The present invention relates to therapeutically active compounds useful in the treatment of a steroid receptor, in particular androgen receptor (AR), dependent conditions and diseases, and to pharmaceutical compositions containing such

compounds.

Background of the invention

Prostate cancer is worldwide the most common cancer in men. Even though the 5 -year survival rate of patients with localized prostate cancer is high, the prognosis for those patients, who develop castration-resistant prostate cancer (CRPC) within that 5-year follow-up period, is poor.

The androgen receptor (AR) signalling axis is critical in all stages of prostate cancer. In the CPRC stage, disease is characterized by high AR expression, AR amplification and persistent activation of the AR signalling axis by residual tissue/tumor androgens and by other steroid hormones and intermediates of steroid biosynthesis. Thus, treatment of advanced prostate cancer involves androgen deprivation therapy (ADT) such as hormonal manipulation using gonadotropin-releasing hormone (GnRH) agonists/antagonists or surgical castration, AR antagonists or CYP17A1 inhibitors (such as abiraterone acetate in combination with prednisone).

Although therapies can initially lead to disease regression, eventually majority of the patients develop a disease that is refractory to currently available therapies. Increased progesterone levels in patients treated with abiraterone acetate has been hypothesized to be one of the resistance mechanisms. Several nonclinical and clinical studies have indicated upregulation of enzymes that catalyse steroid biosynthesis at the late stage of CRPC. Very recently it has been published that 1 Ιβ-OH androstenedione can be

metabolized into 11-ketotestosterone (11-K-T) and 11-ketodehydrotestosterone (11-K-DHT) which can bind and activate AR as efficiently as testosterone and

dihydrotestosterone. It has been shown that these steroids are found in high levels in plasma and tissue in prostate cancer patients, suggesting their role as AR agonists in CRPC. Furthermore, it has been addressed that prostate cancer resistance to CYP17A1 inhibition may still remain steroid dependent and responsive to therapies that can further suppress de novo intratumoral steroid synthesis upstream of CYP17A1, such as by CYPl 1A1 inhibition therapy (Cai, C. et al, Cancer Res., 71(20), 6503-6513, 2011).

Cytochrome P450 monooxygenase 11A1 (CYPl 1A1), also called cholesterol side chain cleavage enzyme, is a mitochondrial monooxygenase which catalyses the conversion of cholesterol to pregnenolone, the precursor of all steroid hormones. By inhibiting CYPl 1A1, the key enzyme of steroid biosynthesis upstream of CYP17A1, the total block of the whole steroid biosynthesis can be achieved. CYPl 1A1 inhibitors may therefore have a great potential for treating steroid hormone dependent cancers, such as prostate cancer, even in advanced stages of the disease, and especially in those patients who appear to be hormone refractory. It has been recently shown that a compound having CYPl 1 Al inhibitory effect significantly inhibited tumor growth in vivo in a murine CRPC xenograft model (Oksala, R. et al, Annals of Oncology, (2017) 28 (suppl. 5): Abstract/Poster 28P).

Summary of the invention

It has been found that compounds of formula (I) are potent CYPl 1 Al inhibitors. The compounds of the invention are therefore useful as medicaments in the treatment of steroid hormone dependent conditions and diseases where CYPl 1 Al inhibition is desired. Such conditions and diseases include, but are not limited to, endocrine cancers and diseases, such as prostate cancer and breast cancer. In particular, the compounds of the invention are useful in the treatment of AR dependent conditions and diseases including prostate cancer.

The present invention relates to a compound of formula (I)

wherein

ring B is a 4-10 membered monocyclic or bicyclic ring containing 0-4 hetero-atoms independently selected form N, O or S

ring A is any of the following groups

L is absent, -CH2- , -CH2-CH2- or -CH2-CH2-CH2-, or in case ring A is (1), L can also be -C(0)-CH2-;

Ri is hydrogen, Ci_7 alkyl, Ci_7 alkoxy, halogen, cyano, nitro, halo Ci_7 alkyl, halo Ci-7 alkoxy or C 1-7 alkylthio;

R2 is hydrogen, Ci_7 alkyl, halogen, hydroxy, halo Ci_7 alkyl, nitro, halo Ci_7 alkoxy or thiol;

or Ri and R2 together with the carbon atoms to which they are attached form a fused 1 ,3 dioxole ring;

R3 is hydrogen, halogen, nitro, cyano, oxo, Ci_7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, hydroxy C3-7 cycloalkyl, Ci_7 alkoxy, hydroxy Ci_7 alkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkylthio, aminocarbonyl C2_7 alkenyl, halo Ci-7 alkylthio, Ci-7 alkoxycarbonyl Ci-7 alkyl, Ci-7 alkoxycarbonyl C2_7 alkenyl, =NSO2R20,

-S(0)-d_7 alkyl, -S(0)(NR14)(R22), -S(NR15)(C1-7 alkyl), -C(S)NR18R19,

-D-C(0)-NR6R7, -C(0)R8, -D-NR9R10, -S02Rn, an optionally substituted 3-10 membered carbocyclyl, an optionally substituted 3-10 membered carbocyclyl Ci-7 alkyl,

an optionally substituted 4-10 membered heterocyclyl or an optionally substituted 4-10 membered heterocyclyl Ci-7 alkyl;

R4 is hydrogen, halogen, hydroxy, Ci_7 alkyl, halo Ci_7 alkyl or oxo;

R5 is hydrogen, halogen or Ci_7 alkyl;

Re is hydrogen, Ci_7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, hydroxy Ci_7 alkyl, cyano

Ci-7 alkyl, -Ci_7 alkyl-0-C(0)Ci_7 alkyl or an optionally substituted 4-10 membered heterocyclyl;

R8 is hydrogen, Ci_7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, Ci_7 alkoxy, halo Ci_7 alkyl, Ci-7 alkoxy Ci_7 alkyl, Ci_7 alkylcarbonyl, Ci_7 alkoxycarbonyl, -Ci_7 alkyl-0-C(0)-Ci_7 alkyl, -C1-7 alkyl-S02(Ci_7 alkyl), -N=S(0)(C1-7 alkyl)(Ci_7 alkyl) or an optionally substituted 4-10 membered heterocyclyl;

R9 is hydrogen, Ci_7 alkyl, C3-7 cycloalkyl, Ci_7 alkylcarbonyl, -S02(Ci_7 alkyl) or -S02(C3-7 cycloalkyl);

R11 is Ci_7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NRi2Ri3, an optionally substituted 3-10 membered carbocyclyl or an optionally substituted 4-10 membered heterocyclyl;

Ri2 is hydrogen, Ci_7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy, Ci_7 alkoxy Ci_7 alkyl or Ci_7 alkylcarbonyl;

R7, Rio, Ri3, Ri8, and R19 are, independently, hydrogen, Ci_7 alkyl or C3-7 cyclo-alkyl;

Ri4 is hydrogen, Ci_7 alkyl, Ci_7 alkylcarbonyl or -S02R2i;

Ri5 is hydrogen, Ci_7 alkyl, C3-7 cycloalkyl, Ci_7 alkylcarbonyl, -S02Ri7;

Ri7 is Ci_7 alkyl or an optionally substituted 3-10 membered carbocyclyl;

R20 and R2i are, independently, Ci_7 alkyl, C3-7 cycloalkyl or an optionally substituted 3-10 membered carbocyclyl;

R22 is Ci_7 alkyl or C3-7 cycloalkyl;

R23 is hydrogen or oxo;

R24 is hydrogen or Ci_7 alkyl;

D is absent, Ci_7 alkyl or C2_7 alkenyl;

wherein the optional substitution in each occurrence is selected from 1-3 substituents independently selected from Ci_7 alkyl, halogen, hydroxy, Ci_7 alkoxy, Ci_7 alkoxy Ci-7 alkyl, Ci_7 alkoxycarbonyl or oxo; and

wherein the heterocyclyl group in each occurrence has 1-4 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof;

with the proviso that the compound is not

2-[(3,4-Dihydro-2(lH)-isoquinolinyl)methyl]-5-[(2,5-dimethylphenyl)methoxy]-4H-pyran-4-one;

5-[(2,4-Dichlorophenyl)methoxy]-2-[(3,4-dihydro-2(lH)-isoquinolinyl)methyl]-4H-pyran-4-one;

5 - [(3 -Chlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(4-methylphenyl)methoxy] -4H-pyran-4-one;

5 - [(3 ,4-Dichlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 -fluorophenyl)methoxy] -4H-pyran-4-one;

2-[(3,4-Dihydro-2(lH)-isoquinolinyl)methyl]-5-(l-naphthalenylmethoxy)-4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [ [3 -(trifluoromethyl)phenyl] methoxy] -4H-pyran-4-one;

5 - [(2-Chlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

5-[(2-Chloro-6-fluorophenyl)methoxy]-2-[(3,4-dihydro-2(lH)-isoquinolinyl) methyl] -4H-pyran-4-one;

5 - [(4-Chlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

5 - [(4-Bromophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(2-fluorophenyl)methoxy] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(2-methylphenyl)methoxy] -4H-pyran-4-one;

2-[(3,4-Dihydro-2(lH)-isoquinolinyl)methyl]-5-(phenylmethoxy)-4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [ [4-(trifluoromethyl)phenyl] methoxy] -4H-pyran-4-one;

Methyl 4-(((6-((3,4-dihydroisoquinolin-2(lH)-yl)methyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)benzoate;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(4-fluorophenyl)methoxy] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 ,5 -dimethoxyphenyl)methoxy] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 -nitrophenyl)methoxy] - 4H-pyran-4-one;

Methyl 5 -(((6-((3 ,4-dihydroisoquinolin-2( 1 H)-yl)methyl)-4-oxo-4H-pyran-3 -yl)oxy)methyl)furan-2-carboxylate;

2-[(3,4-Dihydro-2(lH)-isoquinolinyl)methyl]-5-(2-phenylethoxy)-4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 -methylphenyl)methoxy] -4H-pyran-4-one; or

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(4-nitrophenyl)methoxy] -4H-pyran-4-one.

According to one embodiment, the invention provides a method for the treatment or prevention of a steroid receptor, particularly androgen receptor (AR), dependent conditions and diseases, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I)

wherein

ring B is a 4-10 membered monocyclic or bicyclic ring containing 0-4 hetero-atoms independently selected form N, O or S

ring A is any of the following groups

L is absent, -CH2- , -CH2-CH2- or -CH2-CH2-CH2-, or in case ring A is (1), L can also be -C(0)-CH2-;

Ri is hydrogen, Ci_7 alkyl, Ci_7 alkoxy, halogen, cyano, nitro, halo Ci_7 alkyl, halo Ci-7 alkoxy or C 1-7 alkylthio;

R2 is hydrogen, Ci_7 alkyl, halogen, hydroxy, halo Ci_7 alkyl, nitro, halo Ci_7 alkoxy or thiol;

or Ri and R2 together with the carbon atoms to which they are attached form a fused 1 ,3 dioxole ring;

R3 is hydrogen, halogen, nitro, cyano, oxo, Ci_7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, ydroxyl C3-7 cycloalkyl, Ci_7 alkoxy, ydroxyl Ci_7 alkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkylthio, amino carbonyl C2_7 alkenyl, halo Ci-7 alkylthio, Ci-7 alkoxycarbonyl Ci-7 alkyl, Ci-7 alkoxycarbonyl C2_7 alkenyl, =NSO2R20,

-S(0)-d_7 alkyl, -S(0)(NR14)(R22), -S(NR15)(C1-7 alkyl), -C(S)NR18R19,

-D-C(0)-NR6R7, -C(0)R8, -D-NR9R10, -S02Rn, an optionally substituted 3-10 membered carbocyclyl, an optionally substituted 3-10 membered carbocyclyl Ci-7 alkyl, an optionally substituted 4-10 membered heterocyclyl or an optionally substituted 4-10 membered heterocyclyl Ci-7 alkyl;

R4 is hydrogen, halogen, hydroxy, Ci-7 alkyl, halo Ci-7 alkyl or oxo;

R5 is hydrogen, halogen or Ci_7 alkyl;

Re is hydrogen, Ci_7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, hydroxy Ci_7 alkyl, cyano Ci-7 alkyl, -Ci_7 alkyl-0-C(0)Ci_7 alkyl or an optionally substituted 4-10 membered heterocyclyl;

R8 is hydrogen, Ci_7 alkyl, C2-7 alkenyl, C3_7 cycloalkyl, Ci_7 alkoxy, halo Ci_7 alkyl,

Ci-7 alkoxy Ci_7 alkyl, Ci_7 alkylcarbonyl, Ci_7 alkoxycarbonyl, -Ci_7 alkyl-0-C(0)-Ci_7 alkyl, -C1-7 alkyl-S02(Ci_7 alkyl), -N=S(0)(C1-7 alkyl)(Ci_7 alkyl) or an optionally substituted 4-10 membered heterocyclyl;

R9 is hydrogen, Ci_7 alkyl, C3_7 cycloalkyl, Ci_7 alkylcarbonyl, -S02(Ci_7 alkyl) or -S02(C3-7 cycloalkyl);

R11 is Ci_7 alkyl, C2_7 alkenyl, C3_7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NRi2Ri3, an optionally substituted 3-10 membered carbocyclyl or an optionally substituted 4-10 membered heterocyclyl;

Ri2 is hydrogen, Ci_7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy, Ci_7 alkoxy C 1 _7 alkyl or C 1 _7 alkylcarbonyl;

R7, Rio, Ri3, Ri8, and R19 are, independently, hydrogen, Ci_7 alkyl or C3_7 cycloalkyl;

Ri4 is hydrogen, Ci_7 alkyl, Ci_7 alkylcarbonyl or -S02R2i;

Ri5 is hydrogen, Ci_7 alkyl, C3_7 cycloalkyl, Ci_7 alkylcarbonyl, -S02Ri7;

Ri7 is Ci_7 alkyl or an optionally substituted 3-10 membered carbocyclyl;

R20 and R2i are, independently, Ci_7 alkyl, C3_7 cycloalkyl or an optionally substituted 3-10 membered carbocyclyl;

R22 is Ci_7 alkyl or C3_7 cycloalkyl;

R23 is hydrogen or oxo;

R24 is hydrogen or Ci_7 alkyl;

D is absent, Ci_7 alkyl or C2_7 alkenyl;

wherein the optional substitution in each occurrence is selected from 1-3 substituents independently selected from Ci_7 alkyl, halogen, hydroxy, Ci_7 alkoxy, Ci_7 alkoxy Ci_7 alkyl, Ci_7 alkoxycarbonyl or oxo; and

wherein the heterocyclyl group in each occurrence has 1-4 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof.

