ZA200205832B - Calcilytic compounds. - Google Patents
Calcilytic compounds. Download PDFInfo
- Publication number
- ZA200205832B ZA200205832B ZA200205832A ZA200205832A ZA200205832B ZA 200205832 B ZA200205832 B ZA 200205832B ZA 200205832 A ZA200205832 A ZA 200205832A ZA 200205832 A ZA200205832 A ZA 200205832A ZA 200205832 B ZA200205832 B ZA 200205832B
- Authority
- ZA
- South Africa
- Prior art keywords
- dimethyl
- phenyl
- ethylamino
- hydroxy
- cyano
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 143
- 230000001126 calcilytic effect Effects 0.000 title description 12
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 230000002159 abnormal effect Effects 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 210000000988 bone and bone Anatomy 0.000 claims description 11
- 102000013830 Calcium-Sensing Receptors Human genes 0.000 claims description 8
- 108010050543 Calcium-Sensing Receptors Proteins 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 125000004450 alkenylene group Chemical group 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 208000035475 disorder Diseases 0.000 claims description 7
- -1 2-indan-2-yl-1,1-dimethyl- ethylamino Chemical group 0.000 claims description 6
- 208000010392 Bone Fractures Diseases 0.000 claims description 6
- 206010017076 Fracture Diseases 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- XGBRVSSTLMUVLT-IAIRZMIISA-N 1-methoxypropan-2-yl 3-[4-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound COCC(C)OC(=O)CCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 XGBRVSSTLMUVLT-IAIRZMIISA-N 0.000 claims description 5
- XCBMSUBJOOBHIW-XMMPIXPASA-N 3-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-1-(5,6,7,8-tetrahydronaphthalen-2-yl)propan-2-yl]amino]propoxy]phenyl]propanoic acid Chemical compound C([C@H](O)CNC(C)(CC=1C=C2CCCCC2=CC=1)C)OC1=CC(CCC(O)=O)=CC=C1C#N XCBMSUBJOOBHIW-XMMPIXPASA-N 0.000 claims description 5
- 208000001132 Osteoporosis Diseases 0.000 claims description 5
- 125000004494 ethyl ester group Chemical group 0.000 claims description 5
- 230000035876 healing Effects 0.000 claims description 5
- QTTZOKJQOMEHAT-XMMPIXPASA-N 3-[3-cyano-4-[(2r)-2-hydroxy-3-[[2-methyl-1-(5,6,7,8-tetrahydronaphthalen-2-yl)propan-2-yl]amino]propoxy]phenyl]propanoic acid Chemical compound C([C@H](O)CNC(C)(CC=1C=C2CCCCC2=CC=1)C)OC1=CC=C(CCC(O)=O)C=C1C#N QTTZOKJQOMEHAT-XMMPIXPASA-N 0.000 claims description 4
- 208000037147 Hypercalcaemia Diseases 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 230000000148 hypercalcaemia Effects 0.000 claims description 4
- 208000030915 hypercalcemia disease Diseases 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 230000036210 malignancy Effects 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 201000008968 osteosarcoma Diseases 0.000 claims description 4
- 208000028169 periodontal disease Diseases 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- PJOYQRCYAHRICJ-AREMUKBSSA-N 2-methoxyethyl 3-[4-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound COCCOC(=O)CCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 PJOYQRCYAHRICJ-AREMUKBSSA-N 0.000 claims description 3
- 208000010191 Osteitis Deformans Diseases 0.000 claims description 3
- 208000027868 Paget disease Diseases 0.000 claims description 3
- WEXMMWSMKJOSSJ-VSGBNLITSA-N [(2s)-2-amino-3-methylbutyl] 3-[4-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound CC(C)[C@H](N)COC(=O)CCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 WEXMMWSMKJOSSJ-VSGBNLITSA-N 0.000 claims description 3
