Steroid derivative regulators, method for preparing the same, and uses thereof
Patent Information
- Application Number
- CA3088919
- Authority / Receiving Office
- CA · CA
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2018-11-23
- Filing Date
- 2019-01-31
- Publication Date
- 2026-10-06
- Estimated Expiration
- 2039-01-31
Abstract
Description
STEROID DERIVATIVE REGULATORS, METHOD FOR PREPARING THE SAME, AND USES THEREOF FIELD OF THE INVENTION The present invention belongs to the field of drug synthesis, and in particular relates to a steroid derivative regulator, a method for preparing the same, and a use thereof. BACKGROUND OF THE INVENTION GABA<com:Sub>A< / com:Sub> receptor is a chemically-gated channel on the cell membrane and belongs to an ionic receptor. GABAA receptor is widely distributed in the nervous system, and can bind to the inhibitory neurotransmitter GABA (gamma-aminobutyric acid), leading to the opening of chloride channels and inhibition of neurons. GABA<com:Sub>A< / com:Sub> receptor regulator (tetrahydroprogesterone) is a positive regulator of GABA<com:Sub>A< / com:Sub> receptor. The binding of tetrahydroprogesterone and the intrasynaptic GABA<com:Sub>A< / com:Sub> receptor regulator can increase the opening frequency of chloride channel on the receptor and the influx of chloride ion, thereby increasing the Phasic current, producing a rapid inhibitory effect, reducing nerve excitability, and providing an anti-anxiety and anti-depression effect. The binding of tetrahydroprogesterone and the extrasynaptic GABA<com:Sub>A< / com:Sub> receptor provides a continuous chloride ion current, and mediates a lasting and sustained inhibitory effect. Tetrahydroprogesterone can also increase the content of brain derived neurotrophic factor (BDNF), promote the regeneration of hippocampal neurons, and provide a neuroprotective effect, thereby improving anxiety and depression symptoms; but the specific mechanism of action is not yet clear. Major depressive disorder (MDD) is a common, chronic and recurrent disease. The burden and adverse consequence caused by it are becoming more and more serious. In the past 40 years, the research and clinical application of antidepressants have greatly developed. However, most antidepressants (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, etc.) take 2 to 4 weeks to have an effect. The clinical treatment of major depressive disorder patients, especially patients with suicidal tendency, often needs to be prompt and rapid, thus there is an urgent need to develop fast-acting antidepressants. In the past two decades, there has been little innovation in the research and development of depression treatment. The development goal of GABA<com:Sub>A< / com:Sub> receptor regulators is to change the expectation of patients by changing the treatment regimen of MDD. If successfully developed, the GABA<com:Sub>A< / com:Sub> receptor regulator may become the first drug that provides a truly new mechanism of action for the treatment of depression in more than two decades. At present, foreign pharmaceutical companies, including Sage Therapeutics and Marinus etc., are doing their best to develop GABAA receptor regulators. Published patent applications related to GABA<com:Sub>A< / com:Sub> receptor regulators include: WO2003077919, WO2014169833, WO2016061537, WO2015180679, and WO2015027227. GABA<com:Sub>A< / com:Sub> receptor regulators, as a popular target in the pharmaceutical industry, currently have a good application prospect. First, GABA<com:Sub>A< / com:Sub> receptor regulators can be applied to major depressive disorder (MDD). The annual incidence of MDD in China is about 2%, thus there is a huge market potential. Second, existing antidepressants take a long time, commonly 3 to 4 weeks, to have an effect, have a high failure rate up to 40%, and require long-term medication. GABA<com:Sub>A< / com:Sub> receptor regulators can provide a significant antidepressant effect within 24 hours, and the effect can last for several days to two weeks. Third, GABA<com:Sub>A< / com:Sub> receptor regulators can meet the treatment need of MDD patients with oral administration once a day. SUMMARY OF THE INVENTION The objective of the present invention is to provide a compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the structure of the compound of formula (I) is as follows: [Image disponible dans le document PDF, Image available in the PDF document] (I) wherein: X is selected from the group consisting of <com:Math><semantics>−CR17<annotation encoding="application / x-tex">-CR_{17}< / annotation>< / semantics>< / com:Math>- and <com:Math><semantics>−N<annotation encoding="application / x-tex">-N< / annotation>< / semantics>< / com:Math>-; Y is selected from the group consisting of <com:Math><semantics>−CR23R24<annotation encoding="application / x-tex">-CR_{23}R_{24}< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−S(CH2)n1<annotation encoding="application / x-tex">-S(CH_2)_{n1}< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−P(CH2)n1<annotation encoding="application / x-tex">-P(CH_2)_{n1}< / annotation>< / semantics>< / com:Math>-, [Image disponible dans le document PDF, Image available in the PDF document] Ð R<com:Sup>x< / com:Sup>, R<com:Sup>y< / com:Sup>, R<com:Sup>z< / com:Sup> and R<com:Sup>f< / com:Sup> are identical or different and are each independently selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, thiol, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, <com:Math><semantics>−(CH2)n1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23C(O)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}C(O)R_{24}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR23S(O)m1R24<annotation encoding="application / x-tex">-(CH_2)_{n_1}NR_{23}S(O)_{m_1}R_{24}< / annotation>< / semantics>< / com:Math>, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, thiol, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, <com:Math><semantics>−(CH2)n1R25<annotation encoding="application / x-tex">-(CH_2)_{n_1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26}< / annotation>< / semantics>< / com:Math>; or, any two adjacent or non-adjacent groups of Rx, Ry, Rz and Rt can be bonded to form a cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>R<com:Sub>23< / com:Sub>, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>OR<com:Sub>23< / com:Sub>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23C(O)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}C(O)R_{24}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR23S(O)m1R24;<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}S(O)_{m1}R_{24};< / annotation>< / semantics>< / com:Math> or, any two adjacent groups of R<com:Sup>x< / com:Sup>, R<com:Sup>y< / com:Sup>, R<com:Sup>z< / com:Sup> and R<com:Sup>f< / com:Sup> can form a double bond; <com:Math><semantics>R21<annotation encoding="application / x-tex">R_{21}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>R<com:Sub>23< / com:Sub>, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>OR<com:Sub>23< / com:Sub>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23C(O)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}C(O)R_{24}< / annotation>< / semantics>< / com:Math> and -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>NR<com:Sub>23< / com:Sub>S(O)<com:Sub>m1< / com:Sub>R<com:Sub>24< / com:Sub>, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, <com:Math><semantics>−(CH2)n1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26}< / annotation>< / semantics>< / com:Math>; when X is <com:Math><semantics>−CR17<annotation encoding="application / x-tex">-CR_{17}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R17<annotation encoding="application / x-tex">R_{17}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, hydroxy, amino, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, alkenyl, alkynyl, alkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; or, R<com:Sub>17< / com:Sub> and any group of R<com:Sup>x< / com:Sup>, R<com:Sup>y< / com:Sup>, R<com:Sup>z< / com:Sup> and R<com:Sup>f< / com:Sup> can be bonded to form a cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>R<com:Sub>23< / com:Sub>, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>OR<com:Sub>23< / com:Sub>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23C(O)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}C(O)R_{24}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR23S(O)m1R24;<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}S(O)_{m1}R_{24};< / annotation>< / semantics>< / com:Math> <com:Math><semantics>R22<annotation encoding="application / x-tex">R_{22}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, <com:Math><semantics>−(CH2)n1R23<annotation encoding="application / x-tex">-(CH_2)_{n_1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n_1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23C(O)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}C(O)R_{24}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR23S(O)m1R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}S(O)_{m1}R_{24}< / annotation>< / semantics>< / com:Math>, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, <com:Math><semantics>−(CH2)n1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1C(O)R25,<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25},< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1C(O)OR25,<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{25},< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1S(O)m1R25,<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25},< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26}< / annotation>< / semantics>< / com:Math>; R<com:Sub>23< / com:Sub>, R<com:Sub>24< / com:Sub>, R<com:Sub>25< / com:Sub> and R<com:Sub>26< / com:Sub> are identical or different and are each independently selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, hydroxy, amino, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, alkenyl, alkynyl, alkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; m is an integer of 0, 1, 3, 4, 5, 6, 7, 8, 9 or 10; n is an integer of 0, 1, 2 or 3; o is an integer of 0, 1, 2, 3, 4 or 5; p is an integer of 0, 1, 2, 3, 4, 5 or 6; q is an integer of 0, 1, 2, 3, 4, 5 or 6; <com:Math><semantics>m1<annotation encoding="application / x-tex">m_1< / annotation>< / semantics>< / com:Math> is an integer of 0, 1 or 2; and <com:Math><semantics>n1<annotation encoding="application / x-tex">n_1< / annotation>< / semantics>< / com:Math> is an integer of 0, 1, 2, 3, 4 or 5. In a preferred embodiment of the present invention, the compound of formula (I) is a compound of formula (II), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Image disponible dans le document PDF, Image available in the PDF document] (11) wherein: [Image disponible dans le document PDF, Image available in the PDF document] Y is selected from the group consisting of > [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>R3a<annotation encoding="application / x-tex">R_{3a}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, thiol, nitro, hydroxy, cyano, alkenyl and alkynyl; R<com:Sub>5< / com:Sub> is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl and alkynyl; <com:Math><semantics>R15a<annotation encoding="application / x-tex">R_{15a}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl and alkynyl; <com:Math><semantics>R16a<annotation encoding="application / x-tex">R_{16a}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl and alkynyl; or, <com:Math><semantics>R15a<annotation encoding="application / x-tex">R_{15a}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R16a<annotation encoding="application / x-tex">R_{16a}< / annotation>< / semantics>< / com:Math> are bonded to form a cycloalkyl or heterocyclyl, wherein the resulting cycloalkyl or heterocyclyl is optionally further substituted by one or more substituents selected from the group consisting of hydrogen atom, deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl; R<com:Sub>19< / com:Sub> is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, thiol, hydroxy, cyano, alkenyl, alkynyl, hydroxyalkyl, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)(=NR23)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)(=NR_{23})R_{24}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>; or, R<com:Sub>5< / com:Sub> and R<com:Sub>19< / com:Sub> are bonded to form a cycloalkyl or heterocyclyl, wherein the resulting cycloalkyl or heterocyclyl is optionally further substituted by one or more substituents selected from the group consisting of hydrogen atom, deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl; <com:Math><semantics>R21<annotation encoding="application / x-tex">R_{21}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, <com:Math><semantics>−(CH2)n1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1C(O)NR23R24,<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24},< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1NR23C(O)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}C(O)R_{24}< / annotation>< / semantics>< / com:Math> and -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>NR<com:Sub>23< / com:Sub>S(O)<com:Sub>m1< / com:Sub>R<com:Sub>24< / com:Sub>, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>R<com:Sub>25< / com:Sub>, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>OR<com:Sub>25< / com:Sub>, <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26}< / annotation>< / semantics>< / com:Math>; R<com:Sub>23< / com:Sub>, R<com:Sub>24< / com:Sub>, R<com:Sub>25< / com:Sub> and R<com:Sub>26< / com:Sub> are identical or different and are each independently selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, hydroxy, amino, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, alkenyl, alkynyl, alkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; n is an integer of 1 or 2; <com:Math><semantics>m1<annotation encoding="application / x-tex">m_1< / annotation>< / semantics>< / com:Math> is an integer of 0, 1 or 2; and <com:Math><semantics>n1<annotation encoding="application / x-tex">n_1< / annotation>< / semantics>< / com:Math> is an integer of 0, 1, 2, 3, 4 or 5. In a preferred embodiment of the present invention, the compound of formula (II) is a compound of formula (III-A), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Image disponible dans le document PDF, Image available in the PDF document] (III -A) wherein: Z is selected from the group consisting of <com:Math><semantics>−CR23R24<annotation encoding="application / x-tex">-CR_{23}R_{24}< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−NR23<annotation encoding="application / x-tex">-NR_{23}< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−(CH2)n1O(CH2)n2<annotation encoding="application / x-tex">-(CH_2)_{n1}O(CH_2)_{n2}< / annotation>< / semantics>< / com:Math>- and -O-, and preferably methylene; ring C is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, <com:Math><semantics>−(CH2)n1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26}< / annotation>< / semantics>< / com:Math>; each R<com:Sub>c< / com:Sub> is identical or different and each is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, <com:Math><semantics>−(CH2)n1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)NR23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)NR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n_1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n_1}NR_{23}C(O)R_{23}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR23S(O)m1R24<annotation encoding="application / x-tex">-(CH_2)_{n_1}NR_{23}S(O)_{m_1}R_{24}< / annotation>< / semantics>< / com:Math>, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, <com:Math><semantics>−(CH2)n1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26}< / annotation>< / semantics>< / com:Math>; z is an integer of <com:Math><semantics>0,1,3,4<annotation encoding="application / x-tex">0, 1, 3, 4< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>5<annotation encoding="application / x-tex">5< / annotation>< / semantics>< / com:Math>; and R<com:Sub>3a< / com:Sub>, R<com:Sub>3b< / com:Sub>, R<com:Sub>5< / com:Sub>, R<com:Sub>19< / com:Sub>, R<com:Sub>23< / com:Sub>-R<com:Sub>26< / com:Sub>, n, m<com:Sub>1< / com:Sub> and n<com:Sub>1< / com:Sub> are as defined in the compound of formula <com:Math><semantics>(II)<annotation encoding="application / x-tex">(II)< / annotation>< / semantics>< / com:Math>. In a preferred embodiment of the present invention, the compound of formula (II), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof is a compound of formula (V-7) or (V-8), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Image disponible dans le document PDF, Image available in the PDF document] wherein: ring A is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, <com:Math><semantics>−(CH2)n1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26}< / annotation>< / semantics>< / com:Math>; each R<com:Sub>a< / com:Sub> is identical or different and each is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, <com:Math><semantics>−(CH2)n1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)NR23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)NR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n_1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n_1}NR_{23}C(O)R_{23}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR23S(O)m1R24<annotation encoding="application / x-tex">-(CH_2)_{n_1}NR_{23}S(O)_{m_1}R_{24}< / annotation>< / semantics>< / com:Math>, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, <com:Math><semantics>−(CH2)n1R25,<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{25},< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{25}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26}< / annotation>< / semantics>< / com:Math>; R<com:Sub>19< / com:Sub> is selected from the group consisting of hydrogen atom, alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, <com:Math><semantics>−(CH2)n1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)NR23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)NR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1C(O)NR23R24,<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24},< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1NR23C(O)R23,<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}C(O)R_{23},< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1S(O)(=NR23)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)(=NR_{23})R_{24}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR23S(O)m1R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}S(O)_{m1}R_{24}< / annotation>< / semantics>< / com:Math>, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, <com:Math><semantics>−(CH2)n1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>x<annotation encoding="application / x-tex">x< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>m1<annotation encoding="application / x-tex">m_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>n1<annotation encoding="application / x-tex">n_1< / annotation>< / semantics>< / com:Math> are as defined in formula (II). In a preferred embodiment of the present invention, the compound of formula (II) is a compound of formula (III-B), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Image disponible dans le document PDF, Image available in the PDF document] ( III-B) wherein: <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; <com:Math><semantics>R19<annotation encoding="application / x-tex">R_{19}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>Rc<annotation encoding="application / x-tex">R_c< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, cyano and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; z is an integer of 0, 1 or 2; and n is 0, 1 or 2. In a preferred embodiment of the present invention, the compound of formula (II), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof is a compound of formula (IV-A) or (IV-B), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Image disponible dans le document PDF, Image available in the PDF document] wherein: R<com:Sub>3a< / com:Sub> is selected from the group consisting of C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl and C<com:Sub>1-6< / com:Sub> alkoxy; <com:Math><semantics>R19<annotation encoding="application / x-tex">R_{19}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of cyano, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)(=NR23)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)(=NR_{23})R_{24}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(CH2)n1SR23;<annotation encoding="application / x-tex">(CH_2)_{n1}SR_{23};< / annotation>< / semantics>< / com:Math> R<com:Sub>a< / com:Sub> is selected from the group consisting of hydrogen atom, cyano, halogen, nitro, alkyl, alkoxy, haloalkyl, cycloalkyl, hydroxyalkyl, heterocyclyl, heteroaryl, - <com:Math><semantics>(CH2)n1CR23R24R25<annotation encoding="application / x-tex">(CH_2)_{n1}CR_{23}R_{24}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1<annotation encoding="application / x-tex">-(CH_2)_{n1}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(CH2)n1S(O)(=NR23)R24<annotation encoding="application / x-tex">(CH_2)_{n1}S(O)(=NR_{23})R_{24}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, wherein the alkyl, cycloalkyl, heterocyclyl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of hydrogen atom, alkyl, halogen, cyano, hydroxy, cycloalkyl, heterocyclyl and heteroaryl; x is an integer of 0, 1 or 2; and <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>m1<annotation encoding="application / x-tex">m_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>n1<annotation encoding="application / x-tex">n_1< / annotation>< / semantics>< / com:Math> are as defined in formula (II). In a preferred embodiment of the present invention, the compound of formula (II), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof is a compound of formula (VIII), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Image disponible dans le document PDF, Image available in the PDF document] wherein: ring A, Z, R<com:Sub>a< / com:Sub> and x are as defined in formula (III). In a preferred embodiment of the present invention, the compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof is a compound of formula (VI), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Image disponible dans le document PDF, Image available in the PDF document] wherein: Z is selected from the group consisting of -CR<com:Sub>23< / com:Sub>R<com:Sub>24< / com:Sub>-, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>NR<com:Sub>23< / com:Sub>-, - <com:Math><semantics>(CH2)n1O(CH2)n2<annotation encoding="application / x-tex">(CH_2)_{n1}O(CH_2)_{n2}< / annotation>< / semantics>< / com:Math>- and -O-, and preferably methylene; ring B is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, <com:Math><semantics>−(CH2)n1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR25<annotation