According to one embodiment, the invention provides a pharmaceutical composition comprising a compound of formula (I) as defined in any of the above embodiments together with a pharmaceutically acceptable carrier.

According to one embodiment, the invention provides a method for the treatment or prevention of a steroid receptor, in particular androgen receptor (AR), dependent conditions and diseases. Such conditions and diseases include, but are not limited to, endocrine cancers and diseases, such as prostate cancer and breast cancer. The method comprises administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) as defined in any of the above embodiments.

Detailed description of the invention

The present application provides novel 4H-pyran-4-one derivatives of formula (I) or pharmaceutically acceptable salts thereof which are useful as CYP11 Al inhibitors.

One of the embodiments of the present invention provides a compound of formula I)

wherein

ring B is a 4-10 membered monocyclic or bicyclic ring containing 0-4 hetero-atoms independently selected form N, O or S

ring A is any of the following groups

L is absent, -CH2- , -CH2-CH2- or -CH2-CH2-CH2-, or in case ring A is (1), L can also be -C(0)-CH2-;

Ri is hydrogen, Ci_7 alkyl, Ci_7 alkoxy, halogen, cyano, nitro, halo Ci_7 alkyl, halo

Ci-7 alkoxy or C 1-7 alkylthio;

R2 is hydrogen, Ci_7 alkyl, halogen, hydroxy, halo Ci_7 alkyl, nitro, halo Ci_7 alkoxy or thiol;

or Ri and R2 together with the carbon atoms to which they are attached form a fused 1 ,3 dioxole ring;

R3 is hydrogen, halogen, nitro, cyano, oxo, Ci_7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, hydroxy C3-7 cycloalkyl, Ci_7 alkoxy, hydroxy Ci_7 alkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkylthio, amino carbonyl C2_7 alkenyl, halo Ci-7 alkylthio, Ci-7 alkoxycarbonyl Ci-7 alkyl, Ci-7 alkoxycarbonyl C2_7 alkenyl, =NS02R2o,-S(0)-Ci_7 alkyl, -S(0)(NR14)(R22), -S(NR15)(d_7 alkyl), -C(S)NR18R19,

-D-C(0)-NR6R7, -C(0)R8, -D-NR9R10, -S02Rn, an optionally substituted 3-10 membered carbocyclyl, an optionally substituted 3-10 membered carbocyclyl Ci-7 alkyl, an optionally substituted 4-10 membered heterocyclyl or an optionally substituted 4-10 membered heterocyclyl Ci-7 alkyl;

R4 is hydrogen, halogen, hydroxy, Ci-7 alkyl, halo Ci-7 alkyl or oxo;

R5 is hydrogen, halogen or Ci-7 alkyl;

Re is hydrogen, Ci-7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, hydroxy Ci-7 alkyl, cyano Ci-7 alkyl, -Ci-7 alkyl-0-C(0)Ci_7 alkyl or an optionally substituted 4-10 membered heterocyclyl;

R8 is hydrogen, Ci-7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, Ci-7 alkoxy, halo Ci-7 alkyl,

Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkylcarbonyl, Ci-7 alkoxycarbonyl, -Ci-7 alkyl-0-C(0)-Ci_7 alkyl, -C1-7 alkyl-S02(Ci_7 alkyl), -N=S(0)(C1-7 alkyl)(C1-7 alkyl) or an optionally substituted 4-10 membered heterocyclyl;

R9 is hydrogen, Ci_7 alkyl, C3-7 cycloalkyl, Ci_7 alkylcarbonyl, -S02(Ci_7 alkyl) or -S02(C3-7 cycloalkyl);

R11 is Ci-7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci-7 alkoxy Ci_7 alkyl, -NR12R13, an optionally substituted 3-10 membered carbocyclyl or an optionally substituted 4-10 membered heterocyclyl;

R12 is hydrogen, Ci_7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy, Ci_7 alkoxy Ci-7 alkyl or C 1-7 alkylcarbonyl;

R7, Rio, Ri3, Ri8, and R19 are, independently, hydrogen, Ci-7 alkyl or C3-7 cycloalkyl;

Ri4 is hydrogen, Ci-7 alkyl, Ci-7 alkylcarbonyl or -SO2R21;

Ri5 is hydrogen, Ci-7 alkyl, C3-7 cycloalkyl, Ci-7 alkylcarbonyl, -SO2R17;

Ri7 is Ci-7 alkyl or an optionally substituted 3-10 membered carbocyclyl;

R20 and R2i are, independently, Ci-7 alkyl, C3-7 cycloalkyl or an optionally substituted 3-10 membered carbocyclyl;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

R23 is hydrogen or oxo;

R24 is hydrogen or Ci-7 alkyl;

D is absent, Ci-7 alkyl or C2-7 alkenyl;

wherein the optional substitution in each occurrence is selected from 1-3 substituents independently selected from Ci-7 alkyl, halogen, hydroxy, Ci-7 alkoxy, Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkoxycarbonyl or oxo; and

wherein the heterocyclyl group in each occurrence has 1-4 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof;

with the proviso that the compound is not

2-[(3,4-Dihydro-2(lH)-isoquinolinyl)methyl]-5-[(2,5-dimethylphenyl)methoxy]-4H-pyran-4-one;

5-[(2,4-Dichlorophenyl)methoxy]-2-[(3,4-dihydro-2(lH)-isoquinolinyl)methyl]-4H-pyran-4-one;

5 - [(3 -Chlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(4-methylphenyl)methoxy] -4H-pyran-4-one;

5 - [(3 ,4-Dichlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 -fluorophenyl)methoxy] -4H-pyran-4-one;

2-[(3,4-Dihydro-2(lH)-isoquinolinyl)methyl]-5-(l-naphthalenylmethoxy^ pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [ [3 -(trifluoromethyl)phenyl] methoxy] -4H-pyran-4-one;

5 - [(2-Chlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

5-[(2-Chloro-6-fluorophenyl)methoxy]-2-[(3,4-dihydro-2(lH)-isoquinolinyl) methyl] -4H-pyran-4-one;

5 - [(4-Chlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

5 - [(4-Bromophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(2-fluorophenyl)methoxy] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(2-methylphenyl)methoxy] -4H-pyran-4-one;

2-[(3,4-Dihydro-2(lH)-isoquinolinyl)methyl]-5-(phenylmethoxy)-4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [ [4-(trifluoromethyl)phenyl] methoxy] -4H-pyran-4-one;

Methyl 4-(((6-((3,4-dihydroisoquinolin-2(lH)-yl)methyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)benzoate;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(4-fluorophenyl)methoxy] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 ,5 -dimethoxyphenyl)methoxy] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 -nitrophenyl)methoxy] - 4H-pyran-4-one;

Methyl 5 -(((6-((3 ,4-dihydroisoquinolin-2( 1 H)-yl)methyl)-4-oxo-4H-pyran-3 -yl)oxy)methyl)furan-2-carboxylate;

2-[(3,4-Dihydro-2(lH)-isoquinolinyl)methyl]-5-(2-phenylethoxy)-4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 -methylphenyl)methoxy] -4H-pyran-4-one; or

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(4-nitrophenyl)methoxy] -4H-pyran-4-one.

It is to be understood that the left bond in linker L is attached to the ring B of formula (I).

According to one embodiment, the compound according to the present invention is represented by formula (IA):

wherein Ri, R2, R3, R4, R5, R23, R24, L and B are as defined in any of the above embodiments for formula (I), or a pharmaceutically acceptable salt thereof.

According to one embodiment, the compound according to the present invention is represented by formula (IB):

(IB), wherein Ri, R2, R3, R4, R5, R24, L and B are as defined in any of the above embodiments for formula (I), or a pharmaceutically acceptable salt thereof.

According to one embodiment, specifically provided is a compound of formula (I) wherein L is -CH2- or -CH2-CH2-, for example L is -CH2- or as another example L is -CH2-CH2-.

According to one embodiment, specifically provided is a compound of formula (I), wherein ring B is any one of the following groups

(13') (14-) (15') or (16')

wherein R3, R4 and R5, as defined in any of the above embodiments for formula (I), are attached to the above B-rings.

In a subclass of the above embodiment are compounds wherein ring B is any one of the following groups

(11a') (12') (13a') (14a') (15a') nr (16a')

and wherein R3, R4 and R5, as defined in any of the above embodiments for formula (I), are attached to the above B-rings and wherein the wavy line denotes the site of attachment to L.

According to yet one embodiment, specifically provided are compounds wherein ring B is ring ( ), (5'), (7'), (9'), (13') or (14') as defined above.

In a subclass of the above embodiment are compounds wherein ring B is (1 '), (5a'), (7'), (9a'), (13a') or (14a') as defined above.

According to one embodiment, specifically provided are compounds wherein R3 is hydrogen, Ci_7 alkyl, C2-7 alkenyl, hydroxy Ci_7 alkyl, cyano, Ci_7 alkylthio,

Ci_7 alkoxycarbonyl C2-7 alkenyl, -D-C(0)-NR6R7, -C(0)R8 , -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22), -S(NR15)(C1-7 alkyl), -C(S) R18R19, an optionally substituted 3-10 membered carbocyclyl, an optionally substituted 4-10 membered heterocyclyl, or an optionally substituted 4-10 membered heterocyclyl Ci_7 alkyl; wherein the optional substitution in each occurrence is selected from 1-3 substituents independently selected from Ci-7 alkyl, halogen, hydroxy, Ci_7 alkoxy, Ci_7 alkoxy Ci_7 alkyl, Ci_7 alkoxycarbonyl or oxo, and wherein the heterocyclyl group in each occurrence has 1-3 heteroatoms independently selected from N, O and S.

According to one embodiment, specifically provided are compounds wherein R4 and R5 are hydrogen.

According to one embodiment, the compound according to the present invention is represented b formula (IC):

wherein Ri, R2, R3, R4, R5 and R24 are as defined in any of the above embodiments for formula (I), or a pharmaceutically acceptable salt thereof.

According to one embodiment, the compound according to the present invention is represented b formula (ID):

wherein Ri, R2, R3, R4, R5 and R24 are as defined in any of the above embodiments for formula (I), or a pharmaceutically acceptable salt thereof.

According to one embodiment, the compound according to the present invention is represented by formula (IE):

(IE)

wherein Ri, R2, R3, R4, R5 and R24 are as defined in any of the above embodiments for formula (I), or a pharmaceutically acceptable salt thereof.

According to one embodiment, specifically provided are compounds as defined in any of the above embodiments wherein

Ri is hydrogen, Ci_7 alkyl, Ci_7 alkoxy, halogen, cyano, nitro, halo Ci_7 alkyl, halo Ci-7 alkoxy or C 1-7 alkylthio;

R2 is hydrogen or halogen;

R3 is hydrogen, Ci_7 alkyl, C2-7 alkenyl, hydroxy Ci_7 alkyl, cyano, thio,

Ci_7 alkoxycarbonyl C2-7 alkenyl, -D-C(0)-NR6R7, -C(0)R8 , -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22), -S(NR15)(C1-7 alkyl), -C(S)NRi8Ri9, a 3-6 membered carbocyclyl which is optionally substituted with 1-2 hydroxyl substituents, a 4-6 membered heterocyclyl which is optionally substituted with 1-2 substituents selected from halogen, hydroxyl, Ci_7 alkoxycarbonyl or oxo, or a 4-6 membered heterocyclyl Ci_7 alkyl optionally substituted with 1-2 oxo substituents;

R4 is hydrogen, Ci_7 alkyl, hydroxy or halogen;

R5 is hydrogen or halogen;

Re is Ci_7 alkyl, C3_7 cycloalkyl, hydroxy Ci_7 alkyl, -Ci_7 alkyl-0-C(0)Ci_7 alkyl; R7 is hydrogen or Ci_7 alkyl;

R8 is hydrogen, Ci_7 alkyl, C2-7 alkenyl, C3_7 cycloalkyl, Ci_7 alkoxy, halo Ci_7 alkyl,

Ci_7 alkoxy Ci_7 alkyl, Ci_7 alkylcarbonyl, Ci_7 alkoxycarbonyl,

-Ci_7 alkyl-0-C(0)-Ci_7 alkyl, -C1-7 alkyl-S02(Ci_7 alkyl), -N=S(0)(C1-7 alkyl)(Ci_7 alkyl) or a 4-6 membered heterocyclyl which is optionally substituted with 1-2 halogen

substituents;

R9 is Ci_7 alkylcarbonyl, -S02(Ci_7 alkyl) or -S02(C3-7 cycloalkyl);

Rio is hydrogen, Ci_7 alkyl or C3_7 cycloalkyl;

R11 is Ci_7 alkyl, C3_7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NRi2Ri3, a 3-6 membered carbocyclyl which is optionally substituted with 1-2 substituents selected from halogen or Ci_7 alkyl, or a 4-6 membered heterocyclyl which is optionally substituted with 1-2 substituents selected from halogen or Ci_7 alkyl;

Ri2 is Ci_7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl or

Ci-7 alkylcarbonyl;

Ri3 is hydrogen or Ci_7 alkyl;

Ri4 is hydrogen, Ci_7 alkyl, Ci_7 alkylcarbonyl or -SO2R21;

Ri5 is hydrogen, Ci_7 alkyl, -S02Ri7;

Ri7 is Ci-7 alkyl or a 3-6 membered carbocyclyl which is optionally substituted by

1-2 Ci-7 alkyl substituent;

Ri8, and Rig are, independently, hydrogen or Ci_7 alkyl;

R21 is a 3-6 membered carbocyclyl optionally substituted with 1-2 Ci_7 alkyl substituents;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

R24 is hydrogen or Ci_7 alkyl;

wherein the heterocyclyl group in each occurrence has 1-3 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof.

