SK10982001A3 - Kalcilytické zlúčeniny a ich použitie - Google Patents

Kalcilytické zlúčeniny a ich použitie Download PDF

Info

Publication number: SK10982001A3
Authority: SK; Slovakia
Prior art keywords: cyano; hydroxy; dimethyl; naphthyl; phenoxy
Prior art date: 1999-02-02

Application number

SK1098-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Amparo Maria Lago

Original Assignee

Smithkline Beecham Corporation

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.)

1999-02-02

Filing date

2000-02-02

Publication date

2001-12-03

2000-02-02 Application filed by Smithkline Beecham Corporation filed Critical Smithkline Beecham Corporation

2001-12-03 Publication of SK10982001A3 publication Critical patent/SK10982001A3/sk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 93
230000001126 calcilytic effect Effects 0.000 title claims abstract description 21
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 56
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 52
-1 R 1 Inorganic materials 0.000 claims description 48
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
125000000217 alkyl group Chemical group 0.000 claims description 17
201000010099 disease Diseases 0.000 claims description 16
210000002966 serum Anatomy 0.000 claims description 13
102000013830 Calcium-Sensing Receptors Human genes 0.000 claims description 12
108010050543 Calcium-Sensing Receptors Proteins 0.000 claims description 12
230000002159 abnormal effect Effects 0.000 claims description 12
125000003118 aryl group Chemical group 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 11
210000000988 bone and bone Anatomy 0.000 claims description 8
208000035475 disorder Diseases 0.000 claims description 8
230000000849 parathyroid Effects 0.000 claims description 8
229910004013 NO 2 Inorganic materials 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
208000010392 Bone Fractures Diseases 0.000 claims description 5
206010017076 Fracture Diseases 0.000 claims description 5
229910052801 chlorine Inorganic materials 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
230000035876 healing Effects 0.000 claims description 5
201000008482 osteoarthritis Diseases 0.000 claims description 5
208000010191 Osteitis Deformans Diseases 0.000 claims description 4
208000001132 Osteoporosis Diseases 0.000 claims description 4
208000027868 Paget disease Diseases 0.000 claims description 4
KGKAARBFXKRTTL-VNUFCWELSA-N ethyl 4-[4-cyano-3-[(2R)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]phenyl]benzoate hydrochloride Chemical compound Cl.C1=CC(C(=O)OCC)=CC=C1C1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC=2C=C3C=CC=CC3=CC=2)=C1 KGKAARBFXKRTTL-VNUFCWELSA-N 0.000 claims description 4
125000001072 heteroaryl group Chemical group 0.000 claims description 4
208000027202 mammary Paget disease Diseases 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
230000004079 mineral homeostasis Effects 0.000 claims description 4
201000008968 osteosarcoma Diseases 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
208000028169 periodontal disease Diseases 0.000 claims description 4
208000037147 Hypercalcaemia Diseases 0.000 claims description 3
206010028980 Neoplasm Diseases 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
201000011510 cancer Diseases 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 3
230000000148 hypercalcaemia Effects 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
230000036210 malignancy Effects 0.000 claims description 3
125000000547 substituted alkyl group Chemical group 0.000 claims description 3
IIQLCIPKSPJKEJ-UHFFFAOYSA-N 2-naphthalen-1-ylethylazanium;chloride Chemical compound Cl.C1=CC=C2C(CCN)=CC=CC2=C1 IIQLCIPKSPJKEJ-UHFFFAOYSA-N 0.000 claims description 2
230000003042 antagnostic effect Effects 0.000 claims description 2
229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 claims description 2
239000001257 hydrogen Substances 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
208000030915 hypercalcemia disease Diseases 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
150000003536 tetrazoles Chemical class 0.000 claims description 2
BGOKBURQYJMBLD-LNLSOMNWSA-N Cl.CCOC(=O)C1=CC=CC=C1C1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC=2C=C3C=CC=CC3=CC=2)=C1 Chemical compound Cl.CCOC(=O)C1=CC=CC=C1C1=CC=C(C#N)C(OC[C@H](O)CNC(C)(C)CC=2C=C3C=CC=CC3=CC=2)=C1 BGOKBURQYJMBLD-LNLSOMNWSA-N 0.000 claims 2
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
239000000203 mixture Substances 0.000 description 40
