OA12163A - Calcilytic compounds. - Google Patents

Calcilytic compounds. Download PDF

Info

Publication number: OA12163A
Authority: OA; OAPI
Prior art keywords: dimethyl; hydroxy; propoxy; phenyl; ethylamino
Prior art date: 2000-01-24

Application number

OA1200200218A

Other languages

English (en)

Inventor

Pradip Kumar Bhatnagar

William M Bryan

Joelle L Burgess

James Francis Callahan

Mar Eric G Del

Amparo M Lago

Original Assignee

Nps Pharma Inc

Smithkline Beecham Corp

Priority date (The priority date 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 date listed.)

2000-01-24

Filing date

2001-01-24

Publication date

2006-05-08

2001-01-24 Application filed by Nps Pharma Inc, Smithkline Beecham Corp filed Critical Nps Pharma Inc

2006-05-08 Publication of OA12163A publication Critical patent/OA12163A/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 125
230000001126 calcilytic effect Effects 0.000 title claims abstract description 13
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 57
229940095574 propionic acid Drugs 0.000 claims description 57
125000000217 alkyl group Chemical group 0.000 claims description 34
125000003118 aryl group Chemical group 0.000 claims description 32
229910052736 halogen Inorganic materials 0.000 claims description 23
150000002367 halogens Chemical class 0.000 claims description 23
125000001072 heteroaryl group Chemical group 0.000 claims description 23
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
125000001424 substituent group Chemical group 0.000 claims description 16
201000010099 disease Diseases 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 14
210000000988 bone and bone Anatomy 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
230000002159 abnormal effect Effects 0.000 claims description 11
125000004494 ethyl ester group Chemical group 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
-1 1-ethylamino Chemical group 0.000 claims description 9
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
230000000849 parathyroid Effects 0.000 claims description 8
102000013830 Calcium-Sensing Receptors Human genes 0.000 claims description 7
108010050543 Calcium-Sensing Receptors Proteins 0.000 claims description 7
125000004450 alkenylene group Chemical group 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
150000002148 esters Chemical class 0.000 claims description 7
208000010392 Bone Fractures Diseases 0.000 claims description 6
206010017076 Fracture Diseases 0.000 claims description 6
125000002947 alkylene group Chemical group 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
208000001132 Osteoporosis Diseases 0.000 claims description 5
230000035876 healing Effects 0.000 claims description 5
102000055006 Calcitonin Human genes 0.000 claims description 4
108060001064 Calcitonin Proteins 0.000 claims description 4
230000000123 anti-resoprtive effect Effects 0.000 claims description 4
BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 4
229960004015 calcitonin Drugs 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 4
208000035475 disorder Diseases 0.000 claims description 4
238000004519 manufacturing process Methods 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
AHXMMYNWSVNZRF-UHFFFAOYSA-N 3-(4-cyano-3-hydroxyphenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=C(C#N)C(O)=C1 AHXMMYNWSVNZRF-UHFFFAOYSA-N 0.000 claims description 3
208000010191 Osteitis Deformans Diseases 0.000 claims description 3
208000027868 Paget disease Diseases 0.000 claims description 3
208000027202 mammary Paget disease Diseases 0.000 claims description 3
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 2
229940122361 Bisphosphonate Drugs 0.000 claims description 2
102100022337 Integrin alpha-V Human genes 0.000 claims description 2
QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 2
108010048673 Vitronectin Receptors Proteins 0.000 claims description 2
239000000362 adenosine triphosphatase inhibitor Substances 0.000 claims description 2
230000003042 antagnostic effect Effects 0.000 claims description 2
239000005557 antagonist Substances 0.000 claims description 2
150000004663 bisphosphonates Chemical class 0.000 claims description 2
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 description 2
229940011871 estrogen Drugs 0.000 claims description 2
239000000262 estrogen Substances 0.000 claims description 2