- YPNAYWVOPFBSTN-AREMUKBSSA-N ethyl 3-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-1-(5,6,7,8-tetrahydronaphthalen-2-yl)propan-2-yl]amino]propoxy]phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC=2C=C3CCCCC3=CC=2)=C1 YPNAYWVOPFBSTN-AREMUKBSSA-N 0.000 claims description 3
- 208000027202 mammary Paget disease Diseases 0.000 claims description 3
- 230000004079 mineral homeostasis Effects 0.000 claims description 3
- GCLKSISMFRGUIM-WJOKGBTCSA-N octyl 3-[4-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound CCCCCCCCOC(=O)CCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 GCLKSISMFRGUIM-WJOKGBTCSA-N 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- RQPPSXWWVZBILZ-JOCHJYFZSA-N 3-[2-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoic acid Chemical compound C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC=CC(CCC(O)=O)=C1C#N RQPPSXWWVZBILZ-JOCHJYFZSA-N 0.000 claims description 2
- OZRKKIQUCOTCTG-HHHXNRCGSA-N 3-[4-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoyloxymethyl 2,2-dimethylpropanoate Chemical compound C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC(CCC(=O)OCOC(=O)C(C)(C)C)=CC=C1C#N OZRKKIQUCOTCTG-HHHXNRCGSA-N 0.000 claims description 2
- NJBFJCJKWWIKRD-QHCPKHFHSA-N 3-[4-cyano-3-[(2s)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoic acid Chemical compound C([C@@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC(CCC(O)=O)=CC=C1C#N NJBFJCJKWWIKRD-QHCPKHFHSA-N 0.000 claims description 2
- PKHQFUWTTXDRID-XMMPIXPASA-N 4-[2-cyano-3-[(2r)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]phenyl]butanoic acid Chemical compound C([C@H](O)CNC(C)(CC=1C=C2C=CC=CC2=CC=1)C)OC1=CC=CC(CCCC(O)=O)=C1C#N PKHQFUWTTXDRID-XMMPIXPASA-N 0.000 claims description 2
- MRESEBKQONYCSN-HSZRJFAPSA-N 4-[2-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]butanoic acid Chemical compound C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC=CC(CCCC(O)=O)=C1C#N MRESEBKQONYCSN-HSZRJFAPSA-N 0.000 claims description 2
- ANDWNEZTVWCWTQ-RUZDIDTESA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]phenyl]butanoic acid Chemical compound C([C@H](O)CNC(C)(CC=1C=C2C=CC=CC2=CC=1)C)OC1=CC(CCCC(O)=O)=CC=C1C#N ANDWNEZTVWCWTQ-RUZDIDTESA-N 0.000 claims description 2
- 230000003042 antagnostic effect Effects 0.000 claims description 2
- HXJQUNZGBXBCAQ-KAYWLYCHSA-N ethyl (2r)-2-amino-5-[4-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]pentanoate Chemical compound CCOC(=O)[C@H](N)CCCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 HXJQUNZGBXBCAQ-KAYWLYCHSA-N 0.000 claims description 2
- GCZITLVIJOKRBL-RUZDIDTESA-N ethyl 3-[4-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-5-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC=2C=C3CCCC3=CC=2)=C1 GCZITLVIJOKRBL-RUZDIDTESA-N 0.000 claims description 2
- STTWWZRVCGJXQP-XMMPIXPASA-N ethyl 3-[4-cyano-5-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-2-fluorophenyl]propanoate Chemical compound C1=C(F)C(CCC(=O)OCC)=CC(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1C#N STTWWZRVCGJXQP-XMMPIXPASA-N 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- BRZBZQIHTODFDD-JOCHJYFZSA-N 3-[2-chloro-4-cyano-5-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoic acid Chemical compound C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC(CCC(O)=O)=C(Cl)C=C1C#N BRZBZQIHTODFDD-JOCHJYFZSA-N 0.000 claims 1
- XITQUPZFKAOAOI-JOCHJYFZSA-N 3-[4-cyano-5-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-2-fluorophenyl]propanoic acid Chemical compound C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC(CCC(O)=O)=C(F)C=C1C#N XITQUPZFKAOAOI-JOCHJYFZSA-N 0.000 claims 1