encoding="application / x-tex">-(CH_2)_{n_1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n_1}S(O)_{m_1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n_1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n_1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n_1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n_1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n_1}NR_{25}S(O)_{m_1}R_{26}< / annotation>< / semantics>< / com:Math>; each R<com:Sub>b< / com:Sub> is identical or different and each is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, <com:Math><semantics>−(CH2)n1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)NR23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)NR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}C(O)R_{23}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR23S(O)m1R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}S(O)_{m1}R_{24}< / annotation>< / semantics>< / com:Math>, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, <com:Math><semantics>−(CH2)n1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CH2)n1C(O)OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26}< / annotation>< / semantics>< / com:Math>; and y is an integer of 0, 1, 2, 3 or 4. In a preferred embodiment of the present invention, the compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof is a compound of formula (VIII), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Image disponible dans le document PDF, Image available in the PDF document] wherein: <com:Math><semantics>R21<annotation encoding="application / x-tex">R_{21}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, <com:Math><semantics>−(CH2)n1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23C(O)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}C(O)R_{24}< / annotation>< / semantics>< / com:Math> and -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>NR<com:Sub>23< / com:Sub>S(O)<com:Sub>m1< / com:Sub>R<com:Sub>24< / com:Sub>, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>R<com:Sub>25< / com:Sub>, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>OR<com:Sub>25< / com:Sub>, - <com:Math><semantics>(CH2)n1SR25<annotation encoding="application / x-tex">(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and _ <com:Math><semantics>(CH2)n1NR25S(O)m1R26;<annotation encoding="application / x-tex">(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26};< / annotation>< / semantics>< / com:Math> <com:Math><semantics>R23<annotation encoding="application / x-tex">R_{23}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>R26<annotation encoding="application / x-tex">R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>m1<annotation encoding="application / x-tex">m_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>n1<annotation encoding="application / x-tex">n_1< / annotation>< / semantics>< / com:Math> are as defined in formula (I). In a preferred embodiment of the present invention, the compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof is a compound of formula (X), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Image disponible dans le document PDF, Image available in the PDF document] wherein: M is selected from the group consisting of <com:Math><semantics>−CR23<annotation encoding="application / x-tex">-CR_{23}< / annotation>< / semantics>< / com:Math>- and oxygen atom; w S Y is selected from the group consisting of -S(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>-. [Image disponible dans le document PDF, Image available in the PDF document] D <com:Math><semantics>R21<annotation encoding="application / x-tex">R_{21}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of hydrogen atom, deuterium atom, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>R<com:Sub>23< / com:Sub>, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n1< / com:Sub>OR<com:Sub>23< / com:Sub>, - <com:Math><semantics>(CH2)n1SR23<annotation encoding="application / x-tex">(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR23C(O)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}C(O)R_{24}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR23S(O)m1R24<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{23}S(O)_{m1}R_{24}< / annotation>< / semantics>< / com:Math>, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of deuterium atom, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxy, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, <com:Math><semantics>−(CH2)n1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1OR25<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR25<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R25<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(CH2)n1C(O)OR25<annotation encoding="application / x-tex">(CH_2)_{n1}C(O)OR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R25<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR25R26<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{25}R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(<annotation encoding="application / x-tex">-(< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(CH2)n1C(O)NHR25<annotation encoding="application / x-tex">(CH_2)_{n1}C(O)NHR_{25}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1NR25C(O)R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}C(O)R_{26}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1NR25S(O)m1R26<annotation encoding="application / x-tex">-(CH_2)_{n1}NR_{25}S(O)_{m1}R_{26}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R22<annotation encoding="application / x-tex">R_{22}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>R26<annotation encoding="application / x-tex">R_{26}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>m1<annotation encoding="application / x-tex">m_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>n1<annotation encoding="application / x-tex">n_1< / annotation>< / semantics>< / com:Math> are as defined in formula (I). In a preferred embodiment of the present invention, in the compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof, the ring A, B and C are each selected from the group consisting of: [Image disponible dans le document PDF, Image available in the PDF document] In a preferred embodiment of the present invention, the compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof, wherein R<com:Sub>a< / com:Sub>, R<com:Sub>b< / com:Sub> and R<com:Sub>c< / com:Sub> are each selected from the group consisting of hydrogen atom, cyano, halogen, nitro, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>2-6< / com:Sub> alkynyl, C<com:Sub>1-6< / com:Sub> alkoxy, C<com:Sub>1-6< / com:Sub> haloalkyl, C<com:Sub>3-6< / com:Sub> cycloalkyl, C<com:Sub>1-6< / com:Sub> hydroxyalkyl, 5 to 10 membered heterocyclyl, 5 to 10 membered heteroaryl, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)NR_{23}R_{24}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}C(O)OR_{23}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> hydroxyalkyl, 5 to 10 membered heterocyclyl and 5 to 10 membered heteroaryl are each optionally further substituted by one or more substituents selected from the group consisting of hydrogen atom, C<com:Sub>1-6< / com:Sub> alkyl, halogen, cyano, hydroxy, C<com:Sub>3-6< / com:Sub> cycloalkyl, C<com:Sub>1-6< / com:Sub> hydroxyalkyl, 5 to 10 membered heterocyclyl and 5 to 10 membered heteroaryl; <com:Math><semantics>R23<annotation encoding="application / x-tex">R_{23}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R24<annotation encoding="application / x-tex">R_{24}< / annotation>< / semantics>< / com:Math> are each independently selected from the group consisting of hydrogen atom, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl and 3 to 8 membered heterocyclyl. In a preferred embodiment of the present invention, the compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof, wherein: Z is selected from the group consisting of -CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>NH-, -CH<com:Sub>2< / com:Sub>O-, -CH<com:Sub>2< / com:Sub>-, -NH- and -NHSO<com:Sub>2< / com:Sub>-; <com:Math><semantics>R3a<annotation encoding="application / x-tex">R_{3a}< / annotation>< / semantics>< / com:Math> is selected from the group consisting of <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, preferably <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl and <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, and more preferably methyl and methoxymethyl; R<com:Sub>5< / com:Sub> is selected from the group consisting of hydrogen atom, halogen, cyano, C<com:Sub>1-6< / com:Sub> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, and preferably hydrogen atom and <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; R<com:Sub>19< / com:Sub> is selected from the group consisting of cyano, halogen, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)n1OR23<annotation encoding="application / x-tex">-(CH_2)_{n1}OR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)(=NR23)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)(=NR_{23})R_{24}< / annotation>< / semantics>< / com:Math> and -<com:Math><semantics>(CH2)n1SR23<annotation encoding="application / x-tex">(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, preferably cyano, halogen, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> haloalkyl, -<com:Math><semantics>(CH2)n1SR23<annotation encoding="application / x-tex">(CH_2)_{n1}SR_{23}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1S(O)m1R23<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)_{m1}R_{23}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−(CH2)n1S(O)(=NR23)R24<annotation encoding="application / x-tex">-(CH_2)_{n1}S(O)(=NR_{23})R_{24}< / annotation>< / semantics>< / com:Math>, and more preferably halogen; or, a C<com:Sub>3-6< / com:Sub> cycloalkyl, and preferably cyclopropyl can be formed between any two adjacent groups of R<com:Sub>5< / com:Sub> and R<com:Sub>19< / com:Sub>. In a preferred embodiment of the present invention, the compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof is selected from the group consisting of: [Image disponible dans le document PDF, Image available in the PDF document] ^ 15 [Image disponible dans le document PDF, Image available in the PDF document] J 4 10 1.7 [Image disponible dans le document PDF, Image available in the PDF document] ~ [Image disponible dans le document PDF, Image available in the PDF document] 3 3 [Image disponible dans le document PDF, Image available in the PDF document] . [Image disponible dans le document PDF, Image available in the PDF document] ~~ The present invention further relates to a pharmaceutical composition comprising a therapeutically effective amount of any compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents or excipients. The present invention further relates to a use of any compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprsing the same in the preparation of a GABA<com:Sub>A< / com:Sub> receptor regulator medicament. The present invention further relates to a use of the compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprsing the same in the preparation of a medicament for treating a Central Nervous System (CNS)-related disease, wherein the CNS-related disease is selected from the group consisting of sleep disorder, mood disorder, schizophrenia spectrum disorder, spasmodic disorder, memory disorder and / or cognitive disorder, dyskinesia, personality disorder, autism spectrum disorder, pain, traumatic brain injury, vascular disease, substance abuse disorder and / or withdrawal syndrome or tinnitus. The present invention further relates to the compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprsing the same for use in treating a CNS-related disease. The present invention also relates to a method for treating and / or preventing a CNS- related disease, comprising administrating to a patient a therapeutically effective amount of the compound of formula (I), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprsing the same. According to one particular aspect, the invention relates to a compound of formula (VIII), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Image disponible dans le document PDF, Image available in the PDF document] wherein: ring A is selected from the group consisting of 3 to 12 membered heterocyclyl wherein 1 to 4 atoms are heteroatoms, C6-14 aryl and 5 to 14 membered heteroaryl having 1 to 4 heteroatoms selected from the group consisting of O, S and N; Z is selected from the group consisting of -CR23R24-, -(CH2)n1NR23-, - (CH2)n1O(CH2)n2- and -O-; Ra is each selected from the group consisting of hydrogen atom, cyano, halogen, nitro, C1-6 alkyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 hydroxyalkyl, 5 to 10 membered heterocyclyl, 5 to 10 membered heteroaryl, - <com:Math><semantics>(CH2)n1OR23<annotation encoding="application / x-tex">(CH2)n1OR23< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1SR23<annotation encoding="application / x-tex">-(CH2)n1SR23< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)R23<annotation encoding="application / x-tex">-(CH2)n1C(O)R23< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n1C(O)NR23R24<annotation encoding="application / x-tex">-(CH2)n1C(O)NR23R24< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> (CH2)n1C(O)OR23 and -(CH2)n1S(O)m1R23; R23 and R24 are each independently selected from the group consisting of hydrogen atom, C1-6 alkyl and 3 to 8 membered heterocyclyl; x is an integer of 0, 1, 3, 4 or 5; m1 is an integer of 0, 1 or 2; n1 is an integer of 0, 1, 2, 3, 4 or 5; and n2 is an integer of 0, 1, 3, 4 or 5. According to another particular aspect, the invention relates to a pharmaceutical composition, comprising a therapeutically effective amount of a compound of formula (VIII), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof as defined herein, and one or more pharmaceutically acceptable carriers, diluents or excipients. According to another particular aspect, the invention relates to a the use of a compound of formula (VIII), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof as defined herein, or a pharmaceutical composition as defined herein, in the preparation of a GABAA receptor regulator medicament. According to another particular aspect, the invention relates to the use of a compound of formula (VIII), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof as defined herein, or a pharmaceutical composition as defined herein, in treating a CNS-related disease, wherein the CNS-related disease is selected from the group consisting of sleep disorder, mood disorder, schizophrenia spectrum disorder, spasmodic disorder, memory disorder and / or cognitive disorder, dyskinesia, personality disorder, autism spectrum disorder, pain, traumatic brain injury, vascular disease, substance abuse disorder and / or withdrawal syndrome or tinnitus. DEFINITIONS Unless otherwise stated, the terms used in the specification and claims have the meanings described below. The term "alkyl" refers to a saturated aliphatic hydrocarbon group, which is a straight or branched chain group comprising 1 to 20 carbon atoms, preferably an alkyl having 1 to 8 carbon atoms, more preferably an alkyl having 1 to 6 carbon atoms, and most preferably an alkyl having 1 to 3 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1- dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1- dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2- methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2- methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2,3-dimethylpentyl, 2,4- dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n- octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3- dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2- ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3- ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, and various branched isomers thereof. The alkyl group can be substituted or unsubstituted. When substituted, the substituent group(s) can be substituted at any available connection point. The substituent group(s) is preferably one or more groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocyclyloxy, cycloalkylthio, heterocyclylthio, oxo, carboxy and alkoxycarbonyl, and preferably methyl, ethyl, isopropyl, tert-butyl, haloalkyl, deuterated alkyl, alkoxy- substituted alkyl and hydroxy-substituted alkyl. The term "alkylene" refers to an alkyl of which a hydrogen atom is further substituted, for example, "methylene" refers to -CH<com:Sub>2< / com:Sub>-, "ethylene" refers to -(CH<com:Sub>2< / com:Sub>)<com:Sub>2< / com:Sub>-, "propylene" refers to <com:Math><semantics>−(CH2)3<annotation encoding="application / x-tex">-(CH_2)_3< / annotation>< / semantics>< / com:Math>-, "butylene" refers to <com:Math><semantics>−(CH2)4<annotation encoding="application / x-tex">-(CH_2)_4< / annotation>< / semantics>< / com:Math>- and the like. The term "alkenyl" refers to an alkyl as defined above that consists of at least two carbon atoms and at least one carbon-carbon double bond, for example, ethenyl, 1-propenyl, 2-propenyl, 1-, 2- or 3-butenyl and the like. The alkenyl group can be substituted or unsubstituted. When substituted, the substituent group(s) is preferably one or more groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocyclyloxy, cycloalkylthio and heterocyclylthio. The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent group having 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, and more preferably 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl and the like. Polycyclic cycloalkyl includes a cycloalkyl having a spiro ring, fused ring or bridged ring. The cycloalkyl is preferably cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl and cycloheptyl. The term "spiro cycloalkyl" refers to a 5 to 20 membered polycyclic group with individual rings connected through one shared carbon atom (called a spiro atom), wherein the rings can contain one or more double bonds, but none of the rings has a completely conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. The spiro cycloalkyl is preferably a 6 to 14 membered spiro cycloalkyl, and more preferably a 7 to 10 membered spiro cycloalkyl. According to the number of the spiro atoms shared between the rings, the spiro cycloalkyl can be divided into a mono-spiro cycloalkyl, a di-spiro cycloalkyl, or a poly-spiro cycloalkyl, and the spiro cycloalkyl is preferably a mono-spiro cycloalkyl or di-spiro cycloalkyl, and more preferably a 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered, or 5-membered / 6-membered mono-spiro cycloalkyl. Non-limiting examples of spiro cycloalkyl include: [Image disponible dans le document PDF, Image available in the PDF document] and also include spiro cycloalkyl in which a cycloalkyl and a heterocyclyl are connected through one spiro atom, non-limiting examples thereof include: [Image disponible dans le document PDF, Image available in the PDF document] The term "fused cycloalkyl" refers to a 5 to 20 membered all-carbon polycyclic group, wherein each ring in the system shares an adjacent pair of carbon atoms with another ring, wherein one or more rings can contain one or more double bonds, but none of the rings has a completely conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. The fused cycloalkyl is preferably a 6 to 14 membered fused cycloalkyl, and more preferably a 7 to 10 membered fused cycloalkyl. According to the number of membered rings, the fused cycloalkyl can be divided into a bicyclic, tricyclic, tetracyclic or polycyclic fused cycloalkyl, and the fused cycloalkyl is preferably a bicyclic or tricyclic fused cycloalkyl, and more preferably a 5-membered / 5-membered, or 5-membered / 6-membered bicyclic fused cycloalkyl. Non-limiting examples of fused cycloalkyl include: [Image disponible dans le document PDF, Image available in the PDF document] The term "bridged cycloalkyl" refers to a 5 to 20 membered all-carbon polycyclic group, wherein every two rings in the system share two disconnected carbon atoms, wherein the rings can have one or more double bonds, but none of the rings has a completely conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. The bridged cycloalkyl is preferably a 6 to 14 membered bridged cycloalkyl, and more preferably a 7 to 10 membered bridged cycloalkyl. According to the number of membered rings, the bridged cycloalkyl can be divided into a bicyclic, tricyclic, tetracyclic or polycyclic bridged cycloalkyl, and the bridged cycloalkyl is preferably a bicyclic, tricyclic or tetracyclic bridged cycloalkyl, and more preferably a bicyclic or tricyclic bridged cycloalkyl. Non-limiting examples of bridged cycloalkyl include: [Image disponible dans le document PDF, Image available in the PDF document] The cycloalkyl ring can be fused to the ring of aryl, heteroaryl or heterocyclyl, wherein the ring bound to the parent structure is cycloalkyl. Non-limiting examples include indanyl, tetrahydronaphthyl, benzocycloheptyl and the like. The cycloalkyl can be optionally substituted or unsubstituted. When substituted, the substituent group(s) is preferably one or more group(s) independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocyclylthio, oxo, carboxy and alkoxycarbonyl. The term "heterocyclyl" refers to a 3 to 20 membered saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent group, wherein one or more ring atoms are heteroatoms selected from the group consisting of N, O and S(O)<com:Sub>m< / com:Sub> (wherein m is an integer of 0 to 2), but excluding -O-O-, -O-S- or -S-S- in the ring, with the remaining ring atoms being carbon atoms. Preferably, the heterocyclyl has 3 to 12 ring atoms wherein 1 to 4 atoms are heteroatoms; more preferably, the heterocyclyl has 3 to 8 ring atoms; and most preferably 3 to 8 ring atoms. Non-limiting examples of monocyclic heterocyclyl include pyrrolidinyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothienyl, dihydroimidazolyl, dihydrofuryl, dihydropyrazolyl, dihydropyrrolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, pyranyl, 1,4-diazacyclyl and the like, and preferably tetrahydrofuranyl, pyrazolidinyl, morpholinyl, 1,4-diazacyclyl, piperazinyl and pyranyl. Polycyclic heterocyclyl includes a heterocyclyl having a spiro ring, fused ring or bridged ring. The heterocyclyl having a spiro ring, fused ring or bridged ring is optionally bonded to other group via a single bond, or further bonded to other cycloalkyl, heterocyclyl, aryl and heteroaryl via any two or more atoms on the ring. The term "spiro heterocyclyl" refers to a 5 to 20 membered polycyclic heterocyclyl group with individual rings connected through one shared atom (called a spiro atom), wherein one or more ring atoms are heteroatoms selected from the group consisting of N, O and <com:Math><semantics>S(O)m<annotation encoding="application / x-tex">S(O)_m< / annotation>< / semantics>< / com:Math> (wherein m is an integer of 0 to 2), with the remaining ring atoms being carbon atoms, where the rings can contain one or more double bonds, but none of the rings has a completely conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. The spiro heterocyclyl is preferably a 6 to 14 membered spiro heterocyclyl, and more preferably a 7 to 10 membered spiro heterocyclyl. According to the number of the spiro atoms shared between the rings, the spiro heterocyclyl can be divided into a mono-spiro heterocyclyl, di-spiro heterocyclyl, or poly-spiro heterocyclyl, and the spiro heterocyclyl is preferably a mono-spiro heterocyclyl or di-spiro heterocyclyl, and more preferably a 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered, or 5-membered / 6-membered mono-spiro heterocyclyl. Non-limiting examples of spiro heterocyclyl include: [Image disponible dans le document PDF, Image available in the PDF document] • The term "fused heterocyclyl" refers to a 5 to 20 membered polycyclic heterocyclyl group, wherein each ring in the system shares an adjacent pair of atoms with another ring, wherein one or more rings can contain one or more double bonds, but none of the rings has a completely conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system, and wherein one or more ring atoms are heteroatoms selected from the group consisting of N, O and S(O)<com:Sub>m< / com:Sub> (wherein m is an integer of 0 to 2), with the remaining ring atoms being carbon atoms. The fused heterocyclyl is preferably a 6 to 14 membered fused heterocyclyl, and more preferably a 7 to 10 membered fused heterocyclyl. According to the number of membered rings, the fused heterocyclyl can be divided into a bicyclic, tricyclic, tetracyclic or polycyclic fused heterocyclyl, and the fused heterocyclyl is preferably a bicyclic or tricyclic fused heterocyclyl, and more preferably a 5-membered / 5-membered or 5-membered / 6-membered bicyclic fused heterocyclyl. Non-limiting examples of fused heterocyclyl include: [Image disponible dans le document PDF, Image available in the PDF document] The term "bridged heterocyclyl" refers to a 5 to 14 membered polycyclic heterocyclyl group, wherein every two rings in the system share two disconnected atoms, wherein the rings can have one or more double bonds, but none of the rings has a completely conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system, and wherein one or more ring atoms are heteroatoms selected from the group consisting of N, O and S(O)<com:Sub>m< / com:Sub> (wherein m is an integer of 0 to 2), with the remaining ring atoms being carbon atoms. The bridged heterocyclyl is preferably a 6 to 14 membered bridged heterocyclyl, and more preferably a 7 to 10 membered bridged heterocyclyl. According to the number of membered rings, the bridged heterocyclyl can be divided into a bicyclic, tricyclic, tetracyclic or polycyclic bridged heterocyclyl, and the bridged heterocyclyl is preferably a bicyclic, tricyclic or tetracyclic bridged heterocyclyl, and more preferably a bicyclic or tricyclic bridged heterocyclyl. Non-limiting examples of bridged heterocyclyl include: [Image disponible dans le document PDF, Image available in the PDF document] • The heterocyclyl ring can be fused to the ring of aryl, heteroaryl or cycloalkyl, wherein the ring bound to the parent structure is heterocyclyl. Non-limiting examples thereof include: [Image disponible dans le document PDF, Image available in the PDF document] and the like. The heterocyclyl can be optionally substituted or unsubstituted. When substituted, the substituent group(s) is preferably one or more group(s) independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocyclylthio, oxo, carboxy and alkoxycarbonyl. The term "aryl" refers to a 6 to 14 membered all-carbon monocyclic ring or polycyclic fused ring (i.e. each ring in the system shares an adjacent pair of carbon atoms with another ring in the system) having a conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system, preferably a 6 to 10 membered aryl, for example, phenyl and naphthyl. The aryl is more preferably phenyl. The aryl ring can be fused to the ring of heteroaryl, heterocyclyl or cycloalkyl, wherein the ring bound to the parent structure is aryl ring. Non-limiting examples thereof include: [Image disponible dans le document PDF, Image available in the PDF document] The aryl can be substituted or unsubstituted. When substituted, the substituent group(s) is preferably one or more group(s) independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocyclylthio, carboxy and alkoxycarbonyl. The term "heteroaryl" refers to a 5 to 14 membered heteroaromatic system having 1 to 4 heteroatoms selected from the group consisting of O, S and N. The heteroaryl is preferably a 5 to 10 membered heteroaryl, and more preferably a 5 or 6 membered heteroaryl, for example imidazolyl, furyl, thienyl, thiazolyl, pyrazolyl, oxazolyl, pyrrolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, thiadiazolyl, pyrazinyl and the like, preferably triazolyl, tetrazolyl, thienyl, imidazolyl, pyrazolyl, pyridazinyl, pyrimidinyl, thiazolyl, oxazolyl, isoxazolyl or pyrimidinyl, and more preferably triazolyl, tetrazolyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, thiazolyl, oxazolyl, isoxazolyl or imidazolyl. The heteroaryl ring can be fused to the ring of aryl, heterocyclyl or cycloalkyl, wherein the ring bound to the parent structure is heteroaryl ring. Non-limiting examples thereof include: [Image disponible dans le document PDF, Image available in the PDF document] The heteroaryl can be optionally substituted or unsubstituted. When substituted, the substituent group(s) is preferably one or more group(s) independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocyclylthio, carboxy and alkoxycarbonyl. The term "alkoxy" refers to an -O-(alkyl) or an -O-(unsubstituted cycloalkyl) group, wherein the alkyl is as defined above. Non-limiting examples of alkoxy include methoxy, ethoxy, propoxy, butoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy. The alkoxy group can be optionally substituted or unsubstituted. When substituted, the substituent group(s) is preferably one or more group(s) independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocyclyloxy, cycloalkylthio, heterocyclylthio, carboxy and alkoxycarbonyl. "Haloalkyl" refers to an alkyl group substituted by one or more halogens, wherein the alkyl is as defined above. "Haloalkoxy" refers to an alkoxy group substituted by one or more halogens, wherein the alkoxy is as defined above. "Hydroxyalkyl" refers to an alkyl group substituted by hydroxy(s), wherein the alkyl is as defined above. "Alkenyl" refers to chain alkenyl, also known as alkene group. The alkenyl can be further substituted by other related group, for example alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocyclyloxy, cycloalkylthio, heterocyclylthio, carboxy or alkoxycarbonyl. "Alkynyl" refers to (CH=C-). The alkynyl can be further substituted by other related group, for example alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocyclyloxy, cycloalkylthio, heterocyclylthio, carboxy or alkoxycarbonyl. "Hydroxy" refers to an -OH group. "Halogen" refers to fluorine, chlorine, bromine or iodine. "Amino" refers to a -NH<com:Sub>2< / com:Sub> group. "Cyano" refers to a -CN group. "Nitro" refers to a -NO<com:Sub>2< / com:Sub> group. "Carboxy" refers to a -C(O)OH group. "THF" refers to tetrahydrofuran. "EtOAc" refers to ethyl acetate. "MeOH" refers to methanol. "DMF" refers to N,N-dimethylformamide. "DIPEA" refers to disopropylethylamine. "TFA" refers to trifluoroacetic acid. "MeCN" refers to acetonitrile. "DMA" refers to N,N-dimethylacetamide. "Et<com:Sub>2< / com:Sub>O" refers to diethyl ether. "DCE" refers to 1,2-dichloroethane. "DIPEA" refers to N,N-diisopropylethylamine. "NBS" refers to N-bromosuccinimide. "NIS" refers to N-iodosuccinimide. "Cbz-Cl" refers to benzyl chloroformate. "Pd<com:Sub>2< / com:Sub>(dba)<com:Sub>3< / com:Sub>" refers to tris(dibenzylideneacetone)dipalladium. "Dppf" refers to 1,1'-bisdiphenylphosphinoferrocene. "HATU" refers to 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate. "KHMDS" refers to potassium hexamethyldisilazide. "LiHMDS" refers to lithium bis(trimethylsilyl)amide. "MeLi" refers to methyl lithium. "n-BuLi" refers to n-butyl lithium. "NaBH(OAc)<com:Sub>3< / com:Sub>" refers to sodium triacetoxyborohydride. Different expressions such as "X is selected from the group consisting of A, B or C", "X is selected from the group consisting of A, B and C", "X is A, B or C", "X is A, B and C" and the like, express the same meaning, that is, X can be any one or more of A, B and C. The hydrogen atom of the present invention can be substituted by its isotope deuterium. Any of the hydrogen atoms in the compound of the examples of the present invention can also be substituted by deuterium atom. "Optional" or "optionally" means that the event or circumstance described subsequently can, but need not, occur, and such a description includes the situation in which the event or circumstance does or does not occur. For example, "the heterocyclyl optionally substituted by an alkyl" means that an alkyl group can be, but need not be, present, and such a description includes the situation of the heterocyclyl being substituted by an alkyl and the heterocyclyl being not substituted by an alkyl. "Substituted" refers to one or more hydrogen atoms in a group, preferably up to 5, more preferably 1 to 3 hydrogen atoms, independently substituted by a corresponding number of substituents. It goes without saying that the substituents only exist in their possible chemical position. The person skilled in the art is able to determine whether the substitution is possible or impossible by experiments or theory without excessive effort. For example, the combination of amino or hydroxy having free hydrogen and carbon atoms having unsaturated bonds (such as olefinic) may be unstable. A "pharmaceutical composition" refers to a mixture of one or more of the compounds according to the present invention or physiologically / pharmaceutically acceptable salts or prodrugs thereof with other chemical components, and other components such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of the pharmaceutical composition is to facilitate administration of a compound to an organism, which is conducive to the absorption of the active ingredient so as to show biological activity. A "pharmaceutically acceptable salt" refers to a salt of the compound of the present invention, which is safe and effective in mammals and has the desired biological activity. DETAILED DESCRIPTION OF THE INVENTION The present invention is further described in combination with the following examples, which are not intended to limit the scope of the present invention. EXAMPLES The structures of the compounds of the present invention were identified by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS). NMR chemical shifts (<com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math>) are given in parts per million (ppm). NMR was determined by a Bruker AVANCE-400 machine. The solvents for determination were deuterated-dimethyl sulfoxide (DMSO-<com:Math><semantics>d6<annotation encoding="application / x-tex">d_6< / annotation>< / semantics>< / com:Math>), deuterated-methanol (CD<com:Sub>3< / com:Sub>OD) and deuterated-chloroform (CDCl<com:Sub>3< / com:Sub>), and the internal standard was tetramethylsilane (TMS). Liquid chromatography-mass spectrometry (LC-MS) was determined on an Agilent 1200 Infinity Series mass spectrometer. High performance liquid chromatography (HPLC) was determined on an Agilent 1200DAD high pressure liquid chromatograph (Sunfire C18 150×4.6 mm chromatographic column), and a Waters 2695-2996 high pressure liquid chromatograph (Gimini C18 150×4.6 mm chromatographic column). Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plate was used as the thin-layer silica gel chromatography (TLC) plate. The dimension of the silica gel plate used in TLC was 0.15 mm to 0.2 mm, and the dimension of the silica gel plate used in product purification was 0.4 mm to 0.5 mm. Yantai Huanghai 200 to 300 mesh silica gel was generally used as a carrier for column chromatography. The starting materials used in the examples of the present invention are known and commercially available, or can be synthesized by adopting or according to known methods in the art. Unless otherwise stated, all reactions of the present invention were carried out under continuous magnetic stirring in a dry nitrogen or argon atmosphere, the solvent was dry, and the reaction temperature was in degrees Celsius. Example 1 1-((3R,5R,8S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro-1 H-cyclopenta[a]phenanthren-17-yl)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] Step 1: (8S,9S,10S,13S,14S)-10-Fluoro-13-methyl-7,8,9,10,11,12,13,14,15,16-decahydro-3H-c yclopenta[a]phenanthrene-3,17(6H)-dione [Image disponible dans le document PDF, Image available in the PDF document] (8R,9S,13S,14S)-3-Hydroxy-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H- cyclopenta[a]phenanthren-17-one (2.7 g, 10 mmol) and acetonitrile (100 mL) were added successively to a 100 mL three-necked flask, followed by the addition of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (3.6 g, 10 mmol) under stirring. The reaction solution was heated to 45°C in an oil bath, and reacted for 5 hours. The reaction solution was cooled to room temperature and concentrated. The resulting residue was dissolved in dichloromethane (100 mL), and washed with saturated saline (30 mL×3). The organic phase was dried over anhydrous sodium sulfate, filtrated and concentrated by rotary evaporation to dryness. The crude product was purified by column chromatography (petroleum ether / ethyl acetate: 3 / 1) to obtain (8S,9S,10S,13S,14S)-10-fluoro-13-methyl-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cy clopenta[a]phenanthrene-3,17(6H)-dione (1.8 g, light yellow solid, yield: 62.5%). <com:Math><semantics>MSm / z(ESI):289.1[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 289.1[M+H]^+< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.12-7.05 (m, 1 H), 6.30-6.19 (m, 1H), 6.04 (s, 1H), 2.70-2.60 (m, 1H), 2.52-2.45 (m, 2H), 2.16-1.86 (m, 7H), 1.65-1.18 (m, 5H), 0.98 (s, 3H). <com:Sup>19< / com:Sup>F NMR (376 MHz, CDCl<com:Sub>3< / com:Sub>) δ -165.20. Step 2: (5R,8S,9S,10R,13S,14S)-10-Fluoro-13-methyltetradecahydro-3H-cyclopenta[a]phenant hrene-3,17(2H)-dione [Image disponible dans le document PDF, Image available in the PDF document] (8S,9S,10S,13S,14S)-10-Fluoro-13-methyl-7,8,9,10,11,12,13,14,15,16-decahydro- 3H-cyclopenta[a]phenanthrene-3,17(6H)-dione (1.8 g, 6.25 mmol) was dissolved in ethanol (50 mL) in a 100 mL single-necked flask. After stirring at room temperature for 2-3 minutes, to the solution was added the catalyst Pd / barium sulfate (300 mg). After completion of the addition, the reaction solution was stirred at room temperature under a hydrogen atmosphere for 5 hours. The reaction solution was filtrated, and dissolved in 20 mL of dichloromethane to precipitate a white solid. The mixture was filtrated, and the filtrate was concentrated by rotary evaporation to dryness. The crude product was purified by column chromatography (petroleum ether / ethyl acetate: 3 / 1) to obtain (5R,8S,9S,10R,13S,14S)-10-fluoro-13-methyltetradecahydro-3H-cyclopenta[a]phenant hrene-3,17(2H)-dione (600 mg, white solid, yield: 32.9%). <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 2.63-2.45 (m, 2H), 2.43-2.33 (m, 3H), 2.30-1.80 (m, 8H),1.75-1.55 (m, 5H), 1.45-1.35 (m, 3H), 1.25-1.18 (m, 1H), 0.94 (s, 3H). <com:Sup>19< / com:Sup>F NMR (376 MHz, CDCl<com:Sub>3< / com:Sub>) δ -159.89. Step 3: (3R,5R,8S,10R,13S,14S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro-17H-cycl openta[a]phenanthren-17-one [Image disponible dans le document PDF, Image available in the PDF document] 2,6-Di-tert-butyl-4-methylphenol (1.45 g, 6.6 mmol) was dissolved in anhydrous toluene (15 mL) in a 100 mL three-necked flask. The solution was cooled to 0-5°C in an ice bath, and trimethylaluminum (1.7 mL, 2 M, 3.3 mmol) was added dropwise under a nitrogen atmosphere. After completion of the addition, the reaction solution was naturally warmed to room temperature, and stirred for 1 hour. The reaction solution was cooled to -78°C, and then a solution of (5R,8S,9S,10R,13S,14S)-10-fluoro-13-methyltetradecahydro-3H-cyclopenta[a]phenant hrene-3,17(2H)-dione (320 mg, 1.1 mmol) in toluene (5 mL) was added dropwise to the above reaction solution. The reaction solution was reacted at -78°C for 1 hour. After methylmagnesium bromide (1.0 mL, 3 M, 3 mmol) was added dropwise, the reaction solution was reacted at -78°C for 1 hour. The reaction was quenched with saturated aqueous ammonium chloride solution, and the reaction solution was extracted with ethyl acetate (20 mL) to precipitate a large amount of white solid. The mixture was filtrated, and the filtrate was separated into two phases. The organic phase was dried over anhydrous sodium sulfate, and concentrated by rotary evaporation to dryness. The resulting residue was purified by column chromatography (petroleum ether / ethyl acetate: <com:Math><semantics>2 / 1<annotation encoding="application / x-tex">2 / 1< / annotation>< / semantics>< / com:Math>) to obtain (3R,5R,8S,10R,13S,14S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro-17H-cyclo penta[a]phenanthren-17-one (250 mg, white solid, yield: 74.0%). <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 2.46 (dd, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 19.3, 8.7 Hz, 1H), 2.17 - 1.72 (m, 8H), 1.71 - 1.44 (m, 10H), 1.38 (s, 3H), 1.34 - 1.11 (m, 3H), 0.90 (s, 3H). <com:Sup>19< / com:Sup>F NMR (376 MHz, CDCl<com:Sub>3< / com:Sub>) δ -158.16. Step 4: (3R,5R,8S,10R,13S,14S)-17-Ethylidene-10-fluoro-3,13-dimethylhexadecahydro-1H-cy clopenta[a]phenanthren-3-ol [Image disponible dans le document PDF, Image available in the PDF document] Potassium tert-butoxide (500 mg, 4.5 mmol) and tetrahydrofuran (15 mL) were added successively to a 100 mL three-necked flask. The reaction solution was cooled to 0°C, and ethyltriphenylphosphine bromide (1.82 g, 4.8 mmol) was added in batches. The reaction solution was stirred at 60°C for 2 hours, and then (3R,5R,8S,10R,13S,14S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro-17H-cyclo penta[a]phenanthren-17-one (250 mg, 0.75 mmol) was added to the above reaction solution. The reaction solution was reacted at 60°C for 8 hours. The reaction was quenched with saturated ammonium chloride solution, and then the reaction solution was extracted with ethyl acetate (20 mL) and washed with saturated saline (10 mL×2). The organic phase was dried over anhydrous sodium sulfate, filtrated and concentrated by rotary evaporation to dryness. The resulting residue was purified by column chromatography (petroleum ether / ethyl acetate: 5 / 1) to obtain (3R,5R,8S,10R,13S,14S)-17-ethylidene-10-fluoro-3,13-dimethylhexadecahydro-1H-cyc lopenta[a]phenanthren-3-ol (110 mg, white solid, yield: 42%). <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 5.15-5.08 (m, 1H), 2.40-1.80 (m, 8H), 1.65 – 1.45 <com:Math><semantics>(m,13H),1.36(s,3H),1.31−1.05(m,4H),0.89(s,3H).<annotation encoding="application / x-tex">(m, 13H), 1.36 (s, 3H), 1.31 - 1.05 (m, 4H), 0.89 (s, 3H).< / annotation>< / semantics>< / com:Math> <com:Sup>19< / com:Sup>F NMR (376 MHz, CDCl<com:Sub>3< / com:Sub>) δ -157.91. Step 5: (3R,5R,8S,10R,13S,14S)-10-Fluoro-17-(1-hydroxyethyl)-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-3-ol [Image disponible dans le document PDF, Image available in the PDF document] (3R,5R,8S,10R,13S,14S)-17-Ethylidene-10-fluoro-3,13-dimethylhexadecahydro-1 H-cyclopenta[a]phenanthren-3-ol (110 mg, 0.35 mmol) was dissolved in dry tetrahydrofuran (5 mL). A complex of borane and tetrahydrofuran (1.1 mL, 1 M, 1.05 mmol) was added at room temperature. After completion of the addition, the reaction solution was stirred for 1 hour. The reaction solution was cooled in an ice-water bath, and NaOH (10%, 1.5 mL) was slowly added dropwise to produce a lot of gas. Hydrogen peroxide (30%, 2 mL) was slowly added dropwise, and the reaction solution was stirred at room temperature for 1 hour. The reaction solution was extracted with ethyl acetate (10 mL×2), and washed with 10% sodium thiosulfate solution. The organic phase was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain (3R,5R,8S,10R,13S,14S)-10-fluoro-17-(1-hydroxyethyl)-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-3-ol (100 mg, white solid). Step 6: 1-((3R,5R,8S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro-1 H-cyclopenta[a]phenanthren-17-yl)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] (3R,5R,8S,10R,13S,14S)-10-Fluoro-17-(1-hydroxyethyl)-3,13-dimethylhexadecah ydro-1H-cyclopenta[a]phenanthren-3-ol (100 mg, 0.3 mmol) was dissolved in dichloromethane (5 mL). Pyridinium chlorochromate (130 mg, 0.6 mmol) was added, and the reaction solution was stirred at room temperature for 12 hours. The reaction solution was filtrated and concentrated under reduced pressure. The resulting residue was purified by column chromatography (petroleum ether / ethyl acetate: 5 / 1) to obtain 1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro-1H -cyclopenta[a]phenanthren-17-yl)ethan-1-one (80 mg, white solid, yield: 81%). <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 2.53 (t, J = 9.0 Hz, 1H), 2.23-2.16 (m, 1H), 2.12 (s, 3H), 2.10 - 1.83 (m, 5H), 1.73 - 1.42 (m, 12H), 1.38 (s, 3H), 1.35 - 1.02 (m, 4H), 0.64 (s, 3H). Example 2 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-carbonitrile [Image disponible dans le document PDF, Image available in the PDF document] Step 1: 2-Bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] 1-((3R,5R,8S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydr o-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (80 mg, 0.25 mmol) was dissolved in methanol (5 mL). 3 Drops of hydrogen bromide and 3 drops of liquid bromine were added. After stirring at room temperature for 12 hours, the reaction solution was added to ice-water, and extracted with ethyl acetate (10 mL×2). The organic phase was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (80 mg, 81%), which was used directly in the next step. Step 2: 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-carbonitrile [Image disponible dans le document PDF, Image available in the PDF document] 2-Bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (80 mg, 0.2 mmol) was dissolved in tetrahydrofuran (5 mL). 4-Cyanopyrazole (46 mg, 0.5 mmol) and potassium carbonate (84 mg, 0.6 mmol) wer added, and the reaction solution was stirred at room temperature for 5 hours. The reaction solution was filtrated and concentrated, and the resulting residue was purified by prep-HPLC to obtain the product (25 mg, white solid, yield: 30.3%). <com:Math><semantics>MSm / z(ESI):428.