239000002834 estrogen receptor modulator Substances 0.000 claims description 2
GKLSGASRWCMBDB-UHFFFAOYSA-N ethyl 3-(3-acetyloxy-4-cyanophenyl)propanoate Chemical compound CCOC(=O)CCC1=CC=C(C#N)C(OC(C)=O)=C1 GKLSGASRWCMBDB-UHFFFAOYSA-N 0.000 claims description 2
OOPWKXMGNZJEEE-CYBMUJFWSA-N ethyl 3-[4-cyano-3-[[(2r)-oxiran-2-yl]methoxy]phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=C(C#N)C(OC[C@@H]2OC2)=C1 OOPWKXMGNZJEEE-CYBMUJFWSA-N 0.000 claims description 2
239000003112 inhibitor Substances 0.000 claims description 2
ITYDRDKUXNKSAY-UHFFFAOYSA-N methyl 2-(2,3-dihydro-1h-inden-2-yl)acetate Chemical compound C1=CC=C2CC(CC(=O)OC)CC2=C1 ITYDRDKUXNKSAY-UHFFFAOYSA-N 0.000 claims description 2
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 2
229940044551 receptor antagonist Drugs 0.000 claims description 2
239000002464 receptor antagonist Substances 0.000 claims description 2
239000000126 substance Substances 0.000 claims description 2
QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 claims description 2
235000005282 vitamin D3 Nutrition 0.000 claims description 2
239000011647 vitamin D3 Substances 0.000 claims description 2
229940021056 vitamin d3 Drugs 0.000 claims description 2
ZCKMKRGGJZFAOG-UHFFFAOYSA-N 1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-ol Chemical compound C1=CC=C2CC(CC(C)(O)C)CC2=C1 ZCKMKRGGJZFAOG-UHFFFAOYSA-N 0.000 claims 1
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 1
102000004171 Cathepsin K Human genes 0.000 claims 1
108090000625 Cathepsin K Proteins 0.000 claims 1
101100001676 Emericella variicolor andK gene Proteins 0.000 claims 1
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims 1
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-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
ZJWJGKAOAYRABW-UHFFFAOYSA-N ethyl 3-[3-hydroxy-4-(hydroxyiminomethyl)phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=C(C=NO)C(O)=C1 ZJWJGKAOAYRABW-UHFFFAOYSA-N 0.000 claims 1
NCVLMZNMDMPUTF-UHFFFAOYSA-N n-[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]acetamide Chemical compound C1=CC=C2CC(CC(C)(C)NC(=O)C)CC2=C1 NCVLMZNMDMPUTF-UHFFFAOYSA-N 0.000 claims 1
238000000034 method Methods 0.000 abstract description 27
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
239000000203 mixture Substances 0.000 description 29
239000000243 solution Substances 0.000 description 28
239000003921 oil Substances 0.000 description 27
235000019198 oils Nutrition 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
235000019439 ethyl acetate Nutrition 0.000 description 19
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
239000011575 calcium Substances 0.000 description 18
229940093499 ethyl acetate Drugs 0.000 description 18
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 17
229910052791 calcium Inorganic materials 0.000 description 17
210000004027 cell Anatomy 0.000 description 17
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
108090000445 Parathyroid hormone Proteins 0.000 description 15
102100036893 Parathyroid hormone Human genes 0.000 description 13
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 10
239000007787 solid Substances 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-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 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
229910000041 hydrogen chloride Inorganic materials 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
239000012267 brine Substances 0.000 description 7
239000000872 buffer Substances 0.000 description 7
230000000694 effects Effects 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
239000002775 capsule Substances 0.000 description 6
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 6
238000009472 formulation Methods 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
125000004122 cyclic group Chemical group 0.000 description 5
238000000921 elemental analysis Methods 0.000 description 5
238000001914 filtration Methods 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
238000011534 incubation Methods 0.000 description 5
239000012528 membrane Substances 0.000 description 5
238000010992 reflux Methods 0.000 description 5
239000003826 tablet Substances 0.000 description 5
108010010803 Gelatin Proteins 0.000 description 4
208000000038 Hypoparathyroidism Diseases 0.000 description 4
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
