m, 1H), 1.329 (s, 3H), 1.604-1.592 (m, 2H), 1.761-1.718 (m, 3H), 1.997-1.965 (m, 2H), 2.596-2.483 (m, 2H), 2.687 (s, 3H), 3.876-3.752 (m, 4H), 4.154-4.132 (m, 1H), 4.264-4.230 (m, 2H), 4.404-4.398 (m, 1H), 4.811 (s, 1H), 5.706 (s, 1H), 6.509-6.501 (d, 1H), 6.776-6.763 (m, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 13.55, 17.23, 18.34, 23.51, 30.39, 31.67, 32.56, 36.76, 39.96, 42.37, 43.69, 46.13, 50.79, 56.86, 56.96, 67.72, 69.79, 69.83, 88.84, 112.21, 113.76, 145.92, 149.15, 156.86, 159.76, 169.87; Calculated value 503.3 Experimental value 503.2 for LRMS(ES+)[C.sub.28H.sub.42N.sub.2O.sub.6+H].

Example 12

(2E)-2-((8S,9R,10S,11S,13S,14S,16S,17R)-9-chloro-11,17-dihydroxy-3-(hydroxyimino)-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentane[α]phenanthrene-17-yl)-2-(hydroxyimino)ethyl propionate

[0133] ##STR00066##

[0134] Compound 12 was prepared according to the methods shown in Synthesis Routes I and II in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-12 and (3E)-12.

[0135] Compound 3(Z)-12: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.629 (m, 1H), 0.872-0.833 (m, 7H), 1.249-1.117 (m, 4H), 1.326 (s, 3H), 1.601-1.597 (m, 1H), 1.754-1.718 (m, 3H), 2.002-1.976 (m, 2H), 2.601-2.522 (m, 4H), 4.159-4.134 (m, 1H), 4.274-4.229 (m, 2H), 4.402-4.398 (m, 1H), 4.811 (s, 1H), 6.109-6.085 (m, 1H), 6.353-6.321 (d, 1H), 6.452 (s, 1H), 10.574 (s, 1H), 10.792 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 10.26, 17.27, 18.24, 23.58, 27.29, 27.36, 31.76, 32.44, 38.90, 39.96, 43.55, 43.67, 47.04, 50.91, 55.76, 56.93, 67.77, 88.96, 104.85, 121.63, 141.76, 148.73, 159.74, 161.46, 171.57; Calculated value 496.2 Experimental value 496.3 for LRMS(ES+)[C.sub.25H.sub.35FN.sub.2O.sub.6+H].

[0136] Compound 3(E)-12: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.631 (m, 1H), 0.871-0.837 (m, 7H), 1.252-1.121 (m, 4H), 1.322 (s, 3H), 1.603-1.597 (m, 1H), 1.761-1.723 (m, 3H), 1.998-1.967 (m, 2H), 2.596-2.486 (m, 4H), 4.154-4.133 (m, 1H), 4.272-4.234 (m, 2H), 4.406-4.397 (m, 1H), 4.809 (s, 1H), 5.698 (s, 1H), 6.508-6.497 (d, 1H), 6.772-6.760 (m, 1H), 10.528 (s, 1H), 10.791 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 10.24, 17.25, 18.23, 23.39, 27.31, 27.40, 31.75, 32.48, 38.89, 39.93, 43.54, 43.67, 47.04, 50.93, 55.77, 56.71, 67.68, 88.92, 112.21, 113.78, 145.96, 149.11, 156.82, 159.77, 171.52; Calculated value 496.2 Experimental value 496.3 for LRMS(ES+)[C.sub.25H.sub.35FN.sub.2O.sub.6+H].

Example 13

(6aR,6bS,7S,8aS,8bR,11aR,12aS,12bS)-7-hydroxy-8b-((E)-2-hydroxy-1-(hydroxyimino)ethyl)-6a,8a-dimethyl-10-propyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one oxime

[0137] ##STR00067##

[0138] Compound 13 was prepared according to the methods shown in Synthesis Routes I and III in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-13 and (3E)-13.

