KR20080083044A - Triterpenequinone and triterpenephenol derivatives and their application for the treatment of tumors and parasitic diseases - Google Patents

Abstract

The invention relates to triterpenequinone and triterpenephenol derivatives, their pharmaceutically acceptable 5 salts, prodrugs, solvates or stereoisomers as selective blocking agents of the choline kinase enzyme, pharmaceutical compositions containing them and their use in the treatment of tumors and parasitic diseases or diseases caused by viruses, bacteria or fungi.

Description

TRITERPENEQUINONE AND TRITERPENEPHENOL DERIVATIVES AND THEIR APPLICATION FOR THE TREATMENT OF TUMORS AND PARASITIC DISEASES}

The present invention blocks the biosynthesis of phosphorylcholine by selective blocking of choline kinase enzymes in tumor cells or cells affected by parasitic infections, thereby resulting in viruses, bacteria and in animals including tumors and parasitic diseases or humans. Triterpenequinones and triterpenephenol derivatives applicable to the treatment of diseases caused by fungi, and also methods of preparing these compounds.

Choline kinase is the primary enzyme in the renal pathway or the phosphatidylcholine (PC) synthesis pathway. PCho). The Ras gene forms a so-called oncogenes group that has been the subject of extensive research because it acts on cancers ranging from 25 to 30% and in some cases 90% of all human carcinomas. Ras proteins play an important role in intracellular signal transduction because they are involved in the regulation of cell proliferation, terminal differentiation and senescence. Transformation delivered by various oncogenes, in particular the ras oncogene, leads to high choline kinase activity levels, resulting in abnormally increased intracellular levels of the product of this activity, PCho. Complementary facts indicate that human cancer tissues, including breast cancer, colon cancer, lung cancer and prostate cancer, showed higher PCho levels than normal tissues in a study report using nuclear magnetic resonance (NMR) technology. Supports the role of ChoK in the development of cancer ras is one of the most studied cancer genes in human carcinogenesis, and it is generally known that ChoK inhibition is a new effective anti-cancer treatment for cells modified by the oncogene. This primary observation was later extrapolated from in vivo experiments on nude mice.

Based on the data of the above experiments, effective anticancer therapies can be developed by designing compounds acting directly on choline kinase activity or enzymes activated by phosphorylcholine either individually or in combination.

In this regard, studies of ChoK inhibitors have identified Hemicholinium-3 (HC-3), an excellent potential and selective blocker [Cuadrado A., Carnero A., Dolfi F., Jimenez B.]. and Lacal JC Oncogene 8, 2959-2968 (1963); Jimenez B., del Peso L., Montaner S., Esteve P. and Lacal J.C. J. Cell Biochem. 57, 141-149 (1995); Hernandez-Alcoceba, R., Saniger, L., Campos, J., Nunez, M.C., Khaless, F., Gallo, M. A., Espinosa, A., Lacal, J.C. Oncogene, 15, 2289-2301 (1997). Choline homologues with biphenyl structures have been used to design new anticancer agents, but HC-3 is not a good candidate for clinical applications due to the possibility of respiratory paralysis. The synthesis of some derivatives was based on structural modification of HC-3 which enhances the inhibitory activity of the ChoK enzyme and partially eliminates its toxic effects.

In addition, bisquaternized symmetric compounds derived from pyridinium are also used, which have been evaluated for their ability to inhibit PCho production in whole cells (WO98 / 05644). However, these derivatives have high levels of toxicity and therefore are constrained for widespread use in the therapeutic field.

On the other hand, compounds formed by the 5-ring triterpene structures such as cerastrol and pristimerin are known to induce apoptosis (cellular apoptosis) and this activity has been confirmed in leukemia patient models [Nagase, M., Oto, J., Sugiyama, S., Yube, K., Takaishi, and Sakato, N., Biosci. Biotechnol. Biochem 67, 1883 (2003). Nevertheless, these compounds have severe levels of intracellular toxicity and cannot be used to develop drugs useful for the treatment of tumor diseases. In this regard, US application US 2004/0220267 discloses cerastrol and pristinerin derivatives that can ameliorate such toxicity issues.

However, for use in the treatment of tumors, there is a great demand for the development of new compounds which provide high inhibitory activity of the ChoK enzyme and at the same time greatly reduce the toxicity to the compounds according to the prior art.

As a result of the research efforts, the present inventors can act as a blocker in the biosynthesis of phosphorylcholine by the selective blocking of choline kinase (ChoK) enzymes when certain modifications are made to the structures of the above-described compounds, celllatrol and pristimerin. It has therefore been found that it can provide compounds that have been demonstrated as novel effective anticancer therapies for human cancer cells.

Accordingly, one aspect of the present invention is the use of a compound represented by the following formula (I) or a pharmaceutically acceptable salt, derivative, prodrug, solvent compound or stereoisomer thereof for the treatment and / or prevention of ChoK mediated diseases or disorders. It's about how to:

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ′) (R ″) amino groups, where R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR group, where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; N (R ^IV ) (R ^V ) amino wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

은 2중결합 또는 단일결합을 의미하며; 또한Combining

Means double bond or single bond; Also

The following triple ring structure

Is selected from the following structures;

here,

R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ , R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; An OCOR ^VIII group, wherein R ^VIII is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₇ is hydrogen or a methyl group;

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; A COR ^IX group wherein R ^IX is independently hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; or N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or C _1- C ₁₂ alkyl group or C ₁ -C ₁₂ alkoxyl; Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XIII ) (R ^XIV ) amino, wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen.

In another aspect, the invention uses a compound represented by the following formula (II) or a pharmaceutically acceptable salt, derivative, prodrug, solvent compound or stereoisomer thereof for the treatment and / or prevention of ChoK mediated diseases or disorders It's about how to:

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₁₇ , R ₁₈ , R ₁₉ And R ₂₀ is independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XV ) (R ^XVI ) amino groups, wherein R ^XV and R ^XVI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₇ and R ₈ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^XVII group, wherein R ^XVII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^XVIII ) (R ^XIX ) amino, wherein R ^XVIII and R ^XIX are independently hydrogen or a C ₁ -C ₁₂ alkyl group); (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₂₁ and R ₂₄ are independently substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XX group wherein R ^XX is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXI ) (R ^XXII ) amino, Wherein R ^XXI and R ^XXII are independently hydrogen or C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

R ₂₂ and R ₂₃ are

- Hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXIII group wherein R ^XXIII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXIV ) (R ^XXV ) amino, R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is in the para position with respect to R ₂₀ ; or

OR ₂₂ ′ and OR ₂₃ ′ respectively, wherein R ₂₂ ′ and R ₂₃ ′ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXVI group wherein R ^XXVI is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXVII ) (R ^XXVIII ) amino, Wherein R ^XXVII and R ^XXVIII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is present in the meta position relative to R ₂₀ .

In certain embodiments, the disease or condition is cancer. In another embodiment the disease is a parasitic disease. In another embodiment the disease is a bacterial disease. In another embodiment the disease is a fungal disease.

In another aspect the invention relates to a compound represented by the following formula (I) or a pharmaceutically acceptable salt, derivative, prodrug, solvate or stereoisomer thereof:

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ′) (R ″) amino groups, where R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR group, where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

은 2중결합 또는 단일결합을 의미하며; 또한Combining

Means double bond or single bond; Also

The following triple ring structure

Is selected from the following structures;

here,

R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ , R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ^VI ) (R ^VII ) amino group, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; An OCOR ^VIII group, wherein R ^VIII is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₇ is hydrogen or a methyl group;

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen, provided

When the tricycle is (a), the compound of formula (I) is:

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid;

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester;

3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester;

3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-picene-2 , 10-dione;

3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H- Pisene-2,10-dione;

3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione;

14-bromo-3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a- Dicahydro-6bH, 9H-picene-2,10-dione;

Succinic Mono- (10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3, 4,4a, 5,6,6a, 11,12b , 13,14,14a, 14b-tetradecahydro-picen-4-yl) ester;

Succinic acid ethyl ester 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picen-4-yl ester;

Acetic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester;

Dodecanoic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b , 13,14,14a-tetradecahydro-picen-3-yl ester;

Dimethyl-carbamic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12, 12a, 12b, 13, 14, 14a- tetradecahydro-picen-3-yl ester;

Nicotinic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester;

3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; And

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, Not 14b-tetradecahydro-picene-2-carboxylic acid methylester,

When said tricycle is (b) and said R ₁₉ and R ₂₀ are independently hydrogen or an acyl group,

R ₅ is hydroxyl; or

R ₂₁ and R ₂₂ together with the carbon to which they are attached form C═O and R ₁₀ is not COOH; Also,

When the tricycle is (c) and R ₁₉ and R ₂₀ are both CH ₃ , R ₁₅ and R ₁₆ are subject to the fact that they do not form C═O with the carbon to which they are attached.

In another aspect the present invention relates to a compound represented by the following formula (II) or a pharmaceutically acceptable salt, derivative, prodrug, solvate or stereoisomer thereof:

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₁₇ , R ₁₈ , R ₁₉ And R ₂₀ is independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XV ) (R ^XVI ) amino groups, wherein R ^XV and R ^XVI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₇ and R ₈ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^XVII group, wherein R ^XVII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^XVIII ) (R ^XIX ) amino, wherein R ^XVIII and R ^XIX are independently hydrogen or a C ₁ -C ₁₂ alkyl group); (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₂₁ and R ₂₄ are independently substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XX group wherein R ^XX is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXI ) (R ^XXII ) amino, Wherein R ^XXI and R ^XXII are independently hydrogen or C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

R ₂₂ and R ₂₃ are

- Hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXIII group wherein R ^XXIII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXIV ) (R ^XXV ) amino, R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is in the para position with respect to R ₂₀ ; or

OR ₂₂ ′ and OR ₂₃ ′ respectively, wherein R ₂₂ ′ and R ₂₃ ′ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXVI group wherein R ^XXVI is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXVII ) (R ^XXVIII ) amino, Wherein R ^XXVII and R ^XXVIII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is present in the meta position relative to R ₂₀ .

In another aspect, the present invention provides a compound represented by formula (I) or a compound represented by formula (II) or mixtures thereof, pharmaceutically acceptable salts, derivatives, prodrugs, solvent compounds or stereoisomers thereof. A pharmaceutical composition for administration to a patient, comprising together with a pharmaceutically acceptable carrier, adjuvant or vehicle.

It is an object of the present invention to provide a method of using a compound represented by the following formula (I) or a pharmaceutically acceptable salt, derivative, prodrug, solvent compound or stereoisomer thereof for the treatment and / or prevention of ChoK mediated diseases or diseases. To provide:

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ′) (R ″) amino groups, where R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR group, where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

은 2중결합 또는 단일결합을 의미하며; 또한Combining

Means double bond or single bond; Also

The following triple ring structure

Is selected from the following structures;

here,

R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ , R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; OCOR ^VIII group (where R ^RVIII is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ); Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₇ is hydrogen or a methyl group;

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair, respectively, together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen.