238000009739 binding Methods 0.000 description 4
239000000706 filtrate Substances 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
230000013632 homeostatic process Effects 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
239000011541 reaction mixture Substances 0.000 description 4
102000005962 receptors Human genes 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
235000011121 sodium hydroxide Nutrition 0.000 description 4
229940083608 sodium hydroxide Drugs 0.000 description 4
239000002904 solvent Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
239000000725 suspension Substances 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
UWLHSHAHTBJTBA-UHFFFAOYSA-N 1-iodooctane Chemical compound CCCCCCCCI UWLHSHAHTBJTBA-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
229940123613 Calcium receptor antagonist Drugs 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
206010028980 Neoplasm Diseases 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 3
AIHIHVZYAAMDPM-MRVPVSSYSA-N [(2r)-oxiran-2-yl]methyl 3-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=CC(S(=O)(=O)OC[C@@H]2OC2)=C1 AIHIHVZYAAMDPM-MRVPVSSYSA-N 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
125000000304 alkynyl group Chemical group 0.000 description 3
230000027455 binding Effects 0.000 description 3
201000011510 cancer Diseases 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000002024 ethyl acetate extract Substances 0.000 description 3
239000000284 extract Substances 0.000 description 3
239000000499 gel Substances 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
230000036210 malignancy Effects 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000002674 ointment Substances 0.000 description 3
239000008188 pellet Substances 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
238000012360 testing method Methods 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
238000005406 washing Methods 0.000 description 3
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 2
NJBFJCJKWWIKRD-HSZRJFAPSA-N 3-[4-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(CCC(O)=O)=CC=C1C#N NJBFJCJKWWIKRD-HSZRJFAPSA-N 0.000 description 2
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
206010001497 Agitation Diseases 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
210000003771 C cell Anatomy 0.000 description 2
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
239000005977 Ethylene Substances 0.000 description 2
238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
229910004373 HOAc Inorganic materials 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
208000037147 Hypercalcaemia Diseases 0.000 description 2
206010053198 Inappropriate antidiuretic hormone secretion Diseases 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
102000003982 Parathyroid hormone Human genes 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
230000009102 absorption Effects 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
238000003556 assay Methods 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical group CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
239000001110 calcium chloride Substances 0.000 description 2
235000011148 calcium chloride Nutrition 0.000 description 2
229910001628 calcium chloride Inorganic materials 0.000 description 2
239000000969 carrier Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
239000006071 cream Substances 0.000 description 2
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
150000002118 epoxides Chemical class 0.000 description 2
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
GCILJQRRDBBUBX-UHFFFAOYSA-N ethyl 3-(4-cyano-3-hydroxyphenyl)propanoate Chemical compound CCOC(=O)CCC1=CC=C(C#N)C(O)=C1 GCILJQRRDBBUBX-UHFFFAOYSA-N 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000012458 free base Substances 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
230000000148 hypercalcaemia Effects 0.000 description 2
208000030915 hypercalcemia disease Diseases 0.000 description 2
239000005457 ice water Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000010410 layer Substances 0.000 description 2
229910001629 magnesium chloride Inorganic materials 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 description 2
210000002997 osteoclast Anatomy 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000000199 parathyroid hormone Substances 0.000 description 2