239000011575 calcium Substances 0.000 description 37
239000007787 solid Substances 0.000 description 32
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
239000000243 solution Substances 0.000 description 28
239000002253 acid Substances 0.000 description 26
210000004027 cell Anatomy 0.000 description 25
238000005481 NMR spectroscopy Methods 0.000 description 24
238000000034 method Methods 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
102000003982 Parathyroid hormone Human genes 0.000 description 17
108090000445 Parathyroid hormone Proteins 0.000 description 17
239000000199 parathyroid hormone Substances 0.000 description 17
229960001319 parathyroid hormone Drugs 0.000 description 17
150000003839 salts Chemical class 0.000 description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
239000000047 product Substances 0.000 description 15
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 14
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 14
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
229910052791 calcium Inorganic materials 0.000 description 14
239000010410 layer Substances 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
KBNUZLPQQMVGPR-UHFFFAOYSA-N 4-(4-cyanophenyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(C#N)C=C1 KBNUZLPQQMVGPR-UHFFFAOYSA-N 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
239000008194 pharmaceutical composition Substances 0.000 description 12
238000009472 formulation Methods 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
238000010992 reflux Methods 0.000 description 9
239000003826 tablet Substances 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
235000019439 ethyl acetate Nutrition 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 7
230000028327 secretion Effects 0.000 description 7
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
239000000872 buffer Substances 0.000 description 6
239000002775 capsule Substances 0.000 description 6
230000000694 effects Effects 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 6
239000000284 extract Substances 0.000 description 6
230000003834 intracellular effect Effects 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
238000003756 stirring Methods 0.000 description 6
238000011282 treatment Methods 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
238000011534 incubation Methods 0.000 description 5
239000011734 sodium Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
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
239000000443 aerosol Substances 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
238000009739 binding Methods 0.000 description 4
239000012267 brine Substances 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
238000001914 filtration Methods 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
239000008187 granular material Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
239000012528 membrane Substances 0.000 description 4
239000002674 ointment Substances 0.000 description 4
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
239000002904 solvent Substances 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
WJLIFTJJCTWINV-RUZDIDTESA-N 4-[3-[(2R)-3-[[5-(2-chlorophenyl)-2-methylpentan-2-yl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CCCC1=CC=CC=C1Cl WJLIFTJJCTWINV-RUZDIDTESA-N 0.000 description 3
VSKMEBAGKIFRHD-HSZRJFAPSA-N 4-[3-[(2r)-3-[[1-(1,3-benzodioxol-5-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C([C@H](O)CNC(C)(CC=1C=C2OCOC2=CC=1)C)OC(C(=CC=1)C#N)=CC=1C1=CC=C(C(O)=O)C=C1 VSKMEBAGKIFRHD-HSZRJFAPSA-N 0.000 description 3
WOVZFJHCXJZOGT-XMMPIXPASA-N 4-[3-[(2r)-3-[[1-(1-benzothiophen-3-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C([C@H](O)CNC(C)(CC=1C2=CC=CC=C2SC=1)C)OC(C(=CC=1)C#N)=CC=1C1=CC=C(C(O)=O)C=C1 WOVZFJHCXJZOGT-XMMPIXPASA-N 0.000 description 3
DKLOQYKPTSSCKN-AREMUKBSSA-N 4-[3-[(2r)-3-[[5-(3-chloro-4-methylphenyl)-2-methylpentan-2-yl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C1=C(Cl)C(C)=CC=C1CCCC(C)(C)NC[C@@H](O)COC1=CC(C=2C=CC(=CC=2)C(O)=O)=CC=C1C#N DKLOQYKPTSSCKN-AREMUKBSSA-N 0.000 description 3
MRVXAFFAPSFGOM-AREMUKBSSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[(2-methyl-5-phenylpentan-2-yl)amino]propoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CCCC1=CC=CC=C1 MRVXAFFAPSFGOM-AREMUKBSSA-N 0.000 description 3
JUGKOCQYAQYZTD-XMMPIXPASA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-1-(4-methylsulfanylphenyl)propan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound C1=CC(SC)=CC=C1CC(C)(C)NC[C@@H](O)COC1=CC(C=2C=CC(=CC=2)C(O)=O)=CC=C1C#N JUGKOCQYAQYZTD-XMMPIXPASA-N 0.000 description 3