In certain embodiments, the compound of formula (I) used for the prophylaxis and / or treatment of a ChoK mediated disease or condition is a compound of formula (Ia):

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ′) (R ″) amino groups, where R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR group, where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₄ , R ₁₅ and R ₁₆ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; An OCOR ^VIII group, wherein R ^VIII is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₇ is hydrogen or a methyl group;

R ₁₈ is independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; or N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

In a preferred embodiment, the compound of formula (la) comprises the substructure of formula (la):

here,

R ₅ is a hydroxyl or OCOR group where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ;

R ₇ and R ₈ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₂ is hydrogen or halogen;

R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

Specific examples of the substructure Ia 'include:

3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H- Pisene-2,10-dione;

Acetic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester;

9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13 , 14,14a-tetradecahydro-picen-3-yl propionic acid ester (C1);

Dodecanoic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b , 13,14,14a-tetradecahydro-picen-3-yl ester;

Dimethyl-carbamic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12, 12a, 12b, 13, 14, 14a- tetradecahydro-picen-3-yl ester;

Nicotinic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester;

4-bromo- (9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a , 12b, 13,14,14a-tetradecahydro-picen-3-yl) benzoic acid ester (C2);

14-bromo-3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12, 12a, 12b, 13,14,14a- Decahydro-6bH, 9H-picene-2,10-dione;

12-bromo-9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl dimethyl-carbamic acid ester (C4);

4-bromo- (12-bromo-9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10, 11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl) benzoic acid ester (C5);

12-bromo-3,9-dihydroxy-6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione (C3);

3,9,10-trihydroxy-6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-dodecahydro -6bH-picen-2-one (C6);

Succinic mono- (10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4, 4a, 5,6,6a, 11,12b , 13,14,14a, 14b-tetradecahydro-picen-4-yl) ester;

Succinic acid ethyl ester 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picen-4yl ester and the like.

In a preferred embodiment, the compound of formula (la) comprises the substructure of formula (la):

here,

R ₇ and R ₈ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₅ is hydrogen or halogen;

R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

Specific examples of the substructure Ia "include:

14-bromo-3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione (C7);

4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a- Tetradecahydro-picen-3-yl acetic acid ester (C8);

4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a- Tetradecahydro-picen-3-yl nicotinic acid ester (C9);

3,10-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-dodecahydro -6bH-picen-2-one (C10);

3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 12a, 12b, 13,14,14a-octahydro-6bH, 9H-picene-2,10-dione (C11) and the like.

In a preferred embodiment, the compound of formula (la) comprises the substructure of formula (la) ':

here,

R ₇ is hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Also

R ₁₉ is substituted or unsubstituted C ₁ -C ₁₂ alkyl; COR ^XII group, wherein R ^XII is independently hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl.

Specific examples of the substructure Ia "'include:

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester;

3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (C12);

2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-10-propionyloxy-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a , 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (C13);

10-dimethylcarbamoyloxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (C14) and the like.

In another specific embodiment, the compound of formula (I) used for the prophylaxis and / or treatment of a ChoK mediated disease or condition is a compound of formula (Ib):

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ , R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₇ is hydrogen or a methyl group;

R ₁₈ is independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; or N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

In a preferred embodiment, the compound of formula (lb) comprises a substructure of formula (lb):

here,

R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl.

Specific examples of the substructure (Ib ') include 4-nitro- (3-dimethylcarbamoyloxy-5,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-10-oxo -5,6b, 7,8,8a, 9,10,11,12, 12a, 12b, 13,14,14a- tetradecahydro-picen-2-yl) benzoic acid ester (C15).

In another preferred embodiment, the compound of formula (lb) comprises a substructure of formula (lb):

here,

R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

R ₂₃ is hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group.

Specific examples of the substructure Ib ″ include:

7,10,11-trihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-8-oxo-1,2,3,4,4a, 5,6, 6a, 8,12b, 13 , 14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (F16);

9-formyl-10,11-dihydroxy-2,4a, 6a, 12b, 14a-pentamethyl-8-oxo-1,2,3,4,4a, 5, 6,6a, 8,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (C17);

11-hydroxy-10- (2-methoxy-ethoxymethoxy) -2,4a, 6a, 9,12b, 14a-hexamethyl-8-oxo-1,2,3,4,4a, 5, 6,6a, 8,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (C18) and the like.

In another specific embodiment, the compound of formula (I) used for the prophylaxis and / or treatment of a ChoK mediated disease or condition is a compound of formula (Ic):

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^{IX wherein} R ^IX is independently hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or C ₁ -C ₁₂ An alkyl group or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

In a preferred embodiment, the compound of formula (Ic) used in the present invention comprises a substructure of the following formula (Ic '):

here,

R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; COR ^XII group, wherein R ^XII is independently hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

As a specific example of the substructure Ic ':

10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-1,4,4a, 5,6,6a, 13,14,14a, 14b-decahydro-2H-picene-3 -On (C19); And

10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-4a, 5,6,6a, 13,14,14a, 14b-octahydro-4H-picen-3-one (C20) It includes.

In another preferred embodiment, the compound of formula (Ic) used in the present invention comprises a substructure of the following formula (Ic ″):

here,

R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl.

Specific examples of the substructure Ic ″ include 10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-1,2,3,4,4a, 5,6,6a, 13,14,14a, 14b-dodecahydro-picene-2-carboxylic acid methylester.

In another specific embodiment, the compound of formula (I) above for use in the prophylaxis and / or treatment of a ChoK mediated disease or condition is a compound of formula (Id):

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₅ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ^VI ) (R ^VII ) amino group, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is independently hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or C ₁ -C ₁₂ An alkyl group or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂ ) alkyl-O- (C ₁ -C ₁₂ ) alkyl-] _n groups, where n is an integer from 1 to 3; Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

In a preferred embodiment, the compound of formula (Id) used in the present invention comprises a substructure of the following formula (Id '):

here,

R ₅ and R ₆ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen.

As a specific example of the substructure Id ':

1-bromo-9-hydroxy-4,6b, 8a, 11,12b, 14b-hexamethyl-6b, 7,8,8a, 9,11,12,12a, 12b, 14b-decahydro-1H- Pysene-2,3,10-trione (C22); And

1-bromo-4,6b, 8a, 11,12b, 14b-hexamethyl-6b, 7,8,8a, 9,11,12a, 12b, 14b-decahydro-1H-picene-2,3,10 -Trion (C23), etc. are mentioned.

In a preferred embodiment, the compound of formula (Id) used in the present invention comprises a substructure of the following formula (Id '):

here,

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen.

Specific examples of the substructure Id " include 12-bromo-2,4a, 6a, 9,12a, 14a-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5 , 6,6a, 10,11,12,12a, 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (C24).

In another particular embodiment of the invention, the compound of formula (I) used for the prophylaxis and / or treatment of ChoK mediated disease or condition is a compound of formula (Ie):

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair, respectively, together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ is hydrogen, hydroxyl or halogen; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

In a preferred embodiment, the compound of formula (Ie) used in the present invention comprises a substructure of the following formula (Ie '):

here,

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ is hydrogen, hydroxyl or halogen.

Specific examples of the substructure Ie 'include 9-hydroxy-2,4a, 6a, 9,12b-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5,6 , 6a, 9, 10, 11, 12b, 13, 14, 14a, 14b-hexadecahydro-picene-2-carboxylic acid methyl ester (25).

In another particular embodiment of the invention, the compound of formula (I) used for the prophylaxis and / or treatment of a ChoK mediated disease or condition is a compound of formula (If):

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₄ , R ₁₅ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group;

R ₂₄ is hydrogen, hydroxyl or halogen; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

In a preferred embodiment, the compound of formula (If) used in the present invention comprises the substructure of formula (If '):

here,

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair, respectively, together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ is hydrogen, hydroxyl or halogen.

Specific examples of the substructure If 'include 9-hydroxy-2,4a, 6a, 6b, 9-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5,6 , 6a, 6b, 8a, 9, 10, 11, 14, 14a, 14b-hexadecahydro-picene-2-carboxylic acid methyl ester (C26).

In another particular embodiment of the invention, the compound of formula (II) above for use in the prophylaxis and / or treatment of ChoK mediated disease or condition is a compound of formula (IIa):

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₁₇ , R ₁₈ , R ₁₉ And R ₂₀ is independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XV ) (R ^XVI ) amino groups, wherein R ^XV and R ^XVI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₇ and R ₈ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^XVII group, wherein R ^XVII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^XVIII ) (R ^XIX ) amino, wherein R ^XVIII and R ^XIX are independently hydrogen or a C ₁ -C ₁₂ alkyl group); (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₂₁ and R ₂₄ are independently substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XX group wherein R ^XX is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXI ) (R ^XXII ) amino, Wherein R ^XXI and R ^XXII are independently hydrogen or C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

R ₂₂ and R ₂₃ are

- Hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXIII group wherein R ^XXIII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXIV ) (R ^XXV ) amino, R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is in the para position with respect to R ₂₀ ; or

OR ₂₂ ′ and OR ₂₃ ′ respectively, wherein R ₂₂ ′ and R ₂₃ ′ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXVI group wherein R ^XXVI is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXVII ) (R ^XXVIII ) amino, Wherein R ^XXVII and R ^XXVIII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is present in the meta position relative to R ₂₀ .

In a preferred embodiment, the compound of formula (IIa) used in the present invention comprises a substructure of the following formula (IIa '):

here,

R ₁₉ and R ₂₀ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XV ) (R ^XVI ) amino groups, wherein R ^XV and R ^XVI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₂₁ and R ₂₄ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₁ -C ₁₀ aryl; N (R ^XXI ) (R ^XXII ) amino groups, wherein R ^XXI and R ^XXII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XXIV ) (R ^XXV ) amino groups, wherein R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair together with the carbon attached thereto may form a (C═O) group.

Specific examples of the substructure (IIa ') include 8- [2- (6,7-dihydroxy-1,5-dimethyl-naphthalen-2-yl) -ethyl] -2,4a-tetramethyl-1 , 2,3,4,4a, 5,6,7-octahydro-naphthalene-2-carboxylic acid methyl ester (C27).

Compounds of the invention act as biosynthetic blockers of phosphorylcholine by selectively blocking choline kinase (ChoK) enzymes and selecting for signaling pathways essential for transformation by specific oncogenes that do not affect normal cells at the same intensity Have been shown to be effective in treating tumors and are therefore more effective in treating tumors.

Thus, in certain embodiments, the ChoK mediated disease or condition to be prevented or treated is cancer, among which cancer is selected from breast, lung, intestinal and pancreatic cancer.

On the other hand, biological assays can be used to extend the compounds described herein for the treatment of viruses, parasites, bacteria and fungal diseases, such as Malaria falciparum or Trypanosoma cruci. Parasites, viruses such as adenoviruses, bacteria such as Escherichia coli, and fungi such as Candida albicans require metabolic phosphatidylcholine synthesis pathways through choline kinases to complete the infection cycle in humans and animals. to be. In this regard, the technical background according to the literature is the role of ChoK enzymes in the intracellular metabolism of some nucleosides in Hep-G2 cells, enzyme markers of parasitic diseases or participate in the biosynthesis of phospholipids important in viruses, bacteria and fungi. It supports the use of such enzymes.