In one subclass are compounds represented by formula (IC) wherein

Ri is hydrogen, Ci_7 alkoxy, halogen, nitro, halo Ci_7 alkyl, halo Ci_7 alkoxy or Ci-7 alkylthio;

R2 is hydrogen or halogen;

R3 is C2-7 alkenyl, hydroxy Ci_7 alkyl, cyano, Ci_7 alkoxycarbonyl C2-7 alkenyl,

-D-C(0)-NR6R7, -C(0)R8, -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22), -S(NR15)(C1-7 alkyl), a 3-6 membered carbocyclyl which is optionally substituted with 1-2 hydroxy

substituents, or a 4-6 membered heterocyclyl which is optionally substituted with 1-2 substituents selected from halogen or hydroxy;

R4 is hydrogen, hydroxy or halogen;

R5 is hydrogen or halogen;

Re is Ci_7 alkyl, hydroxy Ci_7 alkyl or -C1-7 alkyl-0-C(0)Ci_7 alkyl;

R7 is hydrogen or Ci-7 alkyl;

R8 is Ci_7 alkyl, halo Ci_7 alkyl, -N=S(0)(Ci_7 alkyl)(Ci_7 alkyl) or a 4-6 membered heterocyclyl which is optionally substituted with 1-2 halogen substituents;

R9 is Ci-7 alkylcarbonyl or -S02(Ci-7 alkyl);

Rio is hydrogen or Ci_7 alkyl;

Rii is Ci-7 alkyl, C3-7 cycloalkyl, halo Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NR12R13 or a 4-6 membered heterocyclyl;

R12 is Ci-7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl or Ci-7 alkylcarbonyl;

Ri3 is hydrogen or Ci_7 alkyl;

Ri4 is hydrogen, Ci_7 alkyl or Ci_7 alkylcarbonyl;

Ri5 is hydrogen or -S02Ri7;

Ri7 is a 3-6 membered carbocyclyl which is optionally substituted by 1-2

Ci-7 alkyl substituents;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

R24 is hydrogen or Ci_7 alkyl;

D is absent, Ci_7 alkyl or C2-7 alkenyl;

wherein the heterocyclyl group in each occurrence has 1-3 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof.

In a subclass of the above embodiment are compounds wherein

Ri is hydrogen, Ci_7 alkoxy, halogen, nitro, halo Ci_7 alkyl or halo Ci_7 alkoxy; R2 and Rio are hydrogen;

R3 is C2-7 alkenyl, hydroxy Ci_7 alkyl, cyano, Ci_7 alkoxycarbonyl C2-7 alkenyl, -D-C(0)-NR6R7, -C(0)R8, -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22), -S(NR15)(C1-7 alkyl), oxazolyl, cyclobutyl optionally substituted with a hydroxy substituent, or oxetanyl optionally substituted with a hydroxy substituent;

R4 and R5 are hydrogen or halogen;

Re is C 1-7 alkyl or hydroxy Ci-7 alkyl;

R7, Ri3, Ri4 and R24 are hydrogen or Ci-7 alkyl;

R8 is Ci-7 alkyl, pyrrolidinyl, oxetanyl, or azetidinyl optionally substituted with 1-2 halogen substituents,-N=S(0)(Ci_7 alkyl)(Ci_7 alkyl);

R9 is -S02(Ci_7 alkyl);

Rii is Ci-7 alkyl, C3-7 cycloalkyl, halo Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NR12R13, pyrrolidinyl, piperidinyl, azetidinyl or morpholinyl;

R12 is Ci-7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl or Ci-7 alkylcarbonyl;

Ri5 is hydrogen or -SO2R17;

Ri7 is phenyl optionally substituted by a Ci_7 alkyl substituent;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

D is absent, Ci_7 alkyl or C2-7 alkenyl;

or a pharmaceutically acceptable salt thereof.

In still another subclass of the above embodiment are compounds wherein Ri is hydrogen, Ci_7 alkoxy, halogen, halo Ci_7 alkyl or halo Ci_7 alkoxy;

R2 and Rio are hydrogen;

R3 is hydroxy Ci_7 alkyl, cyano, Ci_7 alkoxycarbonyl C2-7 alkenyl, -D-C(0)-NR6R7, -C(0)R8, -SO2R11, -D-NR9R10, -S(0)(NRi4)(R22), -S(NR15)(C1-7 alkyl), oxazolyl, cyclobutyl optionally substituted with a hydroxy substituent, or oxetanyl optionally substituted with a hydroxy substituent;

R4 and R5 are hydrogen or halogen;

Re is C 1-7 alkyl;

R7, Ri3, Ri4 and R24 are hydrogen or Ci-7 alkyl;

R8 is pyrrolidinyl, azetidinyl or -N=S(0)(Ci_7 alkyl)(Ci_7 alkyl);

R9 is -S02(Ci_7 alkyl);

R11 is Ci-7 alkyl, halo Ci-7 alkyl, -NR12R13 or pyrrolidinyl;

R12 is Ci-7 alkyl, hydroxy Ci-7 alkyl, cyano Ci-7 alkyl, Ci-7 alkoxy Ci-7 alkyl or Ci-7 alkylcarbonyl;

Ri7 is phenyl optionally substituted by a Ci-7 alkyl substituent;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

D is absent, Ci-7 alkyl or C2-7 alkenyl;

or a pharmaceutically acceptable salt thereof.

In still another subclass of the above embodiment are compounds wherein Ri is hydrogen, halogen, halo Ci_7 alkyl or halo Ci_7 alkoxy;

R2, R4, R5 and Rio are hydrogen;

R3 is hydroxy Ci_7 alkyl, -D-C(0)-NR6R7, -C(0)R8, -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22) or oxetanyl optionally substituted with a hydroxy substituent;

5 and R7 is Ci_7 alkyl;

R8 is pyrrolidinyl, or -N=S(0)(C1-7 alkyl)(Ci_7 alkyl);

R9 is -S02(Ci_7 alkyl);

R11 is Ci-7 alkyl, -NR12R13 or pyrrolidinyl;

R12 is Ci_7 alkyl, hydroxy Ci_7 alkyl, or Ci_7 alkoxy Ci_7 alkyl;

Ri3 and RM is hydrogen or Ci_7 alkyl;

R22 is Ci_7 alkyl or C3_7 cycloalkyl;

D is Ci_7 alkyl or C2-7 alkenyl;

or a pharmaceutically acceptable salt thereof.

In one subclass are compounds represented by formula (ID) wherein

Ri is hydrogen, Ci_7 alkyl, cyano, halogen, nitro, halo Ci_7 alkyl, halo Ci_7 alkoxy or Ci_7 alkylthio;

R2 is hydrogen or halogen;

R3 is -D-C(0)-NR6R7, -C(0)R8 , -S02Rn or -C(S)NRi8Ri9;

R4 is hydrogen, Ci_7 alkyl, hydroxy or halogen;

R5 is hydrogen;

Re is Ci_7 alkyl or C3_7 cycloalkyl;

R7 and R24 are hydrogen or Ci_7 alkyl;

R8 is hydrogen, Ci_7 alkyl, C2-7 alkenyl, C3_7 cycloalkyl, halo Ci_7 alkyl, Ci_7 alkylcarbonyl, Ci_7 alkoxycarbonyl, Ci_7 alkoxy Ci_7 alkyl, -Ci_7 alkyl-0-C(0)-Ci_7 alkyl, -Ci_7 alkyl-S02(Ci-7 alkyl) or a 4-10 membered heterocyclyl;

R11 is Ci_7 alkyl, C3_7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NRi2Ri3, a 3-6 membered carbocyclyl which is optionally substituted with 1-2 halogen substituents, or a 4-6 membered heterocyclyl which is optionally substituted with 1-2 substituents selected from halogen or Ci_7 alkyl;

Ri2 and Ri3 are Ci_7 alkyl;

Ri8, and R19 are, independently, hydrogen or Ci_7 alkyl;

D is absent;

wherein the heterocyclyl group in each occurrence has 1-3 heteroatoms independently selected from N, O and S.

or a pharmaceutically acceptable salt thereof.

In a subclass of the above embodiment are compounds wherein

Ri is hydrogen, Ci_7 alkyl, halogen, halo Ci_7 alkyl or halo Ci_7 alkoxy;

R2 and R5 are hydrogen;

R3 is -D-C(0)-NR6R7, -C(0)R8 , -S02Rn, or -C(S)NRi8Ri9, or oxetanyl optionally substituted by a hydroxy substituent;

R4 is hydrogen, Ci_7 alkyl or halogen;

Re is Ci-7 alkyl;

R7 is hydrogen or Ci_7 alkyl;

R8 is Ci-7 alkyl, C2-7 alkenyl, C3_7 cycloalkyl, halo Ci_7 alkyl, Ci_7 alkylcarbonyl, Ci_7 alkoxycarbonyl, Ci_7 alkoxy Ci_7 alkyl, -Ci_7 alkyl-0-C(0)-Ci_7 alkyl,

-Ci-7 alkyl-S02(Ci-7 alkyl), azetidinyl, morpholinyl, furanyl or pyrrolidinyl;

R11 is Ci-7 alkyl, C3_7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NRi2Ri3, pyrrolidinyl, phenyl optionally substituted with a halogen substituent, oxetanyl, or pyrazolyl optionally substituted with a Ci_7 alkyl substituent;

Ri2 and Ri3 are Ci_7 alkyl;

Ri8 and Rig are, independently, hydrogen or Ci_7 alkyl;

R24 is hydrogen or Ci_7 alkyl;

D is absent;

or a pharmaceutically acceptable salt thereof.

In still another subclass of the above embodiment are compounds wherein Ri is hydrogen, Ci_7 alkyl, halogen, halo Ci_7 alkyl or halo Ci_7 alkoxy;

R2, R5 and R7 are hydrogen;

R3 is -D-C(0)-NR6R7, -C(0)R8 or -S02Rn;

R4 is hydrogen or Ci_7 alkyl;

Re is C 1-7 alkyl;

R8 is Ci-7 alkyl, C3-7 cycloalkyl, halo Ci_7 alkyl, Ci_7 alkylcarbonyl,

-Ci-7 alkyl-0-C(0)-Ci-7 alkyl, -Ci_7 alkyl-S02(Ci_7 alkyl), morpholinyl or pyrrolidinyl;

R11 is Ci-7 alkyl, C3-7 cycloalkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl,

-NR12R13, oxetanyl, or pyrazolyl optionally substituted with a Ci_7 alkyl substituent;

R12 and Ri3 are Ci_7 alkyl;

R24 is hydrogen or Ci_7 alkyl;

D is absent;

or a pharmaceutically acceptable salt thereof.

In still another subclass of the above embodiment are compounds wherein

Ri is hydrogen, halogen, halo Ci_7 alkyl or halo Ci_7 alkoxy;

R2, R4, R5 and R7 are hydrogen;

R3 is -D-C(0)-NR6R7, -C(0)R8 or -S02Rn;

Re , R12 and R13 are Ci_7 alkyl;

R8 is C 1-7 alkyl or halo Ci_7 alkyl;

R11 is Ci-7 alkyl, C3-7 cycloalkyl, Ci_7 alkoxy Ci_7 alkyl, -NR12R13 or oxetanyl; R24 is hydrogen;

D is absent;

or a pharmaceutically acceptable salt thereof.

In one subclass are compounds represented by formula (IE) wherein

Ri, R2, R4, R5 and R24 are hydrogen;

R3 is hydrogen, -D-C(0)-NR6R7, -C(0)R8 , -S02Rn, -D-NR9R10,

-S(0)(NRi4)(R22), a 4-6 membered heterocyclyl which is optionally substituted with 1-2 oxo substituents, or a 4-6 membered heterocyclyl Ci_7 alkyl optionally substituted with 1-2 oxo substituents;

Re, R11 and R22 are Ci_7 alkyl;

R7 is hydrogen or Ci_7 alkyl;

R8 is Ci-7 alkyl, Ci_7 alkoxy, or a 4-6 membered heterocyclyl;

R9 is -S02(Ci_7 alkyl);

Rio is hydrogen, Ci_7 alkyl or C3-7 cycloalkyl;

Ri4 is hydrogen or -SO2R21;

R21 is 3-6 membered carbocyclyl optionally substituted with 1-2 Ci_7 alkyl; D is absent or Ci_7 alkyl;

wherein the heterocyclyl group in each occurrence has 1-3 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof.