DYOYQIWMYDESRX-HHHXNRCGSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-1-(4-propan-2-ylphenyl)propan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1CC(C)(C)NC[C@@H](O)COC1=CC(C=2C=CC(=CC=2)C(O)=O)=CC=C1C#N DYOYQIWMYDESRX-HHHXNRCGSA-N 0.000 description 3
LXRKUTOACVPODY-MUUNZHRXSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-1-(5,6,7,8-tetrahydronaphthalen-2-yl)propan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound C([C@H](O)CNC(C)(CC=1C=C2CCCCC2=CC=1)C)OC(C(=CC=1)C#N)=CC=1C1=CC=C(C(O)=O)C=C1 LXRKUTOACVPODY-MUUNZHRXSA-N 0.000 description 3
SLOZNFGMRVHJMV-XMMPIXPASA-N 4-[4-cyano-3-[(2r)-3-[[1-(4-ethyl-2,5-difluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]benzoic acid Chemical compound C1=C(F)C(CC)=CC(F)=C1CC(C)(C)NC[C@@H](O)COC1=CC(C=2C=CC(=CC=2)C(O)=O)=CC=C1C#N SLOZNFGMRVHJMV-XMMPIXPASA-N 0.000 description 3
MOZNXVKEZLGXNW-AREMUKBSSA-N 4-[4-cyano-3-[(2r)-3-[[5-(4-fluorophenyl)-2-methylpentan-2-yl]amino]-2-hydroxypropoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CCCC1=CC=C(F)C=C1 MOZNXVKEZLGXNW-AREMUKBSSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
230000004094 calcium homeostasis Effects 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000003795 chemical substances by application 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
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000006260 foam Substances 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
125000004356 hydroxy functional group Chemical group O* 0.000 description 3
238000002329 infrared spectrum Methods 0.000 description 3
239000002609 medium Substances 0.000 description 3
239000008188 pellet Substances 0.000 description 3
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
239000002953 phosphate buffered saline Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
230000002265 prevention Effects 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 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
JCGNPQHAXBIDLH-UHFFFAOYSA-N (4-formyloxyphenyl)boronic acid Chemical compound OB(O)C1=CC=C(OC=O)C=C1 JCGNPQHAXBIDLH-UHFFFAOYSA-N 0.000 description 2
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
VFBVTSUHPOOLTP-FYZYNONXSA-N 2-[(2s)-3-[[1-(5-chlorothiophen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4-(4-cyanophenyl)benzoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C#N)C(O)=O)NC(C)(C)CC1=CC=C(Cl)S1 VFBVTSUHPOOLTP-FYZYNONXSA-N 0.000 description 2
WMKNVPNITGXMTJ-HSZRJFAPSA-N 2-[4-cyano-3-[(2r)-2-hydroxy-3-[[1-(4-methoxy-3-methylphenyl)-2-methylpropan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound C1=C(C)C(OC)=CC=C1CC(C)(C)NC[C@@H](O)COC1=CC(C=2C(=CC=CC=2)C(O)=O)=CC=C1C#N WMKNVPNITGXMTJ-HSZRJFAPSA-N 0.000 description 2
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 2
CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical group OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 description 2
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
ILYSAKHOYBPSPC-UHFFFAOYSA-N 2-phenylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=CC=C1 ILYSAKHOYBPSPC-UHFFFAOYSA-N 0.000 description 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
DTYBNDDILACFAY-UQJPIUAXSA-N 4-[3-[(2r)-3-[[1-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C([C@H](O)CNC(C)(CC1CC2CCCCC2CC1)C)OC(C(=CC=1)C#N)=CC=1C1=CC=C(C(O)=O)C=C1 DTYBNDDILACFAY-UQJPIUAXSA-N 0.000 description 2
DNAZSSOFXTZNLX-XMMPIXPASA-N 4-[3-[(2r)-3-[[1-(3-bromophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CC1=CC=CC(Br)=C1 DNAZSSOFXTZNLX-XMMPIXPASA-N 0.000 description 2
KCLCKWAUTYFRHA-AREMUKBSSA-N 4-[3-[(2r)-3-[[5-(4-chlorophenyl)-2-methylpentan-2-yl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CCCC1=CC=C(Cl)C=C1 KCLCKWAUTYFRHA-AREMUKBSSA-N 0.000 description 2
NPWNSGOJIVDGJA-XMMPIXPASA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound C1=CC(OC)=CC=C1CC(C)(C)NC[C@@H](O)COC1=CC(C=2C=CC(=CC=2)C(O)=O)=CC=C1C#N NPWNSGOJIVDGJA-XMMPIXPASA-N 0.000 description 2
GTXUJPDXROFQNN-UFUCKMQHSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[1-hydroxy-2-methyl-1-(6-methylpyridin-2-yl)propan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound CC1=CC=CC(C(O)C(C)(C)NC[C@@H](O)COC=2C(=CC=C(C=2)C=2C=CC(=CC=2)C(O)=O)C#N)=N1 GTXUJPDXROFQNN-UFUCKMQHSA-N 0.000 description 2
MCRZGBOQIRFKMF-HSZRJFAPSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-1-(4-sulfamoylphenyl)propan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CC1=CC=C(S(N)(=O)=O)C=C1 MCRZGBOQIRFKMF-HSZRJFAPSA-N 0.000 description 2