As a result, in another embodiment, the ChoK mediated disease or condition to be prevented and / or treated is a viral disease, particularly a disease caused by adenovirus.

In another embodiment, the ChoK mediated disease or condition to be prevented and / or treated is a parasitic disease, among other things caused by plasmodium or trypanosoma.

In another embodiment, the ChoK mediated disease or condition to be prevented and / or treated is a bacterial disease, particularly a disease caused by pneumococcus.

In another embodiment, the ChoK mediated disease or condition to be prevented and / or treated is a fungal disease, inter alia, a disease caused by candida.

Another object of the present invention is a compound represented by the following formula (I) or a pharmaceutically acceptable salt, derivative, prodrug, solvent compound or stereoisomer thereof:

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ′) (R ″) amino groups, where R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR group, where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

은 2중결합 또는 단일결합을 의미하며; 또한Combining

Means double bond or single bond; Also

The following triple ring structure

Is selected from the following structures;

here,

R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ , R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; An OCOR ^VIII group, wherein R ^VIII is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₇ is hydrogen or a methyl group;

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen, provided

When the tricycle is (a), the compound of formula (I) is:

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid;

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester;

3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester;

3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-picene-2 , 10-dione;

3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H- Pisene-2,10-dione;

3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione;

14-bromo-3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a- Dicahydro-6bH, 9H-picene-2,10-dione;

Succinic Mono- (10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3, 4,4a, 5,6,6a, 11,12b , 13,14,14a, 14b-tetradecahydro-picen-4-yl) ester;

Succinic acid ethyl ester 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picen-4-yl ester;

Acetic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester;

Dodecanoic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b , 13,14,14a-tetradecahydro-picen-3-yl ester;

Dimethyl-carbamic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12, 12a, 12b, 13, 14, 14a- tetradecahydro-picen-3-yl ester;

Nicotinic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester;

3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; And

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, Not 14b-tetradecahydro-picene-2-carboxylic acid methylester,

When said tricycle is (b) and said R ₁₉ and R ₂₀ are independently hydrogen or an acyl group,

R ₅ is hydroxyl; or

R ₂₁ and R ₂₂ together with the carbon to which they are attached form C═O and R ₁₀ is not COOH; Also,

When the tricycle is (c) and R ₁₉ and R ₂₀ are both CH ₃ , R ₁₅ and R ₁₆ are subject to the fact that they do not form C═O with the carbon to which they are attached.

In another aspect the invention relates to compounds of formula (la):

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ′) (R ″) amino groups, where R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR group, where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₄ , R ₁₅ and R ₁₆ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR ^VIII group wherein R ^VIII is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₇ is hydrogen or a methyl group;

R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미하며, 단, 상기 식(Ia)의 화합물은:Combining

Means a double bond or a single bond, provided that the compound of formula (Ia) is:

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid;

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester;

3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester;

3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-picene-2 , 10-dione;

3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H- Pisene-2,10-dione;

3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione;

14-bromo-3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a- Dicahydro-6bH, 9H-picene-2,10-dione;

Succinic Mono- (10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3, 4,4a, 5,6,6a, 11,12b , 13,14,14a, 14b-tetradecahydro-picen-4-yl) ester;

Succinic acid ethyl ester 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picen-4-yl ester;

Acetic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester;

Dodecanoic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b , 13,14,14a-tetradecahydro-picen-3-yl ester;

Dimethyl-carbamic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12, 12a, 12b, 13, 14, 14a- tetradecahydro-picen-3-yl ester;

Nicotinic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, And not 13,14,14a-tetradecahydro-picen-3-yl ester.

In a preferred embodiment, the compound of formula (la) comprises the substructure of formula (la):

here,

R ₅ is a hydroxyl or OCOR group where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ;

R ₇ and R ₈ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₂ is hydrogen or halogen;

R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미하고, 단, 상기 식(Ia')의 화합물은:Combining

Means a double bond or a single bond, provided that the compound of formula (Ia ') is:

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid;

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester;

3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester;

3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-picene-2 , 10-dione;

3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H- Pisene-2,10-dione;

3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione;

14-bromo-3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a- Dicahydro-6bH, 9H-picene-2,10-dione;

Succinic Mono- (10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3, 4,4a, 5,6,6a, 11,12b , 13,14,14a, 14b-tetradecahydro-picen-4-yl) ester;

Succinic acid ethyl ester 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picen-4-yl ester;

Acetic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester;

Dodecanoic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b , 13,14,14a-tetradecahydro-picen-3-yl ester;

Dimethyl-carbamic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12, 12a, 12b, 13, 14, 14a- tetradecahydro-picen-3-yl ester;

Nicotinic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester;

3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; And

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, The condition is not 14b-tetradecahydro-picene-2-carboxylic acid methyl ester.

Specific examples of the substructure Ia 'include:

9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13 , 14,14a-tetradecahydro-picen-3-yl propionic acid ester (C1);

4-bromo- (9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a , 12b, 13,14,14a-tetradecahydro-picen-3-yl) benzoic acid ester (C2);

12-bromo-3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b 13,14,14a-decahydro- 6bH, 9H-Pysene-2,10-dione (C3);

12-bromo-9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl dimethyl-carbamic acid ester (C4);

4-bromo- (12-bromo-9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10, 11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl) benzoic acid ester (C5);

3,9,10-trihydroxy-6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-dodecahydro -6bH-picen-2-one (C6) and the like.

In a preferred embodiment, the compound of formula (la) comprises the substructure of formula (la):

here,

R ₇ and R ₈ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₅ is hydrogen or halogen;

R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is a positive ordination of 1 to 3); Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미하며, 단, 상기 서브구조(Ia")의 화합물은:Combining

Means a double bond or a single bond, provided that the compound of substructure (Ia ″) is:

3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-dodecahydro-6bH- Pysen-2-one; And

3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-picene-2 Subject to non 10-dione

As a specific example of the substructure Ia ",

14-bromo-3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione (C7);

4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a- Tetradecahydro-picen-3-yl acetic acid ester (C8);

4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a- Tetradecahydro-picen-3-yl nicotinic acid ester (C9);

3,10-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-dodecahydro -6bH-picen-2-one (C10);

3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 12a, 12b, 13,14,14a-octahydro-6bH, 9H-picene-2,10-dione (C11) and the like.

In a preferred embodiment, the compound of formula (la) comprises the substructure of formula (la) ':

here,

R ₇ is hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Also

R ₁₉ is substituted or unsubstituted C ₁ -C ₁₂ alkyl; COR ^XII group, wherein R ^XII is independently hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl, provided that the compound of formula (Ia "') is:

3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14a , 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; And

10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, The condition is not 14b-tetradecahydro-picene-2-carboxylic acid methyl ester.

Specific examples of the substructure Ia "'include:

2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-10-propionyloxy-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a , 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (C13);

10-dimethylcarbamoyloxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (C14) and the like.

In another specific embodiment, this invention relates to compounds of Formula (lb):

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; Halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ , R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₇ is hydrogen or a methyl group;

R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미하며, 단, 상기 R₁₉ 및 R₂₀가 독립적으로 수소나 아실기일 때, Combining

Means a double bond or a single bond, provided that R ₁₉ And when R ₂₀ is independently hydrogen or an acyl group,

R ₅ is hydroxyl, or

Provided that R ₂₁ and R ₂₂ together with the carbon attached thereto form a (C═O) group while R ₁₀ is not COOH.

In another preferred embodiment, the compound of formula (lb) comprises a substructure of formula (lb):

here,

R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl.

Specific examples of the substructure Ib ′ include 4-nitro- (3-dimethylcarbamoyloxy-5,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-10-oxo -5,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a- tetradecahydro-picen-2-yl) benzoic acid ester (C15).

In another preferred embodiment, the compound of formula (lb) comprises a substructure of formula (lb):

here,

R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

R ₂₃ is hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group.

Specific examples of the substructure Ib ″ include:

7,10,11-trihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-8-oxo-1,2,3,4,4a, 5,6, 6a, 8,12b, 13 , 14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (F16);

9-formyl-10,11-dihydroxy-2,4a, 6a, 12b, 14a-pentamethyl-8-oxo-1,2,3,4,4a, 5, 6,6a, 8,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (C17);

11-hydroxy-10- (2-methoxy-ethoxymethoxy) -2,4a, 6a, 9,12b, 14a-hexamethyl-8-oxo-1,2,3,4,4a, 5, 6,6a, 8,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (C18) and the like.

In another specific embodiment, this invention relates to compounds of Formula (Ic)

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is independently hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or C ₁ -C ₁₂ An alkyl group or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미하며, Combining

Means double bond or single bond,

However, R ₁₉ And when both R ₂₀ are CH ₃ , R ₁₅ and R ₁₆ do not form a (C═O) group together with the carbon attached thereto.

In a preferred embodiment, the compound of formula (Ic) comprises a substructure of formula (Ic '):

here,

R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; COR ^XII group, wherein R ^XII is independently hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂ ) alkyl-O- (C ₁ -C ₁₂ ) alkyl-] _n groups, where n is an integer from 1 to 3; Or trifluoromethyl; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

As a specific example of the substructure Ic ':

10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-1,4,4a, 5,6,6a, 13,14,14a, 14b-decahydro-2H-picene-3- On (C19); And

10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-4a, 5,6,6a, 13,14,14a, 14b-octahydro-4H-picen-3-one (C20) It includes.

In another preferred embodiment, said compound of formula (Ic) comprises a substructure of the following formula (Ic "):

here,

R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl.

Specific examples of the substructure Ic ″ include 10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-1,2,3,4,4a, 5,6,6a, 13 , 14,14a, 14b-dodecahydro-picene-2-carboxylic acid methyl ester (C21).

In another specific embodiment, this invention relates to compounds of Formula (Id):

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₅ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ^VI ) (R ^VII ) amino group, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is independently hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or C ₁ -C ₁₂ An alkyl group or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

In a preferred embodiment, the compound of formula (Id) comprises a substructure of the following formula (Id '):

here,

R ₅ and R ₆ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen.

As a specific example of the substructure Id ':

1-bromo-9-hydroxy-4,6b, 8a, 11,12b, 14b-hexamethyl-6b, 7,8,8a, 9,11,12,12a, 12b, 14b-decahydro-1H- Pysene-2,3,10-trione (C22); And

1-bromo-4,6b, 8a, 11,12b, 14b-hexamethyl-6b, 7,8,8a, 9,11,12a, 12b, 14b-decahydro-1H-picene-2,3,10 -Trion (C23), etc. are mentioned.

In a preferred embodiment, the compound of formula (Id) comprises a substructure of the following formula (Id "):

here,

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen.

Specific examples of the substructure Id " include 12-bromo-2,4a, 6a, 9,12a, 14a-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5 , 6,6a, 10,11,12,12a, 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester (C24).

In another specific embodiment, this invention relates to compounds of Formula (Ie)

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group;

R ₂₄ is hydrogen, hydroxyl or halogen; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

In a preferred embodiment, the compound of formula (Ie) comprises a substructure of formula (Ie '):

here,

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also

R ₂₄ is hydrogen, hydroxyl or halogen.