- CXFJIMBPPNYGSD-XMMPIXPASA-N 4-[3-cyano-4-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]butanoic acid Chemical compound C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC=C(CCCC(O)=O)C=C1C#N CXFJIMBPPNYGSD-XMMPIXPASA-N 0.000 claims 1
- GHEGNYMFJOZELI-IAIRZMIISA-N butan-2-yl 3-[4-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound CCC(C)OC(=O)CCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 GHEGNYMFJOZELI-IAIRZMIISA-N 0.000 claims 1
- ZGIUUXHOVHXIKY-RPWUZVMVSA-N ethyl (2s)-2-amino-3-[4-[(2r)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]-3-nitrophenyl]propanoate Chemical compound [O-][N+](=O)C1=CC(C[C@H](N)C(=O)OCC)=CC=C1OC[C@H](O)CNC(C)(C)CC1=CC=C(C=CC=C2)C2=C1 ZGIUUXHOVHXIKY-RPWUZVMVSA-N 0.000 claims 1
- PJWYQJZOMUBZBV-RUZDIDTESA-N ethyl 3-[2-cyano-3-[(2r)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=CC(OC[C@H](O)CNC(C)(C)CC=2C=C3C=CC=CC3=CC=2)=C1C#N PJWYQJZOMUBZBV-RUZDIDTESA-N 0.000 claims 1
- SMHJZKJDNBIROQ-XMMPIXPASA-N ethyl 3-[2-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=CC(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1C#N SMHJZKJDNBIROQ-XMMPIXPASA-N 0.000 claims 1
- OXHNGRUCABNPJH-RUZDIDTESA-N ethyl 4-[2-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]butanoate Chemical compound CCOC(=O)CCCC1=CC=CC(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1C#N OXHNGRUCABNPJH-RUZDIDTESA-N 0.000 claims 1
- JAOMNVGHIRSQDO-AREMUKBSSA-N ethyl 4-[3-cyano-4-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]butanoate Chemical compound N#CC1=CC(CCCC(=O)OCC)=CC=C1OC[C@H](O)CNC(C)(C)CC1CC2=CC=CC=C2C1 JAOMNVGHIRSQDO-AREMUKBSSA-N 0.000 claims 1
- ABPJGPGRRIGURC-XMMPIXPASA-N methyl 3-[4-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 ABPJGPGRRIGURC-XMMPIXPASA-N 0.000 claims 1
- PEWPUBAXAIXKCY-HHHXNRCGSA-N pentan-3-yl 3-[4-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound CCC(CC)OC(=O)CCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 PEWPUBAXAIXKCY-HHHXNRCGSA-N 0.000 claims 1
- QSYUQBQDXRVKLI-MUUNZHRXSA-N pentyl 3-[4-cyano-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound CCCCCOC(=O)CCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 QSYUQBQDXRVKLI-MUUNZHRXSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- 239000000203 mixture Substances 0.000 description 34
- 239000000243 solution Substances 0.000 description 29
- 239000003921 oil Substances 0.000 description 27
- 235000019198 oils Nutrition 0.000 description 27
- 238000000034 method Methods 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- 239000011575 calcium Substances 0.000 description 19
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 18
- 108090000445 Parathyroid hormone Proteins 0.000 description 18
- 229910052791 calcium Inorganic materials 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- 102100036893 Parathyroid hormone Human genes 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 210000002966 serum Anatomy 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000000849 parathyroid Effects 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 230000028327 secretion Effects 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- PYDOOGXGXVMZSG-UHFFFAOYSA-N 1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-amine Chemical compound C1=CC=C2CC(CC(C)(N)C)CC2=C1 PYDOOGXGXVMZSG-UHFFFAOYSA-N 0.000 description 4
- 229940123613 Calcium receptor antagonist Drugs 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 208000000038 Hypoparathyroidism Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000009739 binding Methods 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/22—Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/50—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