JMNWGUMMHNEHDY-HHHXNRCGSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-5-(2-methylphenyl)pentan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound CC1=CC=CC=C1CCCC(C)(C)NC[C@@H](O)COC1=CC(C=2C=CC(=CC=2)C(O)=O)=CC=C1C#N JMNWGUMMHNEHDY-HHHXNRCGSA-N 0.000 description 2
VLCSVTIRRDHWRY-RUZDIDTESA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-5-[2-(trifluoromethyl)phenyl]pentan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CCCC1=CC=CC=C1C(F)(F)F VLCSVTIRRDHWRY-RUZDIDTESA-N 0.000 description 2
MWFDEGCBBMSXQJ-RUZDIDTESA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-5-[3-(trifluoromethoxy)phenyl]pentan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CCCC1=CC=CC(OC(F)(F)F)=C1 MWFDEGCBBMSXQJ-RUZDIDTESA-N 0.000 description 2
XVGBGIHEPICZIM-AREMUKBSSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[5-(2-methoxyphenyl)-2-methylpentan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound COC1=CC=CC=C1CCCC(C)(C)NC[C@@H](O)COC1=CC(C=2C=CC(=CC=2)C(O)=O)=CC=C1C#N XVGBGIHEPICZIM-AREMUKBSSA-N 0.000 description 2
QKJNGGPGKZWBRK-RUZDIDTESA-N 4-[4-cyano-3-[(2r)-3-[[1-(4-ethoxyphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]benzoic acid Chemical compound C1=CC(OCC)=CC=C1CC(C)(C)NC[C@@H](O)COC1=CC(C=2C=CC(=CC=2)C(O)=O)=CC=C1C#N QKJNGGPGKZWBRK-RUZDIDTESA-N 0.000 description 2
YRSKHLNORPGMCT-RUZDIDTESA-N 4-[4-cyano-3-[(2r)-3-[[1-(4-ethyl-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]benzoic acid Chemical compound C1=C(F)C(CC)=CC=C1CC(C)(C)NC[C@@H](O)COC1=CC(C=2C=CC(=CC=2)C(O)=O)=CC=C1C#N YRSKHLNORPGMCT-RUZDIDTESA-N 0.000 description 2
WYBQQJVAXDNNIE-HHHXNRCGSA-N 4-[4-cyano-3-[(2r)-3-[[5-(2-cyanophenyl)-2-methylpentan-2-yl]amino]-2-hydroxypropoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CCCC1=CC=CC=C1C#N WYBQQJVAXDNNIE-HHHXNRCGSA-N 0.000 description 2
DUSFYHPZPHREER-RUZDIDTESA-N 4-[4-cyano-3-[(2r)-3-[[5-(2-fluorophenyl)-2-methylpentan-2-yl]amino]-2-hydroxypropoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CCCC1=CC=CC=C1F DUSFYHPZPHREER-RUZDIDTESA-N 0.000 description 2
COAXNGDVGNNVJU-XMMPIXPASA-N 4-[4-cyano-3-[(2r)-3-[[5-(3,4-dichlorophenyl)-2-methylpentan-2-yl]amino]-2-hydroxypropoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CCCC1=CC=C(Cl)C(Cl)=C1 COAXNGDVGNNVJU-XMMPIXPASA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
206010001497 Agitation Diseases 0.000 description 2
208000019901 Anxiety disease Diseases 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
210000003771 C cell Anatomy 0.000 description 2
JNQBRQHMLCZUHH-XMMPIXPASA-N C(#N)C1=C(C=C(C=C1)C1=CC=C(C=C1)C(=O)O)OC[C@@H](CNC(CC1=CC=C(C=C1)Br)(C)C)O Chemical compound C(#N)C1=C(C=C(C=C1)C1=CC=C(C=C1)C(=O)O)OC[C@@H](CNC(CC1=CC=C(C=C1)Br)(C)C)O JNQBRQHMLCZUHH-XMMPIXPASA-N 0.000 description 2
LTSAHXVFFUYKPV-AREMUKBSSA-N C(#N)C1=C(C=C(C=C1)C1=CC=C(C=C1)C(=O)O)OC[C@@H](CNC(CC1=CC=C(C=C1)CC)(C)C)O Chemical compound C(#N)C1=C(C=C(C=C1)C1=CC=C(C=C1)C(=O)O)OC[C@@H](CNC(CC1=CC=C(C=C1)CC)(C)C)O LTSAHXVFFUYKPV-AREMUKBSSA-N 0.000 description 2
JGJKGQIKLGBDFC-AREMUKBSSA-N C(#N)C1=C(C=C(C=C1)C1=CC=C(C=C1)C(=O)O)OC[C@@H](CNC(CCCC1=CC(=CC=C1)OC)(C)C)O Chemical compound C(#N)C1=C(C=C(C=C1)C1=CC=C(C=C1)C(=O)O)OC[C@@H](CNC(CCCC1=CC(=CC=C1)OC)(C)C)O JGJKGQIKLGBDFC-AREMUKBSSA-N 0.000 description 2
102000055006 Calcitonin Human genes 0.000 description 2
108060001064 Calcitonin Proteins 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 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
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-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
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 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
206010053198 Inappropriate antidiuretic hormone secretion Diseases 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
235000019483 Peanut oil Nutrition 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
239000004698 Polyethylene Substances 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
238000006069 Suzuki reaction reaction Methods 0.000 description 2
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 2
230000009102 absorption Effects 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
230000036506 anxiety Effects 0.000 description 2
239000008365 aqueous carrier Substances 0.000 description 2
239000002585 base Substances 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
229940092714 benzenesulfonic acid Drugs 0.000 description 2
230000027455 binding Effects 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