[0139] Compound 3(Z)-13: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.637 (m, 1H), 0.873-0.858 (m, 4H), 0.893-0.882 (m, 3H), 1.233 (s, 2H), 1.272-1.125 (m, 1H), 1.347 (s, 3H), 1.402 (m, 1H), 1.613-1.602 (m, 3H), 1.781-1.779 (m, 2H), 1.994-1.961 (m, 2H), 2.679-2.657 (m, 2H), 3.986 (m, 1H), 4.170-4.168 (m, 1H), 4.283-4.269 (m, 2H), 4.407-4.404 (m, 1H), 4.583-4.563 (m, 1H), 5.396 (m, 1H), 6.118-6.097 (m, 1H), 6.361-6.333 (d, 1H), 6.442 (s, 1H), 10.574 (s, 1H), 10.799 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 13.22, 14.57, 18.36, 23.55, 33.88, 33.91, 34.36, 36.69, 42.85, 43.54, 43.61, 46.97, 52.38, 55.76, 56.98, 70.21, 89.97, 96.91, 103.62 104.83, 120.31, 141.75, 148.73, 159.76, 161.46; Calculated value 461.3 Experimental value 461.4 for LRMS(ES+)[C.sub.25H.sub.36N.sub.2O.sub.6+H].

[0140] Compound 3(E)-13: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.635 (m, 1H), 0.876-0.842 (m, 4H), 0.891-0.884 (m, 3H), 1.231 (s, 2H), 1.269-1.123 (m, 1H), 1.331 (s, 3H), 1.398 (m, 1H), 1.7-1.594 (m, 3H), 1.767-1.728 (m, 2H), 2.001-1.967 (m, 2H), 2.749 (m, 2H), 3.982 (m, 1H), 4.163-4.139 (m, 1H), 4.271-4.262 (m, 2H), 4.409-4.405 (m, 1H), 4.590-4.568 (m, 1H), 5.704 (s, 1H), 6.517-6.501 (d, 1H), 6.778-6.757 (m, 1H), 10.528 (s, 1H), 10.796 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 13.26, 14.55, 18.34, 23.57, 33.87, 33.89, 34.35, 36.72, 42.83, 43.49, 43.63, 46.94, 52.37, 55.74, 56.97, 70.24, 89.95, 96.93, 103.65, 112.29, 113.74, 120.33, 145.94, 149.03, 156.86, 159.73; Calculated value 461.3 Experimental value 461.4 for LRMS(ES+)[C.sub.25H.sub.36N.sub.2O.sub.6+H].

Example 14

(2E)-2-((8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,16,17-trihydroxy (hydroxyimino)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentane[α]phenanthrene-17-yl)-2-(hydroxyimino)ethyl propionate

[0141] ##STR00068##

[0142] Compound 14 was prepared according to the methods shown in Synthesis Routes I and II in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-14 and (3E)-14.

[0143] Compound 3(Z)-14: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.728 (m, 1H), 0.879-0.854 (m, 4H), 1.211-1.199 (m, 3H), 1.284-1.187 (m, 1H), 1.347 (s, 3H), 1.611-1.597 (m, 1H), 1.783-1.774 (m, 2H), 1.998-1.972 (m, 2H), 2.399-2.367 (m, 2H), 2.798 (m, 2H), 3.873 (m, 1H), 4.161-4.148 (m, 2H), 4.376-4.363 (m, 1H), 4.411-4.402 (m, 1H), 5.223 (s, 1H), 5.416 (m, 1H), 6.114-6.093 (m, 1H), 6.358-6.331 (d, 1H), 6.438 (s, 1H), 10.571 (s, 1H), 10.795 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 10.32, 18.21, 23.32, 23.57, 27.46, 33.89, 33.94, 34.29, 39.91, 43.50, 43.71, 47.08, 50.81, 56.69, 70.81, 82.34, 92.73, 100.21, 104.84, 121.60, 141.71, 148.77, 159.72, 161.45; Calculated value 481.2 Experimental value 481.3 for LRMS(ES+)[C.sub.24H.sub.33F.sub.1N.sub.2O.sub.7+H].