229960001319 parathyroid hormone Drugs 0.000 description 2
AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical group CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
239000000843 powder Substances 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
238000007910 systemic administration Methods 0.000 description 2
BFZDZPCIGYEJHA-YADHBBJMSA-N (2s)-2-amino-3-[4-[(2r)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]-3-nitrophenyl]propanoic acid Chemical compound C([C@H](O)CNC(C)(CC=1C=C2C=CC=CC2=CC=1)C)OC1=CC=C(C[C@H](N)C(O)=O)C=C1[N+]([O-])=O BFZDZPCIGYEJHA-YADHBBJMSA-N 0.000 description 1
AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
125000004893 1,1-dimethylethylamino group Chemical group CC(C)(C)N* 0.000 description 1
CHRJZRDFSQHIFI-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;styrene Chemical compound C=CC1=CC=CC=C1.C=CC1=CC=CC=C1C=C CHRJZRDFSQHIFI-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
KMGBZBJJOKUPIA-NUTRPMROSA-N 1-iodobutane Chemical group CCC[11CH2]I KMGBZBJJOKUPIA-NUTRPMROSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
TULDPXYHBFBRGW-UHFFFAOYSA-N 2-(2,3-dihydro-1h-inden-2-yl)acetic acid Chemical compound C1=CC=C2CC(CC(=O)O)CC2=C1 TULDPXYHBFBRGW-UHFFFAOYSA-N 0.000 description 1
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical group COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical group CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
229940093475 2-ethoxyethanol Drugs 0.000 description 1
AZYTZQYCOBXDGY-UHFFFAOYSA-N 2-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=CC=N1 AZYTZQYCOBXDGY-UHFFFAOYSA-N 0.000 description 1
QVWAEZJXDYOKEH-UHFFFAOYSA-N 3-(3-hydroxyphenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC(O)=C1 QVWAEZJXDYOKEH-UHFFFAOYSA-N 0.000 description 1
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 description 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 description 1
RPOHCNSBSXNRIJ-XMMPIXPASA-N 4-[4-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(CCCC(O)=O)=CC=C1C#N RPOHCNSBSXNRIJ-XMMPIXPASA-N 0.000 description 1
CIRMSYBIZHXKKP-UHFFFAOYSA-N 5-(2-methylprop-1-enyl)-2,3-dihydro-1h-indene Chemical compound CC(C)=CC1=CC=C2CCCC2=C1 CIRMSYBIZHXKKP-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
235000003911 Arachis Nutrition 0.000 description 1
244000105624 Arachis hypogaea Species 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
208000020084 Bone disease Diseases 0.000 description 1
RUBPRUAQKZMJQI-AWEZNQCLSA-N C1=C(C#N)C(CCC(=O)OCC)=CC=C1OC[C@@H]1OC1 Chemical compound C1=C(C#N)C(CCC(=O)OCC)=CC=C1OC[C@@H]1OC1 RUBPRUAQKZMJQI-AWEZNQCLSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
206010007559 Cardiac failure congestive Diseases 0.000 description 1
102000005600 Cathepsins Human genes 0.000 description 1
108010084457 Cathepsins Proteins 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
206010010904 Convulsion Diseases 0.000 description 1
AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
QRLVDLBMBULFAL-UHFFFAOYSA-N Digitonin Natural products CC1CCC2(OC1)OC3C(O)C4C5CCC6CC(OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(OC%11OC(CO)C(O)C(O)C%11O)C%10O)C8O)C(O)C7O)C(O)CC6(C)C5CCC4(C)C3C2C QRLVDLBMBULFAL-UHFFFAOYSA-N 0.000 description 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
206010049119 Emotional distress Diseases 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
206010016654 Fibrosis Diseases 0.000 description 1
OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
206010019196 Head injury Diseases 0.000 description 1
208000010496 Heart Arrest Diseases 0.000 description 1
206010019280 Heart failures Diseases 0.000 description 1
208000023105 Huntington disease Diseases 0.000 description 1
GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
206010021143 Hypoxia Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
IJMWOMHMDSDKGK-UHFFFAOYSA-N Isopropyl propionate Chemical compound CCC(=O)OC(C)C IJMWOMHMDSDKGK-UHFFFAOYSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
102000018697 Membrane Proteins Human genes 0.000 description 1
108010052285 Membrane Proteins Proteins 0.000 description 1
208000020161 Mineral related disease Diseases 0.000 description 1
206010049816 Muscle tightness Diseases 0.000 description 1
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical group CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