150000001642 boronic acid derivatives Chemical class 0.000 description 2
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 description 2
229960004015 calcitonin Drugs 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
229960001231 choline Drugs 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
239000006071 cream Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
238000000605 extraction Methods 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
238000000265 homogenisation Methods 0.000 description 2
150000002430 hydrocarbons Chemical group 0.000 description 2
201000008284 inappropriate ADH syndrome Diseases 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
235000019359 magnesium stearate 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
239000000463 material Substances 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
210000002997 osteoclast Anatomy 0.000 description 2
239000000312 peanut oil Substances 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
235000011056 potassium acetate Nutrition 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
230000008569 process Effects 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
230000004044 response Effects 0.000 description 2
239000000523 sample Substances 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000012049 topical pharmaceutical composition Substances 0.000 description 2
PNHBRYIAJCYNDA-VQCQRNETSA-N (4r)-6-[2-[2-ethyl-4-(4-fluorophenyl)-6-phenylpyridin-3-yl]ethyl]-4-hydroxyoxan-2-one Chemical compound C([C@H](O)C1)C(=O)OC1CCC=1C(CC)=NC(C=2C=CC=CC=2)=CC=1C1=CC=C(F)C=C1 PNHBRYIAJCYNDA-VQCQRNETSA-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
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-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
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
MUSKTCTZFQZRIL-UHFFFAOYSA-N 2-Methyl-1-(2-naphthyl)-2-propanamine Chemical compound C1=CC=CC2=CC(CC(C)(N)C)=CC=C21 MUSKTCTZFQZRIL-UHFFFAOYSA-N 0.000 description 1
KFJPKFFLIVPPAJ-UFTMZEDQSA-N 2-[3-cyano-4-[(2R)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]phenyl]benzoic acid hydrochloride Chemical compound Cl.C([C@H](O)CNC(C)(CC=1C=C2C=CC=CC2=CC=1)C)OC(C(=C1)C#N)=CC=C1C1=CC=CC=C1C(O)=O KFJPKFFLIVPPAJ-UFTMZEDQSA-N 0.000 description 1
RILZRCJGXSFXNE-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]ethanol Chemical compound OCCC1=CC=C(OC(F)(F)F)C=C1 RILZRCJGXSFXNE-UHFFFAOYSA-N 0.000 description 1
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
VJPPXKBLHHCXLG-UHFFFAOYSA-N 2-naphthalen-2-ylethanamine;hydrochloride Chemical compound Cl.C1=CC=CC2=CC(CCN)=CC=C21 VJPPXKBLHHCXLG-UHFFFAOYSA-N 0.000 description 1
LCRCBXLHWTVPEQ-UHFFFAOYSA-N 2-phenylbenzaldehyde Chemical group O=CC1=CC=CC=C1C1=CC=CC=C1 LCRCBXLHWTVPEQ-UHFFFAOYSA-N 0.000 description 1
125000006495 3-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 description 1
125000001963 4 membered heterocyclic group Chemical group 0.000 description 1
GCMCRQAYNPGAPH-UHFFFAOYSA-N 4-(4-cyanophenyl)benzoic acid;hydrochloride Chemical compound Cl.C1=CC(C(=O)O)=CC=C1C1=CC=C(C#N)C=C1 GCMCRQAYNPGAPH-UHFFFAOYSA-N 0.000 description 1
YAKFQDWXJZMZFM-XMMPIXPASA-N 4-[3-[(2R)-3-[[1-[(4-bromophenyl)methyl]cyclopropyl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C(#N)C1=C(C=C(C=C1)C1=CC=C(C=C1)C(=O)O)OC[C@@H](CNC1(CC1)CC1=CC=C(C=C1)Br)O YAKFQDWXJZMZFM-XMMPIXPASA-N 0.000 description 1
BWQZIWCHBHNXIH-HSZRJFAPSA-N 4-[3-[(2r)-3-[[1-(2-bromophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CC1=CC=CC=C1Br BWQZIWCHBHNXIH-HSZRJFAPSA-N 0.000 description 1
JXQWDCUUKVJGPS-XMMPIXPASA-N 4-[3-[(2r)-3-[[1-(4-aminophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CC1=CC=C(N)C=C1 JXQWDCUUKVJGPS-XMMPIXPASA-N 0.000 description 1
BDIFSUUCEGMDPL-SSEXGKCCSA-N 4-[3-[(2r)-3-[[1-(4-benzamidophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1 BDIFSUUCEGMDPL-SSEXGKCCSA-N 0.000 description 1
MZMSZAHPVUJCMA-XMMPIXPASA-N 4-[3-[(2r)-3-[[1-[(4-chlorophenyl)methyl]cyclopropyl]amino]-2-hydroxypropoxy]-4-cyanophenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC1(CC=2C=CC(Cl)=CC=2)CC1 MZMSZAHPVUJCMA-XMMPIXPASA-N 0.000 description 1
KIGUDBQCCOFWFO-RUZDIDTESA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[(2-methyl-1-phenylmethoxypropan-2-yl)amino]propoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)COCC1=CC=CC=C1 KIGUDBQCCOFWFO-RUZDIDTESA-N 0.000 description 1