[0144] Compound 3(E)-14: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.731 (m, 1H), 0.872-0.835 (m, 4H), 1.208-1.198 (m, 3H), 1.253-1.119 (m, 1H), 1.329 (s, 3H), 1.607-1.592 (m, 1H), 1.765-1.738 (m, 2H), 2.001-1.969 (m, 2H), 2.334-2.359 (m, 2H), 2.787 (m, 2H), 3.897 (m, 1H), 4.154-4.123 (m, 2H), 4.272-4.259 (m, 1H), 4.406-4.401 (m, 1H), 5.219 (s, 1H), 5.408 (m, 1H), 5.704 (s, 1H), 6.511-6.502 (d, 1H), 6.774-6.758 (m, 1H), 10.523 (s, 1H), 10.798 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 10.29, 18.24, 23.34, 23.56, 27.45, 33.88, 33.95, 34.31, 39.92, 43.49, 43.69, 47.05, 50.83, 56.68, 70.79, 82.36, 92.72, 100.22, 112.23, 113.74, 145.95, 149.07, 156.86, 159.73; Calculated value 481.2 Experimental value 481.3 for LRMS(ES+)[C.sub.24H.sub.33F.sub.1N.sub.2O.sub.7+H].

Example 15

(8S,9R,10S,11S,13S,14S,16S,17R)-9-fluoro-11-hydroxy-17-((E)-2-hydroxy (hydroxyimino)ethyl)-3-(hydroxyimino)-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentaphenanthrene-17-yl butyrate

[0145] ##STR00069##

[0146] Compound 15 was prepared according to the methods shown in Synthesis Routes I and II in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-15 and (3E)-15.

[0147] Compound 3(Z)-15: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.631 (m, 1H), 0.872-0.833 (m, 7H), 1.109-0.998 (m, 3H), 1.249-1.119 (m, 1H), 1.331 (s, 3H), 1.601-1.597 (m, 1H), 1.665-1.621 (m, 2H), 1.754-1.718 (m, 2H), 1.998-1.975 (m, 2H), 2.136-1.109 (m, 1H), 2.322-2.317 (m, 2H), 2.603-2.524 (m, 2H), 4.145-4.122 (m, 1H), 4.275-4.227 (m, 2H), 4.403-4.396 (m, 1H), 4.589-4.560 (m, 1H), 6.113-6.086 (m, 1H), 6.359-6.324 (d, 1H), 6.448 (s, 1H), 10.578 (s, 1H), 10.799 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 14.11, 17.21, 18.25, 18.46, 23.52, 23.66, 31.62, 32.49, 32.79, 36.32, 40.11, 43.46, 43.62, 47.87, 51.12, 55.72, 67.77, 88.91, 100.01, 104.83, 121.67, 141.72, 148.75, 159.71, 161.48, 172.13; Calculated value 493.3 Experimental value 493.2 for LRMS(ES+)[C.sub.26H.sub.37FN.sub.2O.sub.6+H].