In still another subclass of the above embodiment are compounds wherein

Ri, R2, R4, R5 and R24 are hydrogen;

R3 is -D-C(0)-NR6R7, -C(0)R8 , -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22), 1 , 1-dioxidoisothiazolidinyl or 1,1-dioxidoisothiazolidinyl Ci-7 alkyl;

Re, R11 and R22 are Ci_7 alkyl;

R7 is Ci_7 alkyl;

R8 is Ci_7 alkyl or azetidinyl;

R9 is -S02(Ci_7 alkyl);

Rio is hydrogen, Ci_7 alkyl or C3-7 cycloalkyl;

R2i is phenyl optionally substituted with a Ci_7 alkyl substituent;

D is absent or Ci_7 alkyl;

or a pharmaceutically acceptable salt thereof.

According to one embodiment, the invention provides a pharmaceutical composition comprising a compound of formula (I) as defined in any of the above embodiments together with a pharmaceutically acceptable carrier.

According to still one embodiment, the present invention provides a method for the treatment of a steroid receptor, in particular androgen receptor (AR), dependent conditions and diseases, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I)

wherein

ring B is a 4-10 membered monocyclic or bicyclic ring containing 0-4 hetero-atoms independently selected form N, O or S;

ring A is any of the following groups

L is absent, -CH2- , -CH2-CH2- or -CH2-CH2-CH2-, or in case ring A is (1), L can also be -C(0)-CH2-;

Ri is hydrogen, Ci_7 alkyl, Ci_7 alkoxy, halogen, cyano, nitro, halo Ci_7 alkyl, halo C i _7 alkoxy or C i -7 alkylthio ;

R2 is hydrogen, Ci_7 alkyl, halogen, hydroxy, halo Ci_7 alkyl, nitro, halo Ci_7 alkoxy or thiol;

or Ri and R2 together with the carbon atoms to which they are attached form a fused 1 ,3 dioxole ring;

R3 is hydrogen, halogen, nitro, cyano, oxo, Ci_7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, hydroxy C3-7 cycloalkyl, Ci_7 alkoxy, hydroxy Ci_7 alkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkylthio, amino carbonyl C2_7 alkenyl, halo Ci-7 alkylthio, Ci-7 alkoxycarbonyl Ci-7 alkyl, Ci-7 alkoxycarbonyl C2_7 alkenyl, =NS02R2o,-S(0)-Ci_7 alkyl, -S(0)(NR14)(R22), -S(NR15)(d_7 alkyl), -C(S)NR18R19, -D-C(0)NR6R7,

-C(0)R8, -D-NR9R10, -S02Rii, an optionally substituted 3-10 membered carbocyclyl, an optionally substituted 3-10 membered carbocyclyl Ci-7 alkyl, an optionally substituted 4-10 membered heterocyclyl or an optionally substituted 4-10 membered heterocyclyl Ci_ 7 alkyl;

R4 is hydrogen, halogen, hydroxy, Ci-7 alkyl, halo Ci-7 alkyl or oxo;

R5 is hydrogen, halogen or Ci_7 alkyl;

Re is hydrogen, Ci_7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, hydroxy Ci_7 alkyl, cyano Ci-7 alkyl, -Ci_7 alkyl-0-C(0)Ci_7 alkyl or an optionally substituted 4-10 membered heterocyclyl;

R8 is hydrogen, Ci_7 alkyl, C2-7 alkenyl, C3_7 cycloalkyl, Ci_7 alkoxy, halo Ci_7 alkyl,

Ci-7 alkoxy Ci_7 alkyl, Ci_7 alkylcarbonyl, Ci_7 alkoxycarbonyl, -Ci_7 alkyl-0-C(0)-Ci_7 alkyl, -C1-7 alkyl-S02(Ci_7 alkyl), -N=S(0)(C1-7 alkyl)(Ci_7 alkyl) or an optionally substituted 4-10 membered heterocyclyl;

R9 is hydrogen, Ci_7 alkyl, C3_7 cycloalkyl, Ci_7 alkylcarbonyl, -S02(Ci_7 alkyl) or -S02(C3-7 cycloalkyl);

R11 is Ci_7 alkyl, C2_7 alkenyl, C3_7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NRi2Ri3, an optionally substituted 3-10 membered carbocyclyl or an optionally substituted 4-10 membered heterocyclyl;

Ri2 is hydrogen, Ci_7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy, Ci_7 alkoxy C 1 _7 alkyl or C 1 _7 alkylcarbonyl;

R7, Rio, Ri3, Ri8, and R19 are, independently, hydrogen, Ci_7 alkyl or C3_7 cycloalkyl;

Ri4 is hydrogen, Ci_7 alkyl, Ci_7 alkylcarbonyl or -S02R2i;

Ri5 is hydrogen, Ci_7 alkyl, C3_7 cycloalkyl, Ci_7 alkylcarbonyl, -S02Ri7;

Ri7 is Ci_7 alkyl or an optionally substituted 3-10 membered carbocyclyl;

R20 and R2i are, independently, Ci_7 alkyl, C3_7 cycloalkyl or an optionally substituted 3-10 membered carbocyclyl;

R22 is Ci_7 alkyl or C3_7 cycloalkyl;

R23 is hydrogen or oxo;

R24 is hydrogen or Ci_7 alkyl;

D is absent, Ci_7 alkyl or C2_7 alkenyl;

wherein the optional substitution in each occurrence is selected from 1-3 substituents independently selected from Ci_7 alkyl, halogen, hydroxy, Ci_7 alkoxy, Ci_7 alkoxy Ci_7 alkyl, Ci_7 alkoxycarbonyl or oxo; and

wherein the heterocyclyl group in each occurrence has 1-4 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof.

According to one embodiment, the steroid receptor dependent disease or condition is androgen receptor dependent disease or condition including endocrine cancers and diseases, for example prostate cancer or breast cancer, particularly castration-resistant prostate cancer (CRPC). According to one embodiment of the invention, the CRPC to be treated is refractory to CYP17A1 inhibitor treatment.

According to another embodiment, the androgen receptor dependent disease or condition is endocrine cancer which is dependent upon CYP11A1 activation.

The compounds of the invention can be prepared by a variety of synthetic routes analogously to the methods known in the literature using suitable starting materials. The compounds according to formula (I) can be prepared e.g. analogously or according to the following reaction Schemes. Some compounds included in the formula (I) can be obtained by converting the functional groups of the other compounds of formula (I) obtained in accordance with the following Schemes, by well known reaction steps such as oxidation, reduction, hydrolysis, acylation, alkylation, amidation, amination, sulfonation and others. It should be noted that any appropriate leaving groups, e.g. N-protecting groups, such as a t-butoxycarbonyl (t-BOC) group or a phenylsulfonyl group, can be used in well known manner during the syntheses in order to improve the selectivity of the reaction steps.

Compounds of formula (I) can be prepared, for example, according to Scheme 1, wherein Ri, R2, R3, R4, R5, R23, R24, L, A and B, are as defined above, and X is a halogen. In the method of Scheme 1, the 5-hydroxy-4H-pyran-4-one derivative [1] is coupled with ring B derivative [2] where halogen is acting as the leaving group in a suitable solvent in the presence of a base at elevated temperature, for example using K2CO3 in DMF, K2CO3 in DMSO, NaOH/KOH in MeOH/EtOH, NaH in DMF or K2C03 in THF/1,4-dioxane, to produce a compound of formula (I).

Alternatively, compounds of formula (I) can be prepared according to Scheme 2, wherein Ri, R2, R3, R4, R5, R23, R24, L, A and B, are as defined above, and Z is mesyl or tosyl group. In the method of Scheme 2, the 5-hydroxy-4H-pyran-4-one derivative [1] is coupled with ring B derivative [3], where mesylate or tosylate is acting as the leaving group, in a suitable solvent in the presence of a base at elevated temperature, for example using K2CO3 in DMF, K2C03 in DMSO, NaOH/KOH in MeOH/EtOH, NaH in DMF or K2CO3 in THF/l ,4-dioxane, to produce a compound of formula (I).

Compounds of formula (ID) where R3 is coupled to the piperidine ring via acyl or sulfonyl group, can be prepared, for example, according to Scheme 3, wherein Ri, R2, R3, R4; R5 and R24 are as defined above, and X is a halogen. In the method of Scheme 3, the compound of formula (ID') is coupled with a halogen compound [4] in a suitable solvent such as CH2C12 in the presence of suitable base such as triethylamine to produce a compound of formula (ID).

WE CLAIM

The ability of the test compounds to inhibit conversion of cholesterole to pregnenolone and isocaproic acid was measured by modification of isocaproic acid release assay (IARA) described by Ruangwises et. al. (Biology of Reproduction 1991; 45(1): 143-50) except that human H295R adrenocortical carcinoma cell line was used as source of enzyme and extraction was done with dextran-coated charcoal suspension (Isomaa, V. et al, Endocrinology 1982; 111(3):833-843). The H295R cell line has been shown to express all the key steroidogenic enzymes. To determine the half maximal inhibitory concentration (IC50) of the test compounds on CYP11 Al inhibition, the cells were treated for three days with increasing concentrations of the test compounds in the presence of 3 nM [24,25-3H]-labelled cholesterol (American Radiolabeled Chemicals). The final DMSO concentration was 1 %. Cell culture medium was extracted with dextran-coated charcoal suspension and the radiolabeled isocaproic acid was determined by mixing 100 μΐ of supernatant fraction in 200 μΐ of scintillation fluid (OptiPhase SuperMix, Perkin Elmer). Radioactivity was measured using a Microbeta scintillation counter (1450 MicroBeta Trilux, Wallac). All the test compounds were studied at 10 concentrations in duplicates.

The compounds of the invention were screened in the above mentioned assay and the IC50 values of the compounds are set forth in Table 1 below wherein "A" refers to an IC50 value of less than 150 nM, "B" refers to IC50 value in range of 150 to 300 nM and "C" refers to IC50 value in range of 301 nM to 2000 nM.

Table 1.

Group Compound No.

2, 5, 8, 10, 1 1, 12, 15, 21, 22, 23, 36, 37, 44, 47, 49, 65, 69a, 70, 71, 72,

A 73, 74, 83, 84, 89, 90, 91, 92, 93, 95, 103, 104, 109, 11 1, 113, 114, 1 15,

116, 122, 129, 130, 131, 134, 137, 138, 139, 146, 162, 172, 173, 176,

184, 185, 186, 187, 188, 189, 190, 192, 195, 196, 205, 211, 213, 215, 216, 217, 219, 221, 222, 224, 225, 226, 229, 230, 232, 234, 238, 244, 244a, 249, 251, 254, 255, 257, 261 , 262, 271, 272, 278, 285 and 286

1, 4, 6, 7, 9, 20, 24, 25, 26, 28, 29, 30, 31, 34, 39, 46, 53, 56, 61, 63, 64, 67, 68, 69, 81, 82, 82a, 85, 86, 88, 94, 97, 98, 99, 100, 101, 102, 107, 108, 120, 121, 124, 126, 127, 128, 135, 136, 140, 142, 143, 147, 158,

B 161 , 163, 164, 165, 168, 169, 174, 177, 180, 181, 191, 194, 198, 199,

200, 208, 209, 210, 214, 218, 220, 223, 227, 228, 231, 233, 235, 236, 237, 239, 241, 247, 248, 250, 252, 256, 258, 260, 267, 268, 269, 270, 273, 276, 279, 280, 283, 284 and 291

3, 13, 14, 16, 17, 18, 19, 27, 32, 33, 35, 38, 40, 41, 42, 43, 45, 48, 50, 51, 52, 55, 57, 58, 59, 60, 62, 66, 75, 76, 77, 78, 79, 80, 87, 96, 105, 106, 110, 112, 117, 118, 119, 123, 125, 132, 133, 141, 144, 145, 148,

C 149, 150, 151 , 152, 153, 154, 155, 156, 157, 159, 160, 166, 170, 171,

178, 179, 182, 183, 193, 197, 201 , 202, 203, 206, 207, 212, 240, 242, 243, 245, 245a, 253, 263, 264, 265, 274, 275, 277, 281, 282, 287, 289 and 290

Abbreviations

ACN - Acetonitrile

DAST - Diethylaminosulfur trifluoride

DCE - 1 ,2-Dichloroethane

DCM - Dichloromethane

DEA - Diethanolamine

DIBAL-H - Diisobutylaluminum hydride solution

DIPEA - N,N-diisopropylethylamine

DMF - N,N-Dimethylformamide

DMSO - Dimethylsulfoxide

DPPA - Diphenylphosphoryl azide

DBU - l,8-Diazabicyclo[5.4.0]undec-7-ene

EtOAc - Ethyl acetate

EtOH - Ethanol

IPA - Isopropyl Alcohol

LAH - Lithium aluminium hydride

LiHMDS - Hexamethyldisilazane lithium salt TAI Lithium bis(trimethylsilyl)amide m-CPBA - 3-Chloroperoxybenzoic acid

MeOH - Methanol

Ms - Methanesulfonyl

MTBE - Methyl Tertiary Butyl Ether

PPh3 - Triphenylphosphine

Pd2(dba)3 -Tris(dibenzylideneacetone)dipalladium(0)