KTSBXBXHHKLPJE-AREMUKBSSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[(2-methyl-1-quinolin-2-ylpropan-2-yl)amino]propoxy]phenyl]benzoic acid Chemical compound C([C@H](O)CNC(C)(CC=1N=C2C=CC=CC2=CC=1)C)OC(C(=CC=1)C#N)=CC=1C1=CC=C(C(O)=O)C=C1 KTSBXBXHHKLPJE-AREMUKBSSA-N 0.000 description 1
CHNJNSBMMWFNFD-RUZDIDTESA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[(2-methyl-5-pyridin-4-ylpentan-2-yl)amino]propoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CCCC1=CC=NC=C1 CHNJNSBMMWFNFD-RUZDIDTESA-N 0.000 description 1
QQZYBPNDPLGEOP-XMMPIXPASA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[1-(3-methoxyphenyl)-2-methylpropan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound COC1=CC=CC(CC(C)(C)NC[C@@H](O)COC=2C(=CC=C(C=2)C=2C=CC(=CC=2)C(O)=O)C#N)=C1 QQZYBPNDPLGEOP-XMMPIXPASA-N 0.000 description 1
KHVVBVGSBRONGG-RUZDIDTESA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[1-[(2-methylphenyl)methyl]cyclopropyl]amino]propoxy]phenyl]benzoic acid Chemical compound CC1=CC=CC=C1CC1(NC[C@@H](O)COC=2C(=CC=C(C=2)C=2C=CC(=CC=2)C(O)=O)C#N)CC1 KHVVBVGSBRONGG-RUZDIDTESA-N 0.000 description 1
ZAVKVJJLZXLOSM-XMMPIXPASA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[1-[(4-hydroxyphenyl)methyl]cyclopropyl]amino]propoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC1(CC=2C=CC(O)=CC=2)CC1 ZAVKVJJLZXLOSM-XMMPIXPASA-N 0.000 description 1
ZEGRCISGBFQGIJ-HSZRJFAPSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[1-[[2-(trifluoromethyl)phenyl]methyl]cyclopropyl]amino]propoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC1(CC=2C(=CC=CC=2)C(F)(F)F)CC1 ZEGRCISGBFQGIJ-HSZRJFAPSA-N 0.000 description 1
NCZVVBQYHPPCGT-SSEXGKCCSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-1-(3-phenylphenyl)propan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CC(C=1)=CC=CC=1C1=CC=CC=C1 NCZVVBQYHPPCGT-SSEXGKCCSA-N 0.000 description 1
HDYRGQCDUFAMJD-MUUNZHRXSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-1-(4-phenoxyphenyl)propan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CC(C=C1)=CC=C1OC1=CC=CC=C1 HDYRGQCDUFAMJD-MUUNZHRXSA-N 0.000 description 1
HCDFSORKFGYMGY-HSZRJFAPSA-N 4-[4-cyano-3-[(2r)-2-hydroxy-3-[[2-methyl-1-[4-(trifluoromethoxy)phenyl]propan-2-yl]amino]propoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CC1=CC=C(OC(F)(F)F)C=C1 HCDFSORKFGYMGY-HSZRJFAPSA-N 0.000 description 1
MYYPXYHKPXEMSM-JOCHJYFZSA-N 4-[4-cyano-3-[(2r)-3-[[1-(3,4-dichlorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC(C)(C)CC1=CC=C(Cl)C(Cl)=C1 MYYPXYHKPXEMSM-JOCHJYFZSA-N 0.000 description 1
FKGGACQJTWCVAR-HSZRJFAPSA-N 4-[4-cyano-3-[(2r)-3-[[1-(4-ethyl-2,6-difluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]benzoic acid Chemical compound FC1=CC(CC)=CC(F)=C1CC(C)(C)NC[C@@H](O)COC1=CC(C=2C=CC(=CC=2)C(O)=O)=CC=C1C#N FKGGACQJTWCVAR-HSZRJFAPSA-N 0.000 description 1
CWNHULWBKILSAA-RUZDIDTESA-N 4-[4-cyano-3-[(2r)-3-[[1-(4-ethyl-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]benzoic acid Chemical compound FC1=CC(CC)=CC=C1CC(C)(C)NC[C@@H](O)COC1=CC(C=2C=CC(=CC=2)C(O)=O)=CC=C1C#N CWNHULWBKILSAA-RUZDIDTESA-N 0.000 description 1
KZYVUSDQVAVGIM-XMMPIXPASA-N 4-[4-cyano-3-[(2r)-3-[[1-(cyclohexylmethyl)cyclopropyl]amino]-2-hydroxypropoxy]phenyl]benzoic acid Chemical compound C([C@@H](O)COC=1C(=CC=C(C=1)C=1C=CC(=CC=1)C(O)=O)C#N)NC1(CC2CCCCC2)CC1 KZYVUSDQVAVGIM-XMMPIXPASA-N 0.000 description 1
HGXWRDPQFZKOLZ-UHFFFAOYSA-N 4-bromo-2-fluorobenzonitrile Chemical compound FC1=CC(Br)=CC=C1C#N HGXWRDPQFZKOLZ-UHFFFAOYSA-N 0.000 description 1
PAHSHGVACWNGEY-UHFFFAOYSA-N 4-bromo-2-hydroxybenzonitrile Chemical compound OC1=CC(Br)=CC=C1C#N PAHSHGVACWNGEY-UHFFFAOYSA-N 0.000 description 1
125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000000173 4-trifluoromethoxy benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC(F)(F)F)C([H])([H])* 0.000 description 1
125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
GYCNHFWRPJXTSB-UHFFFAOYSA-N 5-bromo-2-fluorobenzonitrile Chemical compound FC1=CC=C(Br)C=C1C#N GYCNHFWRPJXTSB-UHFFFAOYSA-N 0.000 description 1
PVCONXMDUZOPJH-UHFFFAOYSA-N 5-bromo-2-hydroxybenzonitrile Chemical compound OC1=CC=C(Br)C=C1C#N PVCONXMDUZOPJH-UHFFFAOYSA-N 0.000 description 1
125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
125000003341 7 membered heterocyclic group Chemical group 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
208000024827 Alzheimer disease Diseases 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
208000006386 Bone Resorption Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
ZPLOALZRPXRTON-OEXUWWALSA-N C(#N)C1(CC=C(C=C1)C1=CC(=CC=C1)OC[C@@H](CNC(CC1=CC=C(C=C1)OCC)(C)C)O)C(=O)O Chemical compound C(#N)C1(CC=C(C=C1)C1=CC(=CC=C1)OC[C@@H](CNC(CC1=CC=C(C=C1)OCC)(C)C)O)C(=O)O ZPLOALZRPXRTON-OEXUWWALSA-N 0.000 description 1