[0148] Compound 3(E)-15: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.629 (m, 1H), 0.873-0.834 (m, 7H), 1.107-0.997 (m, 3H), 1.246-1.117 (m, 1H), 1.322 (s, 3H), 1.602-1.599 (m, 1H), 1.661-1.618 (m, 2H), 1.755-1.721 (m, 2H), 1.996-1.972 (m, 2H), 2.133-1.107 (m, 1H), 2.317-2.311 (m, 2H), 2.597-2.493 (m, 2H), 4.142-4.120 (m, 1H), 4.272-4.225 (m, 2H), 4.404-4.395 (m, 1H), 4.588-4.571 (m, 1H), 5.683 (s, 1H), 6.507-6.494 (d, 1H), 6.770-6.758 (m, 1H), 10.526 (s, 1H), 10.801 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 14.09, 17.24, 18.23, 18.44, 23.41, 23.64, 31.64, 32.47, 32.75, 36.33, 40.08, 43.42, 43.63, 47.84, 51.11, 55.74, 67.69, 88.90, 99.98, 112.19, 113.75, 145.93, 149.13, 156.83, 159.74, 172.11; Calculated value 493.3 Experimental value 493.2 for LRMS(ES+)[C.sub.26H.sub.37FN.sub.2O.sub.6+H].

Example 16

(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-3-(hydroxyimino)-17-((E) (hydroxyimino)ethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentane[α]phenanthrene-17-yl propionate

[0149] ##STR00070##

[0150] Compound 16 was prepared according to the methods shown in Synthesis Routes I and II in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-16 and (3E)-16.

[0151] Compound 3(Z)-16: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.628 (m, 1H), 0.868-0.835 (m, 4H), 1.226-1.213 (m, 3H), 1.253-1.118 (m, 1H), 1.325 (s, 3H), 1.398-1.364 (m, 1H), 1.606-1.590 (m, 2H), 1.760-1.715 (m, 2H), 1.998-1.972 (m, 2H), 2.339-2.297 (m, 2H), 2.606-2.527 (m, 2H), 2.755 (m, 1H), 3.037 (s, 3H), 4.273-4.224 (m, 1H), 4.402-4.394 (m, 1H), 6.118-6.086 (m, 1H), 6.355-6.329 (d, 1H), 6.447 (s, 1H), 10.575 (s, 1H), 10.794 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 9.97, 10.92, 18.34, 23.56, 23.62, 28.06, 31.67, 32.50, 32.72, 39.98, 43.58, 43.69, 46.24, 50.94, 56.95, 67.72, 95.58, 104.84, 121.59, 141.72, 148.77, 159.71, 161.48, 173.36; Calculated value 431.2 Experimental value 431.3 for LRMS(ES+)[C.sub.24H.sub.34N.sub.2O.sub.5+H].

[0152] Compound 3(E)-16: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.629 (m, 1H), 0.870-0.834 (m, 4H), 1.224-1.210 (m, 3H), 1.250-1.121 (m, 1H), 1.322 (s, 3H), 1.375-1.363 (m, 1H), 1.603-1.595 (m, 2H), 1.755-1.709 (m, 2H), 2.002-1.975 (m, 2H), 2.331-2.295 (m, 2H), 2.603-2.532 (m, 2H), 2.745 (m, 1H), 3.035 (s, 3H), 4.271-4.228 (m, 2H), 4.403-4.398 (m, 1H), 5.704 (s, 1H), 6.515-6.501 (d, 1H), 6.776-6.758 (m, 1H), 10.520 (s, 1H), 10.791 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 9.98, 10.89, 18.33, 23.46, 23.61, 28.04, 31.63, 32.46, 32.84, 39.97, 43.54, 43.66, 46.20, 50.92, 56.97, 67.74, 95.57, 112.19, 113.73, 145.97, 149.08, 156.85, 159.71, 173.34; Calculated value 431.2 Experimental value 431.3 for LRMS(ES+)[C.sub.24H.sub.34N.sub.2O.sub.5+H].

Example 17

(6S,8S,9S,10R,11S,13S,14S,17R,E)-11-hydroxy-17-((E)-2-hydroxy-1-(hydroxyimino)ethyl)-3-(hydroxyimino)-6,10,13-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopentane[α]phenanthrene-17-yl valerate

[0153] ##STR00071##

[0154] Compound 17 was prepared according to the methods shown in Synthesis Routes I and II in the general synthetic methods above using appropriate starting materials and separated to give (3Z)-17 and (3E)-17.