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 428.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.87 (s, 1H), 7.81 (s, 1H), 5.10-4.83 (m, 2H), 2.60 (t, <com:Math><semantics>J=8.8 Hz<annotation encoding="application / x-tex">J = 8.8 \text{ Hz}< / annotation>< / semantics>< / com:Math>, 1H), 2.28-2.18 (m, 1H), 2.15-2.07 (m, 2H), 2.05 – 1.75 (m, 5H), 1.69 – 1.45 <com:Math><semantics>(m,10H),1.38(s,3H),1.35−1.23(m,3H),1.19−1.07(m,1H),0.70(s,3H).<annotation encoding="application / x-tex">(m, 10H), 1.38 (s, 3H), 1.35 - 1.23 (m, 3H), 1.19 - 1.07 (m, 1H), 0.70 (s, 3H).< / annotation>< / semantics>< / com:Math> <com:Sup>19< / com:Sup>F NMR (376 MHz, CDCl<com:Sub>3< / com:Sub>) δ -158.28. Example 3 and Example 4 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-3-carbonitrile (3) 1-(2-((3R,5R,8S,9S,10R,13S,14S,17R)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-3-carbonitrile (4) [Image disponible dans le document PDF, Image available in the PDF document] 2-Bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (80 mg, 0.2 mmol) was dissolved in tetrahydrofuran (5 mL). 3-Cyanopyrazole (46 mg, 0.5 mmol) and potassium carbonate (84 mg, 0.6 mmol) were added, and the reaction solution was stirred at room temperature for 5 hours. The reaction solution was filtrated and concentrated, and the resulting residue was purified by prep-HPLC to obtain the product 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahyd ro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-3-carbonitrile (3) (18 mg, white solid, yield: 21.9%) and the product 1-(2-((3R,5R,8S,9S,10R,13S,14S,17R)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-3-carbonitrile (4) (5) mg, white solid, yield: 6.0%). Example 3: <com:Math><semantics>MSm / z(ESI):428.1[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 428.1[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.50 (d, J = 2.4 Hz, 1H), 6.74 (d, J = 2.4 Hz, 1H), <com:Math><semantics>5.15−4.85<annotation encoding="application / x-tex">5.15-4.85< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.60<annotation encoding="application / x-tex">2.60< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.9<annotation encoding="application / x-tex">J = 8.9< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.26−2.16<annotation encoding="application / x-tex">2.26-2.16< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.05−1.90<annotation encoding="application / x-tex">2.05-1.90< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>1.85<annotation encoding="application / x-tex">1.85< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−1.73<annotation encoding="application / x-tex">-1.73< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>1.67−1.43<annotation encoding="application / x-tex">1.67 - 1.43< / annotation>< / semantics>< / com:Math> (m, 12H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.38−1.25<annotation encoding="application / x-tex">1.38 - 1.25< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>1.18−1.06<annotation encoding="application / x-tex">1.18 - 1.06< / annotation>< / semantics>< / com:Math> (m, 1H), 0.71 (s, 3H). <com:Sup>19< / com:Sup>F NMR (376 MHz, CDCl<com:Sub>3< / com:Sub>) δ -158.21. Example 4: <com:Math><semantics>MSm / z(ESI):428.1[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 428.1[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.50 (d, J =2.4 Hz, 1H), 6.76 (d, J =2.4 Hz, 1H), <com:Math><semantics>5.15−4.85<annotation encoding="application / x-tex">5.15-4.85< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.78<annotation encoding="application / x-tex">2.78< / annotation>< / semantics>< / com:Math> (dd, <com:Math><semantics>J=8.0,2.8<annotation encoding="application / x-tex">J = 8.0, 2.8< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.10−1.73<annotation encoding="application / x-tex">2.10-1.73< / annotation>< / semantics>< / com:Math> (m, 7H), <com:Math><semantics>1.70−1.36<annotation encoding="application / x-tex">1.70 - 1.36< / annotation>< / semantics>< / com:Math> (m, 11H), <com:Math><semantics>1.35<annotation encoding="application / x-tex">1.35< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.32−1.10<annotation encoding="application / x-tex">1.32 - 1.10< / annotation>< / semantics>< / com:Math>(m, 4H), <com:Math><semantics>0.98<annotation encoding="application / x-tex">0.98< / annotation>< / semantics>< / com:Math> (s, 3H). <com:Sup>19< / com:Sup>F NMR (376 MHz, CDCl<com:Sub>3< / com:Sub>) δ -158.42. Example 5 and Example 6 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(3-(trifluoromethyl)-1H-pyrazol-1-yl)ethan-1-o ne (5) 1-((3R,5R,8S,9S,10R,13S,14S,17R)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(3-(trifluoromethyl)-1H-pyrazol-1-yl)ethan-1-o ne (6) [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexad ecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the products 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(1H-tetrazol-1-yl)ethan-1-one (5) (35.5) mg, white solid, yield: 43%) and 1-((3R,5R,8S,9S,10R,13S,14S,17R)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(3-(trifluoromethyl)-1H-pyrazol-1-yl)ethan-1-o ne (6) (12.3 mg, white solid, yield: 14.9%) were obtained. Example 5: <com:Math><semantics>MSm / z(ESI):471.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 471.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.48 (s, 1H), 6.59 (d, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 2.1 Hz, 1H), 5.05-4.92 (m, 2H), 2.59 (t, <com:Math><semantics>J=8.8<annotation encoding="application / x-tex">J = 8.8< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.25-2.15 (m, 1H), 2.15-2.05 (m, 2H), 2.03 – 1.69 (m, 5H), <com:Math><semantics>1.70−1.41<annotation encoding="application / x-tex">1.70 - 1.41< / annotation>< / semantics>< / com:Math> (m, 12H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.06<annotation encoding="application / x-tex">1.06< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>0.71<annotation encoding="application / x-tex">0.71< / annotation>< / semantics>< / com:Math> (s, 3H). Example 6: <com:Math><semantics>MSm / z(ESI):471.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 471.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.48 (d, <com:Math><semantics>J=1.3<annotation encoding="application / x-tex">J = 1.3< / annotation>< / semantics>< / com:Math> Hz, 1H), 6.61 (d, <com:Math><semantics>J=2.3<annotation encoding="application / x-tex">J = 2.3< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>5.07−4.90<annotation encoding="application / x-tex">5.07-4.90< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.77<annotation encoding="application / x-tex">2.77< / annotation>< / semantics>< / com:Math> (dd, <com:Math><semantics>J=7.9<annotation encoding="application / x-tex">J = 7.9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>3.0<annotation encoding="application / x-tex">3.0< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.12−1.72<annotation encoding="application / x-tex">2.12 - 1.72< / annotation>< / semantics>< / com:Math> (m, 9H), <com:Math><semantics>1.72−1.38<annotation encoding="application / x-tex">1.72 - 1.38< / annotation>< / semantics>< / com:Math> (m, 11H), 1.34(s, 3H), 1.33-1.04(m, 4H), 0.96 (s, 3H). Example 7 and Example 8 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(trifluoromethyl)-1H-pyrazol-1-yl)ethan-1-o ne (7) 1-((3R,5R,8S,9S,10R,13S,14S,17R)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(trifluoromethyl)-1H-pyrazol-1-yl)ethan-1-o ne (8) [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(trifluoromethyl)-1H-pyrazol-1-yl)ethan-1-on e (22) mg, white solid, yield: 32.9%) and the product 1-((3R,5R,8S,9S,10R,13S,14S,17R)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(trifluoromethyl)-1H-pyrazol-1-yl)ethan-1-o ne (8) (8 mg, white solid, yield: 11.5%) were obtained. Example 7: <com:Math><semantics>MSm / z(ESI):471.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 471.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.72 (s, 2H), 5.05 – 4.85(m, 2H), 2.60 (t, J = 8.0 Hz, 1H), <com:Math><semantics>2.30−2.15<annotation encoding="application / x-tex">2.30-2.15< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.15−2.05<annotation encoding="application / x-tex">2.15-2.05< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.01−1.93<annotation encoding="application / x-tex">2.01-1.93< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>1.92−1.83<annotation encoding="application / x-tex">1.92-1.83< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>1.81−1.71<annotation encoding="application / x-tex">1.81 - 1.71< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>1.71−1.43<annotation encoding="application / x-tex">1.71 - 1.43< / annotation>< / semantics>< / com:Math> (m, 10H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.35−1.25<annotation encoding="application / x-tex">1.35 - 1.25< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>1.19−1.10<annotation encoding="application / x-tex">1.19 - 1.10< / annotation>< / semantics>< / com:Math> (m, 1H), 0.71 (s, 3H). <com:Sup>19< / com:Sup>F NMR (376 MHz, CDCl<com:Sub>3< / com:Sub>) δ -56.44, -158.26. Example 8: <com:Math><semantics>MSm / z(ESI):471.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 471.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.74 (s, 1H), 7.73 (s, 1H), 5.29 - 5.19 (m, 2H), 2.79 <com:Math><semantics>(dd,J=7.9,2.7Hz,1H),2.10−2.03(m,1H),1.95−1.75(m,6H),1.65−1.25(m,17H),<annotation encoding="application / x-tex">(dd, J = 7.9, 2.7 Hz, 1H), 2.10-2.03 (m, 1H), 1.95-1.75 (m, 6H), 1.65 - 1.25 (m, 17H),< / annotation>< / semantics>< / com:Math> <com:Math><semantics>1.19−1.10<annotation encoding="application / x-tex">1.19 - 1.10< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>0.98<annotation encoding="application / x-tex">0.98< / annotation>< / semantics>< / com:Math> (s, 3H). <com:Sup>19< / com:Sup>F NMR (376 MHz, CDCl<com:Sub>3< / com:Sub>) δ -56.42, -158.43. Example 9 and Example 10 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(1H-1,2,3-triazol-1-yl)ethan-1-one (9) 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(2H-1,2,3-triazol-2-yl)ethan-1-one (10) [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 6, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(1H-1,2,3-triazol-1-yl)ethan-1-one (9) (32 mg, white solid, yield: 32.9%) and the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(2H-1,2,3-triazol-2-yl)ethan-1-one (10) (20 mg, white solid, yield: 20.5%) were obtained. Example 9: <com:Math><semantics>MSm / z(ESI):404.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 404.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.76 (s, 1H), 7.65 (s, 1H), 5.30 - 5.13 (m, 2H), 2.65 <com:Math><semantics>(t,J=8.0 Hz,1H),2.25−2.15 (m, 1H),2.13−2.03 (m, 2H),2.05−1.75 (m, 5H),1.68−<annotation encoding="application / x-tex">(t, J = 8.0 \text{ Hz}, 1\text{H}), 2.25-2.15 \text{ (m, 1H)}, 2.13-2.03 \text{ (m, 2H)}, 2.05 - 1.75 \text{ (m, 5H)}, 1.68 -< / annotation>< / semantics>< / com:Math> <com:Math><semantics>1.43 (m, 10H),1.38 (s, 3H),1.35−1.25 (m, 3H),1.19−1.10 (m, 1H),0.71 (s, 3H).<annotation encoding="application / x-tex">1.43 \text{ (m, 10H)}, 1.38 \text{ (s, 3H)}, 1.35 - 1.25 \text{ (m, 3H)}, 1.19 - 1.10 \text{ (m, 1H)}, 0.71 \text{ (s, 3H)}.< / annotation>< / semantics>< / com:Math> <com:Sup>19< / com:Sup>F NMR (376 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> -158.26. Example 10: <com:Math><semantics>MSm / z(ESI):404.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 404.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.69 (s, 2H), 5.24 (s, 2H), 2.57 (t, J = 8.0 Hz, 1H), <com:Math><semantics>2.27−2.16<annotation encoding="application / x-tex">2.27-2.16< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.15−2.07<annotation encoding="application / x-tex">2.15-2.07< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.05−1.75<annotation encoding="application / x-tex">2.05-1.75< / annotation>< / semantics>< / com:Math> (m, 5H), <com:Math><semantics>1.68−1.43<annotation encoding="application / x-tex">1.68-1.43< / annotation>< / semantics>< / com:Math> (m, 10H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(s,3H),1.35−1.25(m,3H),1.19−1.05(m,1H),0.74(s,3H).<annotation encoding="application / x-tex">(s, 3H), 1.35 - 1.25 (m, 3H), 1.19 - 1.05 (m, 1H), 0.74 (s, 3H).< / annotation>< / semantics>< / com:Math> <com:Sup>19< / com:Sup>F NMR (376 MHz, CDCl<com:Sub>3< / com:Sub>) δ -158.24. Example 11 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4-methyl-1H-pyrazol-1-yl)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 8 of Example 6, 2-bromo-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexad ecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(4-methyl-1H-pyrazol-1-yl)ethan-1-one (11) (24) mg, white solid, yield: 29%) was obtained. <com:Math><semantics>MSm / z(ESI):417.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 417.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.35 (s, 1H), 7.18 (s, 1H), 4.90-4.79 (m, 2H), 2.56 (t, <com:Math><semantics>J=8.9 Hz<annotation encoding="application / x-tex">J = 8.9 \text{ Hz}< / annotation>< / semantics>< / com:Math>, 1H), 2.27-2.13 (m, 1H), 2.11 (s, 3H), 2.06-1.80 (m, 4H), 1.80-1.40 (m, 11H), 1.38 (s, 3H), 1.35-1.19 (m, 5H), 1.18 – 1.03 (m, 1H), 0.71 (s, 3H). Example 12 and Example 13 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(2H-tetrazol-2-yl)ethan-1-one (12) 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(1H-tetrazol-1-yl)ethan-1-one (13) [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] 12 In accordance with Step of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the products 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(2H-tetrazol-2-yl)ethan-1-one (12) (12) mg, white solid, yield: 16%) and 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(1H-tetrazol-1-yl)ethan-1-one (13) (9 mg, white solid, yield: 12%) were obtained. Example 12: <com:Math><semantics>MSm / z(ESI):405.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 405.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 8.57 (s, 1H), 5.46 (s, 2H), 2.64 (t, J = 8.0 Hz, 1H), <com:Math><semantics>2.28−2.19<annotation encoding="application / x-tex">2.28-2.19< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.18−2.07<annotation encoding="application / x-tex">2.18-2.07< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.05−1.75<annotation encoding="application / x-tex">2.05-1.75< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>1.71−1.43<annotation encoding="application / x-tex">1.71-1.43< / annotation>< / semantics>< / com:Math> (m, 11H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(s,3H),1.34−1.26(m,3H),1.21−1.11(m,1H),0.75(s,3H).<annotation encoding="application / x-tex">(s, 3H), 1.34 - 1.26 (m, 3H), 1.21 - 1.11 (m, 1H), 0.75 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 13: <com:Math><semantics>MSm / z(ESI):405.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 405.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 8.75 (s, 1H), 5.35 - 5.15 (m, 2H), 2.67 (t, J = 8.0 Hz, 1H), <com:Math><semantics>2.30−2.19<annotation encoding="application / x-tex">2.30-2.19< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.15−2.07<annotation encoding="application / x-tex">2.15-2.07< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.05−1.75<annotation encoding="application / x-tex">2.05-1.75< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>1.68−1.45<annotation encoding="application / x-tex">1.68-1.45< / annotation>< / semantics>< / com:Math> (m, 11H), <com:Math><semantics>1.39(s,3H),1.35−1.25(m,4H),1.20−1.10(m,1H),0.71(s,3H).<annotation encoding="application / x-tex">1.39 (s, 3H), 1.35 - 1.25 (m, 4H), 1.20 - 1.10 (m, 1H), 0.71 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 14 and Example 15 2-(2H-Benzo[d][1,2,3]triazol-2-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hyd roxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (15) 2-(1H-Benzo[d][1,2,3]triazol-1-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hyd roxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (16) [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 8 of Example 6, 2-bromo-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexad ecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the products 2-(2H-benzo[d][1,2,3]triazol-2-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hyd roxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (14) (11 mg, yield: 14%) and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hyd roxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (15) (31 mg, yield: 41%) were obtained. Example 14: <com:Math><semantics>MSm / z(ESI):453.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 453.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.88 (dd, <com:Math><semantics>J=6.6<annotation encoding="application / x-tex">J = 6.6< / annotation>< / semantics>< / com:Math>, 3.0 Hz, 2H), 7.40 (dd, <com:Math><semantics>J=6.6<annotation encoding="application / x-tex">J = 6.6< / annotation>< / semantics>< / com:Math>, 3.0 Hz, 2H), 5.53 (t, <com:Math><semantics>J=4.7<annotation encoding="application / x-tex">J = 4.7< / annotation>< / semantics>< / com:Math> Hz, 2H), 2.64 (t, <com:Math><semantics>J=8.9<annotation encoding="application / x-tex">J = 8.9< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.34 – 1.41 (m, 16H), 1.38 (s, 3H), <com:Math><semantics>1.35−0.97<annotation encoding="application / x-tex">1.35 - 0.97< / annotation>< / semantics>< / com:Math> (m, 6H), <com:Math><semantics>0.78<annotation encoding="application / x-tex">0.78< / annotation>< / semantics>< / com:Math> (s, 3H). Example 15: <com:Math><semantics>MSm / z(ESI):453.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 453.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 8.11 (d, <com:Math><semantics>J=7.5<annotation encoding="application / x-tex">J = 7.5< / annotation>< / semantics>< / com:Math> Hz, 1H), 7.50 (t, <com:Math><semantics>J=7.5<annotation encoding="application / x-tex">J = 7.5< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>7.46−7.30<annotation encoding="application / x-tex">7.46 - 7.30< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>5.42<annotation encoding="application / x-tex">5.42< / annotation>< / semantics>< / com:Math> (s, 2H), <com:Math><semantics>2.70<annotation encoding="application / x-tex">2.70< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.5<annotation encoding="application / x-tex">J = 8.5< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.35−1.42<annotation encoding="application / x-tex">2.35 - 1.42< / annotation>< / semantics>< / com:Math> (m, 16H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.35−1.01<annotation encoding="application / x-tex">1.35 - 1.01< / annotation>< / semantics>< / com:Math> (m, 6H), <com:Math><semantics>0.77<annotation encoding="application / x-tex">0.77< / annotation>< / semantics>< / com:Math> (s, 3H). Example 16 and Example 17 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(2H-pyrazolo[3,4-c]pyridin-2-yl)ethan-1-one (16) 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(1H-pyrazolo[3,4-c]pyridin-1-yl)ethan-1-one (17) [Image disponible dans le document PDF, Image available in the PDF document] 6, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the products 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(1H-tetrazol-1-yl)ethan-1-one (16) (9.2 mg, white solid, vield: 10.5%) and 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(2H-tetrazol-2-yl)ethan-1-one (17) (16 mg, white solid, yield: 18.3%) were obtained. Example 16: MS m / z (ESI): <com:Math><semantics>454.2[M+H]+<annotation encoding="application / x-tex">454.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 9.33 (s, 1H), 8.19 (s, 1H), 8.13 (s, 1H), 7.72 (s, 1H), <com:Math><semantics>5.42−5.25<annotation encoding="application / x-tex">5.42 - 5.25< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.70<annotation encoding="application / x-tex">2.70< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.0<annotation encoding="application / x-tex">J = 8.0< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.30−2.10<annotation encoding="application / x-tex">2.30 - 2.10< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>2.05−1.85<annotation encoding="application / x-tex">2.05 - 1.85< / annotation>< / semantics>< / com:Math> (m, 8H), <com:Math><semantics>1.70<annotation encoding="application / x-tex">1.70< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−1.45<annotation encoding="application / x-tex">-1.45< / annotation>< / semantics>< / com:Math> (m, 7H), <com:Math><semantics>1.39<annotation encoding="application / x-tex">1.39< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.32−1.25<annotation encoding="application / x-tex">1.32 - 1.25< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>0.90−0.85<annotation encoding="application / x-tex">0.90 - 0.85< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>0.75<annotation encoding="application / x-tex">0.75< / annotation>< / semantics>< / com:Math> (s, 3H). Example 17: <com:Math><semantics>MSm / z(ESI):454.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 454.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 8.88 (s, 1H), 8.36 (s, 1H), 8.13 (s, 1H), 7.71 (s, 1H), <com:Math><semantics>5.32−5.25<annotation encoding="application / x-tex">5.32 - 5.25< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.69<annotation encoding="application / x-tex">2.69< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.0<annotation encoding="application / x-tex">J = 8.0< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.25−2.10<annotation encoding="application / x-tex">2.25 - 2.10< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>2.05−1.75<annotation encoding="application / x-tex">2.05 - 1.75< / annotation>< / semantics>< / com:Math> (m, 5H), <com:Math><semantics>1.70<annotation encoding="application / x-tex">1.70< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−1.45<annotation encoding="application / x-tex">-1.45< / annotation>< / semantics>< / com:Math> (m, 10H), <com:Math><semantics>1.39<annotation encoding="application / x-tex">1.39< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.35−1.25<annotation encoding="application / x-tex">1.35 - 1.25< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>1.20−1.10<annotation encoding="application / x-tex">1.20 - 1.10< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>0.76<annotation encoding="application / x-tex">0.76< / annotation>< / semantics>< / com:Math> (s, 3H). Example 18, Example 19 and Example 20 2-(5-Fluoro-2H-benzo[d][1,2,3]triazol-2-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-flu oro-3-hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan- 1-one (18) 2-(6-Fluoro-1H-benzo[d][1,2,3]triazol-1-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-flu oro-3-hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan- 1-one (19) 2-(5-Fluoro-1H-benzo[d][1,2,3]triazol-1-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-flu oro-3-hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan- 1-one (20) [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, 2-(5-fluoro-2H-benzo[d][1,2,3]triazol-2-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluo ro-3-hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1 -one (18) (20) mg, white solid, yield: 14.9%), 2-(6-fluoro-1H-benzo[d][1,2,3]triazol-1-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluo ro-3-hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1 -one (19) (18) mg, white solid, yield: 13.1%) and 2-(5-fluoro-1H-benzo[d][1,2,3]triazol-1-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluo ro-3-hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1 -one (20) (19 mg, white solid, yield: 13.9%) were obtained. Example 18: MS m / z (ESI): <com:Math><semantics>472.3[M+H]+<annotation encoding="application / x-tex">472.