ISZORLKIAZVMMJ-MUUNZHRXSA-N C(#N)C1=C(C=C(C=C1)C1=CC=C(C=C1)C(=O)O)OC[C@@H](CNC(CC1=CC(=CC=C1)OC1=CC=CC=C1)(C)C)O Chemical compound C(#N)C1=C(C=C(C=C1)C1=CC=C(C=C1)C(=O)O)OC[C@@H](CNC(CC1=CC(=CC=C1)OC1=CC=CC=C1)(C)C)O ISZORLKIAZVMMJ-MUUNZHRXSA-N 0.000 description 1
JYGUOTGFUPKMPG-GDLZYMKVSA-N C(#N)C1=C(C=C(C=C1)C1=CC=C(C=C1)C(=O)O)OC[C@@H](CNC(CC1=CC=C(C=C1)C1=CC=NC=C1)(C)C)O Chemical compound C(#N)C1=C(C=C(C=C1)C1=CC=C(C=C1)C(=O)O)OC[C@@H](CNC(CC1=CC=C(C=C1)C1=CC=NC=C1)(C)C)O JYGUOTGFUPKMPG-GDLZYMKVSA-N 0.000 description 1
NXRYDPAKJWQSAM-UHFFFAOYSA-N CCNC1C=CC2=CC=CC=C2C1(C)C Chemical compound CCNC1C=CC2=CC=CC=C2C1(C)C NXRYDPAKJWQSAM-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
201000009030 Carcinoma Diseases 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
229920002261 Corn starch Polymers 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 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
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 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
238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
206010017999 Gastrointestinal pain Diseases 0.000 description 1
229910004039 HBF4 Inorganic materials 0.000 description 1
239000012981 Hank's balanced salt solution Substances 0.000 description 1
206010019196 Head injury Diseases 0.000 description 1
208000010496 Heart Arrest Diseases 0.000 description 1
241000282412 Homo Species 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
239000005909 Kieselgur Substances 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
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
235000019759 Maize starch Nutrition 0.000 description 1
102000018697 Membrane Proteins Human genes 0.000 description 1
108010052285 Membrane Proteins Proteins 0.000 description 1
206010049816 Muscle tightness Diseases 0.000 description 1
UPKYBTIDDVVFMW-UHFFFAOYSA-N N-ethylnaphthalen-2-amine hydrochloride Chemical compound Cl.C(C)NC1=CC2=CC=CC=C2C=C1 UPKYBTIDDVVFMW-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
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
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
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 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
208000000323 Tourette Syndrome Diseases 0.000 description 1
208000016620 Tourette disease Diseases 0.000 description 1
206010044541 Traumatic shock Diseases 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
235000011054 acetic acid Nutrition 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
238000013019 agitation Methods 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
125000000304 alkynyl group Chemical group 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
238000004458 analytical method Methods 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
230000004888 barrier function Effects 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
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
229940077388 benzenesulfonate 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
230000033558 biomineral tissue development Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000023555 blood coagulation Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
210000002449 bone cell Anatomy 0.000 description 1
230000018678 bone mineralization Effects 0.000 description 1
230000024279 bone resorption Effects 0.000 description 1
NJYKPYJDYQLJIL-UHFFFAOYSA-N boronoformic acid Chemical class OB(O)C(O)=O NJYKPYJDYQLJIL-UHFFFAOYSA-N 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
230000003197 catalytic effect Effects 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
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
235000013339 cereals Nutrition 0.000 description 1
230000008859 change Effects 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
230000007882 cirrhosis Effects 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
239000004927 clay Substances 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
239000003086 colorant Substances 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
229940125872 compound 4d Drugs 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 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
ZHGASCUQXLPSDT-UHFFFAOYSA-N cyclohexanesulfonic acid Chemical compound OS(=O)(=O)C1CCCCC1 ZHGASCUQXLPSDT-UHFFFAOYSA-N 0.000 description 1
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