[0155] Compound 3(Z)-17: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.628 (m, 1H), 0.869-0.833 (m, 4H), 0.942-0.921 (m, 3H), 1.053-1.033 (d, 3H), 1.253-1.117 (m, 1H), 1.325 (s, 3H), 1.387-1.334 (m, 2H), 1.498-1.424 (m, 1H), 1.604-1.588 (m, 2H), 1.755-1.702 (m, 4H), 1.996-1.971 (m, 2H), 2.429-2.402 (m, 2H), 2.634-2.532 (m, 1H), 2.789 (m, 1H), 4.160-4.129 (m, 1H), 4.272-4.227 (m, 2H), 4.403-4.396 (m, 1H), 4.591-4.562 (m, 1H), 6.115-6.089 (m, 1H), 6.353-6.331 (d, 1H), 6.446 (s, 1H), 10.575 (s, 1H), 10.794 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 13.92, 18.34, 18.61, 22.37, 23.57, 23.61, 27.59, 31.65, 32.57, 32.74, 33.98, 40.13, 43.52, 43.69, 45.02, 50.99, 56.32, 56.95, 67.63, 89.34, 104.83, 121.60, 141.72, 148.75, 159.73, 161.48, 173.24; Calculated value 489.3 Experimental value 489.4 for LRMS (ES+) [C.sub.27H.sub.40N.sub.2O.sub.6+H].

[0156] Compound 3(E)-17: .sup.1H-NMR (600 MHz, d.sub.6-DMSO) δ.sub.H 0.623 (m, 1H), 0.874-0.846 (m, 4H), 0.940-0.918 (m, 3H), 1.033-1.018 (d, 3H), 1.252-1.120 (m, 1H), 1.326 (s, 3H), 1.385-1.327 (m, 2H), 1.495-1.443 (m, 1H), 1.603-1.592 (m, 2H), 1.762-1.701 (m, 4H), 2.002-1.958 (m, 2H), 2.411-2.387 (m, 2H), 2.514 (m, 1H), 2.786 (m, 1H), 4.156-4.125 (m, 1H), 4.262-4.230 (m, 2H), 4.410-4.405 (m, 1H), 4.590-4.568 (m, 1H), 5.704 (s, 1H), 6.516-6.500 (d, 1H), 6.781-6.758 (m, 1H), 10.523 (s, 1H), 10.795 (s, 1H); .sup.13C(600 MHz, d.sub.6-DMSO) δ.sub.C 13.91, 18.29, 18.60, 22.35, 23.37, 23.52, 27.61, 31.69, 32.58, 32.75, 33.96, 40.14, 43.51, 43.67, 45.03, 50.98, 56.33, 56.96, 67.71, 89.28, 112.21, 113.76, 145.94, 149.08, 156.85, 159.73, 173.22; Calculated value 489.3 Experimental value 489.4 for LRMS (ES+) [C.sub.27H.sub.40N.sub.2O.sub.6+H].

[0157] The compounds prepared in Examples 1-17 have strong anti-gout efficacy. The specific experiments are as follows. Among them, the compounds of the Examples used in the following experiments are mixtures of two configurations of cis- and trans-oxime group at 3-position of the compounds prepared in each Example in an equal ratio (1:1).

Experiment 1

[0158] Gout is a disease unique to human, and gouty arthritis is an inflammatory reaction caused by the deposition of monosodium urate (MSU) in local joint tissues. Since purine metabolism pathways in some mammals such as mice and rabbits are different from those in humans, it is impossible to construct a gouty arthritis model by the method of interfering with purine metabolism disorders, so the most direct method for causing gouty arthritis is to directly inject MSU into the joint cavity of the model animal. The model is only used for simulating local joint inflammation of gout, is suitable for observation of local arthritis symptoms, is a common method for screening anti-inflammatory effects of gout drugs at present, and has the advantages of stability, easy operation and the like. (Reference: Li Na, Hua Long, and Yuan Hui. Research progress of gout animal models [J]. Medical theory and practice, 2016(24).