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- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
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- A61P5/22—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/04—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C233/05—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/612—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
- C07C69/616—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety polycyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
- Silicates, Zeolites, And Molecular Sieves (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17768300P | 2000-01-24 | 2000-01-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200205832B true ZA200205832B (en) | 2003-03-05 |
Family
ID=22649559
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200205832A ZA200205832B (en) | 2000-01-24 | 2002-07-22 | Calcilytic compounds. |
Country Status (31)
| Country | Link |
|---|---|
| EP (2) | EP1254106B1 (bg) |
| JP (1) | JP2003520265A (bg) |
| KR (1) | KR20020073179A (bg) |
| CN (1) | CN1396906A (bg) |
| AP (1) | AP2002002547A0 (bg) |
| AR (1) | AR030684A1 (bg) |
| AT (1) | ATE423762T1 (bg) |
| AU (1) | AU764746B2 (bg) |
| BG (1) | BG106942A (bg) |
| BR (1) | BR0107592A (bg) |
| CA (1) | CA2397802A1 (bg) |
| CO (1) | CO5251398A1 (bg) |
| DE (1) | DE60137755D1 (bg) |
| DZ (1) | DZ3284A1 (bg) |
| EA (1) | EA200200798A1 (bg) |
| ES (1) | ES2322641T3 (bg) |
| HK (1) | HK1051356A1 (bg) |
| HU (1) | HUP0204106A3 (bg) |
| IL (1) | IL150398A0 (bg) |
| MA (1) | MA25651A1 (bg) |
| MX (1) | MXPA02007173A (bg) |
| MY (1) | MY159417A (bg) |
| NO (1) | NO20023508L (bg) |
| NZ (1) | NZ519480A (bg) |
| OA (1) | OA12163A (bg) |
| PE (1) | PE20011062A1 (bg) |
| PL (1) | PL356808A1 (bg) |
| SK (1) | SK10742002A3 (bg) |
| UY (1) | UY26556A1 (bg) |
| WO (1) | WO2001053254A1 (bg) |
| ZA (1) | ZA200205832B (bg) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE411275T1 (de) * | 2000-08-11 | 2008-10-15 | Japan Tobacco Inc | Calciumrezeptor-antagonisten |
| ES2273909T3 (es) * | 2000-10-25 | 2007-05-16 | Smithkline Beecham Corporation | Compuestos calciliticos. |
| MY143244A (en) | 2002-11-26 | 2011-04-15 | Smithkline Beecham Corp | Calcilytic compounds |
| EP2308828A3 (en) | 2003-04-23 | 2013-05-22 | Japan Tobacco Inc. | CaSR antagonist |
| JP2007522148A (ja) * | 2004-02-06 | 2007-08-09 | スミスクライン・ビーチャム・コーポレイション | カルシウム受容体アンタゴニスト化合物 |
| EP1713767A4 (en) * | 2004-02-06 | 2008-01-16 | Smithkline Beecham Corp | CALCILYTIC COMPOUNDS |
| PL2292592T3 (pl) | 2008-06-05 | 2013-01-31 | Asahi Kasei Pharma Corp | Związki sulfonamidowe i ich zastosowanie |
| NZ593676A (en) | 2008-12-24 | 2012-06-29 | Daiichi Sankyo Co Ltd | Calcium-sensing receptor antagonists |
| CN107417594B (zh) * | 2017-05-08 | 2020-03-27 | 凯莱英医药集团（天津）股份有限公司 | 一种酰胺醇解的方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2530613A1 (de) * | 1974-11-01 | 1976-05-06 | Haessle Ab | Aminderivate, verfahren zu deren herstellung und sie enthaltende arzneimittel |
| US4234595A (en) * | 1977-07-13 | 1980-11-18 | Mead Johnson & Company | 3-Indolyl-tertiary butylaminopropanols |
| FR2533210A1 (fr) * | 1982-09-17 | 1984-03-23 | Lyon I Universite Claude | Edulcorants de synthese |
| DD298506A5 (de) * | 1988-12-30 | 1992-02-27 | Ernst-Moritz-Arndt-Universitaet Greifswald,De | Verfahren zur herstellung halogensubstituierter 1-phenoxy-3-alkylamino-propan-2-ole |