206010029164 Nephrotic syndrome Diseases 0.000 description 1
201000005625 Neuroleptic malignant syndrome Diseases 0.000 description 1
101001068640 Nicotiana tabacum Basic form of pathogenesis-related protein 1 Proteins 0.000 description 1
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
206010033645 Pancreatitis Diseases 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
208000025865 Ulcer Diseases 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
ASVRRMYEVHRXGM-RTBURBONSA-N [(2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butyl] 3-[4-cyano-3-[[(2r)-oxiran-2-yl]methoxy]phenyl]propanoate Chemical compound CC(C)(C)OC(=O)N[C@@H](C(C)C)COC(=O)CCC1=CC=C(C#N)C(OC[C@@H]2OC2)=C1 ASVRRMYEVHRXGM-RTBURBONSA-N 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
238000013019 agitation Methods 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
229960001040 ammonium chloride Drugs 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
125000005841 biaryl group Chemical group 0.000 description 1
239000003833 bile salt Substances 0.000 description 1
229940093761 bile salts Drugs 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
230000023555 blood coagulation Effects 0.000 description 1
210000002449 bone cell Anatomy 0.000 description 1
239000002617 bone density conservation agent Substances 0.000 description 1
239000007975 buffered saline Substances 0.000 description 1
230000004094 calcium homeostasis Effects 0.000 description 1
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
230000005779 cell damage Effects 0.000 description 1
230000003915 cell function Effects 0.000 description 1
208000037887 cell injury Diseases 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
239000013553 cell monolayer Substances 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
230000036755 cellular response Effects 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
229960002023 chloroprocaine Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
230000007882 cirrhosis Effects 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
238000011260 co-administration Methods 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
239000003086 colorant Substances 0.000 description 1
229940126086 compound 21 Drugs 0.000 description 1
238000010276 construction Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000001739 density measurement Methods 0.000 description 1
230000000881 depressing effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000000378 dietary effect Effects 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
UVYVLBIGDKGWPX-KUAJCENISA-N digitonin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O[C@H]5[C@@H]([C@@H](O)[C@@H](O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)CO7)O)[C@H](O)[C@@H](CO)O6)O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O7)O)[C@@H](O)[C@@H](CO)O6)O)[C@@H](CO)O5)O)C[C@@H]4CC[C@H]3[C@@H]2[C@@H]1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVYVLBIGDKGWPX-KUAJCENISA-N 0.000 description 1
UVYVLBIGDKGWPX-UHFFFAOYSA-N digitonine Natural products CC1C(C2(CCC3C4(C)CC(O)C(OC5C(C(O)C(OC6C(C(OC7C(C(O)C(O)CO7)O)C(O)C(CO)O6)OC6C(C(OC7C(C(O)C(O)C(CO)O7)O)C(O)C(CO)O6)O)C(CO)O5)O)CC4CCC3C2C2O)C)C2OC11CCC(C)CO1 UVYVLBIGDKGWPX-UHFFFAOYSA-N 0.000 description 1
GYZLOYUZLJXAJU-UHFFFAOYSA-N diglycidyl ether Chemical compound C1OC1COCC1CO1 GYZLOYUZLJXAJU-UHFFFAOYSA-N 0.000 description 1
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
238000007865 diluting Methods 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
230000009429 distress Effects 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000002500 effect on skin Effects 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
ZECGNJSXCCKHDX-UHFFFAOYSA-N ethyl 3-(3-hydroxyphenyl)propanoate Chemical compound CCOC(=O)CCC1=CC=CC(O)=C1 ZECGNJSXCCKHDX-UHFFFAOYSA-N 0.000 description 1
XZRINIMKJJEFMT-UHFFFAOYSA-N ethyl 3-(4-formyl-3-hydroxyphenyl)propanoate Chemical compound CCOC(=O)CCC1=CC=C(C=O)C(O)=C1 XZRINIMKJJEFMT-UHFFFAOYSA-N 0.000 description 1
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 description 1
DMWBVRRUBDZTBK-RUZDIDTESA-N ethyl 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 CCOC(=O)CCC1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 DMWBVRRUBDZTBK-RUZDIDTESA-N 0.000 description 1
XCXGVFLPUFHBDQ-AREMUKBSSA-N ethyl 4-[4-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=C(C#N)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 XCXGVFLPUFHBDQ-AREMUKBSSA-N 0.000 description 1