[0159] The anti-gout effect of the compound prepared in the above Example was detected by using a rat paw swelling model induced by monosodium urate (MSU), and the control sample was methylprednisolone.

[0160] Experimental method: MSU was used as an inflammatory agent, injected subcutaneously into the hind paws of rats to cause paw swelling, and then the volume of the paws was measured, and the swelling rates and swelling inhibition rates of the treatment group and the control group were compared. On the day of the experiment, the volume of right hind paw (ml) of each rat was measured firstly, and then after the onset of inflammation, the volume of right hind paw was measured so that the difference of volume of paw before and after inflammation was swelling degree, and the swelling inhibition rate of paw (swelling inhibition rate %=(C−T)/C*100%); C=swelling rate of the control group %, and T=swelling rate of the treatment group) was calculated. This method is one of the commonly used methods for screening anti-inflammatory effects of gout drugs, and the model is stable and easy to operate.

[0161] (1) The dosage is positively correlated with the anti-gout effect, and the specific experimental results are as follows:

TABLE-US-00002 Dosage 0.36 1.8 9 90 Swelling inhibition rate mg/kg mg/kg mg/kg mg/kg Blank control group — — — — Model control group — — — — Methylprednisolone group 12.31 17.56 43.51 55.41 Compound of Example 1 12.12 45.23 68.15 97.43 Compound of Example 2 15.14 32.14 52.13 98.21 Compound of Example 3 10.21 25.16 32.14 82.14 Compound of Example 5 23.45 35.26 56.32 80.14 Compound of Example 8 17.21 32.15 41.25 93.54 Compound of Example 10 9.21 32.14 51.24 65.24 Compound of Example 11 10.24 35.16 48.98 67.54 Compound of Example 14 5.23 34.21 65.21 86.31 Compound of Example 17 10.31 56.12 78.15 97.01

[0162] (2) One week before the subcutaneous injection of MSU into the feet and soles of the rats, the rats were given different doses of the test drugs, and the drugs were given by gavage once a day, for seven consecutive days. The circumference of the right hind paw was marked and measured before the last administration, and the average value of the two measurements was taken as the standard. 1 h after the last administration, animals in other groups were given 50 μL of 2% MSU in addition to the blank control group, and the paw circumference was measured 1 h after the onset of inflammation. The results of administering to mice 90 mg/kg methylprednisolone, and the compound of the above Example were as follows:

TABLE-US-00003 Mean volume of Mean volume of Swelling paw before paw after Swelling Swelling inhibition administration (ml) administration (ml) value (ml) degree (%) rate (%) Blank control group 1.21 1.22 0.01 0.83 — Model control group 1.23 5.28 4.05 329.27 — Methylprednisolone group 1.23 3.1 1.87 152.03 53.83 Compound of Example 1 1.18 1.19 0.01 0.85 99.74 Compound of Example 2 1.24 1.28 0.04 3.23 99.02 Compound of Example 3 1.2 1.97 0.77 64.17 80.51 Compound of Example 5 1.22 1.94 0.72 59.02 82.08 Compound of Example 8 1.23 1.56 0.33 26.83 91.85 Compound of Example 10 1.21 2.45 1.24 102.48 68.88 Compound of Example 11 1.22 2.64 1.42 116.39 64.65 Compound of Example 14 1.18 1.74 0.56 47.46 85.59 Compound of Example 17 1.18 1.32 0.14 11.86 96.4

[0163] In this experiment, SD rats were consecutively administered different doses of the compounds one week before the subcutaneous injection of MSU into the soles. The test results showed that the swelling inhibition rate (%) of the compounds of the above Examples was in the range of 64.65% to 99.74%, and within the safe dose, the anti-gout effect of the compound is stronger as the dosage is continuously increased. The compounds of the above Examples have remarkably higher swelling inhibition rate for relieving gout symptoms than the methylprednisolone (53.83%), and with the substituted bis-oxime group, the in vivo metabolic cycle is prolonged, so as to have a relatively long-term effect of relieving gout.