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.86 (dd, J = 9.3, 4.7 Hz, 1H), 7.47 (dd, J = 8.7, 1.9) Hz, 1H), 7.21 (m, 1H), 5.55-5.45 (m, 2H), 2.65 (t, <com:Math><semantics>J=8.8Hz<annotation encoding="application / x-tex">J = 8.8 Hz< / annotation>< / semantics>< / com:Math>, 1H), 2.32 – 2.08 (m, 3H), <com:Math><semantics>2.04−1.45<annotation encoding="application / x-tex">2.04 - 1.45< / annotation>< / semantics>< / com:Math> (m, 15H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.35−1.23<annotation encoding="application / x-tex">1.35 - 1.23< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>1.20−1.10<annotation encoding="application / x-tex">1.20 - 1.10< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>0.78<annotation encoding="application / x-tex">0.78< / annotation>< / semantics>< / com:Math> (s, 3H). Example 19: <com:Math><semantics>MSm / z(ESI):472.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 472.3[M+H]^{+}< / annotation>< / semantics>< / com:Math> <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 8.04 (dd, J = 8.9, 4.4 Hz, 1H), 7.20-7.10 (m, 1H), <com:Math><semantics>6.99<annotation encoding="application / x-tex">6.99< / annotation>< / semantics>< / com:Math> (d, <com:Math><semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>5.45−5.35<annotation encoding="application / x-tex">5.45-5.35< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.69<annotation encoding="application / x-tex">2.69< / annotation>< / semantics>< / com:Math> (d, <com:Math><semantics>J=8.7<annotation encoding="application / x-tex">J = 8.7< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.31−2.08<annotation encoding="application / x-tex">2.31 - 2.08< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>2.04−1.45<annotation encoding="application / x-tex">2.04 - 1.45< / annotation>< / semantics>< / com:Math> (m, 15H), <com:Math><semantics>1.39<annotation encoding="application / x-tex">1.39< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.35−1.25<annotation encoding="application / x-tex">1.35-1.25< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>1.20−1.10<annotation encoding="application / x-tex">1.20-1.10< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>0.76<annotation encoding="application / x-tex">0.76< / annotation>< / semantics>< / com:Math> (s, 3H). Example 20: <com:Math><semantics>MSm / z(ESI):472.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 472.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.71 (d, J = 7.9 Hz, 1H), 7.35-7.28 (m, 2H), <com:Math><semantics>5.45−5.35<annotation encoding="application / x-tex">5.45-5.35< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.69<annotation encoding="application / x-tex">2.69< / annotation>< / semantics>< / com:Math> (d, <com:Math><semantics>J=8.7<annotation encoding="application / x-tex">J = 8.7< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.31−2.08<annotation encoding="application / x-tex">2.31 - 2.08< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>2.04−1.45<annotation encoding="application / x-tex">2.04 - 1.45< / annotation>< / semantics>< / com:Math> (m, 15H), 1.39 (s, 3H), 1.35-1.25 (m, 3H), 1.20-1.10 (m, 1H), 0.76 (s, 3H). Example 21 and Example 22 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4,5,6,7-tetrahydro-2H-indazol-2-yl)ethan-1-on e (21) 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4,5,6,7-tetrahydro-1H-indazol-1-yl)ethan-1-on e (22) [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 6, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(4,5,6,7-tetrahydro-2H-indazol-2-yl)ethan-1-one (21) (15.0) mg, white solid, yield: 27.2%) and 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(4,5,6,7-tetrahydro-1H-indazol-1-yl)ethan-1-one (22) (8.0 mg, white solid, yield: 12.1%) were obtained. Example 21: <com:Math><semantics>MSm / z(ESI):457.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 457.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.10 (s, 1H), 4.90 – 4.85 (m, 2H), 2.72-2.66 (m, 2H), <com:Math><semantics>2.62−2.52<annotation encoding="application / x-tex">2.62-2.52< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>2.25−1.40<annotation encoding="application / x-tex">2.25-1.40< / annotation>< / semantics>< / com:Math> (m, 22H), <com:Math><semantics>1.37<annotation encoding="application / x-tex">1.37< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.33−1.23<annotation encoding="application / x-tex">1.33-1.23< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>1.17−1.07<annotation encoding="application / x-tex">1.17-1.07< / annotation>< / semantics>< / com:Math> (m, 1H), 0.71 (s, 3H). Example 22: <com:Math><semantics>MSm / z(ESI):457.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 457.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.31 (s, 1H), 4.85 – 4.75 (m, 2H), 2.60-2.50 (m, 3H), 2.45-2.39 (m, 2H), 2.25-1.40 (m, 22H), 1.37 (s, 3H), 1.33 – 1.23 (m, 3H), 1.15-1.05 (m, 1H), 0.71 (s, 3H). Example 23 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-((4-fluorophenyl)amino)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] 2-Bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (80 mg, 0.2 mmol) was dissolved in tetrahydrofuran (5 mL). 4-Fluoroaniline (42 mg, 0.4 mmol) and triethylamine (60 mg, 0.6 mmol) were added, and the reaction solution was stirred at room temperature for 5 hours. The reaction solution was concentrated, and the resulting residue was purified by prep-HPLC to obtain the product (18 mg, white solid, yield: 21%). <com:Math><semantics>MSm / z(ESI):446.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 446.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 6.94-6.88 (m, 2H), 6.58 – 6.53(m, 2H), 3.96 – <com:Math><semantics>3.85(m,2H),2.57(t,J=8.0Hz,1H),2.30−2.20(m,1H),2.15−2.06(m,1H),2.05−1.71<annotation encoding="application / x-tex">3.85(m, 2H), 2.57(t, J = 8.0 Hz, 1H), 2.30-2.20(m, 1H), 2.15-2.06(m, 1H), 2.05 - 1.71< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(m,6H),1.68−1.43(m,10H),1.38(s,3H),1.34−1.20(m,3H),1.18−1.07(m,1H),<annotation encoding="application / x-tex">(m, 6H), 1.68 - 1.43 (m, 10H), 1.38 (s, 3H), 1.34 - 1.20 (m, 3H), 1.18 - 1.07 (m, 1H),< / annotation>< / semantics>< / com:Math> <com:Math><semantics>0.68<annotation encoding="application / x-tex">0.68< / annotation>< / semantics>< / com:Math> (s, <com:Math><semantics>3H<annotation encoding="application / x-tex">3H< / annotation>< / semantics>< / com:Math>). Example 24 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-((2-fluorophenyl)amino)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Example 23, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-((2-fluorophenyl)amino)ethan-1-one (11 mg, white solid, yield: 20.5%) was obtained. <com:Math><semantics>MSm / z(ESI):446.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 446.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.04 – 6.92 (m, 2H), 6.71 – 6.61 (m, 1H), 6.60 – <com:Math><semantics>6.52<annotation encoding="application / x-tex">6.52< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>4.03−3.86<annotation encoding="application / x-tex">4.03 - 3.86< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.58<annotation encoding="application / x-tex">2.58< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.8<annotation encoding="application / x-tex">J = 8.8< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.33−1.44<annotation encoding="application / x-tex">2.33 - 1.44< / annotation>< / semantics>< / com:Math> (m, 18H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(s,3H),1.33−1.05(m,4H),0.69(s,3H).<annotation encoding="application / x-tex">(s, 3H), 1.33 - 1.05 (m, 4H), 0.69 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 25 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-((3-fluorophenyl)amino)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Example 23, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-((3-fluorophenyl)amino)ethan-1-one <com:Math><semantics>(4.5mg)<annotation encoding="application / x-tex">(4.5 \mathrm{mg})< / annotation>< / semantics>< / com:Math> white solid, yield: 7.0%) was obtained. <com:Math><semantics>MSm / z(ESI):446.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 446.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.15 – 7.07 (m, 1H), 6.51 – 6.38 (m, 2H), 6.30 (d, J = 11.4 Hz, 1H), <com:Math><semantics>3.98−3.85<annotation encoding="application / x-tex">3.98 - 3.85< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.57<annotation encoding="application / x-tex">2.57< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.8<annotation encoding="application / x-tex">J = 8.8< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.12−1.64<annotation encoding="application / x-tex">2.12 - 1.64< / annotation>< / semantics>< / com:Math> (m, 18H), <com:Math><semantics>1.38(s,3H),1.30−1.26(m,3H),1.18−1.11(m,1H),0.68(s,3H).<annotation encoding="application / x-tex">1.38 (s, 3H), 1.30 - 1.26 (m, 3H), 1.18 - 1.11 (m, 1H), 0.68 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 26 2-((2,4-Difluorophenyl)amino)-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3 13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] 2-Bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (80 mg, 0.193 mmol) was dissolved in tetrahydrofuran (3 mL). 2,4-Difluoroaniline (37 mg, 0.289 mmol) and potassium carbonate (53 mg, 0.438 mmol) were added, and the reaction solution was stirred at room temperature for 16 hours. Water (15 mL) was added, and the reaction solution was extracted with ethyl acetate (20 mL×3). The organic phases were combined, washed with saturated saline (15 mL), dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative chromatography to obtain a white solid, 2-((2,4-difluorophenyl)amino)-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3, 13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (7 mg, yield: 7.8%). <com:Math><semantics>MSm / z(ESI):464.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 464.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 6.84 – 6.70 (m, 2H), 6.50-6.45 (m, 1H), 3.98-3.88 <com:Math><semantics>(m,2H),2.57(t,J=8.9Hz,1H),2.31−2.19(m,1H),2.10(m,1H),2.04−1.74(m,1H)<annotation encoding="application / x-tex">(m, 2H), 2.57 (t, J = 8.9 Hz, 1H), 2.31 - 2.19 (m, 1H), 2.10 (m, 1H), 2.04 - 1.74 (m, 1H)< / annotation>< / semantics>< / com:Math> 7H), <com:Math><semantics>1.51−1.44<annotation encoding="application / x-tex">1.51 - 1.44< / annotation>< / semantics>< / com:Math> (m, 5H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.37−1.20<annotation encoding="application / x-tex">1.37 - 1.20< / annotation>< / semantics>< / com:Math> (m, 8H), <com:Math><semantics>1.13<annotation encoding="application / x-tex">1.13< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>0.69<annotation encoding="application / x-tex">0.69< / annotation>< / semantics>< / com:Math> (s, 3H). Example 27 5-Fluoro-2-((2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhe xadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)amino)benzonitrile [Image disponible dans le document PDF, Image available in the PDF document] 6m ł 2-Amino-5-fluorobenzonitrile (147 mg, 1.08 mmol) was dissolved in tetrahydrofuran (5 mL) at 0°C. Sodium hydride (29 mg, 0.72 mmol) was added, and the reaction solution was stirred at 0°C for 40 minutes. A mixed solution of 2-bromo-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexad ecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (150 mg, 0.36 mmol) and tetrahydrofuran (2 mL) was added, and the reaction solution was stirred at 0°C for 30 minutes. Water (20 mL) was added, and the reaction solution was extracted with ethyl acetate (20 mL×3). The organic phases were combined, washed with saturated saline (30 mL), dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness, and the resulting residue was purified by preparative chromatography to obtain 5-fluoro-2-((2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhe xadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)amino)benzonitrile (10) mg, white solid, yield: 6%). <com:Math><semantics>MSm / z(ESI):471.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 471.2 [M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.62 (dd, <com:Math><semantics>J=9.6<annotation encoding="application / x-tex">J = 9.6< / annotation>< / semantics>< / com:Math>, 3.0 Hz, 1H), 7.10 – 7.01 (m, 1H), <com:Math><semantics>6.62 (dd, J=9.1,4.5 Hz, 1H),4.90−4.73 (m, 2H),2.58 (t, J=8.8 Hz, 1H),2.28−1.78<annotation encoding="application / x-tex">6.62 \text{ (dd, } J = 9.1, 4.5 \text{ Hz, 1H)}, 4.90 - 4.73 \text{ (m, 2H)}, 2.58 \text{ (t, } J = 8.8 \text{ Hz, 1H)}, 2.28-1.78< / annotation>< / semantics>< / com:Math> (m, 9H), 1.65-1.58 (m, 3H), 1.61-1.44 (m, 4H), 1.38(s, 3H), 1.31-1.26 (m, 4H), 1.15-1.09 (m, 2H), 0.90-0.86 (m, 2H), 0.73 (s, 3H). Example 28 1-((3S,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-((3-fluoropyridin-4-yl)amino)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] 4-Amino-3-fluoropyridine (32.4) mg, 0.28 mmol) and 2-bromo-1-((3S,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexad ecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (60 mg, 0.14 mmol) were dissolved in N,N-dimethylformamide (5 mL). Triethylamine (42.5 mg, 0.42 mmol) was added, and the reaction solution was stirred at room temperature overnight. 5 mL of water was added, and the reaction solution was extracted with ethyl acetate (30 mL×3). The organic phase was washed with saturated saline (20 mL) once, dried over anhydrous sodium sulfate and concentrated by rotary evaporation to dryness. The resulting residue was purified by prep-HPLC to obtain the product 1-((3S,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-((3-fluoropyridin-4-yl)amino)ethan-1-one (6.1mg, white solid, yield: 9.7%). <com:Math><semantics>MSm / z(ESI):447.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 447.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. Example 29 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(pyridazin-4-yloxy)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(pyridazin-4-yloxy)ethan-1-one (19 mg, white solid, yield 30.5%) was obtained. MS m / z (ESI): <com:Math><semantics>431.2[M+H]+<annotation encoding="application / x-tex">431.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.92 (s, 1H), 7.72 (s, 1H), 6.60 (s, 1H), 4.99 – 4.73 <com:Math><semantics>(m,2H),2.67−2.54(m,1H),2.32−1.49(m,18H),1.38(s,3H),1.31−1.01(m,4H),<annotation encoding="application / x-tex">(m, 2H), 2.67 - 2.54 (m, 1H), 2.32 - 1.49 (m, 18H), 1.38 (s, 3H), 1.31 - 1.01 (m, 4H),< / annotation>< / semantics>< / com:Math> <com:Math><semantics>0.71<annotation encoding="application / x-tex">0.71< / annotation>< / semantics>< / com:Math> (s, <com:Math><semantics>3H<annotation encoding="application / x-tex">3H< / annotation>< / semantics>< / com:Math>). Example 30 and Example 32 5-Fluoro-2-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile (30) 5-Fluoro-2-(2-((3R,5R,8S,9S,10R,13S,14S,17R)-10-fluoro-3-hydroxy-3,13-dimethylhe xadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile (32) [Image disponible dans le document PDF, Image available in the PDF document] Br CN K<com:Sub>2< / com:Sub>CO<com:Sub>3< / com:Sub> THF H Н Ĥ HO HO 30 In accordance with Step of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the products 5-fluoro-2-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile (30) (14.5 mg, white solid, yield: 21.2%) and 5-fluoro-2-(2-((3R,5R,8S,9S,10R,13S,14S,17R)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile (32) (13.5 mg, white solid, yield: 19.8%) were obtained. Example 30: <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.31 (dd, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 7.4, 3.1 Hz, 1H), 7.25 – 7.18 (m, 1H), <com:Math><semantics>6.74 (dd, J=9.3,4.0 Hz, 1H),4.69−4.53 (m, 2H),2.90 (t, J=8.7 Hz, 1H),2.32−1.43<annotation encoding="application / x-tex">6.74 \text{ (dd, } J = 9.3, 4.0 \text{ Hz, } 1\text{H}), 4.69 - 4.53 \text{ (m, } 2\text{H}), 2.90 \text{ (t, } J = 8.7 \text{ Hz, } 1\text{H}), 2.32 - 1.43< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(m,18H),1.37(s,3H),1.31−1.03(m,4H),0.70(s,3H).<annotation encoding="application / x-tex">(m, 18H), 1.37 (s, 3H), 1.31 - 1.03 (m, 4H), 0.70 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 32: <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.37 – 7.32 (m, 1H), 7.25 – 7.17 (m, 2H), 5.67 – 5.40 (m, 2H), 3.40 (t, <com:Math><semantics>J=8.9<annotation encoding="application / x-tex">J = 8.9< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.44 – 1.08 (m, 25H), 0.73 (s, 3H). Example 31 3-Fluoro-4-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 3-fluoro-4-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile (13 mg, white solid, yield 19.0%) was obtained. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.50 – 7.34 (m, 2H), 6.86 (t, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 8.4 Hz, 1H), 4.76 – 4.59 (m, 2H), 2.79 (t, <com:Math><semantics>J=8.9<annotation encoding="application / x-tex">J = 8.9< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.29 – 1.42 (m, 17H), 1.38 (s, 3H), 1.34 – 1.07 (m, 5H), 0.70 (s, 3H). Example 33 4-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 4-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahyd ro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile (27.5mg, white solid, yield: 41.9%) was obtained. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.60 (d, <com:Math><semantics>J=8.8<annotation encoding="application / x-tex">J = 8.8< / annotation>< / semantics>< / com:Math> Hz, 2H), 6.92 (d, <com:Math><semantics>J=8.8<annotation encoding="application / x-tex">J = 8.8< / annotation>< / semantics>< / com:Math> Hz, 2H), <com:Math><semantics>4.65−4.52<annotation encoding="application / x-tex">4.65 - 4.52< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.77<annotation encoding="application / x-tex">2.77< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.7<annotation encoding="application / x-tex">J = 8.7< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.24−1.49<annotation encoding="application / x-tex">2.24 - 1.49< / annotation>< / semantics>< / com:Math> (m, 18H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.32<annotation encoding="application / x-tex">1.32< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−1.25<annotation encoding="application / x-tex">-1.25< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>1.18−1.06<annotation encoding="application / x-tex">1.18-1.06< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>0.71<annotation encoding="application / x-tex">0.71< / annotation>< / semantics>< / com:Math> (s, 3H). Example 34 4-Fluoro-3-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 4-fluoro-3-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile (32) mg, white solid, yield: 46.9%) was obtained. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.36 – 7.27 (m, 1H), 7.20 (dd, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 10.6, 8.4 Hz, 1H), 7.11 (dd, <com:Math><semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics>< / com:Math>, 1.9 Hz, 1H), <com:Math><semantics>4.76−4.51<annotation encoding="application / x-tex">4.76 - 4.51< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.77<annotation encoding="application / x-tex">2.77< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.9<annotation encoding="application / x-tex">J = 8.9< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.24−1.51<annotation encoding="application / x-tex">2.24 - 1.51< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(m,18H),1.38(s,3H),1.32−1.23(m,3H),1.19−1.06(m,1H),0.71(s,3H).<annotation encoding="application / x-tex">(m, 18H), 1.38 (s, 3H), 1.32 - 1.23 (m, 3H), 1.19 - 1.06 (m, 1H), 0.71 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 35 2-Fluoro-4-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 2-fluoro-4-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)benzonitrile (23 mg, white solid, yield: 33.7%) was obtained. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.36 – 7.27 (m, 1H), 7.20 (dd, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 10.6, 8.4 Hz, 1H), 7.11 (dd, <com:Math><semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics>< / com:Math>, 1.9 Hz, 1H), <com:Math><semantics>4.76−4.51<annotation encoding="application / x-tex">4.76 - 4.51< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.77<annotation encoding="application / x-tex">2.77< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.9<annotation encoding="application / x-tex">J = 8.9< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.24−1.51<annotation encoding="application / x-tex">2.24 - 1.51< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(m,18H),1.38(s,3H),1.32−1.23(m,3H),1.19−1.06(m,1H),0.71(s,3H).<annotation encoding="application / x-tex">(m, 18H), 1.38 (s, 3H), 1.32 - 1.23 (m, 3H), 1.19 - 1.06 (m, 1H), 0.71 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 36 2-(2,4-Difluorophenoxy)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13 -dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8R,9R,10S,13S,14S,15R,17S)-3-hydroxy-3,13,15-trimethylhexadec ahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 2-(2,4-difluorophenoxy)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13 -dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (16.4 mg, white solid, yield: 24.4%) was obtained. <com:Sup>1< / com:Sup>H NMR (400 MHz, Chloroform-d) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 6.95 – 6.83 (m, 2H), 6.82 – 6.69 (m, 1H), <com:Math><semantics>4.67−4.45<annotation encoding="application / x-tex">4.67 - 4.45< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.81<annotation encoding="application / x-tex">2.81< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.8<annotation encoding="application / x-tex">J = 8.8< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.36−2.16<annotation encoding="application / x-tex">2.36 - 2.16< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.14−2.04<annotation encoding="application / x-tex">2.14 - 2.04< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.03−1.78<annotation encoding="application / x-tex">2.03 - 1.78< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>1.76−1.69<annotation encoding="application / x-tex">1.76 - 1.69< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>1.65−1.44<annotation encoding="application / x-tex">1.65 - 1.44< / annotation>< / semantics>< / com:Math> (m, 11H), <com:Math><semantics>1.37<annotation encoding="application / x-tex">1.37< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.32−1.78<annotation encoding="application / x-tex">1.32 - 1.78< / annotation>< / semantics>< / com:Math> <com:Math><semantics>1.21 (m, 3H),1.19−0.99 (m, 1H),0.69 (s, 3H).