Specific examples of the substructure Ie 'include 9-hydroxy-2,4a, 6a, 9,12b-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5,6 , 6a, 9, 10, 11, 12b, 13, 14, 14a, 14b-hexadecahydro-picene-2-carboxylic acid methyl ester (25).

In another specific embodiment, this invention relates to compounds of Formula (If):

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; Halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₁₃ , R ₁₄ , R ₁₅ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ^VI ) (R ^VII ) amino group, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group;

R ₂₄ is hydrogen, hydroxyl or halogen; Also

은 2중결합 또는 단일결합을 의미한다.Combining

Means double bond or single bond.

In a preferred embodiment, the compound of formula (If) comprises a substructure of formula (If ′):

here,

R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl;

R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair, respectively, together with the carbon to which they are attached may form a C═O group;

R ₂₄ is hydrogen, hydroxyl or halogen.

Specific examples of the substructure If 'include 9-hydroxy-2,4a, 6a, 6b, 9-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5,6 , 6a, 6b, 8a, 9, 10, 11, 14, 14a, 14b-hexadecahydro-picene-2-carboxylic acid methyl ester (C26).

Another aspect of the invention consists of a compound of formula (II) or a pharmaceutically acceptable salt, derivative, prodrug, solvent compound or stereoisomer thereof:

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₁₇ , R ₁₈ , R ₁₉ And R ₂₀ is independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XV ) (R ^XVI ) amino groups, wherein R ^XV and R ^XVI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₇ and R ₈ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^XVII group, wherein R ^XVII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^XVIII ) (R ^XIX ) amino, wherein R ^XVIII and R ^XIX are independently hydrogen or a C ₁ -C ₁₂ alkyl group); (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₂₁ and R ₂₄ are independently substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XX group wherein R ^XX is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXI ) (R ^XXII ) amino, Wherein R ^XXI and R ^XXII are independently hydrogen or C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

R ₂₂ and R ₂₃ are

- Hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXIII group wherein R ^XXIII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXIV ) (R ^XXV ) amino, R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is in the para position with respect to R ₂₀ ; or

OR ₂₂ ′ and OR ₂₃ ′ respectively, wherein R ₂₂ ′ and R ₂₃ ′ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXVI group wherein R ^XXVI is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXVII ) (R ^XXVIII ) amino, Wherein R ^XXVII and R ^XXVIII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is present in the meta position relative to R ₂₀ .

In certain embodiments, the invention relates to compounds of formula (IIa)

here,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₁₇ , R ₁₈ , R ₁₉ And R ₂₀ is independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XV ) (R ^XVI ) amino groups, wherein R ^XV and R ^XVI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₇ and R ₈ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^XVII group, wherein R ^XVII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^XVIII ) (R ^XIX ) amino, wherein R ^XVIII and R ^XIX are independently hydrogen or a C ₁ -C ₁₂ alkyl group); (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group;

R ₂₁ and R ₂₄ are independently substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XX group wherein R ^XX is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXI ) (R ^XXII ) amino, Wherein R ^XXI and R ^XXII are independently hydrogen or C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also

R ₂₂ and R ₂₃ are

- Hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXIII group wherein R ^XXIII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXIV ) (R ^XXV ) amino, R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is in the para position with respect to R ₂₀ ; or

OR ₂₂ ′ and OR ₂₃ ′ respectively, wherein R ₂₂ ′ and R ₂₃ ′ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXVI group wherein R ^XXVI is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXVII ) (R ^XXVIII ) amino, Wherein R ^XXVII and R ^XXVIII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is present in the meta position relative to R ₂₀ .

In a preferred embodiment, the compound of formula (IIa) comprises a substructure of formula (IIa '):

here,

R ₁₉ and R ₂₀ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ^XV ) (R ^XVI ) amino group, wherein R ^XV and R ^XVI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto;

R ₂₁ and R ₂₄ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₁ -C ₁₀ aryl; N (R ^XXI ) (R ^XXII ) amino groups, wherein R ^XXI and R ^XXII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; Also,

R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XXIV ) (R ^XXV ) amino groups, wherein R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair together with the carbon attached thereto may form a (C═O) group.

Specific examples of the substructure (IIa ') include 8- [2- (6,7-dihydroxy-1,5-dimethyl-naphthalen-2-yl) -ethyl] -2,4a-tetramethyl-1 , 2,3,4,4a, 5,6,7-octahydro-naphthalene-2-carboxylic acid methyl ester (C27).

Another aspect of the invention relates to a process for the preparation of a compound of formula (I), which comprises the following features:

a) A conventional method of chemically introducing hydroxyl at the C-3 position of a naturally occurring Friedelane derivative of a pristine-methylene triterpenequinone species is to extract phenol protons and other kinds of acylation reactions. It is essential to analyze basic conditions for subsequent reaction with the indicator.

b) The chemoselective introduction of the indicator to the C-23 position is carried out in accordance with a controlled oxidation reaction with reagents specific for the allyl aromatic system and subsequent modification of the functional groups obtained thereby.

c) By known methods according to the existing studies, C-25 is transformed into a fluoromethyl group and its subsequent modification results an indicator is formed.

d) Forms part of the process for preparing the desired object by using heterogeneous and homologous halogenation reactions in combination with chemical selective oxidation reactions and introducing nitrogen using azide.

e) Taking advantage of the functionalization reaction of C-11, to produce C-11-C12 double bonds using well-known methods, these resulting double bonds can be applied to the FGT ( Functional group transformation reaction).

f) The C-15 and C-16 positions were functionalized by performing allyl oxidation from the double bonds in rings (E) and (C) and then applying FGT.

g) The C-19, C-20, C-21 and C-22 positions can be partially functionalized in some starting substrates and the chemical principles regarding the introduction of functional groups to the rings are well known.

Specific embodiments of the present invention are described in detail in the preparation examples, but those skilled in the art are not limited thereto, and the above-described compounds may be synthesized using synthetic compounds known in the art.

"Pharmaceutically acceptable salts, solvates, prodrugs" means pharmaceutical salts, esters, solvates or other compounds that, when administered to a receptor, can provide (directly or indirectly) the compounds described herein. Say However, salts that are not pharmaceutically acceptable may also be useful in the preparation of the pharmaceutically acceptable salts, thus confirming that they are also included in the scope of the present invention. The preparation of salts, prodrugs and derivatives is in accordance with known methods in the art.

For example, pharmaceutically acceptable salts of the compounds described herein are synthesized from conventional compounds containing base or acid residues through conventional chemical methods. Such salts are generally prepared by reacting a compound in free acid or base form in water or an organic solvent or a mixture thereof, using, for example, a stoichiometric amount of an appropriate base or acid. The non-aqueous medium is preferably ether, ethyl acetate, ethanol, isopropanol or acetonitrile and the like, for example. Examples of acid addition salts include inorganic acid addition salts such as hydrochloric acid, bromine hydroxide, iodine hydroxide, sulfates, nitrates and phosphates, and also acetates, maleates, fumarates, citrate, oxalates, succinates, tartarates and maleates. Organic acid addition salts such as mandelate, methanesulfonate and p-toluenesulfonate. Examples of basic addition salts include inorganic salts such as sodium salts, potassium salts, calcium salts, ammonium salts, magnesium salts, aluminum salts and lithium salts, and also ethylenediamine, ethanolamine, N, N-dialkyleneethanolamine and triethanolamine. Organic basic salts such as glucamine and basic amino acid salts.

Particularly preferred derivatives or prodrugs increase the bioavailability of the compound when the compound of the invention is administered to a patient (e.g., prepared for oral administration so that it can be readily absorbed into the blood), or It refers to a substance that can improve the release of the original compound in its native form into a biological zone (eg, brain or lymphatic system, etc.).

Compounds which are prodrugs of the compounds of formula (I) or (II) are also within the scope of the present invention. The term “prodrug” is broad in its meaning and includes derivatives that are converted into the body of the compounds of the invention. Such derivatives are well known to those skilled in the art and vary depending on the intramolecular functional groups and include, but are not particularly limited to, derivatives of the compounds of the present invention: esters, amino acid esters, phosphate esters, metal salt sulfonate esters, carbamate and amides. And so on. Specific examples of methods for preparing prodrugs of certain active compounds are known to those of skill in the art, and examples thereof include Krogsgaard-Larsen et al. See "Textbook of Drug design and Discovery" (Taylor & Francis, April 2002).

The compounds of the present invention may be in crystalline form, such as free compounds or solvent compounds, all of which are within the scope of the present invention. Solvation reactions are known in the art. Suitable solvent compounds are pharmaceutically acceptable solvent compounds. In certain embodiments, the solvent compound is a hydrate.

As described above, the compounds of the present invention represented by formula (I) may include enantiomers depending on the presence of chiral centers on C, or isomers (eg, Z, E) depending on the presence of multiple bonds. Can be. Each isomer, enantiomer or diastereomer and mixtures thereof are also within the scope of the present invention.

Various substituents selected for the various compounds of the present invention provide several factors that have a significant effect on the P log value. Accordingly, the hydroxyl group serves as a hydrogen bond donor, and also intramolecular or intermolecular bonds can be formed in phenols and the like. The presence of carbonyl or carboxyl groups creates proton acceptors in the molecule. The presence of halogens creates highly deficient carbon and greatly alters its biological properties. Amino groups impart good nucleophilicity to the molecule, and in most cases greatly alter the deflection and flattening properties, and in addition, when the alkyl and / or aryl groups are present, the molecule's lymphocyte properties become large.

The present invention also provides formulas (I), (Ia), (Ia '), (Ia "), (Ia"'), (Ib), (Ib '), (Ib "), (Ic), (Ic '), (Ic "), (Id), (Id'), (Id"), (Ie), (Ie '), (If), (If'), (If), (II), (IIa Or a pharmaceutically acceptable salt, derivative, prodrug, solvent compound or stereoisomer thereof in combination with a pharmaceutically acceptable carrier, adjuvant or vehicle in administration to a patient. It provides a pharmaceutical composition comprising.

The pharmaceutical compositions can be administered via any suitable route of administration, eg, oral, topical, rectal or parenteral routes (including subcutaneous, intraperitoneal, intradermal, intramuscular, intravenous, etc.).

Pharmaceutical forms suitable for oral administration include, but are not limited to, solid compositions (tablets, pastel tablets, capsules, granules, and the like) or liquid compositions (solutions, suspensions, emulsions, syrups, etc.), together with conventional excipients known in the art. , For example: binders such as syrup, acacia, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone; Lubricants for tablet manufacture such as magnesium stearate or disintegrants such as starch, polyvinylpyrrolidone, sodium starch glycolate or microcrystalline cellulose; Or pharmaceutically acceptable humectants such as sodium lauryl sulfate and the like.

Solid oral compositions can be prepared by conventional methods for mixing, filling or tablet preparation. Repeated mixing treatment with a large amount of filler allows the active ingredient to be evenly distributed throughout the composition. Such operations are common in the art. Tablets can be prepared, for example, by wet or dry granulation, optionally coated with a method known in the conventional Pharmacopoeia, and particularly enteric coated.