229940093476 ethylene glycol Drugs 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
230000000763 evoking effect Effects 0.000 description 1
230000005284 excitation Effects 0.000 description 1
210000003722 extracellular fluid Anatomy 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
238000007429 general method Methods 0.000 description 1
239000011521 glass Substances 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
230000005484 gravity Effects 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
125000000592 heterocycloalkyl group Chemical group 0.000 description 1
230000003284 homeostatic effect Effects 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
239000011539 homogenization buffer Substances 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
229940097277 hygromycin b Drugs 0.000 description 1
230000007954 hypoxia Effects 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical group CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
210000003292 kidney cell Anatomy 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
108010052968 leupeptin Proteins 0.000 description 1
239000003446 ligand Substances 0.000 description 1
238000005567 liquid scintillation counting Methods 0.000 description 1
239000006193 liquid solution Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
238000011068 loading method Methods 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
239000003068 molecular probe Substances 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
DMDOTRUOIVBPSF-UHFFFAOYSA-N naphthalene;hydrochloride Chemical compound Cl.C1=CC=CC2=CC=CC=C21 DMDOTRUOIVBPSF-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
208000009928 nephrosis Diseases 0.000 description 1
231100001027 nephrosis Toxicity 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
239000002687 nonaqueous vehicle Substances 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000011164 ossification Effects 0.000 description 1
208000019906 panic disease Diseases 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000006072 paste Substances 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
TWSRVQVEYJNFKQ-UHFFFAOYSA-N pentyl propanoate Chemical compound CCCCCOC(=O)CC TWSRVQVEYJNFKQ-UHFFFAOYSA-N 0.000 description 1
229950000964 pepstatin Drugs 0.000 description 1
108010091212 pepstatin Proteins 0.000 description 1
FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
238000001050 pharmacotherapy Methods 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000011505 plaster Substances 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
208000028173 post-traumatic stress disease Diseases 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000008569 process Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000000047 product Substances 0.000 description 1
RVGKZGROEYJDQL-UHFFFAOYSA-N propan-2-yl 3-(4-cyano-3-hydroxyphenyl)propanoate Chemical compound CC(C)OC(=O)CCC1=CC=C(C#N)C(O)=C1 RVGKZGROEYJDQL-UHFFFAOYSA-N 0.000 description 1
239000003380 propellant Substances 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000000746 purification Methods 0.000 description 1
ZHNFLHYOFXQIOW-LPYZJUEESA-N quinine sulfate dihydrate Chemical compound [H+].[H+].O.O.[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 ZHNFLHYOFXQIOW-LPYZJUEESA-N 0.000 description 1
230000009103 reabsorption Effects 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
108091006082 receptor inhibitors Proteins 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
239000006215 rectal suppository Substances 0.000 description 1
230000004044 response Effects 0.000 description 1
239000000523 sample Substances 0.000 description 1
201000000306 sarcoidosis Diseases 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
208000020431 spinal cord injury Diseases 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
ITVAJPHHXPJNHZ-UHFFFAOYSA-N tert-butyl 2-hydroxyhexanoate Chemical compound CCCCC(O)C(=O)OC(C)(C)C ITVAJPHHXPJNHZ-UHFFFAOYSA-N 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
230000002485 urinary effect Effects 0.000 description 1
239000012178 vegetable wax Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A61P5/22—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Hematology (AREA)
Obesity (AREA)
Immunology (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)