<annotation encoding="application / x-tex">1.21 \text{ (m, 3H)}, 1.19 - 0.99 \text{ (m, 1H)}, 0.69 \text{ (s, 3H)}.< / annotation>< / semantics>< / com:Math> Example 37 2-(4-Chloro-1H-pyrazol-1-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy -3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 2-(4-chloro-1H-pyrazol-1-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy- 3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (22 mg, white solid, yield: 34.9%) was obtained. <com:Math><semantics>MSm / z(ESI):437.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 437.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.46 (s, 1H), 7.42 (s, 1H), 5.04–4.62 (m, 2H), 2.57 <com:Math><semantics>(t,J=8.8 Hz,1H),2.31−1.45 (m, 18H),1.38 (s, 3H),1.33−1.23 (m, 3H),1.18−1.05 (m, 18Hz)<annotation encoding="application / x-tex">(t, J = 8.8 \text{ Hz}, 1\text{H}), 2.31-1.45 \text{ (m, } 18\text{H}), 1.38 \text{ (s, } 3\text{H}), 1.33-1.23 \text{ (m, } 3\text{H}), 1.18-1.05 \text{ (m, } 18\text{Hz})< / annotation>< / semantics>< / com:Math> 1H), 0.70 (s, 3H). Example 38 and Example 39 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-3-methyl-1H-pyrazole-4-carbonitr ile (38) 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-5-methyl-1H-pyrazole-4-carbonitr ile (39) [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the products 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahyd ro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-3-methyl-1H-pyrazole-4-carbonitri 1e (38) <com:Math><semantics>(16.5mg)<annotation encoding="application / x-tex">(16.5 \mathrm{mg})< / annotation>< / semantics>< / com:Math> white solid, yield: 19.5%) and 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahyd ro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-5-methyl-1H-pyrazole-4-carbonitri le (39) (9.5 mg, white solid, yield: 11%) were obtained. Example 38: <com:Math><semantics>MSm / z(ESI):442.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 442.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.75 (s, 1H), 4.96 – 4.79 (m, 2H), 2.65 – 2.54 (m, 1H), <com:Math><semantics>2.38<annotation encoding="application / x-tex">2.38< / annotation>< / semantics>< / com:Math> (s, <com:Math><semantics>3H<annotation encoding="application / x-tex">3H< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>2.17−1.58<annotation encoding="application / x-tex">2.17 - 1.58< / annotation>< / semantics>< / com:Math> (m, <com:Math><semantics>18H<annotation encoding="application / x-tex">18H< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, <com:Math><semantics>3H<annotation encoding="application / x-tex">3H< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>1.33−1.24<annotation encoding="application / x-tex">1.33 - 1.24< / annotation>< / semantics>< / com:Math> (m, <com:Math><semantics>3H<annotation encoding="application / x-tex">3H< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>1.18−1.06<annotation encoding="application / x-tex">1.18 - 1.06< / annotation>< / semantics>< / com:Math> (m, 1H), 0.70 (s, 3H). Example 39: <com:Math><semantics>MSm / z(ESI):442.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 442.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.71 (s, 1H), 4.86 – 4.80 (m, 2H), 2.61 – 2.54 (m, 1H), <com:Math><semantics>2.33<annotation encoding="application / x-tex">2.33< / annotation>< / semantics>< / com:Math> (s, <com:Math><semantics>3H<annotation encoding="application / x-tex">3H< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>2.23−1.55<annotation encoding="application / x-tex">2.23 - 1.55< / annotation>< / semantics>< / com:Math> (m, <com:Math><semantics>18H<annotation encoding="application / x-tex">18H< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, <com:Math><semantics>3H<annotation encoding="application / x-tex">3H< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>1.30−1.27<annotation encoding="application / x-tex">1.30 - 1.27< / annotation>< / semantics>< / com:Math> (m, <com:Math><semantics>3H<annotation encoding="application / x-tex">3H< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>1.15−1.11<annotation encoding="application / x-tex">1.15 - 1.11< / annotation>< / semantics>< / com:Math> (m, 1H), 0.71 (s, 3H). Example 40 3-Cyclopropyl-1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimet hylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-car bonitrile [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 3-cyclopropyl-1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimeth ylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-carb onitrile (15 mg, white solid, yield: 22.2%) was obtained. <com:Math><semantics>MSm / z(ESI):468.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 468.2[M+H]^+< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.72 (s, 1H), 4.92 – 4.72 (m, 2H), 2.57 (t, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 8.8 Hz, 1H), <com:Math><semantics>2.26−1.40<annotation encoding="application / x-tex">2.26 - 1.40< / annotation>< / semantics>< / com:Math> (m, 19H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.37−1.05<annotation encoding="application / x-tex">1.37 - 1.05< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>1.05−0.91<annotation encoding="application / x-tex">1.05 - 0.91< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>0.69<annotation encoding="application / x-tex">0.69< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(s,3H)<annotation encoding="application / x-tex">(s, 3H)< / annotation>< / semantics>< / com:Math>. Example 41 and Example 42 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(5-methyl-2H-tetrazol-2-yl)ethan-1-one (41) 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(5-methyl-1H-tetrazol-1-yl)ethan-1-one (42) [Image disponible dans le document PDF, Image available in the PDF document] Br HN_L N=N Н <com:Math><semantics>K2CO3<annotation encoding="application / x-tex">K_2CO_3< / annotation>< / semantics>< / com:Math> THF П 41 42 In accordance with Step of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the products 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(5-methyl-2H-tetrazol-2-yl)ethan-1-one (41) (23 mg, white solid, yield: 22.8%) and 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(5-methyl-1H-tetrazol-1-yl)ethan-1-one (42) (6.5 mg, white solid, yield: 6.5%) were obtained. Example 41: <com:Math><semantics>MSm / z(ESI):419.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 419.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 5.46 – 5.27 (m, 2H), 2.63 (d, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 8.5 Hz, 1H), 2.57 <com:Math><semantics>(s,3H),2.31−1.46(m,18H),1.38(s,3H),1.35−1.03(m,4H),0.75(s,3H).<annotation encoding="application / x-tex">(s, 3H), 2.31 - 1.46 (m, 18H), 1.38 (s, 3H), 1.35 - 1.03 (m, 4H), 0.75 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 42: <com:Math><semantics>MSm / z(ESI):419.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 419.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 5.19 – 5.02 (m, 2H), 2.66 (t, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 8.5 Hz, 1H), 2.48 (s, 3H), <com:Math><semantics>2.30−1.48<annotation encoding="application / x-tex">2.30 - 1.48< / annotation>< / semantics>< / com:Math> (m, 18H), <com:Math><semantics>1.39<annotation encoding="application / x-tex">1.39< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.33−1.07<annotation encoding="application / x-tex">1.33 - 1.07< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>0.72<annotation encoding="application / x-tex">0.72< / annotation>< / semantics>< / com:Math> (s, 3H). Example 43 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(thiazol-2-ylamino)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(thiazol-2-ylamino)ethan-1-one (13 mg, white solid, yield: 20.7%) was obtained. <com:Math><semantics>MSm / z(ESI):435.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 435.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 6.37 (d, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 4.9 Hz, 1H), 5.92 (d, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 4.9 Hz, 1H), <com:Math><semantics>4.70−4.46<annotation encoding="application / x-tex">4.70 - 4.46< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.68<annotation encoding="application / x-tex">2.68< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.9<annotation encoding="application / x-tex">J = 8.9< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.32−1.46<annotation encoding="application / x-tex">2.32 - 1.46< / annotation>< / semantics>< / com:Math> (m, 17H), <com:Math><semantics>1.37<annotation encoding="application / x-tex">1.37< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.35−1.46<annotation encoding="application / x-tex">1.35 - 1.46< / annotation>< / semantics>< / com:Math> <com:Math><semantics>1.20(m,4H),1.16−1.06(m,1H),0.70(s,3H).<annotation encoding="application / x-tex">1.20 \, (m, 4H), 1.16 - 1.06 \, (m, 1H), 0.70 \, (s, 3H).< / annotation>< / semantics>< / com:Math> Example 44 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-((1-methyl-1H-pyrazol-4-yl)amino)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Example 23, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-((1-methyl-1H-pyrazol-4-yl)amino)ethan-1-one (8.2 mg, white solid, yield: 13.2%) was obtained. <com:Math><semantics>MSm / z(ESI):432.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 432.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.30 (s, 1H), 7.26 (s, 1H), 3.94 – 3.88 (m, 2H), 3.83 (s, 3H), 2.52 (t, <com:Math><semantics>J=8.7<annotation encoding="application / x-tex">J = 8.7< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.27 – 1.46 (m, 16H), 1.37 (s, 3H), 1.33 – 1.05 (m, 6H), <com:Math><semantics>0.65(s,3H)<annotation encoding="application / x-tex">0.65 (s, 3H)< / annotation>< / semantics>< / com:Math>. Example 45 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(isoxazol-4-ylamino)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(isoxazol-4-ylamino)ethan-1-one (8.5 mg, white solid, yield 14.0%) was obtained. <com:Math><semantics>MSm / z(ESI):419.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 419.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 8.08 (s, 1H), 7.91 (s, 1H), 3.85 – 3.65 (m, 2H), 2.53 <com:Math><semantics>(t,J=8.7 Hz,1H),2.23−1.72 (m, 8H),1.51−1.13 (m, 17H),0.67 (s, 3H).<annotation encoding="application / x-tex">(t, J = 8.7 \text{ Hz}, 1\text{H}), 2.23 - 1.72 \text{ (m, 8H)}, 1.51 - 1.13 \text{ (m, 17H)}, 0.67 \text{ (s, 3H)}.< / annotation>< / semantics>< / com:Math> Example 46, Example 47 and Example 48 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)eth an-1-one (46) 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(6-methoxy-1H-benzo[d][1,2,3]triazol-1-yl)eth an-1-one (47) 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(5-methoxy-1H-benzo[d][1,2,3]triazol-1-yl)eth an-1-one (48) [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the products 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)etha n-1-one (46) (13.5) mg, white solid, yield: 11.6%), 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(6-methoxy-1H-benzo[d][1,2,3]triazol-1-yl)etha n-1-one (47) (14 mg, white solid, yield: 12.0%) and 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(5-methoxy-1H-benzo[d][1,2,3]triazol-1-yl)etha n-1-one (48) (14 mg, white solid, yield: 12.0%) were obtained. Example 46: MS m / z (ESI): 484.2[M+H]<com:Sup>+< / com:Sup>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.75 – 7.70 (m, 1H), 7.11 – 7.04 (m, 2H), 5.49 – 5.40 (m, 2H), 3.88 (s, 3H), 2.62 (t, <com:Math><semantics>J=8.8<annotation encoding="application / x-tex">J = 8.8< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.30 – 1.46 (m, 18H), 1.38 (s, 3H), <com:Math><semantics>1.34−1.10<annotation encoding="application / x-tex">1.34 - 1.10< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>0.78<annotation encoding="application / x-tex">0.78< / annotation>< / semantics>< / com:Math> (s, 3H). Example 47: <com:Math><semantics>MSm / z(ESI):484.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 484.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDC13) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.39 (d, <com:Math><semantics>J=2.2<annotation encoding="application / x-tex">J = 2.2< / annotation>< / semantics>< / com:Math> Hz, 1H), 7.22 (d, <com:Math><semantics>J=9.0<annotation encoding="application / x-tex">J = 9.0< / annotation>< / semantics>< / com:Math> Hz, 1H), 7.15 (dd, <com:Math><semantics>J=9.0<annotation encoding="application / x-tex">J = 9.0< / annotation>< / semantics>< / com:Math>, 2.2 Hz, 1H), 5.39 – 5.35 (m, 2H), 3.90 (s, 3H), 2.70 – 2.64 (m, 1H), <com:Math><semantics>2.26−1.45<annotation encoding="application / x-tex">2.26 - 1.45< / annotation>< / semantics>< / com:Math> (m, 18H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.32−1.12<annotation encoding="application / x-tex">1.32 - 1.12< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>0.76<annotation encoding="application / x-tex">0.76< / annotation>< / semantics>< / com:Math> (s, 3H). Example 48: <com:Math><semantics>MSm / z(ESI):484.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 484.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.92 (d, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 9.1 Hz, 1H), 7.01 (dd, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 9.1, 2.2 Hz, 1H), 6.60 (d, <com:Math><semantics>J=2.2<annotation encoding="application / x-tex">J = 2.2< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>5.35−5.31<annotation encoding="application / x-tex">5.35 - 5.31< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>3.87<annotation encoding="application / x-tex">3.87< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>2.73−2.65<annotation encoding="application / x-tex">2.73 - 2.65< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.26−1.46<annotation encoding="application / x-tex">2.26 - 1.46< / annotation>< / semantics>< / com:Math> (m, 18H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.34−1.10<annotation encoding="application / x-tex">1.34 - 1.10< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>0.77<annotation encoding="application / x-tex">0.77< / annotation>< / semantics>< / com:Math> (s, 3H). Example 49 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(pyrimidin-5-yloxy)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(pyrimidin-5-yloxy)ethan-1-one (10.3 mg, white solid, yield: 20.0%) was obtained. <com:Math><semantics>MSm / z(ESI):431.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 431.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 8.92 (s, 1H), 8.44 (s, 2H), 4.78 – 4.63 (m, 2H), 2.75-2.70 (m, 1H), 2.29-2.20 (m, 1H), 2.15-2.05 (m, 3H), 2.02-1.93 (m, 3H), 1.92 - 1.82 (m, 1H), 1.81-1.73 (m, 2H), 1.62-1.60 (m, 2H), 1.59 – 1.43 (m, 6H), 1.38 (s, 3H), 1.35-1.25 (m, 3H), 1.20-1.07 (m, 1H), 0.72 (s, 3H). Example 50 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-3,5-dicarbonitrile [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahyd ro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-3,5-dicarbonitrile (26 mg, white solid, yield: 39.7%) was obtained. <com:Math><semantics>MSm / z(ESI):451.2[M−H]<annotation encoding="application / x-tex">MS m / z (ESI): 451.2[M-H]< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.21 (s, 1H), 5.19 – 5.14 (m, 2H), 2.63 (t, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 8.9 Hz, 1H), <com:Math><semantics>2.29−1.49<annotation encoding="application / x-tex">2.29 - 1.49< / annotation>< / semantics>< / com:Math> (m, 18H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.32−1.30<annotation encoding="application / x-tex">1.32 - 1.30< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>1.20−1.10<annotation encoding="application / x-tex">1.20 - 1.10< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>0.75<annotation encoding="application / x-tex">0.75< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(s,3H)<annotation encoding="application / x-tex">(s, 3H)< / annotation>< / semantics>< / com:Math>. Example 51 3-Chloro-1-(2-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexad ecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-carbonitrile [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 3-chloro-1-(2-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexade cahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-carbonitrile (12 mg, white solid, yield: 22%) was obtained. <com:Math><semantics>MSm / z(ESI):462.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 462.2 [M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.82 (s, 1H), 4.98-4.85 (m, 2H), 2.58 (t, <com:Math><semantics>J=8.5<annotation encoding="application / x-tex">J = 8.5< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.26−2.18<annotation encoding="application / x-tex">2.26-2.18< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.15−1.75<annotation encoding="application / x-tex">2.15-1.75< / annotation>< / semantics>< / com:Math> (m, 7H), <com:Math><semantics>1.66−1.45<annotation encoding="application / x-tex">1.66-1.45< / annotation>< / semantics>< / com:Math> (m, 10H), <com:Math><semantics>1.40−1.25<annotation encoding="application / x-tex">1.40-1.25< / annotation>< / semantics>< / com:Math> (m, 7H), 1.15-1.09 (m, 1H), 0.70 (s, 3H). Example 52 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(oxazol-2-yl)-1H-pyrazol-1-yl)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] Step 1: Preparation of 2-(1H-pyrazol-4-yl)oxazole [Image disponible dans le document PDF, Image available in the PDF document] Α mixture of 1H-pyrazole-4-carbaldehyde (0.8 g, 8.33 mmol), 1-((isocyanomethyl)sulfonyl)-4-methylbenzene (1.79 g, 9.16 mmol), potassium carbonate (2.53 g, 18.33 mmol) and methanol (20 mL) were stirred at 70°C for 16 hours. The reaction solution was concentrated under reduced pressure to dryness, and the resulting residue was purified by column chromatography (dichloromethane / methanol=10:1) to obtain a white solid, 2-(1H-pyrazol-4-yl)oxazole (160 mg, yield: 14%). <com:Math><semantics>MSm / z(ESI):136.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 136.2 [M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, DMSO) δ 13.19 (s, 1H), 8.30 (s, 1H), 8.15 (s, 1H), 7.83 (s, 1H), 7.26 (s, 1H). Step 2: 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(oxazol-2-yl)-1H-pyrazol-1-yl)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] A mixture of 2-bromo-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexad ecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (60 mg, 0.14 mmol), 2-(1H-pyrazol-4-yl)oxazole (28 mg, 0.21 mmol), potassium carbonate (39 mg, 0.28 mmol) and tetrahydrofuran (3 mL) were stirred at room temperature for 16 hours. The reaction solution was concentrated under reduced pressure to dryness, and the resulting residue was purified by preparative chromatography to obtain 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(oxazol-2-yl)-1H-pyrazol-1-yl)ethan-1-one (13 mg, white solid, yield: 20%). <com:Math><semantics>MSm / z(ESI):470.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 470.2 [M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.85 (s, 1H), 7.76 (s, 1H), 7.69 (s, 1H), 7.13 (s, 1H), <com:Math><semantics>4.99−4.89<annotation encoding="application / x-tex">4.99-4.89< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.61<annotation encoding="application / x-tex">2.61< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.8<annotation encoding="application / x-tex">J = 8.8< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.28−2.18<annotation encoding="application / x-tex">2.28 - 2.18< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.15−2.08<annotation encoding="application / x-tex">2.15 - 2.08< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.03−1.82<annotation encoding="application / x-tex">2.03 - 1.82< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>1.78−1.76<annotation encoding="application / x-tex">1.78 - 1.76< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>1.64−1.62<annotation encoding="application / x-tex">1.64 - 1.62< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>1.52−1.43<annotation encoding="application / x-tex">1.52 - 1.43< / annotation>< / semantics>< / com:Math> (m, 5H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), 1.31-1.26 (m, 4H), 1.16-1.11 (m, 2H), 0.73 (s, 3H). Example 53 and Example 54 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(6-(2-hydroxypropan-2-yl)-1H-benzo[d]imidaz ol-1-yl)ethan-1-one (53) 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(5-(2-hydroxypropan-2-yl)-1H-benzo[d]imidaz ol-1-yl)ethan-1-one (54) [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(6-(2-hydroxypropan-2-yl)-1H-benzo[d]imidazo 1-1-yl)ethan-1-one <com:Math><semantics>(53)<annotation encoding="application / x-tex">(53)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(20 mg,<annotation encoding="application / x-tex">(20 \text{ mg},< / annotation>< / semantics>< / com:Math> white solid, yield: 27.1%) and 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(5-(2-hydroxypropan-2-yl)-1H-benzo[d]imidazo 1-1-yl)ethan-1-one (54) (15 mg, white solid, yield: 20.3%) were obtained. Example 53: <com:Math><semantics>MSm / z(ESI):511.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 511.