The pharmaceutical compositions may also be applied for parenteral administration in sterile solutions, suspensions or lyophilisates in appropriate single pharmaceutical forms. Suitable excipients such as bulking agents, buffers or surfactants can be used.

The formulations described above are prepared using conventional methods described in the Spanish Pharmacopoeia, United States Pharmacopoeia, and similar references.

Administration of the composition or compound used in the present invention can be carried out by any suitable method such as intravenous injection, oral and intraperitoneal administration and intravenous administration. Nevertheless, the preferred route of administration depends on the disease state of the patient. Based on the convenience of the patient and the chronic nature of the disease to be treated, oral administration is preferred.

In application to therapy, the compounds of formulas (I) and (II) are identified in pharmaceutically acceptable or pure form. That is, the compounds of formulas (I) and (II) have a range of pharmaceutically acceptable purity that excludes pharmaceutically acceptable excipients and does not include substances that are considered to be toxic in the normal dosage range. The range of purity for the compound of formula (I) or compound of formula (II) is preferably greater than 50%, more preferably greater than 70% and even more preferably greater than 90%. In a preferred embodiment, they are greater than 95%.

The therapeutically effective amount of a compound of formula (I) or a compound of formula (II) to be administered depends, among other factors, in particular on the subject to be treated, the severity of the disease suffered by the subject, the dosage form and the like. For this reason, the dosages referred to in the present invention are judged according to the guidance of those skilled in the art and those skilled in the art should adjust the dosages according to the variables described above. Nevertheless, the compound of formula (I) may be administered at least once per day, for example, 1 to 200 mg / kg body weight / day, preferably 1 to 10 mg / kg body weight / day, as a total amount to be administered per day. Administration may be divided into 2, 3 or 4 times. In the same way, the compound of formula (II) may be administered at least once per day, eg, 1,200 mg / kg body weight / day, preferably 1-10 mg / kg body weight / day, as a total amount to be administered per day. It can be administered in two, three or four divided doses.

The compounds described herein, their pharmaceutically acceptable salts, prodrugs and / or solvent compounds, as well as pharmaceutical compositions containing them, can be used in combination therapy with other drugs. Said additional drug may form part of the same pharmaceutical composition or comprises a compound of formula (I) or a compound of formula (II), or a pharmaceutically acceptable precursor, solvate or salt thereof It may be provided in the form of another composition for simultaneous or non-simultaneous administration with the pharmaceutical composition.

The other drug may form part of the same composition or be in the form of another composition to be administered at the same time or at different times.

The final object of the present invention is formula (I), (Ia), (Ia '), (Ia "), (Ia"'), (Ib), (Ib '), (Ib "), (Ic), ( Ic '), (Ic "), (Id), (Id'), (Id"), (Ie), (Ie '), (If), (If'), (II), (IIa) or ( Or a pharmaceutically acceptable salt, derivative, prodrug, solvent compound or stereoisomer thereof, for use in the treatment of cancer, parasitic diseases, bacterial diseases or fungal diseases.

The following examples are intended to illustrate the invention and are not to be construed as limiting the scope of the invention, which is defined by the claims.

Produce Example

Example  One

Compound ( C3 ): 12- Bromo -3,9-dihydroxy-6b, 8a, 11,12b, 14a- Hexamethyl -7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6 bH , 9H- Pysen -2,10- Dion

300 g of Methenus amazonica dermis was extracted in a 1: 1 mixture of 2 liters of n-hexane-ethylether and solvent in a soxhlet apparatus under reflux for 48 hours to obtain 70 g of a red solid after evaporation of the solvent. did. The extract was chromatographed using a 2: 1: 1 mixture of n-hexane-CHCl ₃ -MeOH as eluent on a Sephadex LH-20 column. A total of 41 g fractions were obtained and collected in seven groups (A, B, C, D, E, F and G) according to thin layer chromatography. These groups were fractionated with Sephadex LH-20 columns, medium pressure silica gel columns and preparative plates, resulting in 22β-hydroxy-tinzenone or [3,9-dihydroxy-6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-picene-2,10-dione] was obtained as a starting material.

A solution of 342 mg (0.78 mmoles) of 22β-hydroxy-tingenone in 50 ml of anhydrous CH ₂ Cl ₂ was treated with 1.5 eq BBr ₃ (1M) at inert atmosphere and 0 ° C. The reaction mixture was subjected to thin layer chromatography and stirred for about 30 minutes until the starting product was used up. Thereafter, 50 ml of cooled laminar water was added and the mixture was stirred for another 30 minutes. Next, extraction was performed with CH ₂ Cl ₂ . The organic phase was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by LH-20 Sephadex chromatography using a 2: 1: 1 mixture of n-hexane: chloroform: methanol as eluent and silica gel chromatography using a 7: 3 mixture of n-hexane-ethyl acetate. did. 111 mg (27%) of the product (C3) were obtained.

21), calcd for high resolution MS (M ⁺ -Br) C ₂₈ H ₃₆ O ₄ : 436.2614, obsd .: 436.2695.

Example  2

Compound ( C7 ): 14- Bromo -3-dihydroxy-4,6b, 8a, 11,12b, 14a- Hexamethyl -7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6 bH , 9H- Pysen -2,10- Dion

100 mg (0.23 mmoles) of 22β-hydroxy-tinxenone obtained according to Example 1 was dissolved in 10 ml of CH ₂ Cl ₂ and treated with 82 mg of NBS (2eq) for 2 hours at room temperature. The reaction mixture was TLC and extraction was done with CH ₂ Cl ₂ without starting. The organic phase was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of n-hexane: AcOEt (ethyl acetate) having a high polarization of 10% to 60% as eluent to give 1.2 mg (1%) of Compound (C7). A mixture of other compounds was also obtained.

21), calcd for high resolution MS C ₂₈ H ₃₅ BrO ₃ : 498.1770, obsd: 498.1801.

Example  3

Compound ( C8 ): (4,6b, 8a, 11,12b, 14a- Hexamethyl -2,10- Dioxo -2,6b, 7,8,8a, 9,10 11,12,12a, 12b, 13,14,14a-tetradecahydro- Pysen -3-yl) acetic acid ester

300 g of Methenus amazonica dermis was extracted under reflux for 48 hours in a 1: 1 mixture of 2 liters of n-hexane-ethylether and solvent in a soxhlet apparatus to give 70 g of a red solid after evaporation of the solvent. The extract was chromatographed using a 2: 1: 1 mixture of n-hexane-CHCl ₃ -MeOH as eluent on a Sephadex LH-20 column. A total of 41 g fractions were obtained and collected in seven groups (A, B, C, D, E, F and G) according to thin layer chromatography. These groups were fractionated with a Sephadex LH-20 column, a medium pressure silica gel column and a preparation plate, whereby tin xenon was obtained as starting material.

A solution of 40 mg (0.096 mmoles) of tingenone in 10 ml of anhydrous CH ₂ Cl ₂ was treated with 0.04 ml (3 eq) of anhydrous Et ₃ N and 0.01 ml (1.5 eq) of acetyl chloride. The reaction was carried out at room temperature, then treated with TLC and stirred for 2 hours. The procedure of the reaction described above was followed. The initial product was purified by crude chromatography on silica gel using n-hexane: AcOEt (2: 3) as the mobile phase to give 24 mg (54%) of product (C8). The residue was used as starting material.

Calcd for high resolution MS C ₃₀ H ₃₈ O ₄ : 462.2770, obsd: 462.2784.

Example  4

Compound ( C9 ): (4,6b, 8a, 11,12b, 14a- Hexamethyl -2,10- Dioxo -2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro- Pysen -3-yl) nicotinic acid ester

98 mg (0.23 mmoles) of tin xenon (obtained according to Example 3) was dissolved in 10 ml of anhydrous CH ₂ Cl ₂ , 0.097 ml (3 eq) of anhydrous Et ₃ N, 62.12 mg (1.5 eq) of nicotin chloride and catalytic amount Dealt with DMAP. The reaction was carried out at room temperature, then treated with TLC and stirred for 20 minutes. The reaction procedure described above was followed and the initial product was purified by preparative chromatography on silica gel using CH ₂ Cl ₂ : AcOEt (1: 1) as the mobile phase to give 55 mg (46%) of product (C9). The residue was used as starting material.

21), calcd for high resolution MS C ₃₄ H ₃₉ NO ₄ : 525.2879, obsd .: 525.2899.

Example  5

Compound ( C12 ): 3,10-dihydroxy-2,4a, 6a, 9,12b, 14a- Hexamethyl -11-oxo-1,2,3,4,4a, 5,6,6a, 12,12b, 13,14,14a, 14b-tetradecahydro- Pysen -2- Carboxylic acid Methyl ester

5 g of a red solid was obtained after evaporation of the solvent in a 1: 1 mixture of 2 liters of n-hexane-ethylether to solvent containing 1500 g of Salacia dermis in a Soxhlet apparatus. The extract was chromatographed on a silica gel column to give compound (C12).

Example  6

Compound ( C14 ): 10- Dimethylcarbamoyloxy -2,4a, 6a, 9,12b, 14a- Hexamethyl -11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b- Tetradecahydro - Pysen -2- Carboxy practice Methyl ester

300 g of Methenus amazonica dermis was extracted under reflux for 48 hours in a 1: 1 mixture of 2 liters of n-hexane-ethylether and solvent in a soxhlet apparatus to give 70 g of a red solid after evaporation of the solvent. This extract was chromatographed using a 2: 1: 1 mixture of n-hexane-CHCl ₃ -MeOH as eluent on a Sephadex LH-20 column. A total of 41 g fractions were obtained and collected in seven groups (A, B, C, D, E, F and G) according to thin layer chromatography. These groups were fractionated with a Sephadex LH-20 column, a medium pressure silica gel column and a preparation plate to give a starting material called pristine.

A solution of 65 mg (0.14 mmoles) of prestimerin in 5 ml of anhydrous CH ₂ Cl ₂ was added 0.062 ml (3 eq) of anhydrous Et ₃ N, 0.02 ml (1.5 eq) of N, N-dimethylcarbamoyl chloride and a catalytic amount. Treatment was done using DMAP. The reaction was carried out at 0 ° C. under inert atmosphere, then treated with TLC and stirred for 24 hours. Then, 5% dilute hydrochloric acid was added during the neutralization reaction. The organic phase was then extracted with CH ₂ Cl ₂ and dried over anhydrous magnesium sulfate. Filtration was concentrated under reduced pressure. The initial product was purified by crude chromatography using n-hexane: AcOEt (2: 3) as a mobile phase to give 36 mg (48%) of the product (C14). The residue was used as starting material.