OA1200200218A 2000-01-24 2001-01-24 Calcilytic compounds. OA12163A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US17768300P	2000-01-24	2000-01-24

Publications (1)

Publication Number	Publication Date
OA12163A true OA12163A (en)	2006-05-08

Family

ID=22649559

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200200218A OA12163A (en)	2000-01-24	2001-01-24	Calcilytic compounds.

Country Status (31)

Country	Link
EP (2)	EP2141146A1 (de)
JP (1)	JP2003520265A (de)
KR (1)	KR20020073179A (de)
CN (1)	CN1396906A (de)
AP (1)	AP2002002547A0 (de)
AR (1)	AR030684A1 (de)
AT (1)	ATE423762T1 (de)
AU (1)	AU764746B2 (de)
BG (1)	BG106942A (de)
BR (1)	BR0107592A (de)
CA (1)	CA2397802A1 (de)
CO (1)	CO5251398A1 (de)
DE (1)	DE60137755D1 (de)
DZ (1)	DZ3284A1 (de)
EA (1)	EA200200798A1 (de)
ES (1)	ES2322641T3 (de)
HK (1)	HK1051356A1 (de)
HU (1)	HUP0204106A3 (de)
IL (1)	IL150398A0 (de)
MA (1)	MA25651A1 (de)
MX (1)	MXPA02007173A (de)
MY (1)	MY159417A (de)
NO (1)	NO20023508L (de)
NZ (1)	NZ519480A (de)
OA (1)	OA12163A (de)
PE (1)	PE20011062A1 (de)
PL (1)	PL356808A1 (de)
SK (1)	SK10742002A3 (de)
UY (1)	UY26556A1 (de)
WO (1)	WO2001053254A1 (de)
ZA (1)	ZA200205832B (de)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6916956B2 (en)	2000-08-11	2005-07-12	Japan Tobacco, Inc.	Calcium receptor antagonist
WO2002034204A2 (en) *	2000-10-25	2002-05-02	Smithkline Beecham Corporation	Calcilytic compounds
MY143244A (en)	2002-11-26	2011-04-15	Smithkline Beecham Corp	Calcilytic compounds
PE20050460A1 (es)	2003-04-23	2005-07-08	Japan Tobacco Inc	COMPUESTOS HETEROCICLICOS COMO ANTAGONISTAS CaSR (RECEPTOR SENSIBLE AL CALCIO)
US20070155819A1 (en) *	2004-02-06	2007-07-05	Marquis Robert W Jr	Calcilytic compounds
JP2007523076A (ja) *	2004-02-06	2007-08-16	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
CA2726610C (en)	2008-06-05	2015-05-05	Asahi Kasei Pharma Corporation	Sulfonamide compounds and use thereof
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)

* Cited by examiner, † Cited by third party
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
SG99290A1 (en) *	1996-04-09	2003-10-27	Nps Pharma Inc	Calcilytic compounds
UY24949A1 (es) *	1997-04-08	2001-04-30	Smithkline Beecham Corp	Compuestos calcilíticos
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
PE20000415A1 (es) *	1998-04-08	2000-05-21	Smithkline Beecham Corp	Compuestos calciliticos
ECSP003590A (es) *	1999-07-31	2002-02-25	Smithkline Beecham Corp	Compuestos calcioliticos

2001
- 2001-01-22 AR ARP010100268A patent/AR030684A1/es not_active Application Discontinuation
- 2001-01-22 MY MYPI20010288A patent/MY159417A/en unknown
- 2001-01-23 PE PE2001000069A patent/PE20011062A1/es not_active Application Discontinuation
- 2001-01-24 EP EP09002553A patent/EP2141146A1/de not_active Withdrawn
- 2001-01-24 HK HK03102155.4A patent/HK1051356A1/zh unknown
- 2001-01-24 IL IL15039801A patent/IL150398A0/xx unknown
- 2001-01-24 JP JP2001553259A patent/JP2003520265A/ja not_active Withdrawn
- 2001-01-24 HU HU0204106A patent/HUP0204106A3/hu unknown
- 2001-01-24 WO PCT/US2001/002402 patent/WO2001053254A1/en not_active Ceased
- 2001-01-24 EP EP01910349A patent/EP1254106B1/de not_active Expired - Lifetime
- 2001-01-24 PL PL01356808A patent/PL356808A1/xx not_active Application Discontinuation
- 2001-01-24 KR KR1020027009415A patent/KR20020073179A/ko not_active Withdrawn
- 2001-01-24 CN CN01804024A patent/CN1396906A/zh active Pending
- 2001-01-24 AT AT01910349T patent/ATE423762T1/de not_active IP Right Cessation
- 2001-01-24 NZ NZ519480A patent/NZ519480A/en not_active IP Right Cessation
- 2001-01-24 SK SK1074-2002A patent/SK10742002A3/sk not_active Application Discontinuation
- 2001-01-24 CA CA002397802A patent/CA2397802A1/en not_active Abandoned
- 2001-01-24 OA OA1200200218A patent/OA12163A/en unknown
- 2001-01-24 EA EA200200798A patent/EA200200798A1/ru unknown
- 2001-01-24 BR BR0107592-6A patent/BR0107592A/pt not_active IP Right Cessation
- 2001-01-24 MX MXPA02007173A patent/MXPA02007173A/es unknown
- 2001-01-24 AP APAP/P/2002/002547A patent/AP2002002547A0/en unknown
- 2001-01-24 DE DE60137755T patent/DE60137755D1/de not_active Expired - Lifetime
- 2001-01-24 CO CO01005224A patent/CO5251398A1/es not_active Application Discontinuation
- 2001-01-24 UY UY26556A patent/UY26556A1/es not_active Application Discontinuation
- 2001-01-24 ES ES01910349T patent/ES2322641T3/es not_active Expired - Lifetime
- 2001-01-24 AU AU37966/01A patent/AU764746B2/en not_active Expired
- 2001-01-24 DZ DZ013284A patent/DZ3284A1/fr active
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