| DE4040186A1 (de) * | 1989-12-20 | 1991-06-27 | Hoechst Ag | Hypoglykaemisch aktive propandiolaminderivate mit insulin-aehnlicher wirkung und deren verwendung, neue propandiolaminderivate, diese substanzen enthaltende pharmazeutische zubereitungen und ihre verwendung zur behandlung von krankheiten |
| IL126458A (en) * | 1996-04-09 | 2004-06-20 | Nps Pharma Inc | Calcium receptor inhibiting calcilytic compounds |
| UY24949A1 (es) * | 1997-04-08 | 2001-04-30 | Smithkline Beecham Corp | Compuestos calcilíticos |
| AR018177A1 (es) * | 1998-04-08 | 2001-10-31 | Smithkline Beecham Corp | Compuestos calciliticos, una composicion farmaceutica que los comprende y el uso de los mismos para la manufactura de un medicamento. |
| AR014975A1 (es) * | 1998-04-08 | 2001-04-11 | Nps Pharma Inc | Compuestos calciliticos, una composicion farmaceutica que los comprende, y el uso de los mismos para la fabricacion de un medicamento |
| ECSP003590A (es) * | 1999-07-31 | 2002-02-25 | Smithkline Beecham Corp | Compuestos calcioliticos |
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2001
- 2001-01-22 MY MYPI20010288A patent/MY159417A/en unknown
- 2001-01-22 AR ARP010100268A patent/AR030684A1/es not_active Application Discontinuation
- 2001-01-23 PE PE2001000069A patent/PE20011062A1/es not_active Application Discontinuation
- 2001-01-24 EP EP01910349A patent/EP1254106B1/en not_active Expired - Lifetime
- 2001-01-24 HU HU0204106A patent/HUP0204106A3/hu unknown
- 2001-01-24 OA OA1200200218A patent/OA12163A/en unknown
- 2001-01-24 CO CO01005224A patent/CO5251398A1/es not_active Application Discontinuation
- 2001-01-24 SK SK1074-2002A patent/SK10742002A3/sk not_active Application Discontinuation
- 2001-01-24 BR BR0107592-6A patent/BR0107592A/pt not_active IP Right Cessation
- 2001-01-24 UY UY26556A patent/UY26556A1/es not_active Application Discontinuation
- 2001-01-24 JP JP2001553259A patent/JP2003520265A/ja not_active Withdrawn
- 2001-01-24 AU AU37966/01A patent/AU764746B2/en not_active Expired
- 2001-01-24 CA CA002397802A patent/CA2397802A1/en not_active Abandoned
- 2001-01-24 CN CN01804024A patent/CN1396906A/zh active Pending
- 2001-01-24 DE DE60137755T patent/DE60137755D1/de not_active Expired - Lifetime
- 2001-01-24 IL IL15039801A patent/IL150398A0/xx unknown
- 2001-01-24 EA EA200200798A patent/EA200200798A1/ru unknown
- 2001-01-24 WO PCT/US2001/002402 patent/WO2001053254A1/en active IP Right Grant
- 2001-01-24 DZ DZ013284A patent/DZ3284A1/fr active
- 2001-01-24 PL PL01356808A patent/PL356808A1/xx not_active Application Discontinuation
- 2001-01-24 EP EP09002553A patent/EP2141146A1/en not_active Withdrawn
- 2001-01-24 AP APAP/P/2002/002547A patent/AP2002002547A0/en unknown
- 2001-01-24 ES ES01910349T patent/ES2322641T3/es not_active Expired - Lifetime
- 2001-01-24 KR KR1020027009415A patent/KR20020073179A/ko not_active Application Discontinuation
- 2001-01-24 MX MXPA02007173A patent/MXPA02007173A/es unknown
- 2001-01-24 NZ NZ519480A patent/NZ519480A/en not_active IP Right Cessation
- 2001-01-24 AT AT01910349T patent/ATE423762T1/de not_active IP Right Cessation
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2002
- 2002-07-22 ZA ZA200205832A patent/ZA200205832B/en unknown
- 2002-07-23 BG BG106942A patent/BG106942A/bg unknown
- 2002-07-23 NO NO20023508A patent/NO20023508L/no unknown
- 2002-07-24 MA MA26743A patent/MA25651A1/fr unknown
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2003
- 2003-03-25 HK HK03102155.4A patent/HK1051356A1/zh unknown
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