Calcd for high resolution MS C ₃₃ H ₄₅ NO ₅ : 535,3298. Observation: 536.3294.

human CHoK  In vitro analysis of activity

Recombinant human alpha-1 expressed in E. coli in the assay of buffer (including 100 mM Tris-HCl pH8.0, 100 mM MgCl ₂ , 10 mM ATP and 200 μM choline) in the presence of methyl chloride [ ¹⁴ C] -choline (50-60 μCi / mmol) Choline kinase was used for in vitro analysis. The reaction was carried out at 37 ° C. for 30 minutes and then stopped with ice-cooled trichloroacetic acid to achieve a final 16% concentration. The sample was washed with diethyl ether saturated with water and then lyophilized. Hydrophilic choline derivatives were digested in thin-film chromatography plates according to the methods described above (see Ramiroz, A., Penalva, V., Lucas, L., Lacal, JC Oncogene 21, 937-946 (2002)).

This analysis was carried out using eight compounds known in the art, as well as compounds C3, C7, C8, C10, C12 and C14 of the present invention (IS 2 117 950). The results are summarized in Table I.

These results confirm that the compounds of the present invention can significantly and selectively reduce the activity of choline kinase (ChoK) enzymes in cell models.

Cell proliferation assay

HT-29 cells were seeded in 24-well plates (35 H 10 ³ cells / well) and incubated for 24 hours. The cells were then treated with different concentrations of ChoK inhibitors in normal culture medium. After 3 days, the wells were aspirated off, fresh medium and drug added and the cells treated for 3 more days. Quantification of cells remaining in each well was determined by crystal violet method [Gillies, RJ, Didier, N., Denton, M. Anal. Biochem. 159, 109-113 (1986)] with some modifications [Hernandez-Alcoceba, R., Saniger, L., Campos, J., Nunez, MC, Khaless, F., Gallo, MA, Espinosa, A., Lacal, JC Oncogene, 15, 2289-2301 (1997). In summary, cells were washed with TD buffer and fixed with 1% glutaraldehyde for 15 minutes. After washing again with TD, the nuclei were stained with 0.1% crystal violet for at least 30 minutes and washed three times with distilled water. The adsorbed dye was suspended in 10% acetic acid and the absorbance at 595 nm was measured by spectrometer. The results obtained are summarized in IC ₅₀ value format, ie the concentration of compound required to achieve 50% inhibition. This value is determined by repeatedly adjusting the curve. Two values were measured at each point in the curve and the experiment was repeated two or three times to calculate the average. If the two values differ by more than 50%, a third experiment was conducted to determine the measured value. Concentration measurements, IC ₅₀ values, are used to link the biological activity of a compound with its chemical structure.

This analysis is carried out using the compounds C3, C7, C8, C9, C10, C12 and C14 of the present invention, as well as eight known compounds (ES 2 117 950). The results are summarized in Table I.

The following table is exemplified in the Examples of the present invention as a result of the analysis performed.

number Compound code In vitro IC ₅₀ (μM) IC ₅₀ HT-29 (μM) One C3 3.3 8.8 2 C7 13.6 27.5 3 C8 5.3 26.4 4 C9 8.8 13.3 5 C10 11.2 25.9 6 C12 7.4 3.8 7 C14 7.1 11.3 8 3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H- Pissen-2,10-dion 4.9 6.5 9 (9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl) acetic acid methyl ester 4.8 11.1 10 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13 , 14,14a-tetradecahydro-picen-3-yl dodecanoic acid ester 5.2 9.6 11 (9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl) dimethyl-carbamic acid ester 14.6 17.0 12 (9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl) nicotinic acid ester 8,6 7.2 13 14-bromo-3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12a, 12b, 13,14,14a-decahydro-6bH , 9H-Pysene-2,10-dione 10.8 12.1 14 Mono- (13-bromo-10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4,4a, 5,6,6a , 11,12b, 13,14,14a, 14b-tetradecahydro-picen-4-yl) succinic acid ester 4.7 11.3 15 13-bromo-10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4,4a, 5,6,6a, 11, 12b, 13,14,14a, 14b-tetradecahydro-picen-4-yl ethylsuccinic acid ester 2.1 4.1

From the data in Table I above, it can be seen that the compounds of the present invention have similar antiproliferative values from cells derived from cultured tumors.

Triterpenequinone and triterpenephenol derivatives according to the present invention, pharmaceutically acceptable salts thereof, prodrugs, solvent compounds or stereoisomers, pharmaceutical compositions containing them, and the like are selective blocking agents of choline kinase enzymes for tumors and parasites. It can be applied to sexual diseases or other diseases caused by viruses, bacteria or fungi.

Claims (71)

Use of a compound represented by the following formula (I) or a pharmaceutically acceptable salt, derivative, prodrug, solvate or stereoisomer thereof in the manufacture of a medicament for the treatment and / or prevention of a ChoK mediated disease or condition:

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ′) (R ″) amino groups, where R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR group, where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; Combining

Means double bond or single bond; Also The following triple ring structure

Is selected from the following structures;

here, R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ , R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; An OCOR ^VIII group, wherein R ^VIII is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₇ is hydrogen or a methyl group; R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen. The method of claim 1, The compound of formula (I) is a compound of formula (Ia):

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ′) (R ″) amino groups, where R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR group, where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₄ , R ₁₅ and R ₁₆ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR ^VIII group wherein R ^VIII is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₇ is hydrogen or a methyl group; R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means double bond or single bond. The method of claim 2, Wherein said compound of formula (Ia) is a compound of formula (Ia ')

here, R ₅ is a hydroxyl or OCOR group where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; R ₇ and R ₈ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₂ is hydrogen or halogen; R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means double bond or single bond. The method of claim 3, wherein The compound of formula (la) is: 3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H- Pisene-2,10-dione; Acetic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester; 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13 , 14,14a-tetradecahydro-picen-3-yl propionic acid ester; Dodecanoic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b , 13,14,14a-tetradecahydro-picen-3-yl ester; Dimethyl-carbamic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12, 12a, 12b, 13, 14, 14a- tetradecahydro-picen-3-yl ester; Nicotinic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester; 4-bromo- (9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a , 12b, 13,14,14a-tetradecahydro-picen-3-yl) benzoic acid ester; 14-bromo-3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12, 12a, 12b, 13,14,14a- Decahydro-6bH, 9H-picene-2,10-dione; 12-bromo-9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl dimethyl-carbamic acid ester; 4-bromo- (12-bromo-9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10, 11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl) benzoic acid ester; 12-bromo-3,9-dihydroxy-6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione; 3,9,10-trihydroxy-6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-dodecahydro -6bH-picen-2-one; Succinic mono- (10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4, 4a, 5,6,6a, 11,12b , 13,14,14a, 14b-tetradecahydro-picen-4-yl) ester; or Succinic acid ethyl ester 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picen-4yl ester. The method of claim 2, Wherein said compound of formula (Ia) is a compound of formula (Ia "):

here, R ₇ and R ₈ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₅ is hydrogen or halogen; R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means double bond or single bond. The method of claim 5, The compound of formula (la) is: 14-bromo-3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione; 4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a- Tetradecahydro-picen-3-yl acetic acid ester; 4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a- Tetradecahydro-picen-3-yl nicotinic acid ester; 3,10-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-dodecahydro -6bH-picen-2-one; or 3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 12a, 12b, 13,14,14a-octahydro-6bH, 9H-picene-2,10-dione Uses. The method of claim 2, Wherein said compound of formula (Ia) is a compound of formula (Ia "'):

here, R ₇ is hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Also R ₁₉ is substituted or unsubstituted C ₁ -C ₁₂ alkyl; COR ^XII group, wherein R ^XII is independently hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl, provided that R ₇ is not hydrogen when R ₁₉ is hydrogen. The method of claim 7, wherein The compound of formula (la) 'is: 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; 3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; 2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-10-propionyloxy-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a , 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; or 10-dimethylcarbamoyloxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester. The method of claim 1, Wherein said compound of formula (I) is a compound of formula (Ib)

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ , R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₇ is hydrogen or a methyl group; R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means double bond or single bond. The method of claim 9, Wherein said compound of formula (Ib) is a compound of formula (lb):

here, R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl. The method of claim 10, The compound of formula (Ib ') is 4-nitro- (3-dimethylcarbamoyloxy-5,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-10-oxo-5 , 6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-2-yl) benzoic acid ester. The method of claim 9, Wherein said compound of formula (lb) is a compound of formula (lb):

here, R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also R ₂₃ is hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group. The method of claim 12, The compound of formula (lb) is: 7,10,11-trihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-8-oxo-1,2,3,4,4a, 5,6, 6a, 8,12b, 13 , 14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; 9-formyl-10,11-dihydroxy-2,4a, 6a, 12b, 14a-pentamethyl-8-oxo-1,2,3,4,4a, 5, 6,6a, 8,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; or 11-hydroxy-10- (2-methoxy-ethoxymethoxy) -2,4a, 6a, 9,12b, 14a-hexamethyl-8-oxo-1,2,3,4,4a, 5, 6,6a, 8,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester. The method of claim 1, Wherein said compound of formula (I) is a compound of formula (Ic)

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is independently hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or C ₁ -C ₁₂ An alkyl group or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means double bond or single bond. The method of claim 14, Wherein said compound of formula (Ic) is a compound of formula (Ic ')

here, R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; COR ^XII group, wherein R ^XII is independently hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means double bond or single bond. The method of claim 15, The compound of formula (Ic ') is: 10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-1,4,4a, 5,6,6a, 13,14,14a, 14b-decahydro-2H-picene-3- On; or 10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-4a, 5,6,6a, 13,14,14a, 14b-octahydro-4H-picen-3-one. The method of claim 14, Wherein said compound of formula (Ic) is a compound of formula (Ic "):

here, R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl. The method of claim 17, The compound of formula (Ic ″) is 10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-1,2,3,4,4a, 5,6,6a, 13,14, 14a, 14b-dodecahydro-picene-2-carboxylic acid methyl ester. The method of claim 1, Wherein said compound of formula (I) is a compound of formula (Id)

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₅ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ^VI ) (R ^VII ) amino group, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is independently hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or C ₁ -C ₁₂ An alkyl group or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen; Also Combining

Means double bond or single bond. The method of claim 19, Wherein said compound of formula (Id) is a compound of formula (Id ')

here, R ₅ and R ₆ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair, respectively, together with the carbon to which they are attached may form a C═O group; Also R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen. The method of claim 20, The compound of formula (Id ') is: 1-bromo-9-hydroxy-4,6b, 8a, 11,12b, 14b-hexamethyl-6b, 7,8,8a, 9,11,12,12a, 12b, 14b-decahydro-1H- Pisene-2,3,10-trione; or 1-bromo-4,6b, 8a, 11,12b, 14b-hexamethyl-6b, 7,8,8a, 9,11,12a, 12b, 14b-decahydro-1H-picene-2,3,10 -Use as trion. The method of claim 19, Wherein said compound of formula (Id) is a compound of formula (Id "):

here, R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen. The method of claim 22, The compound of formula (Id ") is 12-bromo-2,4a, 6a, 9,12a, 14a-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5,6, 6a, 10, 11, 12, 12a, 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester. The method of claim 1, Wherein said compound of formula (I) is a compound of formula (Ie)

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; R ₂₄ is hydrogen, hydroxyl or halogen; Also Combining