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, Chloroform-d) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.93 (s, 1H), 7.87 (s, 1H), 7.51 (d, <com:Math><semantics>J=8.5<annotation encoding="application / x-tex">J = 8.5< / annotation>< / semantics>< / com:Math> Hz, 1H), 7.14 (d, <com:Math><semantics>J=8.5<annotation encoding="application / x-tex">J = 8.5< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>4.96−4.84<annotation encoding="application / x-tex">4.96 - 4.84< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.64<annotation encoding="application / x-tex">2.64< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.7<annotation encoding="application / x-tex">J = 8.7< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.31−2.17<annotation encoding="application / x-tex">2.31 - 2.17< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(m,1H),2.16−2.06(m,2H),2.04−1.93(m,2H),1.92−1.75(m,2H),1.71−1.43(m,2H),1.71−1.43(m,2H),1.71−1.43(m,2H),1.71−1.43(m,2H),1.71−1.43(m,2H),1.71−1.43(m,2H),1.71−1.43(m,2H),1<annotation encoding="application / x-tex">(m, 1H), 2.16 - 2.06 (m, 2H), 2.04 - 1.93 (m, 2H), 1.92 - 1.75 (m, 2H), 1.71 - 1.43 (m, 2H), 1.71 - 1.43 (m, 2H), 1.71 - 1.43 (m, 2H), 1.71 - 1.43 (m, 2H), 1.71 - 1.43 (m, 2H), 1.71 - 1.43 (m, 2H), 1.71 - 1.43 (m, 2H), 1< / annotation>< / semantics>< / com:Math> 15H), <com:Math><semantics>1.39<annotation encoding="application / x-tex">1.39< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.35−1.20<annotation encoding="application / x-tex">1.35 - 1.20< / annotation>< / semantics>< / com:Math> (m, 5H), <com:Math><semantics>1.18−1.05<annotation encoding="application / x-tex">1.18 - 1.05< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>0.75<annotation encoding="application / x-tex">0.75< / annotation>< / semantics>< / com:Math> (s, 3H). Example 54: <com:Math><semantics>MSm / z(ESI):511.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 511.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, Chloroform-d) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 8.19 (s, 1H), 7.77 (d, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 8.5 Hz, 1H), 7.46 (s, 1H), 7.39 (d, <com:Math><semantics>J=8.1<annotation encoding="application / x-tex">J = 8.1< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>5.12−4.89<annotation encoding="application / x-tex">5.12 - 4.89< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.68<annotation encoding="application / x-tex">2.68< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.2<annotation encoding="application / x-tex">J = 8.2< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.31−2.06<annotation encoding="application / x-tex">2.31 - 2.06< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(m,7H),2.04−1.47(m,15H),1.38(s,3H),1.35−1.21(m,5H),1.20−1.02(m,1H),<annotation encoding="application / x-tex">(m, 7H), 2.04 - 1.47 (m, 15H), 1.38 (s, 3H), 1.35 - 1.21 (m, 5H), 1.20 - 1.02 (m, 1H),< / annotation>< / semantics>< / com:Math> <com:Math><semantics>0.75<annotation encoding="application / x-tex">0.75< / annotation>< / semantics>< / com:Math> (s, <com:Math><semantics>3H<annotation encoding="application / x-tex">3H< / annotation>< / semantics>< / com:Math>). Example 55 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(methylthio)-1H-pyrazol-1-yl)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(methylthio)-1H-pyrazol-1-yl)ethan-1-one (25 mg, white solid, yield: 38%) was obtained. <com:Math><semantics>MS m / z (ESI): 449.2[M+H]+.<annotation encoding="application / x-tex">MS \text{ m / z (ESI): } 449.2 [M+H]^{+}.< / annotation>< / semantics>< / com:Math> <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.53 (s, 1H), 7.43 (s, 1H), 4.95-4.85 (m, 2H), 2.58 (t, <com:Math><semantics>J=8.9 Hz<annotation encoding="application / x-tex">J = 8.9 \text{ Hz}< / annotation>< / semantics>< / com:Math>, 1H), 2.35 (s, 3H), 2.25-2.17 (m, 1H), 2.10 (d, <com:Math><semantics>J=11.4 Hz<annotation encoding="application / x-tex">J = 11.4 \text{ Hz}< / annotation>< / semantics>< / com:Math>, 2H), 2.02 – 1.82 <com:Math><semantics>(m,4H),1.77−1.74(m,2H),1.68−1.42(m,9H),1.38(s,3H),1.35−1.21(m,4H),1.17<annotation encoding="application / x-tex">(m, 4H), 1.77-1.74 (m, 2H), 1.68 - 1.42 (m, 9H), 1.38 (s, 3H), 1.35 - 1.21 (m, 4H), 1.17< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−1.04<annotation encoding="application / x-tex">-1.04< / annotation>< / semantics>< / com:Math> (m, 1H), 0.71 (s, 3H). Example 56 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(methylsulfinyl)-1H-pyrazol-1-yl)ethan-1-on e [Image disponible dans le document PDF, Image available in the PDF document] 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecah ydro-1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(methylthio)-1H-pyrazol-1-yl)ethan-1-o ne (35 mg, 0.078 mmol) was dissolved in dichloromethane (3 mL). m-Chloroperoxybenzoic acid (17 mg, 0.0858 mmol) was added, and the reaction solution was stirred at -78°C for 2 hours. The reaction was quenched with saturated sodium sulfite solution, and the reaction solution was extracted with ethyl acetate (20) mL×3). The organic phases were combined, washed with saturated saline (30 mL), dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness, and the resulting residue was purified by preparative chromatography to obtain a white solid, 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(methylsulfinyl)-1H-pyrazol-1-yl)ethan-1-on e (25 mg, white solid, yield: 69%). <com:Math><semantics>MSm / z(ESI):465.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 465.2 [M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.81 (d, <com:Math><semantics>J=4.6<annotation encoding="application / x-tex">J = 4.6< / annotation>< / semantics>< / com:Math> Hz, 2H), 4.96-4.85 (m, 2H), 2.90 (s, 3H), 2.61 (t, <com:Math><semantics>J=8.7<annotation encoding="application / x-tex">J = 8.7< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.27−2.17<annotation encoding="application / x-tex">2.27 - 2.17< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.13−2.07<annotation encoding="application / x-tex">2.13 - 2.07< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.04−1.73<annotation encoding="application / x-tex">2.04 - 1.73< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>1.66−1.62<annotation encoding="application / x-tex">1.66-1.62< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>1.50−1.48<annotation encoding="application / x-tex">1.50-1.48< / annotation>< / semantics>< / com:Math> (m, 5H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.33−1.22<annotation encoding="application / x-tex">1.33 - 1.22< / annotation>< / semantics>< / com:Math> (m, 5H), 1.14-1.11(m, 2H), 0.71 (s, 3H). Example 57 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(methylsulfonyl)-1H-pyrazol-1-yl)ethan-1-o ne [Image disponible dans le document PDF, Image available in the PDF document] 57 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecah ydro-1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(methylthio)-1H-pyrazol-1-yl)ethan-1-o ne (15 mg, 0.033 mmol) was dissolved in dichloromethane (3 mL). T m-Chloroperoxybenzoic acid (17 mg, 0.1 mmol) was added, and the reaction solution was stirred at room temperature for 6 hours. The reaction solution was concentrated under reduced pressure to dryness, and the resulting residue was purified by preparative chromatography to obtain 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(4-(methylsulfonyl)-1H-pyrazol-1-yl)ethan-1-on e (10 mg, white solid, yield: 63%). MS m / z (ESI): <com:Math><semantics>481.2[M+H]+<annotation encoding="application / x-tex">481.2 [M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.93 (s, 1H), 7.87 (s, 1H), 4.99-4.90 (m, 2H), 3.13 (s, 3H), 2.62 (t, <com:Math><semantics>J=8.7<annotation encoding="application / x-tex">J = 8.7< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.24-2.20 (m, 1H), 2.12-2.09 (m, 2H), 2.03 – 1.74 (m, 5H), 1.66-1.63 (m, 4H), 1.53 – 1.42 (m, 6H), 1.38 (s, 3H), 1.28 -1.26(m, 3H), 1.15 (m, 1H), 0.89-0.86 (m, 1H), 0.71 (s, 3H). Example 58 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-(4-nitro-1H-pyrazol-1-yl)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(4-nitro-1H-pyrazol-1-yl)ethan-1-one (39 mg, white solid, yield: 60.3%) was obtained. <com:Math><semantics>MSm / z(ESI):448.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 448.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 8.18 (s, 1H), 8.08 (s, 1H), 5.08 – 4.81 (m, 2H), 2.62 <com:Math><semantics>(t,J=8.7 Hz,1H),2.30−1.46 (m, 16H),1.38 (s, 3H),1.34−1.04 (m, 6H),0.71 (s, 16H),0.71 (s, 16H)<annotation encoding="application / x-tex">(t, J = 8.7 \text{ Hz}, 1\text{H}), 2.30 - 1.46 \text{ (m, 16H)}, 1.38 \text{ (s, 3H)}, 1.34 - 1.04 \text{ (m, 6H)}, 0.71 \text{ (s, 16H)}, 0.71 \text{ (s, 16H)}< / annotation>< / semantics>< / com:Math> 3H). Example 59 Ethyl 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahyd ro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-carboxylate [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product ethyl 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahyd ro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-carboxylate (32 mg, white solid, yield: 46.6%) was obtained. <com:Math><semantics>MSm / z(ESI):475.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 475.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.94 (s, 1H), 7.92 (s, 1H), 5.04 – 4.80 (m, 2H), 4.38 <com:Math><semantics>−4.19<annotation encoding="application / x-tex">-4.19< / annotation>< / semantics>< / com:Math> (m, 2H), 2.60 (t, <com:Math><semantics>J=8.7<annotation encoding="application / x-tex">J = 8.7< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.27 <com:Math><semantics>−1.45<annotation encoding="application / x-tex">-1.45< / annotation>< / semantics>< / com:Math> (m, 21H), 1.38 (s, 3H), 1.37 <com:Math><semantics>−1.25<annotation encoding="application / x-tex">-1.25< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(m,3H),1.20−1.07(m,1H),0.71(s,3H).<annotation encoding="application / x-tex">(m, 3H), 1.20 - 1.07 (m, 1H), 0.71 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 60 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-N,N-dimethyl-1H-pyrazole-4-car boxamide [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahyd ro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-N,N-dimethyl-1H-pyrazole-4-carb oxamide (10 mg, white solid, yield: 14.6%) was obtained. <com:Math><semantics>MSm / z(ESI):474.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 474.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.75 (s, 2H), 5.09 – 4.82 (m, 2H), 3.16 (s, 6H), 2.69 <com:Math><semantics>−2.53<annotation encoding="application / x-tex">-2.53< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.30−1.45<annotation encoding="application / x-tex">2.30 - 1.45< / annotation>< / semantics>< / com:Math> (m, 18H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.32−1.05<annotation encoding="application / x-tex">1.32 - 1.05< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>0.72<annotation encoding="application / x-tex">0.72< / annotation>< / semantics>< / com:Math> (s, 3H). Example 61 N-Ethyl-1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-N-methyl-1H-pyrazole-4- carboxamide [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product N-ethyl-1-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexa decahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-N-methyl-1H-pyrazole-4-c arboxamide (14 mg, white solid, yield: 19.8%) was obtained. <com:Math><semantics>MSm / z(ESI):488.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 488.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.76 (s, 1H), 7.73 (s, 1H), 5.02 – 4.80 (m, 2H), 3.66 <com:Math><semantics>−3.44<annotation encoding="application / x-tex">-3.44< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>3.28−2.93<annotation encoding="application / x-tex">3.28 - 2.93< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>2.60<annotation encoding="application / x-tex">2.60< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.6<annotation encoding="application / x-tex">J = 8.6< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.30−1.45<annotation encoding="application / x-tex">2.30 - 1.45< / annotation>< / semantics>< / com:Math> (m, 18H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(s,3H),1.34−1.06(m,7H),0.71(s,3H).<annotation encoding="application / x-tex">(s, 3H), 1.34 - 1.06 (m, 7H), 0.71 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 62 2-(4-(Azetidine-1-carbonyl)-1H-pyrazol-1-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fl uoro-3-hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)etha n-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 2-(4-(azetidine-1-carbonyl)-1H-pyrazol-1-yl)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fl uoro-3-hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)etha n-1-one (12 mg, white solid, yield: 17.1%) was obtained. <com:Math><semantics>MSm / z(ESI):486.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 486.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.87 (s, 1H), 7.76 (s, 1H), 5.02 – 4.82 (m, 2H), 4.39 <com:Math><semantics>−4.21<annotation encoding="application / x-tex">-4.21< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>2.59<annotation encoding="application / x-tex">2.59< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.5<annotation encoding="application / x-tex">J = 8.5< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.46−1.59<annotation encoding="application / x-tex">2.46 - 1.59< / annotation>< / semantics>< / com:Math> (m, 20H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.34−1.19<annotation encoding="application / x-tex">1.34 - 1.19< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(m,3H),1.17−1.05(m,1H),0.71(s,3H).<annotation encoding="application / x-tex">(m, 3H), 1.17 - 1.05 (m, 1H), 0.71 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 63 and Example 64 2-(4-Cyclopropyl-2H-1,2,3-triazol-2-yl)-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-h ydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (63) 2-(4-Cyclopropyl-1H-1,2,3-triazol-1-yl)-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-h ydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (64) [Image disponible dans le document PDF, Image available in the PDF document] Step 1: Preparation of 4,5-dibromo-2H-1,2,3-triazole [Image disponible dans le document PDF, Image available in the PDF document] Liquid bromine (3 mL) was slowly added to a solution of 2H-1,2,3-triazole (3 g, 43.43 mmol) in water (30 mL) at 0°C to precipitate a light yellow solid. The reaction solution was stirred at room temperature for 16 hours and then filtrated. The filter cake was washed with water (20 mL), and dried to obtain 4,5-dibromo-2H-1,2,3-triazole (5.7 g, white solid, yield: 58%), which was used directly in the next step without purification. <com:Math><semantics>MSm / z(ESI):227.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 227.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. Step 2: Preparation of 4-bromo-2H-1,2,3-triazole [Image disponible dans le document PDF, Image available in the PDF document] 4,5-Dibromo-2H-1,2,3-triazole (5.7 g, 25.13 mmol) was suspended in water (50 mL). Sodium sulfite (9.5 g, 75.38 mmol) was added, and the reaction solution was stirred at 100°C for 3 days. The reaction solution was cooled to room temperature, and extracted with ethyl acetate (30 mL×6). The organic phases were combined, washed with saturated saline (100 mL), dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness to obtain 4-bromo-2H-1,2,3-triazole (3 g, white solid, yield: 81%). MS m / z (ESI): <com:Math><semantics>148.2[M+H]+<annotation encoding="application / x-tex">148.2 [M+H]^+< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>150.2[M+2+H]+<annotation encoding="application / x-tex">150.2 [M+2+H]^+< / annotation>< / semantics>< / com:Math>. Step 3: Preparation of 4-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-1,2,3-triazole [Image disponible dans le document PDF, Image available in the PDF document] Sodium hydride (760 mg, 18.9 mmol) was slowly added to a solution of 4-bromo-2H-1,2,3-triazole (2 g, 13.51 mmol) in tetrahydrofuran (20 mL) at 0°C, and the reaction solution was stirred at 0°C for 0.5 hour. 2-(Trimethylsilyl)ethoxymethyl chloride (2.48 g, 14.86 mmol) was added dropwise. After completion of the addition, the reaction solution was stirred at room temperature for 2 hours. The reaction was quenched with water (50 mL), and the reaction solution was extracted with ethyl acetate (30 mL×3). The organic phases were combined, washed with saturated saline (50 mL), dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness, and the resulting residue was purified by column chromatography to obtain 4-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-1,2,3-triazole (1.4 g, white solid, yield: 38%). [Image disponible dans le document PDF, Image available in the PDF document] of 4-cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-1,2,3-triazole [Image disponible dans le document PDF, Image available in the PDF document] 4-Bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-1,2,3-triazole (0.5 g, 1.79 mmol) and potassium cyclopropyltrifluoroborate (530 mg, 3.58 mmol) were dissolved in 1,4-dioxane (10 mL). [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.5 g, 1.79 mmol) and sodium carbonate (0.5 g, 1.79 mmol) were added. After purging with nitrogen three times, the reaction solution was stirred under a nitrogen atmosphere at 100°C for 16 hours. The reaction solution was filtrated through celite, and the filtrate was concentrated under reduced pressure to obtain a residue. To the residue was added water (30 mL), and the mixture was extracted with ethyl acetate (30 mL×3). The organic phases were combined, washed with saturated saline (50 mL), dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness, and the resulting residue was purified by column chromatography (petroleum ether / ethyl acetate=4:1) to obtain 4-cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-1,2,3-triazole (70 mg, light yellow oil, yield: 16%). <com:Math><semantics>MS m / z (ESI): 240.2 [M+H]+.<annotation encoding="application / x-tex">MS \text{ m / z (ESI): } 240.2 \text{ [M+H]}^{+}.< / annotation>< / semantics>< / com:Math> Step 5: Preparation of 4-cyclopropyl-2H-1,2,3-triazole [Image disponible dans le document PDF, Image available in the PDF document] 4-Cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-1,2,3-triazole (50 mg, 0.208 mmol) was dissolved in dichloromethane (1 mL). Trifluoroacetic acid (1 mL) was added, and the reaction solution was stirred at room temperature for 3 hours. Water (10 mL) was added, and then saturated sodium carbonate solution was added to the reaction solution to adjust pH=8, and the reaction solution was extracted with ethyl acetate (20) mL×3). The organic phases were combined, washed with saturated saline (50 mL), dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness to obtain 4-cyclopropyl-2H-1,2,3-triazole (35 mg, white solid, crude product). <com:Math><semantics>MSm / z(ESI):110.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 110.2 [M+H]^{+}< / annotation>< / semantics>< / com:Math>. Step 6: Preparation of 2-(4-cyclopropyl-2H-1,2,3-triazol-2-yl)-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-h ydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (63) and 2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-h ydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (64) [Image disponible dans le document PDF, Image available in the PDF document] Potassium carbonate (80 mg, 0.579 mmol) was added to a mixed solution of 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (80 mg, 0.193mmol) and tetrahydrofuran (3 mL), and the reaction solution was stirred at room temperature for 16 hours. Water (20 mL) was added, and the reaction solution was extracted with ethyl acetate (20 mL×3). The organic phases were combined, washed with saturated saline (30 mL), dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness, and the resulting residue was purified by preparative chromatography to obtain a white solid, 2-(4-cyclopropyl-2H-1,2,3-triazol-2-yl)-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-h ydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (63) (34 mg, white solid, yield: 39.8%) and a white solid, 2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-h ydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (64) (14 mg, white solid, yield: 16.4%). Example 63: <com:Math><semantics>MSm / z(ESI):444.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 444.2 [M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.35 (s, 1H), 5.15-5.05 (m, 2H), 3.91 (d, <com:Math><semantics>J=3.0<annotation encoding="application / x-tex">J = 3.0< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>2.61−2.47<annotation encoding="application / x-tex">2.61 - 2.47< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.25−2.08<annotation encoding="application / x-tex">2.25 - 2.08< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>2.04−1.81<annotation encoding="application / x-tex">2.04 - 1.81< / annotation>< / semantics>< / com:Math> (m, 5H), <com:Math><semantics>1.78−1.71<annotation encoding="application / x-tex">1.78 - 1.71< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>1.54−1.42<annotation encoding="application / x-tex">1.54 - 1.42< / annotation>< / semantics>< / com:Math> (m, 6H), <com:Math><semantics>1.37<annotation encoding="application / x-tex">1.37< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.33−1.20<annotation encoding="application / x-tex">1.33 - 1.20< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>1.18−1.04<annotation encoding="application / x-tex">1.18 - 1.04< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>0.99−0.96<annotation encoding="application / x-tex">0.99 - 0.96< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(m,2H),0.80−0.75(m,2H),0.73(s,3H).<annotation encoding="application / x-tex">(m, 2H), 0.80 - 0.75 (m, 2H), 0.73 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 64: MS m / z (ESI): <com:Math><semantics>444.2[M+H]+<annotation encoding="application / x-tex">444.2 [M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.35 (s, 1H), 5.16-5.06 (m, 2H), 3.91 (d, <com:Math><semantics>J=3.0<annotation encoding="application / x-tex">J = 3.0< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.54 (t, <com:Math><semantics>J=8.8<annotation encoding="application / x-tex">J = 8.8< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.24-2.09 (m, 4H), 2.04 – 1.81 (m, 5H), 1.78-1.70 (m, 2H), <com:Math><semantics>1.54−1.42<annotation encoding="application / x-tex">1.54 - 1.42< / annotation>< / semantics>< / com:Math> (m, 6H), <com:Math><semantics>1.37<annotation encoding="application / x-tex">1.37< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.31−1.22<annotation encoding="application / x-tex">1.31 - 1.22< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>1.18−1.04<annotation encoding="application / x-tex">1.18 - 1.04< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>0.99−0.96<annotation encoding="application / x-tex">0.99 - 0.96< / annotation>< / semantics>< / com:Math> (m, 2H), 0.80-0.76(m, 2H), 0.73 (s, 3H). Example 66 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-((2-(trifluoromethyl)pyrimidin-5-yl)oxy)ethan- 1-one [Image disponible dans le document PDF, Image available in the PDF document] ~~ In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-((2-(trifluoromethyl)pyrimidin-5-yl)oxy)ethan-1 -one (39.2 mg, white solid, yield: 65.5%) was obtained. <com:Math><semantics>MSm / z(ESI):499.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 499.