Pd(PPh3)4 - Tetrakis(triphenylphosphine)palladium(0)

PPTS - Pyridinium p-toluenesulfonate

rac-BINAP - rac-2,2'-bis(diphenylphosphino)-l, -binaphthyl

RT - Room temperature

rt - Retention time

TBABr - Tetrabutylammonium bromide

TBAF - Tetrabutylammonium fluoride

TBME - Methyl tert-butyl ether

TBSC1 - tert-Butyldimethylsilyl chloride

TEA - Triethylamine

TFA - Trifluoroacetic acid

TFAA - Trifluoroacetic anhydride

THF - Tetrahydrofuran

TMEDA - Tetramethylethylenediamine

Tf - trifluoromethanesulfonyl

Ts - /?-Toluenesulfonyl

Claims

1. A com ound of formula (I)

wherein

ring B is a 4-10 membered monocyclic or bicyclic ring containing 0-4 hetero-atoms independently selected form N, O or S

ring A is any of the following groups

L is absent, -CH2- , -CH2-CH2- or -CH2-CH2-CH2-, or in case ring A is (1), L can also be -C(0)-CH2-;

Ri is hydrogen, Ci_7 alkyl, Ci_7 alkoxy, halogen, cyano, nitro, halo Ci_7 alkyl, halo Ci-7 alkoxy or C 1-7 alkylthio;

R2 is hydrogen, Ci_7 alkyl, halogen, hydroxy, halo Ci_7 alkyl, nitro, halo Ci_7 alkoxy or thiol;

or Ri and R2 together with the carbon atoms to which they are attached form a fused 1 ,3 dioxole ring;

R3 is hydrogen, halogen, nitro, cyano, oxo, Ci_7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, hydroxy C3-7 cycloalkyl, Ci_7 alkoxy, hydroxy Ci_7 alkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkylthio, aminocarbonyl C2_7 alkenyl, halo Ci-7 alkylthio, Ci-7 alkoxycarbonyl Ci-7 alkyl, Ci-7 alkoxycarbonyl C2_7 alkenyl, =NS02R2o,-S(0)-Ci_7 alkyl, -S(0)(NR14)(R22), -S(NR15)(d_7 alkyl), -C(S)NR18R19, -D-C(0)-NR6R7,

-C(0)R8, -D-NR9R10, -S02Rii, optionally substituted 3-10 membered carbocyclyl,

optionally substituted 3-10 membered carbocyclyl Ci_7 alkyl, optionally substituted 4-10 membered heterocyclyl or optionally substituted 4-10 membered heterocyclyl Ci-7 alkyl;

R4 is hydrogen, halogen, hydroxy, Ci_7 alkyl, halo Ci_7 alkyl or oxo;

R5 is hydrogen, halogen or Ci_7 alkyl;

Re is hydrogen, Ci_7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, hydroxy Ci_7 alkyl, cyano

Ci-7 alkyl, -Ci_7 alkyl-0-C(0)Ci-7 alkyl or optionally substituted 4-10 membered heterocyclyl;

R8 is hydrogen, Ci_7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, Ci_7 alkoxy, halo Ci_7 alkyl, Ci-7 alkoxy Ci_7 alkyl, Ci_7 alkylcarbonyl, Ci_7 alkoxycarbonyl, -Ci_7 alkyl-0-C(0)-Ci-7 alkyl, -C1-7 alkyl-S02(Ci_7 alkyl), -N=S(0)(C1-7 alkyl)(Ci_7 alkyl) or optionally substituted 4-10 membered heterocyclyl;

R9 is hydrogen, Ci_7 alkyl, C3-7 cycloalkyl, Ci_7 alkylcarbonyl, -S02(Ci_7 alkyl) or -S02(C3-7 cycloalkyl);

R11 is Ci_7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NRi2Ri3, optionally substituted 3-10 membered carbocyclyl or optionally substituted 4-10 membered heterocyclyl;

Ri2 is hydrogen, Ci_7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy, Ci_7 alkoxy Ci_7 alkyl or Ci_7 alkylcarbonyl;

R7, Rio, Ri3, Ri8, and R19 are, independently, hydrogen, Ci_7 alkyl or C3-7 cyclo-alkyl;

Ri4 is hydrogen, Ci_7 alkyl, Ci_7 alkylcarbonyl or -S02R2i;

Ri5 is hydrogen, Ci_7 alkyl, C3-7 cycloalkyl, Ci_7 alkylcarbonyl, -S02Ri7;

Ri7 is Ci_7 alkyl or an optionally substituted 3-10 membered carbocyclyl;

R20 and R2i are, independently, Ci_7 alkyl, C3-7 cycloalkyl or optionally substituted 3-10 membered carbocyclyl;

R22 is Ci_7 alkyl or C3-7 cycloalkyl;

R23 is hydrogen or oxo;

R24 is hydrogen or Ci_7 alkyl;

D is absent, Ci_7 alkyl or C2_7 alkenyl;

wherein the optional substitution in each occurrence is selected from 1-3 substituents independently selected from Ci_7 alkyl, halogen, hydroxy, Ci_7 alkoxy, Ci_7 alkoxy Ci-7 alkyl, Ci_7 alkoxy carbonyl or oxo; and

wherein the heterocyclyl group in each occurrence has 1-4 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof;

with the proviso that the compound is not

2-[(3,4-Dihydro-2(lH)-isoquinolinyl)methyl]-5-[(2,5-dimethylphenyl)methoxy]-4H-pyran-4-one;

5-[(2,4-Dic orophenyl)methoxy]-2-[(3,4-dihydro-2(lH)-isoquinolinyl)methyl]-4H-pyran-4-one;

5 - [(3 -Chlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(4-methylphenyl)methoxy] -4H-pyran-4-one;

5 - [(3 ,4-Dichlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 -fluorophenyl)methoxy] -4H-pyran-4-one;

2-[(3,4-Dihydro-2(lH)-isoquinolinyl)methyl]-5-(l-naphthalenylmethoxy)-4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [ [3 -(trifluoromethyl)phenyl] methoxy] -4H-pyran-4-one;

5 - [(2-Chlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

5-[(2-Chloro-6-fluorophenyl)methoxy]-2-[(3,4-dihydro-2(lH)-isoquinolinyl) methyl] -4H-pyran-4-one;

5 - [(4-Chlorophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

5 - [(4-Bromophenyl)methoxy] -2- [(3 ,4-dihydro-2( lH)-isoquinolinyl)methyl] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(2-fluorophenyl)methoxy] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(2-methylphenyl)methoxy] -4H-pyran-4-one;

2-[(3 ,4-Dihydro-2( lH)-isoquinolinyl)

one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [ [4-(trifluoromethyl)phenyl] methoxy] -4H-pyran-4-one;

Methyl 4-(((6-((3 ,4-dihydroisoquinolin-2( 1 H)-yl)methyl)-4-oxo-4H-pyran-3 -yl)oxy)methyl)benzoate;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(4-fluorophenyl)methoxy] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 ,5 -dimethoxyphenyl)methoxy] -4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 -nitrophenyl)methoxy] - 4H-pyran-4-one;

Methyl 5 -(((6-((3 ,4-dihydroisoquinolin-2( 1 H)-yl)methyl)-4-oxo-4H-pyran-3 -yl)oxy)methyl)furan-2-carboxylate;

2-[(3,4-Dihydro-2(lH)-isoquinolinyl)methyl]-5-(2-phenylethoxy)-4H-pyran-4-one;

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(3 -methylphenyl)methoxy] -4H-pyran-4-one; or

2- [(3 ,4-Dihydro-2( lH)-isoquinolinyl)methyl] -5 - [(4-nitrophenyl)methoxy] -4H-pyran-4-one.

2. A compound according to claim 1, wherein the compound is represented by formula (IA):

wherein Ri, R2, R3, R4, R5, R23, R24, L and B are as defined in claim 1 , or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 1 , wherein the compound is represented by formula (IB):

(IB), wherein Ri, R2, R3, R4, R5, R24, L and B are as defined in claim 1 , or a pharmaceutically acceptable salt thereof.

4. A compound according to any of claims 1 to 3, wherein L is -CH2- or -CH2- CH2-.

5. A compound according to claim 4, wherein L is -CH2-

6. A compound according to claim 5, wherein L is -CH2-CH2-.

7. A compound according to any of the preceding claims, wherein ring B is any one of the followin rou s

(10 ') (1C) (12 *)

R3, R4 and R5 being attached to the above B-rings.

8. A compound according to claim 7, wherein ring B is any one of the following

(11a') (12') (13a') (14a') (15a') nr (16a')

R3, R4 and R5 being attached to the above B-rings and the wavy line denoting the site of attachment to L.

9. A compound according to claim 8, wherein ring B is (1 '), (5'), (7'), (9'), (13') or (14').

10. A compound according to claim 8, wherein ring B is (1 '), (5a'), (7'), (9a'),

(13a') or (14a').

11. A compound according to any of the preceding claims, wherein R3 is hydrogen, Ci_7 alkyl, C2-7 alkenyl, hydroxy Ci_7 alkyl, cyano, Ci_7 alkylthio,

Ci_7 alkoxycarbonyl C2-7 alkenyl, -D-C(0)-NR6R7, -C(0)R8 , -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22), -S(NR15)(C1-7 alkyl), -C(S)NRi8Ri9, an optionally substituted 3-10 membered carbocyclyl, an optionally substituted 4-10 membered heterocyclyl, or an optionally substituted 4-10 membered heterocyclyl Ci_7 alkyl;

wherein the optional substitution in each occurrence is selected from 1-3 substituents independently selected from Ci_7 alkyl, halogen, hydroxy, Ci_7 alkoxy, Ci_7 alkoxy Ci_7 alkyl, Ci_7 alkoxycarbonyl or oxo, and

wherein the heterocyclyl group in each occurrence has 1-3 heteroatoms independently selected from N, O and S.

12. A compound according to any of the preceding claims, wherein R4 and R5 are hydrogen.

13. A compound according to claim 1 or 2, wherein the compound is represented by formula IC):

wherein Ri , R2, R3, R4, R5 and R24 are as defined in claim 1 , or a pharmaceutically acceptable salt thereof.

14. A compound according to claim 1 or 2, wherein the compound is represented b formula (ID):

wherein Ri, R2, R3, R4, R5 and R24 are as defined in claim 1, or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 1 or 2, wherein the compound is represented by form la (IE):

wherein Ri, R2, R3, R4, R5 and R24 are as defined in claim 1, or a pharmaceutically acceptable salt thereof.

16. A compound according to any of claims 13-15, wherein

Ri is hydrogen, Ci_7 alkyl, Ci_7 alkoxy, halogen, cyano, nitro, halo Ci_7 alkyl, halo Ci-7 alkoxy or C 1-7 alkylthio;

R2 is hydrogen or halogen;

R3 is hydrogen, Ci_7 alkyl, C2-7 alkenyl, hydroxy Ci_7 alkyl, cyano, Ci_7 alkylthio, Ci_7 alkoxycarbonyl C2-7 alkenyl, -D-C(0)-NR6R7, -C(0)R8 , -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22), -S(NR15)(C1-7 alkyl), -C(S)NRi8Ri9, 4-6 membered carbocyclyl which is optionally substituted with 1-2 hydroxyl substituents, 4-6 membered heterocyclyl which is optionally substituted with 1-2 substituents selected from halogen, hydroxyl, Ci_ 7 alkoxycarbonyl or oxo, or 4-6 membered heterocyclyl Ci_7 alkyl optionally substituted with 1-2 oxo substituents;

R4 is hydrogen, Ci_7 alkyl, hydroxy or halogen;

R5 is hydrogen or halogen;

Re is Ci_7 alkyl, C3-7 cycloalkyl, hydroxy Ci_7 alkyl, -Ci_7 alkyl-0-C(0)Ci_7 alkyl;

R7 is hydrogen or Ci_7 alkyl;

R8 is hydrogen, Ci_7 alkyl, C2-7 alkenyl, C3_7 cycloalkyl, Ci_7 alkoxy, halo Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, Ci_7 alkylcarbonyl, Ci_7 alkoxycarbonyl,

-Ci_7 alkyl-0-C(0)-Ci_7 alkyl, -C1-7 alkyl-S02(Ci_7 alkyl), -N=S(0)(C1-7 alkyl)(Ci_7 alkyl) or a 4-6 membered heterocyclyl which is optionally substituted with 1-2 halogen

substituents;

R9 is Ci_7 alkylcarbonyl, -S02(Ci_7 alkyl) or -S02(C3_7 cycloalkyl);

Rio is hydrogen, Ci_7 alkyl or C3_7 cycloalkyl;

Rii is Ci-7 alkyl, C3-7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl,

Ci-7 alkoxy Ci_7 alkyl, -NR12R13, 3-6 membered carbocyclyl which is optionally substituted with 1-2 substituents selected from halogen or Ci_7 alkyl, or 4-6 membered heterocyclyl which is optionally substituted with 1-2 substituents selected from halogen or C 1-7 alkyl;

R12 is Ci-7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl or Ci-7 alkylcarbonyl;

Ri3 is hydrogen or Ci_7 alkyl;

Ri4 is hydrogen, Ci_7 alkyl, Ci_7 alkylcarbonyl or -SO2R21;

Ri5 is hydrogen, Ci_7 alkyl, -SO2R17;

Ri7 is Ci-7 alkyl or 3-6 membered carbocyclyl which is optionally substituted by 1-2 Ci-7 alkyl substituent;

Ri8, and Rig are, independently, hydrogen or Ci_7 alkyl;

R21 is 3-6 membered carbocyclyl optionally substituted with 1-2 Ci_7 alkyl;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

R24 is hydrogen or Ci_7 alkyl;

wherein the heterocyclyl group in each occurrence has 1-3 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof.