Means double bond or single bond. The method of claim 24, Wherein said compound of formula (Ie) is a compound of formula (Ie '):

here, R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also R ₂₄ is hydrogen, hydroxyl or halogen. The method of claim 25, The compound of formula (Ie ') is 9-hydroxy-2,4a, 6a, 9,12b-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5,6,6a, 9,10,11,12b, 13,14,14a, 14b-hexadecahydro-picene-2-carboxylic acid methyl ester. The method of claim 1, The compound of formula (I) is a compound of formula (If):

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₄ , R ₁₅ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ^VI ) (R ^VII ) amino group, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; R ₂₄ is hydrogen, hydroxyl or halogen; Also Combining

Means double bond or single bond. The method of claim 27, The compound of formula (If) is a compound of formula (If ′):

here, R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also R ₂₄ is hydrogen, hydroxyl or halogen. The method of claim 28, The compound of formula (If ') is 9-hydroxy-2,4a, 6a, 6b, 9-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5,6,6a, 6b, 8a, 9,10,11,14,14a, 14b-hexadecahydro-picene-2-carboxylic acid methyl ester. Use of a compound represented by the following formula (II) or a pharmaceutically acceptable salt, derivative, prodrug, solvent compound or stereoisomer thereof in the manufacture of a medicament for the treatment and / or prevention of a ChoK mediated disease or disorder:

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₁₇ , R ₁₈ , R ₁₉ And R ₂₀ is independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XV ) (R ^XVI ) amino groups, wherein R ^XV and R ^XVI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₇ and R ₈ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^XVII group, wherein R ^XVII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^XVIII ) (R ^XIX ) amino, wherein R ^XVIII and R ^XIX are independently hydrogen or a C ₁ -C ₁₂ alkyl group); (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₂₁ and R ₂₄ are independently substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XX group wherein R ^XX is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXI ) (R ^XXII ) amino, Wherein R ^XXI and R ^XXII are independently hydrogen or C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also R ₂₂ and R ₂₃ are - Hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXIII group wherein R ^XXIII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXIV ) (R ^XXV ) amino, R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is in the para position with respect to R ₂₀ ; or OR ₂₂ ′ and OR ₂₃ ′ respectively, wherein R ₂₂ ′ and R ₂₃ ′ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXVI group wherein R ^XXVI is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXVII ) (R ^XXVIII ) amino, Wherein R ^XXVII and R ^XXVIII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is present in the meta position relative to R ₂₀ . The method of claim 30, Wherein said compound of formula (II) is a compound of formula (IIa)

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₁₇ , R ₁₈ , R ₁₉ And R ₂₀ is independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XV ) (R ^XVI ) amino group, wherein R ^XV and R ^XVI are independently hydrogen or C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₇ and R ₈ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^XVII group, wherein R ^XVII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^XVIII ) (R ^XIX ) amino, wherein R ^XVIII and R ^XIX are independently hydrogen or a C ₁ -C ₁₂ alkyl group); (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₂₁ and R ₂₄ are independently substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XX group wherein R ^XX is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXI ) (R ^XXII ) amino, Wherein R ^XXI and R ^XXII are independently hydrogen or C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also R ₂₂ and R ₂₃ are - Hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXIII group, wherein R ^XXIII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXIV ) (R ^XXV ) amino Wherein R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is in the para position with respect to R ₂₀ ; or OR ₂₂ ′ and OR ₂₃ ′ respectively, wherein R ₂₂ ′ and R ₂₃ ′ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXVI group wherein R ^XXVI is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXVII ) (R ^XXVIII ) amino, Wherein R ^XXVII and R ^XXVIII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is present in the meta position relative to R ₂₀ . The method of claim 31, wherein Wherein said compound of formula (IIa) is a compound of formula (IIa ')

here, R ₁₉ and R ₂₀ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ^XV ) (R ^XVI ) amino group, wherein R ^XV and R ^XVI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₂₁ and R ₂₄ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₁ -C ₁₀ aryl; N (R ^XXI ) (R ^XXII ) amino groups, wherein R ^XXI and R ^XXII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; Also, R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XXIV ) (R ^XXV ) amino groups, wherein R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair together with the carbon attached thereto may form a (C═O) group. The method of claim 32, The compound of formula (IIa ') is 8- [2- (6,7-dihydroxy-1,5-dimethyl-naphthalen-2-yl) -ethyl] -2,4a-tetramethyl-1,2, 3,4,4a, 5,6,7-octahydro-naphthalene-2-carboxylic acid methyl ester. The method according to any one of claims 1 to 33, The ChoK mediated disease or condition to be prevented and / or treated is cancer, among which cancer is selected from breast cancer, lung cancer, bowel cancer and pancreatic cancer. The method according to any one of claims 1 to 33, The ChoK mediated disease or condition to be prevented and / or treated is a parasitic disease, among which is a disease caused by plasmodium or tripanosoma. The method according to any one of claims 1 to 33, The ChoK mediated disease or condition to be prevented and / or treated is a parasitic disease, a disease caused by a bacterial disease, among other things, a disease caused by pneumococcus. The method according to any one of claims 1 to 33, The ChoK mediated disease or condition to be prevented and / or treated is a fungal disease, among which is a disease caused by Candida. Compounds represented by the following formula (I) or pharmaceutically acceptable salts, derivatives, prodrugs, solvates or stereoisomers thereof:

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ′) (R ″) amino groups, where R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR group, where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; Combining

Means double bond or single bond; Also The following triple ring structure

Is selected from the following structures;

here, R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ , R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; An OCOR ^VIII group, wherein R ^VIII is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₇ is hydrogen or a methyl group; R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen, provided When the tricycle is (a), the compound of formula (I) is: 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid; 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; 3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; 3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-picene-2 , 10-dione; 3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H- Pisene-2,10-dione; 3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione; 14-bromo-3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a- Dicahydro-6bH, 9H-picene-2,10-dione; Succinic Mono- (10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3, 4,4a, 5,6,6a, 11,12b , 13,14,14a, 14b-tetradecahydro-picen-4-yl) ester; Succinic acid ethyl ester 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picen-4-yl ester; Acetic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester; Dodecanoic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b , 13,14,14a-tetradecahydro-picen-3-yl ester; Dimethyl-carbamic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12, 12a, 12b, 13, 14, 14a- tetradecahydro-picen-3-yl ester; Nicotinic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester; 3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; And 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, Not 14b-tetradecahydro-picene-2-carboxylic acid methylester, When said tricycle is (b) and said R ₁₉ and R ₂₀ are independently hydrogen or an acyl group, R ₅ is hydroxyl; or R ₂₁ and R ₂₂ together with the carbon to which they are attached form C═O and R ₁₀ is not COOH; Also, When the tricycle is (c) and R ₁₉ and R ₂₀ are both CH ₃ , R ₁₅ and R ₁₆ are subject to the fact that they do not form C═O with the carbon to which they are attached. The method of claim 38, A compound represented by the following formula (Ia):

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ′) (R ″) amino groups, where R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR group, where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₄ , R ₁₅ and R ₁₆ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or an OCOR ^VIII group wherein R ^VIII is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₇ is hydrogen or a methyl group; R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means a double bond or a single bond, provided that the compound of formula (Ia) is: 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid; 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; 3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; 3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-picene-2 , 10-dione; 3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H- Pisene-2,10-dione; 3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione; 14-bromo-3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a- Dicahydro-6bH, 9H-picene-2,10-dione; Succinic Mono- (10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3, 4,4a, 5,6,6a, 11,12b , 13,14,14a, 14b-tetradecahydro-picen-4-yl) ester; Succinic acid ethyl ester 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picen-4-yl ester; Acetic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester; Dodecanoic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b , 13,14,14a-tetradecahydro-picen-3-yl ester; Dimethyl-carbamic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12, 12a, 12b, 13, 14, 14a- tetradecahydro-picen-3-yl ester; Nicotinic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester; 3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; or 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, The condition is not 14b-tetradecahydro-picene-2-carboxylic acid methyl ester. The method of claim 39, A compound represented by the following formula (Ia '):

here, R ₅ is a hydroxyl or OCOR group where R is (CH ₂ ) ₂ COOH or (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ ; R ₇ and R ₈ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₂ is hydrogen or halogen; R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means a double bond or a single bond, provided that the compound of formula (Ia ') is: 3,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H- Pisene-2,10-dione; 14-bromo-3,7,9-trihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a- Dicahydro-6bH, 9H-picene-2,10-dione; Succinic Mono- (10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3, 4,4a, 5,6,6a, 11,12b , 13,14,14a, 14b-tetradecahydro-picen-4-yl) ester; Succinic acid ethyl ester 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-3,11-dioxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, 14b-tetradecahydro-picen-4-yl ester; Acetic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl ester; Dodecanoic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b , 13,14,14a-tetradecahydro-picen-3-yl ester; Dimethyl-carbamic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12, 12a, 12b, 13, 14, 14a- tetradecahydro-picen-3-yl ester; or Nicotinic acid 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, And not 13,14,14a-tetradecahydro-picen-3-yl ester. The method of claim 40, The compound is: 9-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13 , 14,14a-tetradecahydro-picen-3-yl propionic acid ester; 4-bromo- (9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a , 12b, 13,14,14a-tetradecahydro-picen-3-yl) benzoic acid ester; 12-bromo-3,9-dihydroxy-6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione; 12-bromo-9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl dimethyl-carbamic acid ester; 4-bromo- (12-bromo-9-hydroxy-6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10, 11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-3-yl) benzoic acid ester; or 3,9,10-trihydroxy-6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-dodecahydro -6bH-picen-2-one. The method of claim 39, A compound represented by the following formula (Ia "):

here, R ₇ and R ₈ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₅ is hydrogen or halogen; R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means a double bond or a single bond, provided that the compound of substructure (Ia ″) is: 3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-dodecahydro-6bH- Pysen-2-one; And 3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-picene-2 Subject to non 10-dione The method of claim 42, wherein The compound is: 14-bromo-3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 11,12,12a, 12b, 13,14,14a-decahydro-6bH, 9H-Pysene-2,10-dione; 4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a- Tetradecahydro-picen-3-yl acetic acid ester; 4,6b, 8a, 11,12b, 14a-hexamethyl-2,10-dioxo-2,6b, 7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a- Tetradecahydro-picen-3-yl nicotinic acid ester; 3,10-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 9,10,11,12,12a, 12b, 13,14,14a-dodecahydro -6bH-picen-2-one; or 3-hydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-7,8,8a, 12a, 12b, 13,14,14a-octahydro-6bH, 9H-picene-2,10-dione Phosphorus compounds. The method of claim 39, A compound represented by the following formula (Ia "'):

here, R ₇ is hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, where R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Also R ₁₉ is substituted or unsubstituted C ₁ -C ₁₂ alkyl; COR ^XII group, wherein R ^XII is independently hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl, provided that the compound of formula (Ia "') is: 3,10-dihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14a , 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; And 10-hydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a, The condition is not 14b-tetradecahydro-picene-2-carboxylic acid methyl ester. The method of claim 44, The compound is: 2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-10-propionyloxy-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14,14a , 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; or 10-dimethylcarbamoyloxy-2,4a, 6a, 9,12b, 14a-hexamethyl-11-oxo-1,2,3,4,4a, 5,6,6a, 11,12b, 13,14 , 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester. The method of claim 38, A compound represented by the following formula (lb):