Experiment 2

[0164] The compounds prepared in Examples 1-17 have strong anti-inflammatory efficacy.

[0165] The anti-inflammatory effects of the compounds prepared in the above Examples were detected using a carrageenan-induced mouse paw swelling model, and the control sample was methylprednisolone:

[0166] Carrageenan-induced mouse paw swelling model is a classical acute inflammation model commonly used for evaluating or screening anti-inflammatory effects of drugs. When carrageenan is injected into the paw of mice, a series of reactions similar to human acute inflammation such as local capillary dilatation, increased vascular permeability, exudation and edema can be caused, so the model can be widely used in the evaluation of new drugs.

[0167] Reference for experimental method: Yang Huan, Cheng Xiao, Wang Yuehua, Du Guanhua. Effects of esculin on the swelling of toes and inflammation induced by carrageenan in mice [J]. Chinese Journal of New Drugs, 2016(25):2322.

[0168] On the day of the experiment, the circumference of right hind paw (cm) of each mouse was measured firstly, and then, after the onset of inflammation, the circumference of right hind paw was measured so that the difference of the circumferences of the paws before and after inflammation was swelling degree, and the swelling inhibition rate of paw (swelling inhibition rate %=(C−T)/C*100%); C=swelling rate of the control group %, and T=swelling rate of the treatment group) was calculated.

[0169] (1) The dosage is positively correlated with the anti-inflammatory effect, and the specific experimental results are as follows:

TABLE-US-00004 Dosage 0.26 13 130 Swelling inhibition rate mg/kg mg/kg mg/kg Blank control group — — — Model control group — — — Methylprednisolone group 12.1 31.41 51.21 Compound of Example 1 10.34 58.12 97.41 Compound of Example 2 15.14 63.12 96.24 Compound of Example 3 9.12 42.31 78.21 Compound of Example 5 13.54 56.78 88.14 Compound of Example 8 24.54 46.78 93.21 Compound of Example 10 8.12 30.87 62.41 Compound of Example 11 15.46 35.78 68.14 Compound of Example 14 20.31 49.21 92.13 Compound of Example 17 28.19 60.34 98.71

[0170] (2) Gavage administration was performed once a day for seven consecutive days. The circumference of the right hind paw was marked and measured before the last administration, and the average value of the two measurements was taken as the standard. 30 min after the last administration, 20 μL/mice of 0.5% carrageenan was injected into the right hind ankle of the mice to induce inflammation, and the circumference of paw was measured 180 min after the onset of inflammation. The results of administering to mice 130 mg/kg methylprednisolone, and the compound of the above Example were as follows:

TABLE-US-00005 Circumference of Circumference of Swelling the paw before the paw after Swelling Swelling inhibition administration (cm) administration (cm) value (cm) degree (%) rate (%) Blank control group 1.48 1.48 0.00 0.00 — Model control group 1.55 1.85 0.30 19.35 — Methylprednisolone group 1.48 1.63 0.15 10.14 47.64 Compound of Example 1 1.45 1.46 0.01 0.69 96.44 Compound of Example 2 1.42 1.43 0.01 0.7 96.36 Compound of Example 3 1.48 1.53 0.05 3.38 82.55 Compound of Example 5 1.48 1.52 0.04 2.7 86.04 Compound of Example 8 1.47 1.49 0.02 1.36 92.97 Compound of Example 10 1.47 1.58 0.11 7.48 61.34 Compound of Example 11 1.43 1.53 0.1 6.99 63.87 Compound of Example 14 1.42 1.45 0.03 2.11 89.08 Compound of Example 17 1.42 1.43 0.01 0.7 96.36

[0171] In this experiment, the ICR mice were consecutively administered different doses of the compounds one week before the plantar injection of 0.5% carrageenan. The test results showed that the swelling inhibition rate (%) of the compounds of the above Examples was in the range of 61.34% to 96.44%, and within the safe dose, the anti-inflammatory of the compound is stronger as the dosage is continuously increased; the compounds prepared in the above Examples have better inhibitory effects on paw swelling than methylprednisolone (47.64%), and with the substituted bis-oxime group, the in vivo metabolic cycle is prolonged, so as to have a relatively long-term anti-inflammatory effect.