17. A compound according to claim 13, wherein

Ri is hydrogen, Ci_7 alkoxy, halogen, nitro, halo Ci_7 alkyl, halo Ci_7 alkoxy or Ci-7 alkylthio;

R2 is hydrogen or halogen;

R3 is C2-7 alkenyl, hydroxy Ci_7 alkyl, cyano, Ci_7 alkoxycarbonyl C2-7 alkenyl,

-D-C(0)-NR6R7, -C(0)R8, -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22), -S(NR15)(C1-7 alkyl), a 3-6 membered carbocyclyl which is optionally substituted with 1-2 hydroxyl substituents, or a 4-6 membered heterocyclyl which is optionally substituted with 1-2 substituents selected from halogen or hydroxyl;

R4 is hydrogen, hydroxy or halogen;

R5 is hydrogen or halogen;

Re is Ci_7 alkyl, hydroxy Ci_7 alkyl or -C1-7 alkyl-0-C(0)Ci_7 alkyl;

R7 is hydrogen or Ci_7 alkyl;

R8 is Ci_7 alkyl, halo Ci_7 alkyl, -N=S(0)(Ci_7 alkyl)(Ci_7 alkyl) or a 4-6 membered heterocyclyl which is optionally substituted with 1-2 halogen substituents;

R9 is Ci-7 alkylcarbonyl or -S02(Ci_7 alkyl);

Rio is hydrogen or Ci_7 alkyl;

Rii is Ci-7 alkyl, C3-7 cycloalkyl, halo Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NR12R13 or a 4-6 membered heterocyclyl;

R12 is Ci-7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl or C 1 -7 alkylcarbonyl;

Ri3 is hydrogen or Ci_7 alkyl;

Ri4 is hydrogen, Ci_7 alkyl or Ci_7 alkylcarbonyl;

Ri5 is hydrogen or -S02Ri7;

Ri7 is a 3-6 membered carbocyclyl which is optionally substituted by 1-2

Ci-7 alkyl substituents;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

R24 is hydrogen or Ci_7 alkyl;

D is absent, Ci_7 alkyl or C2-7 alkenyl;

wherein the heterocyclyl group in each occurrence has 1-3 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof.

18. A compound according to claim 17, wherein

Ri is hydrogen, Ci_7 alkoxy, halogen, nitro, halo Ci_7 alkyl or halo Ci_7 alkoxy; R2 and Rio are hydrogen;

R3 is C2-7 alkenyl, hydroxy Ci_7 alkyl, cyano, Ci_7 alkoxycarbonyl C2-7 alkenyl, -D-C(0)-NR6R7, -C(0)R8, -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22), -S(NR15)(C1-7 alkyl), oxazolyl, cyclobutyl optionally substituted with a hydroxy substituent, or oxetanyl optionally substituted with a hydroxy substituent;

R4 and R5 are hydrogen or halogen;

Re is C 1-7 alkyl or hydroxy Ci_7 alkyl;

R7, Ri3, Ri4 and R24 are hydrogen or Ci_7 alkyl;

R8 is Ci-7 alkyl, pyrrolidinyl, oxetanyl, or azetidinyl optionally substituted with 1-2 halogen substituents,-N=S(0)(Ci_7 alkyl)(Ci_7 alkyl);

R9 is -S02(Ci_7 alkyl);

Rii is Ci-7 alkyl, C3-7 cycloalkyl, halo Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NR12R13, pyrrolidinyl, piperidinyl, azetidinyl or morpholinyl;

R12 is Ci-7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl or Ci-7 alkylcarbonyl;

Ri5 is hydrogen or -SO2R17;

Ri7 is phenyl optionally substituted by a Ci_7 alkyl substituent;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

D is absent, Ci_7 alkyl or C2-7 alkenyl;

or a pharmaceutically acceptable salt thereof.

19. A compound according to claim 18, wherein

Ri is hydrogen, Ci_7 alkoxy, halogen, halo Ci_7 alkyl or halo Ci_7 alkoxy;

R2 and Rio are hydrogen;

R3 is hydroxy Ci_7 alkyl, cyano, Ci_7 alkoxycarbonyl C2-7 alkenyl,

-D-C(0)-NR6R7, -C(0)R8, -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22), -S(NR15)(C1-7 alkyl), oxazolyl, cyclobutyl optionally substituted with a hydroxy substituent, or oxetanyl optionally substituted with a hydroxy substituent;

R4 and R5 are hydrogen or halogen;

Re is C 1-7 alkyl;

R7, Ri3, Ri4 and R24 are hydrogen or Ci-7 alkyl;

R8 is pyrrolidinyl, azetidinyl or -N=S(0)(Ci_7 alkyl)(Ci_7 alkyl);

R9 is -S02(Ci_7 alkyl);

R11 is Ci-7 alkyl, halo Ci-7 alkyl, -NR12R13 or pyrrolidinyl;

R12 is Ci-7 alkyl, hydroxy Ci-7 alkyl, cyano Ci-7 alkyl, Ci-7 alkoxy Ci-7 alkyl or Ci-7 alkylcarbonyl;

Ri7 is phenyl optionally substituted by a Ci-7 alkyl substituent;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

D is absent, Ci_7 alkyl or C2-7 alkenyl;

or a pharmaceutically acceptable salt thereof.

20. A compound according to claim 19, wherein

Ri is hydrogen, halogen, halo Ci_7 alkyl or halo Ci_7 alkoxy;

R2, R4, R5 and Rio are hydrogen;

R3 is hydroxy Ci_7 alkyl, -D-C(0)-NR6R7, -C(0)R8, -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22) or oxetanyl optionally substituted with a hydroxy substituent;

Re and R7 is Ci_7 alkyl;

R8 is pyrrolidinyl, or -N=S(0)(C1-7 alkyl)(Ci_7 alkyl);

R9 is -S02(Ci_7 alkyl);

R11 is Ci-7 alkyl, -NR12R13 or pyrrolidinyl;

R12 is Ci-7 alkyl, hydroxy Ci-7 alkyl, or Ci-7 alkoxy Ci-7 alkyl;

Ri3 and RM is hydrogen or Ci-7 alkyl;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

D is Ci-7 alkyl or C2-7 alkenyl;

or a pharmaceutically acceptable salt thereof.

21. A compound according to claim 14, wherein

Ri is hydrogen, Ci-7 alkyl, cyano, halogen, nitro, halo Ci-7 alkyl, halo Ci-7 alkoxy or C 1-7 alkylthio;

R2 is hydrogen or halogen;

R3 is -D-C(0)-NR6R7, -C(0)R8 , -S02Rn, or -C(S)NRi8Ri9;

R4 is hydrogen, Ci-7 alkyl, hydroxy or halogen;

R5 is hydrogen;

Re is Ci-7 alkyl or C3-7 cycloalkyl;

R7 and R24 are hydrogen or Ci-7 alkyl;

R8 is hydrogen, Ci-7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, halo Ci-7 alkyl, Ci-7 alkylcarbonyl, Ci-7 alkoxycarbonyl, Ci-7 alkoxy Ci-7 alkyl, -Ci-7 alkyl-0-C(0)-Ci-7 alkyl, -Ci-7 alkyl-S02(Ci-7 alkyl) or a 4-10 membered heterocyclyl;

Rii is Ci-7 alkyl, C3-7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NR12R13, a 3-6 membered carbocyclyl which is optionally substituted with 1-2 halogen substituents, or a 4-6 membered heterocyclyl which is optionally substituted with 1-2 substituents selected from halogen or Ci_7 alkyl;

R12 and Ri3 are Ci_7 alkyl;

Ri8, and Rig are, independently, hydrogen or Ci_7 alkyl;

D is absent;

wherein the heterocyclyl group in each occurrence has 1-3 heteroatoms independently selected from N, O and S.

or a pharmaceutically acceptable salt thereof.

22. A compound according to claim 21 , wherein

Ri is hydrogen, Ci_7 alkyl, halogen, halo Ci_7 alkyl or halo Ci_7 alkoxy;

R2 and R5 are hydrogen;

R3 is -D-C(0)-NR6R7, -C(0)R8 , -S02Rn, or -C(S)NRi8Ri9, or oxetanyl optionally substituted by a hydroxy substituent;

R4 is hydrogen, Ci_7 alkyl or halogen;

Re is C 1-7 alkyl;

R7 is hydrogen or Ci_7 alkyl;

R8 is Ci-7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, halo Ci_7 alkyl, Ci_7 alkylcarbonyl, Ci_7 alkoxycarbonyl, Ci_7 alkoxy Ci_7 alkyl, -Ci_7 alkyl-0-C(0)-Ci-7 alkyl,

-Ci-7 alkyl-S02(Ci-7 alkyl), azetidinyl, morpholinyl, furanyl or pyrrolidinyl;

R11 is Ci-7 alkyl, C3-7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl, -NR12R13, pyrrolidinyl, phenyl optionally substituted with a halogen substituent, oxetanyl, or pyrazolyl optionally substituted with a Ci_7 alkyl substituent;

R12 and Ri3 are Ci_7 alkyl;

Ri8, and Rig are, independently, hydrogen or Ci_7 alkyl;

R24 is hydrogen or Ci_7 alkyl;

D is absent;

or a pharmaceutically acceptable salt thereof.

23. A compound according to claim 22, wherein

Ri is hydrogen, Ci_7 alkyl, halogen, halo Ci_7 alkyl or halo Ci_7 alkoxy;

R2, R5 and R7 are hydrogen;

R3 is -D-C(0)-NR6R7, -C(0)R8 or -S02Rn;

R4 is hydrogen or Ci_7 alkyl;

Re is Ci-7 alkyl;

R8 is Ci-7 alkyl, C3-7 cycloalkyl, halo Ci_7 alkyl, Ci_7 alkylcarbonyl,

-Ci-7 alkyl-0-C(0)-Ci-7 alkyl, -Ci_7 alkyl-S02(Ci-7 alkyl), morpholinyl or pyrrolidinyl;

R11 is Ci-7 alkyl, C3-7 cycloalkyl, cyano Ci_7 alkyl, Ci_7 alkoxy Ci_7 alkyl,

-NR12R13, oxetanyl, or pyrazolyl optionally substituted with a Ci_7 alkyl substituent;

R12 and Ri3 are Ci_7 alkyl;

R24 is hydrogen or Ci_7 alkyl;

D is absent;

or a pharmaceutically acceptable salt thereof.

24. A compound according to claim 23, wherein

Ri is hydrogen, halogen, halo Ci_7 alkyl or halo Ci_7 alkoxy;

R2, R4, R5 and R7 are hydrogen;

R3 is -D-C(0)-NR6R7, -C(0)R8 or -S02Rn;

Re , R12 and R13 are Ci_7 alkyl;

R8 is C 1-7 alkyl or halo Ci_7 alkyl;

R11 is Ci-7 alkyl, C3-7 cycloalkyl, Ci_7 alkoxy Ci_7 alkyl, -NR12R13 or oxetanyl; R24 is hydrogen;

D is absent;

or a pharmaceutically acceptable salt thereof.

25. A compound according to claim 15, wherein

Ri, R2, R4, R5 and R24 are hydrogen;

R3 is hydrogen, -D-C(0)-NR6R7, -C(0)R8 , -S02Rn, -D-NR9R10,

-S(0)(NRi4)(R22), a 4-6 membered heterocyclyl which is optionally substituted with 1-2 oxo substituents, or a 4-6 membered heterocyclyl Ci_7 alkyl optionally substituted with 1-2 oxo substituents;

Re, Rii and R22 are Ci_7 alkyl;

R7 is hydrogen or Ci_7 alkyl;

R8 is Ci-7 alkyl, Ci_7 alkoxy, or a 4-6 membered heterocyclyl;

R9 is -S02(Ci_7 alkyl);

Rio is hydrogen, Ci_7 alkyl or C3-7 cycloalkyl;

Ri4 is hydrogen or -SO2R21;

R21 is 3-6 membered carbocyclyl optionally substituted with 1-2 Ci_7 alkyl;

D is absent or Ci_7 alkyl;

wherein the heterocyclyl group in each occurrence has 1-3 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof.

26. A compound according to claim 25, wherein

Ri, R2, R4, R5 and R24 are hydrogen;

R3 is -D-C(0)-NR6R7, -C(0)R8 , -S02Rn, -D-NR9R10, -S(0)(NRi4)(R22), 1,1-dioxidoisothiazolidinyl or 1,1-dioxidoisothiazolidinyl Ci_7 alkyl;

Re, R11 and R22 are Ci_7 alkyl;

R7 is Ci_7 alkyl;

R8 is Ci-7 alkyl or azetidinyl;

R9 is -S02(Ci_7 alkyl);

Rio is hydrogen, Ci_7 alkyl or C3_7 cycloalkyl;

R2i is phenyl optionally substituted with a Ci_7 alkyl substituent;

D is absent or Ci_7 alkyl;

or a pharmaceutically acceptable salt thereof.