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 8.45 (s, 2H), 4.84 – 4.70 (m, 2H), 2.68 (t, J = 8.9 Hz, 1H), 2.23 (m, 1H), 2.09 (d, <com:Math><semantics>J=10.8 Hz<annotation encoding="application / x-tex">J = 10.8 \text{ Hz}< / annotation>< / semantics>< / com:Math>, 1H), 1.98 (t, <com:Math><semantics>J=12.6 Hz<annotation encoding="application / x-tex">J = 12.6 \text{ Hz}< / annotation>< / semantics>< / com:Math>, 3H), 1.91 – 1.83 (m, 1H), <com:Math><semantics>1.79<annotation encoding="application / x-tex">1.79< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=8.4<annotation encoding="application / x-tex">J = 8.4< / annotation>< / semantics>< / com:Math> Hz, 2H), <com:Math><semantics>1.60−1.52<annotation encoding="application / x-tex">1.60 - 1.52< / annotation>< / semantics>< / com:Math> (m, 4H), <com:Math><semantics>1.48<annotation encoding="application / x-tex">1.48< / annotation>< / semantics>< / com:Math> (dd, <com:Math><semantics>J=19.5<annotation encoding="application / x-tex">J = 19.5< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>12.9<annotation encoding="application / x-tex">12.9< / annotation>< / semantics>< / com:Math> Hz, 5H), <com:Math><semantics>1.38<annotation encoding="application / x-tex">1.38< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(s,3H),1.35−1.21(m,4H),1.20−1.05(m,1H),0.73(s,3H).<annotation encoding="application / x-tex">(s, 3H), 1.35 - 1.21 (m, 4H), 1.20 - 1.05 (m, 1H), 0.73 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 67 3-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)thiazolidine-2,4-dione [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 3-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahyd ro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)thiazolidine-2,4-dione (18.5 mg, white solid, yield: 28.3%) was obtained. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 4.43 – 4.32 (m, 2H), 4.03 (s, 2H), 2.56 (t, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 8.7 Hz, 1H), <com:Math><semantics>2.21−1.54<annotation encoding="application / x-tex">2.21 - 1.54< / annotation>< / semantics>< / com:Math> (m, 18H), <com:Math><semantics>1.37<annotation encoding="application / x-tex">1.37< / annotation>< / semantics>< / com:Math> (s, 3H), <com:Math><semantics>1.32−1.25<annotation encoding="application / x-tex">1.32 - 1.25< / annotation>< / semantics>< / com:Math> (m, 3H), <com:Math><semantics>1.17−1.08<annotation encoding="application / x-tex">1.17 - 1.08< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>0.68<annotation encoding="application / x-tex">0.68< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(s,3H)<annotation encoding="application / x-tex">(s, 3H)< / annotation>< / semantics>< / com:Math>. Example 68 (1R,3R,5R)-2-(2-((3R,5R,8S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhe xadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-2-azabicyclo[3.1.0]hexa ne-3-carbonitrile [Image disponible dans le document PDF, Image available in the PDF document] Step 1: Preparation of tert-butyl (1R,3R,5R)-3-cyano-2-azabicyclo[3.1.0]hexane-2-carboxylate [Image disponible dans le document PDF, Image available in the PDF document] Trifluoroacetic anhydride (5 mL, 35.3 mmol) was slowly added dropwise to a suspension of tert-butyl (1R,3R,5R)-3-carbamoyl-2-azabicyclo[3.1.0]hexane-2-carboxylate (2 g, 8.85 mmol) and pyridine (25 mL) at -20°C. After stirring at -20°C for 1 hour, the reaction solution was warmed up to room temperature, and stirred for 8 hours. Ice-water was added to quench the reaction, and the reaction solution was extracted with ethyl acetate (30 mL×3). The organic phases were combined, washed with dilute hydrochloric acid (10%) and saturated saline, dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness, and the resulting residue was purified by column chromatography (petroleum ether / ethyl acetate=4:1) to obtain tert-butyl (1R,3R,5R)-3-cyano-2-azabicyclo[3.1.0]hexane-2-carboxylate (1.5 g, white solid, yield: 83%). <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 4.71 (dd, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 41.1, 9.6 Hz, 1H), 3.58 (d, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 33.8 Hz, 1H), <com:Math><semantics>2.63−2.47<annotation encoding="application / x-tex">2.63 - 2.47< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>2.35<annotation encoding="application / x-tex">2.35< / annotation>< / semantics>< / com:Math> (d, <com:Math><semantics>J=12.7<annotation encoding="application / x-tex">J = 12.7< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>1.70−1.60<annotation encoding="application / x-tex">1.70 - 1.60< / annotation>< / semantics>< / com:Math> (m, 1H), <com:Math><semantics>1.52<annotation encoding="application / x-tex">1.52< / annotation>< / semantics>< / com:Math> (s, 9H), 1.02 (s, 1H), 0.90-0.81 (m, 1H). Step 2: Preparation of (1R,3R,5R)-2-azabicyclo[3.1.0]hexane-3-carbonitrile [Image disponible dans le document PDF, Image available in the PDF document] Tert-butyl (1R,3R,5R)-3-cyano-2-azabicyclo[3.1.0]hexane-2-carboxylate (0.8 g, 3.85 mmol) was dissolved in dioxane (2 mL). Hydrochloric acid-dioxane (8 mL) was added, and the reaction solution was stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure to dryness, to the resulting residue was added water (50 mL), and the mixture was extracted with dichloromethane / methanol=10:1. The organic phases were combined, washed with saturated saline, dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness to obtain (1R,3R,5R)-2-azabicyclo[3.1.0]hexane-3-carbonitrile (0.5 g, brown oil, crude product). Step 3: Preparation of (1R,3R,5R)-2-(2-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-2-azabicyclo[3.1.0]hexan e-3-carbonitrile [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product (1R,3R,5R)-2-(2-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhex adecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-2-azabicyclo[3.1.0]hexan e-3-carbonitrile (12 mg, white solid, yield: 23%) was obtained. <com:Math><semantics>MSm / z(ESI):443.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 443.2 [M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 4.08 (s, 2H), 3.70 (s, 2H), 2.49 (t, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 8.7 Hz, 1H), <com:Math><semantics>2.24−2.16<annotation encoding="application / x-tex">2.24 - 2.16< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>2.12−1.82<annotation encoding="application / x-tex">2.12 - 1.82< / annotation>< / semantics>< / com:Math> (m, 11H), <com:Math><semantics>1.74−1.70<annotation encoding="application / x-tex">1.74 - 1.70< / annotation>< / semantics>< / com:Math> (m, 2H), <com:Math><semantics>1.60−1.48<annotation encoding="application / x-tex">1.60 - 1.48< / annotation>< / semantics>< / com:Math> (m, 6H), <com:Math><semantics>1.37<annotation encoding="application / x-tex">1.37< / annotation>< / semantics>< / com:Math> (s, 3H), 1.31-1.25 (m, 6H), 1.12-1.07 (m, 1H), 0.65 (s, 3H). Example 69 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahydro -1H-cyclopenta[a]phenanthren-17-yl)-2-((1-methyl-1H-pyrazol-4-yl)oxy)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-((1-methyl-1H-pyrazol-4-yl)oxy)ethan-1-one (20 mg, white solid, yield: 32.0%) was obtained. <com:Math><semantics>MSm / z(ESI):433.3[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 433.3[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.21 (s, 1H), 7.08 (s, 1H), 4.48 – 4.28 (m, 2H), 3.82 (s, 3H), 2.74 (t, <com:Math><semantics>J=8.9<annotation encoding="application / x-tex">J = 8.9< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.22 – 1.50 (m, 18H), 1.37 (s, 3H), 1.30 – 1.10 (m, 4H), <com:Math><semantics>0.68<annotation encoding="application / x-tex">0.68< / annotation>< / semantics>< / com:Math> (s, <com:Math><semantics>3H<annotation encoding="application / x-tex">3H< / annotation>< / semantics>< / com:Math>). Example 70 7-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)quinolone 1-oxide [Image disponible dans le document PDF, Image available in the PDF document] Step 1: Preparation of 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(quinolin-7-yloxy)ethan-1-one [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Step 2 of Example 2, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, accordingly, the product 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)-2-(quinolin-7-yloxy)ethan-1-one (60.0 mg, white solid, yield 52.1%) was obtained. <com:Math><semantics>MSm / z(ESI):480.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 480.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. Step 2: Preparation of 7-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahyd ro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)quinolone 1-oxide [Image disponible dans le document PDF, Image available in the PDF document] 1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecah ydro-1H-cyclopenta[a]phenanthren-17-yl)-2-(quinolin-7-yloxy)ethan-1-one (60 mg, 0.125 mmol) and dichloromethane (10 ml) were added to a 100 ml single-neck flask, followed by the addition of m-chloroperoxybenzoic acid (78 mg, 0.313 mmol). The reaction solution was stirred at room temperature overnight. The reaction solution was washed with saturated sodium bicarbonate solution and concentrated. The crude product obtained after concentration was purified by prep-HPLC to obtain 7-(2-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahyd ro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)quinolone 1-oxide (29.2 mg, white solid, yield 47.1%). <com:Math><semantics>MSm / z(ESI):496.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 496.2[M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 8.59 (d, J = 6.0 Hz, 1H), 7.97 (d, J = 2.2 Hz, 1H), <com:Math><semantics>7.83<annotation encoding="application / x-tex">7.83< / annotation>< / semantics>< / com:Math> (d, <com:Math><semantics>J=9.0<annotation encoding="application / x-tex">J = 9.0< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>7.78<annotation encoding="application / x-tex">7.78< / annotation>< / semantics>< / com:Math> (d, <com:Math><semantics>J=8.3<annotation encoding="application / x-tex">J = 8.3< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>7.43<annotation encoding="application / x-tex">7.43< / annotation>< / semantics>< / com:Math> (dd, <com:Math><semantics>J=9.0<annotation encoding="application / x-tex">J = 9.0< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>2.4<annotation encoding="application / x-tex">2.4< / annotation>< / semantics>< / com:Math> Hz, 1H), <com:Math><semantics>7.26−1.00<annotation encoding="application / x-tex">7.26 - 1.00< / annotation>< / semantics>< / com:Math> <com:Math><semantics>7.20 (m, 1H),4.87−4.73 (m, 2H),2.83−2.75 (m, 1H),2.33−2.21 (m, 1H),2.13−2.07 (m, 1H)<annotation encoding="application / x-tex">7.20 \text{ (m, 1H)}, 4.87 - 4.73 \text{ (m, 2H)}, 2.83 - 2.75 \text{ (m, 1H)}, 2.33 - 2.21 \text{ (m, 1H)}, 2.13 - 2.07 \text{ (m, 1H)}< / annotation>< / semantics>< / com:Math> 1H), 2.06-1.95 (m, 4H), 1.94-1.84 (m, 2H), 1.82-1.74 (m, 2H), 1.62-1.42 (m, 8H), 1.38 <com:Math><semantics>(s,3H),1.35−1.25(m,3H),1.20−1.06(m,1H),0.75(s,3H).<annotation encoding="application / x-tex">(s, 3H), 1.35 - 1.25 (m, 3H), 1.20 - 1.06 (m, 1H), 0.75 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 71 N-(2-((3S,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-3-hydroxy-3,13-dimethylhexadecahy dro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)benzenesulfonamide [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] Benzenesulfonamide (28 mg, 0.18 mmol) was dissolved 11 N,N-dimethylformamide (5 mL). Sodium hydride (7.2 mg, 0.18 mmol) was added at 0°C, and the reaction solution was stirred at 0°C for 0.5 hour. 2-Bromo-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexad ecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (50 mg, 0.12 mmol) was added at 0°C, and the reaction solution was stirred at room temperature overnight. 5 mL of water was added, and the reaction solution was extracted with ethyl acetate (30 mL×3). The organic phase was washed with saturated saline (20 mL) once, dried over anhydrous sodium sulfate and concentrated by rotary evaporation to dryness. The resulting residue was purified by prep-HPLC to obtain the product (7.1 mg, white solid, yield: 12%). <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.86 (d, <com:Math><semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics>< / com:Math> Hz, 2H), 7.58 (t, <com:Math><semantics>J=7.4<annotation encoding="application / x-tex">J = 7.4< / annotation>< / semantics>< / com:Math> Hz, 1H), 7.51 (t, <com:Math><semantics>J=7.5<annotation encoding="application / x-tex">J = 7.5< / annotation>< / semantics>< / com:Math> Hz, 2H), 5.48 (s, 1H), 3.87 – 3.68 (m, 2H), 2.36 (t, <com:Math><semantics>J=8.9<annotation encoding="application / x-tex">J = 8.9< / annotation>< / semantics>< / com:Math> Hz, 1H), 2.06-2.08 (m, 2H), 1.94-1.97 (m, 2H), 1.90-1.80 (m, 1H), 1.71 – 1.62 (m, 4H), 1.52 – <com:Math><semantics>1.39 (m, 6H),1.37 (s, 3H),1.34−1.25 (m, 4H),1.24−1.01 (m, 3H),0.38 (s, 3H).<annotation encoding="application / x-tex">1.39 \text{ (m, 6H)}, 1.37 \text{ (s, 3H)}, 1.34 - 1.25 \text{ (m, 4H)}, 1.24 - 1.01 \text{ (m, 3H)}, 0.38 \text{ (s, 3H)}.< / annotation>< / semantics>< / com:Math> Example 72 (3R,5R,8S,9S,10R,13S,14S,17S)-10-Fluoro-N-(4-fluorophenyl)-3-hydroxy-3,13-dimeth ylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-carboxamide [Image disponible dans le document PDF, Image available in the PDF document] 72 Step 1: Preparation of (3R,5R,8S,9S,10R,13S,14S)-10-fluoro-3,13-dimethyl-17-methylenehexadecahydro-1H- cyclopenta[a]phenanthren-3-ol [Image disponible dans le document PDF, Image available in the PDF document] Potassium tert-butoxide (4.36 g, 38.961 mmol) was added to a solution of methyltriphenylphosphonium bromide (13.9 g, 38.961 mmol) and tetrahydrofuran (50 mL), and the reaction solution was stirred at 65°C for 1 hour. A mixed solution of (3R,5R,8S,9S,10R,13S,14S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro-17H-cy clopenta[a]phenanthren-17-one (2 g, 6.494 mmol) and tetrahydrofuran (30 mL) was added dropwise. After stirring at 65°C for 1 hour, the reaction solution was cooled to room temperature. Water was added to quench the reaction, and the reaction solution was extracted with ethyl acetate (50 mL×3). The organic phases were combined, washed with saturated saline, dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness, and the resulting residue was purified by column chromatography (petroleum ether / ethyl acetate=10:1) to obtain (3R,5R,8S,9S,10R,13S,14S)-10-fluoro-3,13-dimethyl-17-methylenehexadecahydro-1H- cyclopenta[a]phenanthren-3-ol (1.8 g, white solid, yield: 90%). Step 2: Preparation of (3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-17-(hydroxymethyl)-3,13-dimethylhexadec ahydro-1H-cyclopenta[a]phenanthren-3-ol [Image disponible dans le document PDF, Image available in the PDF document] (3R,5R,8S,9S,10R,13S,14S)-10-Fluoro-3,13-dimethyl-17-methylenehexadecahydr o-1H-cyclopenta[a]phenanthren-3-ol (0.5 g, 1.634 mmol) was dissolved in tetrahydrofuran (8 mL). Borane-tetrahydrofuran (8.2 mL, 8.169 mmol) was added dropwise, and the reaction solution was stirred at room temperature for 1.5 hours. The reaction solution was cooled to 0°C, and a solution of sodium hydroxide (327 mg, 8.169 mmol) in water (3 mL) was added. Hydrogen peroxide (3 mL, 30%) was slowly added dropwise, and the reaction solution was stirred at room temperature for 1.5 hours. Water (50 mL) was added, and the reaction solution was extracted with ethyl acetate (50 mL×3). The organic phases were combined, washed with saturated saline, dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness to obtain (3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-17-(hydroxymethyl)-3,13-dimethylhexadec ahydro-1H-cyclopenta[a]phenanthren-3-ol (600 mg, crude product). Step 3: Preparation of (3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro-1H -cyclopenta[a]phenanthrene-17-carboxylic acid [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] Pyridinium dichromate (4.6 g, 12.34 mmol) was added to a mixture of (3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-17-(hydroxymethyl)-3,13-dimethylhexadec ahydro-1H-cyclopenta[a]phenanthren-3-ol (400 mg, 1.234 mmol), N,N-dimethylformamide (15 mL) and water (1 mL), and the reaction solution was stirred at room temperature for 16 hours. Saturated sodium sulfite solution (50 mL) was added to quench the reaction, and the reaction solution was extracted with ethyl acetate (40 mL×3). The organic phases were combined, washed with saturated saline, dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness to obtain a light yellow solid, (3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro-1H -cyclopenta[a]phenanthrene-17-carboxylic acid (400 mg, light yellow solid, crude product). <com:Sup>1< / com:Sup>H NMR (400 MHz, DMSO) δ 11.92 (s, 1H), 4.38 (s, 1H), 2.90-2.70 (m, 2H), 2.05 -1.52 (m, 9H), 1.39-1.19(m, 15H), 0.61 (s, 3H). Step 4: Preparation of (3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-N-(4-fluorophenyl)-3-hydroxy-3,13-dimeth ylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-carboxamide [Image disponible dans le document PDF, Image available in the PDF document] A mixture of (3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadecahydro-1H -cyclopenta[a]phenanthrene-17-carboxylic acid (200) mg, 0.592 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethylurea hexafluorophosphate (270 mg, 0.71 mmol), triethylamine (119 mg, 1.18 mmol) and dichloromethane (5 mL) was stirred at room temperature for 30 minutes. p-Fluoroaniline (79 mg, 0.71 mmol) was added, and the reaction solution was stirred at room temperature for 3 hours. Water (30 mL) was added, and the reaction solution was extracted with dichloromethane (40 mL×3). The organic phases were combined, washed with saturated saline, dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated under reduced pressure to dryness, and the resulting residue was purified by preparative chromatography to obtain (3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-N-(4-fluorophenyl)-3-hydroxy-3,13-dimeth ylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-carboxamide (25 mg, white solid, yield: 10%). <com:Math><semantics>MSm / z(ESI):432.2[M+H]+<annotation encoding="application / x-tex">MS m / z (ESI): 432.2 [M+H]^{+}< / annotation>< / semantics>< / com:Math>. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.51 – 7.41 (m, 2H), 7.05-6.95 (m, 2H), 2.43 – 2.17 <com:Math><semantics>(m,2H),2.14−1.80(m,8H),1.72−1.69(m,3H),1.51−1.11(m,15H),0.93(s,3H).<annotation encoding="application / x-tex">(m, 2H), 2.14 - 1.80 (m, 8H), 1.72 - 1.69 (m, 3H), 1.51 - 1.11 (m, 15H), 0.93 (s, 3H).< / annotation>< / semantics>< / com:Math> Example 73 2-((4-Fluoro-2-methoxyphenyl)amino)-1-((3R,5R,8S,9S,10R,13S,14S,17S)-10-fluoro-3 -hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-on e [Image disponible dans le document PDF, Image available in the PDF document] In accordance with Example 23, 2-bromo-1-((3R,5R,8S,10R,13S,14S,17S)-10-fluoro-3-hydroxy-3,13-dimethylhexadeca hydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one was used as the starting material, acco...
Claims
1. A compound of formula (VIII), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Image disponible dans le document PDF, Image available in the PDF document] wherein: ring A is selected from the group consisting of 3 to 12 membered heterocyclyl wherein 1 to 4 atoms are heteroatoms, C 6-14 aryl and 5 to 14 membered heteroaryl having 1 to 4 heteroatoms selected from the group consisting of O, S and N; Z is selected from the group consisting of -CR 23 R 24 -, -(CH 2 ) n1 NR 23 -, - ( C H 2 ) n 1 O ( C H 2 ) n 2 (CH_2)_{n1}O(CH_2)_{n2} - and -O-; Ra is each selected from the group consisting of hydrogen atom, cyano, halogen, nitro, C 1-6 alkyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 1-6 hydroxyalkyl, 5 to 10 membered heterocyclyl, 5 to 10 membered heteroaryl, - ( C H 2 ) n 1 O R 23 (CH_2)_{n1}OR_{23} , − ( C H 2 ) n 1 S R 23 -(CH_2)_{n1}SR_{23} , − ( C H 2 ) n 1 C ( O ) R 23 -(CH_2)_{n1}C(O)R_{23} , − ( C H 2 ) n 1 C ( O ) N R 23 R 24 -(CH_2)_{n1}C(O)NR_{23}R_{24} , − ( C H 2 ) n 1 C ( O ) O R 23 -(CH_2)_{n1}C(O)OR_{23} and − ( C H 2 ) n 1 S ( O ) m 1 R 23 -(CH_2)_{n1}S(O)_{m1}R_{23} ; R 23 and R 24 are each independently selected from the group consisting of hydrogen atom, C 1-6 alkyl and 3 to 8 membered heterocyclyl; x is an integer of 0, 1, 3, 4 or 5; m1 is an integer of 0, 1 or 2; n1 is an integer of 0, 1, 2, 3, 4 or 5; and n2 is an integer of 0, 1, 3, 4 or 5.
2. The compound of formula (VIII), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, wherein the ring A is selected from the group consisting of: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]3. The compound of formula (VIII), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, wherein R a is selected from the group consisting of hydrogen atom, cyano, halogen, nitro, C 1-3 alkyl, C 2-3 alkynyl, C 1-1 3 alkoxy, C 1-3 haloalkyl, C 3-6 cycloalkyl, C 1-3 hydroxyalkyl, 5 to 6 membered heteroaryl, − O R 23 -OR_{23} , − S R 23 -SR_{23} , − C ( O ) R 23 -C(O)R_{23} , − C ( O ) N R 23 R 24 -C(O)NR_{23}R_{24} , − C ( O ) O R 23 -C(O)OR_{23} and − S ( O ) m 1 R 23 -S(O)_{m1}R_{23} ; R 23 and R 24 are each independently selected from the group consisting of hydrogen atom, C 1-3 alkyl and 3 to 8 membered heterocyclyl.
4. The compound of formula (VIII), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, wherein: Z is selected from the group consisting of -CH 2 -, -CH 2 NH-, -CH 2 O-, -CH 2 -, -NH- and -NHSO 2 -.
5. The compound of formula (VIII), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, selected from the group consisting of: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] --- [Image disponible dans le document PDF, Image available in the PDF document]6. A pharmaceutical composition, comprising a therapeutically effective amount of the compound of formula (VIII), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1-5, and one or more pharmaceutically acceptable carriers, diluents or excipients.
7. Use of the compound of formula (VIII), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1-5, or the pharmaceutical composition according to claim 6 in the preparation of a GABAA receptor regulator medicament.
8. Use of the compound of formula (VIII), the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1-5, or the pharmaceutical composition according to claim 6 in treating a CNS-related disease, wherein the CNS-related disease is selected from the group consisting of sleep disorder, mood disorder, schizophrenia spectrum disorder, spasmodic disorder, memory disorder and / or cognitive disorder, dyskinesia, personality disorder, autism spectrum disorder, pain, traumatic brain injury, vascular disease, substance abuse disorder and / or withdrawal syndrome or tinnitus.