[0172] From the perspective of biochemical indicators, when an inflammatory reaction occurs, the expression level of glucocorticoid receptor a (GRa) protein is inhibited, the expression level of glucocorticoid receptor (3 (GRb) protein is promoted, the expression level of pro-inflammatory factor TNF-α protein is significantly increased, and the expression of inflammatory protective factor IL-10 is inhibited. Experiments show that the compounds of the above Examples can promote the expression of the GRa protein, inhibit the expression of the GRb protein, inhibit the increase of TNF-α, and increase the amount of IL-10 until it returns to normal.

Experiment 3 Acute Toxicity Test

[0173] The experiment was designed according to the “Technical Guideline for Acute Toxicity Test of Chemical Drugs” issued by the State Food and Drug Administration in March 2005. The doses administered were 4 g/kg, 4.91 g/kg, 6.14 g/kg, 7.68 g/kg, 9.6 g/kg, 12 g/kg, and 15 g/kg (the dose could be adjusted according to the actual test results), 12 ICR mice per dose group. If the administration volume is greater than 0.5 ml, it is better to perform the drug administration in two or more times (Note: according to the national standard GB 15193.3-2014, if multiple drug administrations are required, the time interval should be 4 h to 6 h each time, and the patient should be fasted on the day before drug administration). The results of the acute toxicity tests are shown in the following table:

TABLE-US-00006 Mortality (deaths/12) 4 g/kg 4.91 g/kg 6.14 g/kg 7.68 g/kg 9.6 g/kg 12 g/kg 15 g/kg Methylprednisolone (p.o.) 0/12 0/12 0/12 1/12 3/12 5/12 7/12 Compound of Example 1 (p.o.) 0/12 0/12 0/12 0/12 0/12 0/12 0/12 Compound of Example 2 (p.o.) 0/12 0/12 0/12 0/12 1/12 4/12 6/12 Compound of Example 3 (p.o.) 0/12 0/12 0/12 0/12 0/12 0/12 1/12 Compound of Example 5 (p.o.) 0/12 0/12 0/12 0/12 1/12 2/12 4/12 Compound of Example 8 (p.o.) 0/12 0/12 0/12 0/12 0/12 0/12 1/12 Compound of Example 9 (p.o.) 0/12 0/12 0/12 0/12 0/12 0/12 2/12 Compound of Example 10 (p.o.) 0/12 0/12 1/12 1/12 3/12 4/12 5/12 Compound of Example 11 (p.o.) 0/12 0/12 0/12 0/12 0/12 0/12 0/12 Compound of Example 14 (p.o.) 0/12 0/12 0/12 0/12 1/12 1/12 3/12 Compound of Example 17 (p.o.) 0/12 0/12 0/12 0/12 0/12 0/12 0/12

[0174] Although the present invention has been described in detail by general description and specific embodiments, some modifications or improvements can be made on the basis of the present invention, which is obvious to a person skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention are within the scope of the present invention.

INDUSTRIAL APPLICABILITY

[0175] The present invention provides a compound for treating gout, a preparation method therefor and the use thereof. The compound is as represented by formula I. Disclosed in the present invention are a method for preparing the compound and the use of the compound in the preparation of a drug for treating or preventing gout. Further disclosed in the present invention is a composition product containing the compound. The compound provided by the present invention can be used for treating inflammation and gout, and can also be used for treating cancers, and has good economic value and application prospect.

##STR00072##