27. A compound according to claim 1, which is

Methyl (E)-3-(4-(((6-(isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)-methyl)phenyl)acrylate (Compound 2);

2-(Isomdolin-2-ylmethyl)-5-((4-(pyre

one (Compound 5);

4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-N-methyl-benzenesulfonamide (Compound 8);

4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-N,N-di-methylbenzenesulfonamide (Compound 10);

4- (((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-N-(2-methoxyethyl)benzenesulfonamide (Compound 11);

N-(2-Hydroxyethyl)-4-(((6-(isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)-oxy)methyl)-N-methylbenzenesulfonamide (Compound 12);

N-(2-Hydroxyethyl)-4-(((6-(isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)-oxy)methyl)benzenesulfonamide (Compound 15);

N-Ethyl-N-(2-hydroxyethyl)-4-(((6-(isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)benzenesulfonamide (Compound 21);

5- ((4-((Difluoromethyl)sulfonyl)benzyl)oxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 22);

N-(2-Cyanoethyl)-4-(((6-(isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)-methyl)-N-methylbenzenesulfonamide (Compound 23);

2-(Isoindolin-2-ylmethyl)-5 -(( 1 -(oxetan-3 -ylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (Compound 36);

5-((4-(Methylsulfonyl)benzyl)oxy)-2-((5-(trifluoromethoxy)isoindolin-2-yl)-methyl)-4H-pyran-4-one (Compound 37);

2-((3 ,4-dihydroisoquinolin-2( 1 H)-yl)methyl)-5 -((4-(2-hydroxypropan-2-yl)-benzyl)oxy)-4H-pyran-4-one (Compound 44);

2-Isoindolin-2-ylmethyl)-5 -((4-(prop- 1 -en-2-yl)benzyl)oxy)-4H-pyran-4-one (Compound 47);

5-((4-(2-Hydroxypropan-2-yl)benzyl)oxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 49);

5-(Cyclohexylmethoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound

65);

5 -(( 1 -(Oxetan-3 -ylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl)-isoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 69a);

N-((4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)phenyl)-sulfonyl)-N-methylacetamide (Compound 70);

5-((4-(Cyclobutanesulfonimidoyl)benzyl)oxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 71);

5-((4-(Cyclopropylsulfonyl)benzyl)oxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 72);

5-((4-(Isobutylsulfonyl)benzyl)oxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 73);

5-((4-(S-methylsulimimidoyl)benzyl)oxy)-2-((5-(trifluoromethyl)isoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 74);

4- ({[6-(l,3-Dihydro-2H-isoindol-2-ylmethyl)-4-oxo-4H-pyran-3-yl]oxy}methyl)-N-[dimethyl(oxido)- 6-sulfanylidene]benzamide (Compound 83);

N-[Dimethyl(oxido)- 6-sulfanylidene]-4-[( {6-[(5-fluoro- 1 ,3-dihydro-2H-iso-indol-2-yl)methyl]-4-oxo-4H-pyran-3-yl}oxy)methyl]benzamide (Compound 84);

5- ((4-(S-Methylsulfonimidoyl)benzyl)oxy)-2-((5-(trifluoromethyl)isoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 89);

5-((4-(S-Methylsulfonimidoyl)benzyl)oxy)-2-((5-(trifluoromethoxy)isoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 90);

2-(l-(Isoindolin-2-yl)ethyl)-5-((4-(S-methylsulfonimidoyl)benzyl)oxy)-4H-pyran-4-one (Compound 91);

5-((4-(N,S-Dimethylsulfonimidoyl)benzyl)oxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 92);

N-{[4-({[6-(l,3-dihydro-2H-isoindol-2-ylmethyl)-4-oxo-4H-pyran-3-yl]oxy}-methyl)phenyl](methyl)- 4-sulfanylidene} -4-methylbenzenesulfonamide (Compound 93);

5 -((4-(Azetidine- 1 -carbonyl)-2-fluorobenzyl)oxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 95);

2-(Isoindolin-2-ylmethyl)-5-((4-(propan-2-ylsulfonimidoyl)benzyl)oxy)-4H-pyran-4-one (Compound 103);

5-((5-Fluoro-l-(methylsulfonyl)-l,2,3,6-tetrahydropyridin-4-yl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 104);

2-(Isoindolin-2-ylmethyl)-5-((4-(oxazol-2-yl)benzyl)oxy)-4H-pyran-4-one (Compound 109);

5 -((4-( 1 -Hydroxycyclobutyl)benzyl)oxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 111);

N-(4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)benzyl)-methanesulfonamide (Compound 113);

5 -((4-(3 -Hydroxyoxetan-3 -yl)benzyl)oxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 114);

2-((5 -Fluoroisoindolin-2-yl)methyl)-5 -((4-(3 -hydroxyoxetan-3 -yl)benzyl)oxy)-4H-pyran-4-one (Compound 115);

5 -((4-(3 -Hydroxyoxetan-3 -yl)benzyl)oxy)-2-((5 -(trifluoromethyl)isoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 116);

2-(Isoindolin-2-ylmethyl)-5-((4-(pyrrolidine-l-carbonyl)benzyl)oxy)-4H-pyran-4 one (Compound 122);

5 -((4-(Azetidine- 1 -carbonyl)benzyl)oxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 129);

2-((5-Bromoisoindolin-2-yl)methyl)-5-((4-(pyrrolidine-l-carbonyl)benzyl)oxy)-4H-pyran-4-one (Compound 130);

N-(tert-Butyl)-4-(((6-(isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-benzamide (Compound 131);

4-(((6-Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-N,N-diiso-propylbenzamide (Compound 134);

4-(((6-((5-Chloroisoindolin-2-yl)methyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-N,N dimethylbenzamide (Compound 137);

4-(((6-((5-Methoxyisoindolin-2-yl)methyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-Ν,Ν-dimethylbenzamide (Compound 138);

N,N-Dimethyl-4-(((4-oxo-6-((5-(trifluoromethyl)isoindolin-2-yl)methyl)-4H-pyran-3-yl)oxy)methyl)benzamide (Compound 139);

(E)-3-(4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)phenyl)-Ν,Ν-dimethylacrylamide (Compound 146);

5-((4-(3,3-Difluoroazetidine-l-carbonyl)benzyl)oxy)-2-((5-methoxyisoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 162);

3,5-Difluoro-4-(((6-(isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-Ν,Ν-dimethylbenzamide (Compound 172);

N-((4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)cyclohexyl)-methyl)methanesulfonamide (Compound 173);

5 -((4-(( 1 , 1 -Dioxidoisothiazolidin-2-yl)methyl)cyclohexyl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 176);

5 -(( 1 -(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl)isoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 184);

2-(Isoindolin-2-ylmethyl)-5 -(( 1 -(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (Compound 185);

2-((5 -Fluoroisoindolin-2-yl)methyl)-5 -(( 1 -(methylsulfonyl)piperidin-4-yl)-methoxy)-4H-pyran-4-one (Compound 186);

5 -(( 1 -(Cyclopropylsulfonyl)piperidin-4-yl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 187);

5 -(( 1 -(Ethylsulfonyl)piperidin-4-yl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 188);

5 -(( 1 -(Ethylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -fluoroisoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 189);

5 -(( 1 -(Cyclopropylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -fluoroisoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 190);

5 -(( 1 -(Ethylsulfonyl)-4-methylpiperidin-4-yl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 192);

2-( 1 -Isoindolin-2-yl)ethyl)-5 -(( 1 -(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (Compound 195);

2-(Isoindolin-2-ylmethyl)-5-((tetrahydro-2H-thiopyran-4-yl)methoxy)-4H-pyran-4-one (Compound 196);

5 -(( 1 -(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -(trifluoromethoxy)-isoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 205);

2-((5 -Methylisoindolin-2-yl)methyl)-5 -(( 1 -(methylsulfonyl)piperidin-4-yl)-methoxy)-4H-pyran-4-one (Compound 211);

2-(Isoindolin-2-ylmethyl)-5 -(3 -( 1 -(methylsulfonyl)piperidin-4-yl)propoxy)-4H-pyran-4-one (Compound 213);

2-(Isoindolin-2-ylmethyl)-5-((l -(pyrrolidine- l-carbonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (Compound 215);

5 -((( 1 r,4r)-4-( 1 , 1 -Dioxidoisothiazolidin-2-yl)cyclohexyl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 216);

4- (((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-N,N-dimethylcyclohexane-l-carboxamide (Compound 217);

N-Cyclopropyl-N-(4-(((6-(isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)-methyl)cyclohexyl)methanesulfonamide (Compound 219);

5 -(( 1 -Butyrylpiperidin-4-yl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 221);

5- ((l-(2,2-Difluoropropanoyl)piperidin-4-yl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 222);

2-((5 -Fluoroisoindolin-2-yl)methyl)-5 -(( 1 -propionylpiperidin-4-yl)methoxy)-4H-pyran-4-one (Compound 224);

4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-N,N-di-methylpiperidine-1 -sulfonamide (Compound 225);

5 -(( 1 -(Cyclopropanecarbonyl)piperidin-4-yl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 226);

4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-N-iso-propylpiperidine-l-carboxamide (Compound 229);

4-(((6-((5-Fluoroisoindolin-2-yl)methyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-N,N-dimethylpiperidine-1 -sulfonamide (Compound 230);

2-(Isoindolin-2-ylmethyl)-5 -(( 1 -(morpholine-4-carbonyl)piperidin-4-yl)methoxy) 4H-pyran-4-one (Compound 232);

5 -((4-(Azetidine- 1 -carbonyl)cyclohexyl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 234);

2-(Isoindolin-2-ylmethyl)-5 -(( 1 -(2-(methylsulfonyl)acetyl)piperidin-4-yl)-methoxy)-4H-pyran-4-one (Compound 238);

5 -((( 1 r,4r)-4- Acetylcyclohexyl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 244);

5 -(( 1 -Propionylpiperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl)isoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 244a);

2-((5-((l-(methylsulfonyl)piperidin-4-yl)methoxy)-4-oxo-4H-pyran-2-yl)methyl)isoindoline-5-carbonitrile (Compound 245a);

1 -(4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)piperidin- 1 -yl)-4-methylpentane-l,2-dione (Compound 249);

2-(Isoindolin-2-ylmethyl)-5 -(( 1 -pivaloylpiperidin-4-yl)methoxy)-4H-pyran-4-one (Compound 251);

2-((4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)piperidin-l-yl)sulfonyl)acetonitrile (Compound 254);

2-(Isoindolin-2-ylmethyl)-5 -(( 1 -(( 1 -methyl- 1 H-pyrazol-5 -yl)sulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (Compound 255);

2-(4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)piperidin-l-yl)-2-oxoethyl acetate (Compound 257);

2-(Isoindolin-2-ylmethyl)-5 -(( 1 -propionylpiperidin-4-yl)methoxy)-4H-pyran-4-one (Compound 261);

2-(Isoindolin-2-ylmethyl)-5 -(( 1 -((2-methoxyethyl)sulfonyl)piperidin-4-yl)-methoxy)-4H-pyran-4-one (Compound 262);

5 -(( 1 -(Isobutylsulfonyl)piperidin-4-yl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 271);

5 -(( 1 -Isobutyrylpiperidin-4-yl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 272);

4-((6-((5-Bromoisoindolin-2-yl)methyl)-4-oxo-4H-pyran-3-yloxy)methyl)benzo-nitrile (Compound 278);

5-((4-(S-Methylsulfonimidoyl)benzyl)oxy)-2-((5-(trifluoromethyl)isoindolm^ yl)methyl)-4H-pyran-4-one (Compound 285);

5-((4-(R-Methylsulfonimidoyl)benzyl)oxy)-2-((5-(trifluoromethyl)isoindolin-yl)methyl)-4H-pyran-4-one (Compound 286);

and tautomers and pharmaceutically acceptable salts thereof.

28. A compound according to claim 27, which is

N-Ethyl-N-(2-hydroxyethyl)-4-(((6-(isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)benzenesulfonamide (Compound 21);

5-((4-(2-Hydroxypropan-2-yl)benzyl)oxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 49);

4- ({[6-(l,3-Dihydro-2H-isoindol-2-ylmethyl)-4-oxo-4H-pyran-3-yl]oxy}methyl)-N-[dimethyl(oxido)- 6-sulfanylidene]benzamide (Compound 83);

5- ((4-(S-Methylsulfonimidoyl)benzyl)oxy)-2-((5-(trifluoromethoxy)isoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 90);

2-(l-(Isoindolin-2-yl)ethyl)-5-((4-(S-methylsulfonimidoyl)benzyl)oxy)-4H-pyran-4-one (Compound 91);

2-(Isoindolin-2-ylmethyl)-5-((4-(pyrrolidine-l-carbonyl)benzyl)oxy)-4H-pyran-4-one (Compound 122);

5 -((4-(( 1 , 1 -Dioxidoisothiazolidin-2-yl)methyl)cyclohexyl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 176);

5 -(( 1 -(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl)isoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 184);

2-(Isoindolin-2-ylmethyl)-5 -(( 1 -(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (Compound 185);

5 -(( 1 -(Cyclopropylsulfonyl)piperidin-4-yl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 187);

5 -(( 1 -(Ethylsulfonyl)piperidin-4-yl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 188);

5 -(( 1 -(Ethylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -fluoroisoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 189);

2-( 1 -Isoindolin-2-yl)ethyl)-5 -(( 1 -(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (Compound 195);

2-(Isoindolin-2-ylmethyl)-5 -(3 -( 1 -(methylsulfonyl)piperidin-4-yl)propoxy)-4H-pyran-4-one (Compound 213);

5 -((( 1 r,4r)-4-( 1 , 1 -Dioxidoisothiazolidin-2-yl)cyclohexyl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 216);

4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-N,N-dimethylcyclohexane-l-carboxamide (Compound 217);

4-(((6-(Isoindolin-2-ylmethyl)-4-oxo-4H-pyran-3-yl)oxy)methyl)-N,N-di-methylpiperidine-1 -sulfonamide (Compound 225);

5 -((( 1 r,4r)-4- Acetylcyclohexyl)methoxy)-2-(isoindolin-2-ylmethyl)-4H-pyran-4-one (Compound 244);

5 -(( 1 -Propionylpiperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl)isoindolin-2-yl)methyl)-4H-pyran-4-one (Compound 244a);

2-(Isoindolin-2-ylmethyl)-5 -(( 1 -propionylpiperidin-4-yl)methoxy)-4H-pyran-4-one (Compound 261);

4-((6-((5-Bromoisoindolin-2-yl)methyl)-4-oxo-4H-pyran-3-yloxy)methyl)benzo-nitrile (Compound 278);

and tautomers and pharmaceutically acceptable salts thereof.