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N ( R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ , R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₇ is hydrogen or a methyl group; R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means a double bond or a single bond, provided that R ₁₉ And when R ₂₀ is independently hydrogen or an acyl group, R ₅ is hydroxyl, or Provided that R ₂₁ and R ₂₂ together with the carbon attached thereto form a (C═O) group while R ₁₀ is not COOH. The method of claim 46, A compound represented by the following formula (Ib '):

here, R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl. The method of claim 47, The compound is 4-nitro- (3-dimethylcarbamoyloxy-5,9-dihydroxy-4,6b, 8a, 11,12b, 14a-hexamethyl-10-oxo-5,6b, 7,8 , 8a, 9,10,11,12,12a, 12b, 13,14,14a-tetradecahydro-picen-2-yl) benzoic acid ester. The method of claim 46, A compound represented by the following formula (lb):

here, R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ is hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also R ₂₃ is hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group. The method of claim 49, The compound is: 7,10,11-trihydroxy-2,4a, 6a, 9,12b, 14a-hexamethyl-8-oxo-1,2,3,4,4a, 5,6, 6a, 8,12b, 13 , 14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; 9-formyl-10,11-dihydroxy-2,4a, 6a, 12b, 14a-pentamethyl-8-oxo-1,2,3,4,4a, 5, 6,6a, 8,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester; or 11-hydroxy-10- (2-methoxy-ethoxymethoxy) -2,4a, 6a, 9,12b, 14a-hexamethyl-8-oxo-1,2,3,4,4a, 5, 6,6a, 8,12b, 13,14,14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester. The method of claim 38, Compound represented by the following formula (Ic):

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is independently hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or C ₁ -C ₁₂ An alkyl group or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means a double bond or a single bond, provided that R ₁₉ And when both R ₂₀ are CH ₃ , R ₁₅ and R ₁₆ do not form a (C═O) group together with the carbon attached thereto. The method of claim 51, A compound represented by the following formula (Ic '):

here, R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; COR ^XII group, wherein R ^XII is independently hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also Combining

Means double bond or single bond. The method of claim 52, wherein The compound is: 10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-1,4,4a, 5,6,6a, 13,14,14a, 14b-decahydro-2H-picene-3- On; or 10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-4a, 5,6,6a, 13,14,14a, 14b-octahydro-4H-picen-3-one. The method of claim 51, A compound represented by the following formula (Ic "):

here, R ₁₉ And R ₂₀ is independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl. The method of claim 54, The compound is 10,11-dihydroxy-2,4a, 6a, 9,14a-pentamethyl-1,2,3,4,4a, 5,6,6a, 13,14,14a, 14b-dodeca A compound that is hydro-picene-2-carboxylic acid methyl ester. The method of claim 38, A compound represented by the following formula (Id):

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₅ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ^VI ) (R ^VII ) amino group, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₈ is hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is independently hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or C ₁ -C ₁₂ An alkyl group or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen; Also Combining

Means double bond or single bond. The method of claim 56, wherein A compound represented by the following formula (Id '):

here, R ₅ and R ₆ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen. The method of claim 57, The compound is: 1-bromo-9-hydroxy-4,6b, 8a, 11,12b, 14b-hexamethyl-6b, 7,8,8a, 9,11,12,12a, 12b, 14b-decahydro-1H- Pisene-2,3,10-trione; or 1-bromo-4,6b, 8a, 11,12b, 14b-hexamethyl-6b, 7,8,8a, 9,11,12a, 12b, 14b-decahydro-1H-picene-2,3,10 A compound that is -trione. The method of claim 56, wherein A compound represented by the following formula (Id "):

here, R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also R ₂₄ and R ₂₅ are independently hydrogen, hydroxyl or halogen. The method of claim 59, The compound is 12-bromo-2,4a, 6a, 9,12a, 14a-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5,6,6a, 10,11, 12,12a, 14a, 14b-tetradecahydro-picene-2-carboxylic acid methyl ester. The method of claim 38, A compound represented by the following formula (Ie):

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^VI ) (R ^VII ) amino groups, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; R ₂₄ is hydrogen, hydroxyl or halogen; Also Combining

Means double bond or single bond. 62. The method of claim 61, A compound represented by the following formula (Ie '):

here, R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; Also R ₂₄ is hydrogen, hydroxyl or halogen. The method of claim 62, The compound is 9-hydroxy-2,4a, 6a, 9,12b-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5,6,6a, 9,10,11, 12b, 13,14,14a, 14b-hexadecahydro-picene-2-carboxylic acid methyl ester. The method of claim 38, A compound represented by the following formula (If):

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁₁ and R ₁₂ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ′) (R ″) amino group, wherein R ′ and R ″ are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₉ and R ₁₀ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ″ ′ group wherein R ″ is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^IV ) (R ^V ) amino, wherein R ^IV and R ^V are independently hydrogen or a C ₁ -C ₁₂ alkyl group; (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₁₃ , R ₁₄ , R ₁₅ , R ₂₁ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ^VI ) (R ^VII ) amino group, wherein R ^VI and R ^VII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair, respectively, together with the carbon to which they are attached may form a C═O group; R ₂₄ is hydrogen, hydroxyl or halogen; Also Combining

Means double bond or single bond. The method of claim 64, wherein A compound represented by the following formula (If '):

here, R ₁₈ and R _{18 '} are independently hydrogen; Hydroxyl; halogen; C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^IX where R ^IX is hydrogen; hydroxyl; C ₁ -C ₁₂ alkyl; N (R ^X ) (R ^XI ) amino, wherein R ^X and R ^XI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or C ₁ -C ₁₂ alkoxyl); Or trifluoromethyl; R ₁₉ , R _{19 '} , R ₂₀ and R _20' are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XII group wherein R ^XII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XIII ) (R ^XIV ) amino, Wherein R ^XIII and R ^XIV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Or a 19-19 'pair or a 20-20' pair together with the carbon to which they are attached may form a C═O group; R ₂₄ is hydrogen, hydroxyl or halogen. 66. The matter of claim 65, The compound is 9-hydroxy-2,4a, 6a, 6b, 9-hexamethyl-10,11-dioxo-1,2,3,4,4a, 5,6,6a, 6b, 8a, 9, 10,11,14,14a, 14b-hexadecahydro-picene-2-carboxylic acid methyl ester. A compound of formula (II): or a pharmaceutically acceptable salt, derivative, prodrug, solvent compound, or stereoisomer thereof

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₁₇ , R ₁₈ , R ₁₉ And R ₂₀ is independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XV ) (R ^XVI ) amino groups, wherein R ^XV and R ^XVI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₇ and R ₈ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^XVII group, wherein R ^XVII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^XVIII ) (R ^XIX ) amino, wherein R ^XVIII and R ^XIX are independently hydrogen or a C ₁ -C ₁₂ alkyl group); (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₂₁ and R ₂₄ are independently substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XX group wherein R ^XX is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXI ) (R ^XXII ) amino, Wherein R ^XXI and R ^XXII are independently hydrogen or C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also R ₂₂ and R ₂₃ are - Hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXIII group wherein R ^XXIII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXIV ) (R ^XXV ) amino, R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is in the para position with respect to R ₂₀ ; or OR ₂₂ ′ and OR ₂₃ ′ respectively, wherein R ₂₂ ′ and R ₂₃ ′ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXVI group wherein R ^XXVI is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXVII ) (R ^XXVIII ) amino, Wherein R ^XXVII and R ^XXVIII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is present in the meta position relative to R ₂₀ . The method of claim 67, Compound represented by the following formula (IIa):

here, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , R ₁₅ , R ₁₆ , R ₁₇ , R ₁₈ , R ₁₉ And R ₂₀ is independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XV ) (R ^XVI ) amino group, wherein R ^XV and R ^XVI are independently hydrogen or C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₇ and R ₈ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; C ₆ -C ₁₀ aryl; COR ^XVII group, wherein R ^XVII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; OC ₁ -C ₁₂ alkyl; or N (R ^XVIII ) (R ^XIX ) amino, wherein R ^XVIII and R ^XIX are independently hydrogen or a C ₁ -C ₁₂ alkyl group); (CH ₂ ) _n -OH carbinol group where n is an integer from 1 to 10; Or together form a methylene group; R ₂₁ and R ₂₄ are independently substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XX group wherein R ^XX is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXI ) (R ^XXII ) amino, Wherein R ^XXI and R ^XXII are independently hydrogen or C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl; Also R ₂₂ and R ₂₃ are - Hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXIII group, wherein R ^XXIII is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXIV ) (R ^XXV ) amino Wherein R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is in the para position with respect to R ₂₀ ; or OR ₂₂ ′ and OR ₂₃ ′ respectively, wherein R ₂₂ ′ and R ₂₃ ′ are independently hydrogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; A COR ^XXVI group wherein R ^XXVI is hydrogen; hydroxyl; substituted or unsubstituted C ₁ -C ₁₂ alkyl; substituted or unsubstituted C ₆ -C ₁₀ aryl; or N (R ^XXVII ) (R ^XXVIII ) amino, Wherein R ^XXVII and R ^XXVIII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; [(C ₁ -C ₁₂₎ alkyl, -O- (C ₁ -C ₁₂₎ alkyl -] _n group (where n is an integer of 1 to 3); Or trifluoromethyl when R ₂₄ is present in the meta position relative to R ₂₀ . The method of claim 68, wherein Compound represented by the following formula (IIa '):

here, R ₁₉ and R ₂₀ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; Or an N (R ^XV ) (R ^XVI ) amino group, wherein R ^XV and R ^XVI are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₂₁ and R ₂₄ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₁ -C ₁₀ aryl; N (R ^XXI ) (R ^XXII ) amino groups, wherein R ^XXI and R ^XXII are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair may form a (C═O) group with carbon attached thereto; R ₂₂ and R ₂₃ are independently hydrogen; Hydroxyl; halogen; Substituted or unsubstituted C ₁ -C ₁₂ alkyl; Substituted or unsubstituted C ₆ -C ₁₀ aryl; N (R ^XXIV ) (R ^XXV ) amino groups, wherein R ^XXIV and R ^XXV are independently hydrogen or a C ₁ -C ₁₂ alkyl group; Or each pair together with the carbon attached thereto may form a (C═O) group. 70. A method of administering to a patient a compound of formula (I) or (II) or a mixture thereof, a pharmaceutically acceptable salt, derivative, prodrug, solvent compound or stereoisomer thereof according to any one of claims 38 to 69 A pharmaceutical composition comprising, together with a pharmaceutically acceptable carrier, adjuvant or vehicle. A compound of formula (I) or (II) according to any one of claims 38 to 69 or a mixture thereof, a pharmaceutically acceptable salt, derivative, prodrug thereof, for use in the treatment of a ChoK mediated disease or condition, Solvent Compounds or Stereoisomers.