NO342531B1 - Tetrahydrocyklopenta[b]indolforbindelser som androgenreseptormodulatorer - Google Patents

Info

Publication number

NO342531B1

NO342531B1 NO20092103A NO20092103A NO342531B1 NO 342531 B1 NO342531 B1 NO 342531B1 NO 20092103 A NO20092103 A NO 20092103A NO 20092103 A NO20092103 A NO 20092103A NO 342531 B1 NO342531 B1 NO 342531B1

Authority

NO

Norway

Prior art keywords

cyano

pyridin

compound

ylmethyl

cyclopenta

Prior art date

2006-11-20

Links

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• IAZKTAKWBHQCGF-UHFFFAOYSA-N 1,2,3,3a-tetrahydrocyclopenta[b]indole Chemical class N1=C2C=CC=CC2=C2C1CCC2 IAZKTAKWBHQCGF-UHFFFAOYSA-N 0.000 title description 10
• 239000000849 selective androgen receptor modulator Substances 0.000 title description 9
• 150000001875 compounds Chemical class 0.000 claims abstract description 170
• 150000003839 salts Chemical class 0.000 claims abstract description 47
• 230000002829 reductive effect Effects 0.000 claims abstract description 28
• 210000000988 bone and bone Anatomy 0.000 claims abstract description 23
• 208000001132 Osteoporosis Diseases 0.000 claims abstract description 18
• 210000003205 muscle Anatomy 0.000 claims abstract description 18
• 208000029725 Metabolic bone disease Diseases 0.000 claims abstract description 15
• 206010049088 Osteopenia Diseases 0.000 claims abstract description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
• 239000003085 diluting agent Substances 0.000 claims abstract description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 6
• -1 -CHF2 Chemical group 0.000 claims description 146
• 238000011282 treatment Methods 0.000 claims description 33
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 24
• 239000000460 chlorine Chemical group 0.000 claims description 22
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
• 229910052799 carbon Inorganic materials 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 14
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
• 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 claims description 14
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 13
• 238000002360 preparation method Methods 0.000 claims description 11
• 125000001072 heteroaryl group Chemical group 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 10
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
• 229910052794 bromium Inorganic materials 0.000 claims description 8
• 229910052801 chlorine Inorganic materials 0.000 claims description 8
• 229910052731 fluorine Inorganic materials 0.000 claims description 8
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 8
• 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 8
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
• 239000011737 fluorine Chemical group 0.000 claims description 7
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 7
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 7
• 125000004076 pyridyl group Chemical group 0.000 claims description 7
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
• 125000000335 thiazolyl group Chemical group 0.000 claims description 7
• 206010012205 Delayed puberty Diseases 0.000 claims description 6
• 206010058359 Hypogonadism Diseases 0.000 claims description 6
• 208000007502 anemia Diseases 0.000 claims description 6
• 229940079593 drug Drugs 0.000 claims description 6
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 6
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
• 208000010228 Erectile Dysfunction Diseases 0.000 claims description 5
• 206010024264 Lethargy Diseases 0.000 claims description 5
• 201000001880 Sexual dysfunction Diseases 0.000 claims description 5
• 201000001881 impotence Diseases 0.000 claims description 5
• 125000001793 isothiazol-3-yl group Chemical group [H]C1=C([H])C(*)=NS1 0.000 claims description 5
• 208000001076 sarcopenia Diseases 0.000 claims description 5
• 231100000872 sexual dysfunction Toxicity 0.000 claims description 5
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
• 230000003247 decreasing effect Effects 0.000 claims description 4
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• QIODLAKLXOMDJQ-INIZCTEOSA-N propan-2-yl n-[(2s)-4-[(2-aminopyridin-3-yl)methyl]-7-cyano-2,3-dihydro-1h-cyclopenta[b]indol-2-yl]carbamate Chemical compound C([C@H](C1)NC(=O)OC(C)C)C2=C1C1=CC(C#N)=CC=C1N2CC1=CC=CN=C1N QIODLAKLXOMDJQ-INIZCTEOSA-N 0.000 claims description 4
• IHIWYQYVBNODSV-KRWDZBQOSA-N propan-2-yl n-[(2s)-7-cyano-4-(pyridin-2-ylmethyl)-2,3-dihydro-1h-cyclopenta[b]indol-2-yl]carbamate Chemical group C([C@H](C1)NC(=O)OC(C)C)C2=C1C1=CC(C#N)=CC=C1N2CC1=CC=CC=N1 IHIWYQYVBNODSV-KRWDZBQOSA-N 0.000 claims description 4
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 4
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 4
• 230000008717 functional decline Effects 0.000 claims description 3
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 3
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• 125000003545 alkoxy group Chemical group 0.000 claims description 2
• CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical group BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 claims description 2
• CFZPNDIMNLMLED-AWEZNQCLSA-N propan-2-yl n-[(2s)-7-cyano-4-(1,3-thiazol-5-ylmethyl)-2,3-dihydro-1h-cyclopenta[b]indol-2-yl]carbamate Chemical compound C([C@H](C1)NC(=O)OC(C)C)C2=C1C1=CC(C#N)=CC=C1N2CC1=CN=CS1 CFZPNDIMNLMLED-AWEZNQCLSA-N 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• ZVPPVUXLWCZUHD-GFCCVEGCSA-N 4-amino-5-[[(2r)-7-cyano-2-(dimethylsulfamoylamino)-2,3-dihydro-1h-cyclopenta[b]indol-4-yl]methyl]-1,3-thiazole Chemical compound C([C@@H](C1)NS(=O)(=O)N(C)C)C2=C1C1=CC(C#N)=CC=C1N2CC=1SC=NC=1N ZVPPVUXLWCZUHD-GFCCVEGCSA-N 0.000 claims 1
• 206010057671 Female sexual dysfunction Diseases 0.000 claims 1
• 206010057672 Male sexual dysfunction Diseases 0.000 claims 1
• 125000000217 alkyl group Chemical group 0.000 claims 1
• QOGITFZSMDQJMF-ZDUSSCGKSA-N propan-2-yl n-[(2s)-4-[(4-amino-1,3-thiazol-5-yl)methyl]-7-cyano-2,3-dihydro-1h-cyclopenta[b]indol-2-yl]carbamate Chemical compound C([C@H](C1)NC(=O)OC(C)C)C2=C1C1=CC(C#N)=CC=C1N2CC=1SC=NC=1N QOGITFZSMDQJMF-ZDUSSCGKSA-N 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 53
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 16
• 208000035475 disorder Diseases 0.000 abstract description 11
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 143
• 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 99
• 239000000203 mixture Substances 0.000 description 83
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 75
• 239000007787 solid Substances 0.000 description 72
• 239000000543 intermediate Substances 0.000 description 68
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 65
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
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