Also Published As

Publication number	Publication date
EP1254106B1 (de)	2009-02-25
ES2322641T3 (es)	2009-06-24
KR20020073179A (ko)	2002-09-19
BR0107592A (pt)	2002-11-19
NO20023508D0 (no)	2002-07-23
EA200200798A1 (ru)	2002-12-26
WO2001053254A1 (en)	2001-07-26
DZ3284A1 (fr)	2001-07-26
HK1051356A1 (zh)	2003-08-01
DE60137755D1 (de)	2009-04-09
HUP0204106A3 (en)	2003-05-28
PL356808A1 (en)	2004-07-12
CN1396906A (zh)	2003-02-12
UY26556A1 (es)	2001-08-27
SK10742002A3 (sk)	2002-12-03
ZA200205832B (en)	2003-03-05
CA2397802A1 (en)	2001-07-26
ATE423762T1 (de)	2009-03-15
MA25651A1 (fr)	2002-12-31
NO20023508L (no)	2002-07-23
CO5251398A1 (es)	2003-02-28
NZ519480A (en)	2004-05-28
AU764746B2 (en)	2003-08-28
JP2003520265A (ja)	2003-07-02
EP1254106A1 (de)	2002-11-06
IL150398A0 (en)	2002-12-01
AR030684A1 (es)	2003-09-03
EP2141146A1 (de)	2010-01-06
AU3796601A (en)	2001-07-31
PE20011062A1 (es)	2001-11-29
MXPA02007173A (es)	2004-09-06
MY159417A (en)	2017-01-13
HUP0204106A2 (hu)	2003-03-28
BG106942A (bg)	2003-01-31
AP2002002547A0 (en)	2002-06-30
EP1254106A4 (de)	2005-09-14

Publication	Publication Date	Title
WO1999051241A1 (en)	1999-10-14	Calcilytic compounds and method of use
US6335338B1 (en)	2002-01-01	Calcilytic compounds
US7902394B2 (en)	2011-03-08	Calcilytic compounds
AU764746B2 (en)	2003-08-28	Calcilytic compounds
US7109238B2 (en)	2006-09-19	Calcilytic compounds
US20040009980A1 (en)	2004-01-15	Calcilytic compounds
EP1383511B1 (de)	2006-10-25	Kalzilytische verbindungen
EP1664013B1 (de)	2008-05-14	Kalzilytische verbindungen
US20080234370A1 (en)	2008-09-25	Calcilytic Compounds
US20070155819A1 (en)	2007-07-05	Calcilytic compounds
WO2005030746A1 (en)	2005-04-07	Calcilytic compounds
US20020052509A1 (en)	2002-05-02	Calcilytic compounds and method of use
WO2006042007A2 (en)	2006-04-20	Chromenone compounds as calcilytics