29. A method for the treatment of a steroid receptor, particularly androgen receptor, dependent conditions and diseases comprising administering to a subject in need thereof a thera eutically effective amount of a compound of formula (I)

wherein

ring B is a 4-10 membered monocyclic or bicyclic ring containing 0-4 hetero-atoms independently selected form N, O or S

ring A is any of the following groups

L is absent, -CH2- , -CH2-CH2- or -CH2-CH2-CH2-, or in case ring A is (1), L can also be -C(0)-CH2-;

Ri is hydrogen, Ci_7 alkyl, Ci_7 alkoxy, halogen, cyano, nitro, halo Ci_7 alkyl, halo

Ci-7 alkoxy or C 1-7 alkylthio;

R2 is hydrogen, Ci_7 alkyl, halogen, hydroxy, halo Ci_7 alkyl, nitro, halo Ci_7 alkoxy or thiol;

or Ri and R2 together with the carbon atoms to which they are attached form a fused 1 ,3 dioxole ring;

R3 is hydrogen, halogen, nitro, cyano, oxo, Ci_7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, hydroxy C3-7 cycloalkyl, Ci_7 alkoxy, hydroxy Ci_7 alkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkylthio, amino carbonyl C2_7 alkenyl, halo Ci-7 alkylthio, Ci-7 alkoxycarbonyl Ci-7 alkyl, Ci-7 alkoxycarbonyl C2_7 alkenyl, =NS02R2o,-S(0)-Ci_7 alkyl, -S(0)(NRi4)(R22), -S(NRi5)(Ci_7 alkyl), -C(S)NRi8Ri9, -D-C(0)-NR6R7,

-C(0)R8, -D-NR9R10, -S02Rii, optionally substituted 3-10 membered carbocyclyl, optionally substituted 3-10 membered carbocyclyl Ci-7 alkyl, optionally substituted 4-10 membered heterocyclyl or optionally substituted 4-10 membered heterocyclyl Ci-7 alkyl;

R4 is hydrogen, halogen, hydroxy, Ci-7 alkyl, halo Ci-7 alkyl or oxo;

R5 is hydrogen, halogen or Ci-7 alkyl;

Re is hydrogen, Ci-7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, hydroxy Ci-7 alkyl, cyano Ci-7 alkyl, -Ci-7 alkyl-0-C(0)Ci-7 alkyl or optionally substituted 4-10 membered heterocyclyl;

R8 is hydrogen, Ci-7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, Ci-7 alkoxy, halo Ci-7 alkyl, Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkylcarbonyl, Ci-7 alkoxycarbonyl, -Ci-7 alkyl-0-C(0)-Ci-7 alkyl, -C1-7 alkyl-S02(Ci_7 alkyl), -N=S(0)(C1-7 alkyl)(C1-7 alkyl) or optionally substituted 4-10 membered heterocyclyl;

R9 is hydrogen, Ci_7 alkyl, C3-7 cycloalkyl, Ci_7 alkylcarbonyl, -S02(Ci_7 alkyl) or -S02(C3-7 cycloalkyl);

Rii is Ci-7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci-7 alkoxy Ci_7 alkyl, -NR12R13, optionally substituted 3-10 membered carbocyclyl or optionally substituted 4-10 membered heterocyclyl;

R12 is hydrogen, Ci_7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy, Ci_7 alkoxy C 1 -7 alkyl or C 1 -7 alkylcarbonyl;

R7, Rio, Ri3, Ri8, and R19 are, independently, hydrogen, Ci_7 alkyl or C3-7 cycloalkyl;

Ri4 is hydrogen, Ci_7 alkyl, Ci_7 alkylcarbonyl or -SO2R21;

Ri5 is hydrogen, Ci_7 alkyl, C3-7 cycloalkyl, Ci_7 alkylcarbonyl, -SO2R17;

Ri7 is Ci-7 alkyl or an optionally substituted 3-10 membered carbocyclyl;

R20 and R2i are, independently, Ci_7 alkyl, C3-7 cycloalkyl or optionally substituted 3-10 membered carbocyclyl;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

R23 is hydrogen or oxo;

R24 is hydrogen or Ci_7 alkyl;

D is absent, Ci_7 alkyl or C2-7 alkenyl;

wherein the optional substitution in each occurrence is selected from 1-3 substituents independently selected from Ci_7 alkyl, halogen, hydroxy, Ci_7 alkoxy, Ci_7 alkoxy Ci-7 alkyl, Ci-7 alkoxycarbonyl or oxo; and

wherein the heterocyclyl group in each occurrence has 1-4 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof.

30. A method according to claim 29, wherein the steroid receptor dependent disease is cancer.

31. A method according to claim 30, wherein the cancer is prostate cancer.

32. A method according to claim 31 , wherein the prostate cancer is castration-resistant prostate cancer (CRPC).

33. A method according to any of claims 29-32 wherein a therapeutically effective amount of a compound of formula (I) is administered in addition to a glucocorticoid and/or a mineralocorticoid and, optionally, one or more anti-cancer agent.

34. A method according to any of claims 29-33 wherein a therapeutically effective amount of a compound of formula (I) is administered in addition to one or more anti-cancer agents selected from the group consisting of

- non-steroidal androgen receptor antagonists;

- steroidogenesis inhibitors;

- chemotherapeutic agents;

- antiestrogens;

- epigenetic modulators;

- mTOR inhibitors (e.g. everolimus);

- AKT inhibitors (eg AZ5363);

- radiopharmaceuticals (e.g. alpharadin);

- GnRH/LHRH analogues (such as leuprorelin);

- PI3K inhibitors; and

- CDK4/6 inhibitors.

35. A method according to any of claims 29-34 wherein a therapeutically effective amount of a compound of formula (I) and a therapeutically effective amount of a non-steroidal androgen receptor antagonist is administered.

36. A compound according to formula (I)

ring B is a 4-10 membered monocyclic or bicyclic ring containing 0-4 hetero-atoms independently selected form N, O or S

ring A is any of the following groups

L is absent, -CH2- , -CH2-CH2- or -CH2-CH2-CH2-, or in case ring A is (1), L can also be -C(0)-CH2-;

Ri is hydrogen, Ci_7 alkyl, Ci_7 alkoxy, halogen, cyano, nitro, halo Ci_7 alkyl, halo Ci-7 alkoxy or C 1-7 alkylthio;

R2 is hydrogen, Ci_7 alkyl, halogen, hydroxy, halo Ci_7 alkyl, nitro, halo Ci_7 alkoxy or thiol;

or Ri and R2 together with the carbon atoms to which they are attached form a fused 1 ,3 dioxole ring;

R3 is hydrogen, halogen, nitro, cyano, oxo, Ci_7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, hydroxy C3-7 cycloalkyl, Ci_7 alkoxy, hydroxy Ci_7 alkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkylthio, amino carbonyl C2_7 alkenyl, halo Ci-7 alkylthio, Ci-7 alkoxycarbonyl Ci-7 alkyl, Ci-7 alkoxycarbonyl C2_7 alkenyl, =NS02R2o,-S(0)-Ci_7 alkyl, -S(0)(NR14)(R22), -S(NR15)(d_7 alkyl), -C(S)NR18R19, -D-C(0)-NR6R7,

-C(0)R8, -D-NR9R10, -S02Rii, optionally substituted 3-10 membered carbocyclyl, optionally substituted 3-10 membered carbocyclyl Ci-7 alkyl, optionally substituted 4-10 membered heterocyclyl or optionally substituted 4-10 membered heterocyclyl Ci-7 alkyl;

R4 is hydrogen, halogen, hydroxy, Ci-7 alkyl, halo Ci-7 alkyl or oxo;

R5 is hydrogen, halogen or Ci-7 alkyl;

Re is hydrogen, Ci-7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, hydroxy Ci-7 alkyl, cyano Ci-7 alkyl, -Ci-7 alkyl-0-C(0)Ci_7 alkyl or optionally substituted 4-10 membered heterocyclyl;

R8 is hydrogen, Ci-7 alkyl, C2_7 alkenyl, C3-7 cycloalkyl, Ci-7 alkoxy, halo Ci-7 alkyl, Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkylcarbonyl, Ci-7 alkoxycarbonyl, -Ci-7 alkyl-0-C(0)-Ci_7 alkyl, -C1-7 alkyl-S02(Ci_7 alkyl), -N=S(0)(C1-7 alkyl)(Ci_7 alkyl) or optionally substituted 4-10 membered heterocyclyl;

R9 is hydrogen, Ci_7 alkyl, C3-7 cycloalkyl, Ci_7 alkylcarbonyl, -S02(Ci_7 alkyl) or -S02(C3-7 cycloalkyl);

R11 is Ci-7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, halo Ci_7 alkyl, cyano Ci_7 alkyl, Ci-7 alkoxy Ci_7 alkyl, -NR12R13, optionally substituted 3-10 membered carbocyclyl or optionally substituted 4-10 membered heterocyclyl;

R12 is hydrogen, Ci_7 alkyl, hydroxy Ci_7 alkyl, cyano Ci_7 alkyl, Ci_7 alkoxy, Ci_7 alkoxy Ci-7 alkyl or C 1-7 alkylcarbonyl;

R7, Rio, Ri3, Ri8, and R19 are, independently, hydrogen, Ci-7 alkyl or C3-7 cycloalkyl;

Ri4 is hydrogen, Ci-7 alkyl, Ci-7 alkylcarbonyl or -SO2R21;

Ri5 is hydrogen, Ci-7 alkyl, C3-7 cycloalkyl, Ci-7 alkylcarbonyl, -S02Ri7;

Ri7 is Ci-7 alkyl or an optionally substituted 3-10 membered carbocyclyl;

R20 and R2i are, independently, Ci-7 alkyl, C3-7 cycloalkyl or optionally substituted 3-10 membered carbocyclyl;

R22 is Ci-7 alkyl or C3-7 cycloalkyl;

R23 is hydrogen or oxo;

R24 is hydrogen or Ci-7 alkyl;

D is absent, Ci-7 alkyl or C2-7 alkenyl;

wherein the optional substitution in each occurrence is selected from 1-3 substituents independently selected from Ci-7 alkyl, halogen, hydroxy, Ci-7 alkoxy, Ci-7 alkoxy Ci-7 alkyl, Ci-7 alkoxycarbonyl or oxo; and

wherein the heterocyclyl group in each occurrence has 1-4 heteroatoms independently selected from N, O and S;

or a pharmaceutically acceptable salt thereof,

for use in the treatment of steroid receptor, particularly androgen receptor, dependent diseases.

37. A compound according to claim 36 wherein the steroid receptor dependent disease is cancer.

38. A compound according to claim 37 wherein the cancer is prostate cancer.

39. A compound according to claim 38 wherein prostate cancer is castration-resistant prostate cancer (CRPC).

40. A compound according to any of claims 36-39 wherein the compound of formula (I) is administered in addition to a glucocorticoid and/or a mineralocorticoid and, optionally, one or more anti-cancer agent.

41. A compound according to any of claims 36-40 wherein a therapeutically effective amount of a compound of formula (I) is administered in addition to one or more anti-cancer agents selected from the group consisting of

- non-steroidal androgen receptor antagonists;

- steroidogenesis inhibitors;

- chemotherapeutic agents;

- antiestrogens;

- epigenetic modulators;

- mTOR inhibitors (e.g. everolimus);

- AKT inhibitors (eg AZ5363);

- radiopharmaceuticals (e.g. alpharadin);

- GnRH/LHRH analogues (such as leuprorelin);

- PI3K inhibitors; and

- CDK4/6 inhibitors.

42. A compound according to any of claims 36-41 wherein the compound of formula (I) is administered in addition to a non-steroidal androgen receptor antagonist.

43. A pharmaceutical composition comprising a compound according to claim 1 together with a pharmaceutically acceptable carrier.

44. Pharmaceutical combination comprising a compound according to claim 1 and at least one additional active ingredient selected from the list consisting of - glucocorticoids;

- mineralocorticoids;

- non-steroidal androgen receptor antagonists;

- steroidogenesis inhibitors;

- chemotherapeutic agents;

- antiestrogens;

- epigenetic modulators;

- mTOR inhibitors (e.g. everolimus);

- A T inhibitors (e.g. AZ5363);

- radiopharmaceuticals (e.g. alpharadin);

- GnRH/LHRH analogues (such as leuprorelin);

- PI3K inhibitors; and

- CDK4/6 inhibitors;

ultaneous, separate or sequential administration.