AU2006251154B2 - 17beta-HSD1 and STS inhibitors - Google Patents

Info

Publication number

AU2006251154B2

AU2006251154B2 AU2006251154A AU2006251154A AU2006251154B2 AU 2006251154 B2 AU2006251154 B2 AU 2006251154B2 AU 2006251154 A AU2006251154 A AU 2006251154A AU 2006251154 A AU2006251154 A AU 2006251154A AU 2006251154 B2 AU2006251154 B2 AU 2006251154B2

Authority

AU

Australia

Prior art keywords

alkyl

group

estra

trien

hydroxy

Prior art date

2005-05-26

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Ceased

Links

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• 239000003112 inhibitor Substances 0.000 title abstract description 47
• 108010070743 3(or 17)-beta-hydroxysteroid dehydrogenase Proteins 0.000 title abstract description 5
• 102100037426 17-beta-hydroxysteroid dehydrogenase type 1 Human genes 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 343
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 115
• 201000010099 disease Diseases 0.000 claims abstract description 59
• 208000035475 disorder Diseases 0.000 claims abstract description 56
• 230000001419 dependent effect Effects 0.000 claims abstract description 55
• 229960005309 estradiol Drugs 0.000 claims abstract description 41
• 150000003839 salts Chemical class 0.000 claims abstract description 37
• 238000011282 treatment Methods 0.000 claims abstract description 37
• VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 claims abstract description 31
• 239000003270 steroid hormone Substances 0.000 claims abstract description 24
• 230000002265 prevention Effects 0.000 claims abstract description 12
• -1 nitro, sulfamoyl Chemical group 0.000 claims description 325
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 191
• 125000001424 substituent group Chemical group 0.000 claims description 179
• 125000000217 alkyl group Chemical group 0.000 claims description 136
• 125000003118 aryl group Chemical group 0.000 claims description 129
• 229910052736 halogen Inorganic materials 0.000 claims description 117
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 105
• 150000002367 halogens Chemical group 0.000 claims description 103
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 83
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 80
• 125000004122 cyclic group Chemical group 0.000 claims description 75
• 125000001072 heteroaryl group Chemical group 0.000 claims description 72
• 125000004432 carbon atom Chemical group C* 0.000 claims description 64
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 60
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 51
• 125000005842 heteroatom Chemical group 0.000 claims description 43
• 125000000623 heterocyclic group Chemical group 0.000 claims description 42
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 39
• 230000003637 steroidlike Effects 0.000 claims description 39
• 229910052739 hydrogen Inorganic materials 0.000 claims description 37
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 34
• 150000002825 nitriles Chemical group 0.000 claims description 34
• 125000003545 alkoxy group Chemical group 0.000 claims description 30
• 125000005037 alkyl phenyl group Chemical group 0.000 claims description 30
• 239000003098 androgen Substances 0.000 claims description 30
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• 229910052757 nitrogen Inorganic materials 0.000 claims description 30
• 125000004434 sulfur atom Chemical group 0.000 claims description 30
• 125000002252 acyl group Chemical group 0.000 claims description 28
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 28
• 229920006395 saturated elastomer Polymers 0.000 claims description 28
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
• 125000004043 oxo group Chemical group O=* 0.000 claims description 26
• 229940124530 sulfonamide Drugs 0.000 claims description 25
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 24
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
• 125000005843 halogen group Chemical group 0.000 claims description 24
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• 210000001519 tissue Anatomy 0.000 claims description 23
• 125000003368 amide group Chemical group 0.000 claims description 22
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 22
• 125000005110 aryl thio group Chemical group 0.000 claims description 22
• 125000004104 aryloxy group Chemical group 0.000 claims description 22
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 22
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 22
• TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 claims description 21
• 125000004442 acylamino group Chemical group 0.000 claims description 21
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 21
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• 125000004076 pyridyl group Chemical group 0.000 claims description 16
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• DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 14
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• 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
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• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
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• 206010020112 Hirsutism Diseases 0.000 claims description 7
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 7
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• 239000013543 active substance Substances 0.000 claims description 6
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• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
• 230000004064 dysfunction Effects 0.000 claims description 6
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• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 6
• 230000002485 urinary effect Effects 0.000 claims description 6
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• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 5
• 206010068168 androgenetic alopecia Diseases 0.000 claims description 5
• 201000009274 endometriosis of uterus Diseases 0.000 claims description 5
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 4
• 206010014733 Endometrial cancer Diseases 0.000 claims description 4
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• 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 4
• 206010039792 Seborrhoea Diseases 0.000 claims description 4
• 208000002495 Uterine Neoplasms Diseases 0.000 claims description 4
• 201000002996 androgenic alopecia Diseases 0.000 claims description 4
• 201000006828 endometrial hyperplasia Diseases 0.000 claims description 4
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
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• OLLZXQIFCRIRMH-UHFFFAOYSA-N n-methylbutanamide Chemical compound CCCC(=O)NC OLLZXQIFCRIRMH-UHFFFAOYSA-N 0.000 claims 1
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• FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
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• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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