125000006317 cyclopropyl amino group Chemical group 0.000 description 1
238000010908 decantation Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
229910052805 deuterium Inorganic materials 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 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
125000004188 dichlorophenyl group Chemical group 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
208000037765 diseases and disorders Diseases 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
230000002500 effect on skin Effects 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
150000002118 epoxides Chemical class 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
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 1
125000004494 ethyl ester group Chemical group 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
230000005284 excitation Effects 0.000 description 1
210000003722 extracellular fluid Anatomy 0.000 description 1
238000010265 fast atom bombardment Methods 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
239000003269 fluorescent indicator Substances 0.000 description 1
YHOMCUREJOXFPI-UHFFFAOYSA-N formylboronic acid Chemical class OB(O)C=O YHOMCUREJOXFPI-UHFFFAOYSA-N 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000007429 general method Methods 0.000 description 1
235000011187 glycerol Nutrition 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
208000019622 heart disease Diseases 0.000 description 1
230000011132 hemopoiesis Effects 0.000 description 1
230000003284 homeostatic effect Effects 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
150000003840 hydrochlorides Chemical class 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
230000000121 hypercalcemic effect Effects 0.000 description 1
230000007954 hypoxia Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 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
230000002045 lasting effect Effects 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
239000006193 liquid solution Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 1
229910001486 lithium perchlorate Inorganic materials 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 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
JCBKDXJYQCLMLK-UHFFFAOYSA-N n-ethyl-2,3-dihydro-1h-inden-5-amine Chemical compound CCNC1=CC=C2CCCC2=C1 JCBKDXJYQCLMLK-UHFFFAOYSA-N 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
231100000417 nephrotoxicity 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
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
210000000056 organ Anatomy 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
230000011164 ossification Effects 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000006072 paste Substances 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
239000000546 pharmaceutical excipient 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
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
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000002953 preparative HPLC Methods 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
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
230000000644 propagated effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
239000003380 propellant Substances 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 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
239000000376 reactant Substances 0.000 description 1
239000006215 rectal suppository Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000033987 renal water absorption Effects 0.000 description 1
201000003068 rheumatic fever Diseases 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
238000007127 saponification reaction Methods 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
239000000661 sodium alginate Substances 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000008259 solid foam Substances 0.000 description 1
208000020431 spinal cord injury Diseases 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000007920 subcutaneous administration Methods 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
239000004094 surface-active agent Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000007916 tablet composition 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
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
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
238000012546 transfer Methods 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
230000000450 urinary calcium excretion Effects 0.000 description 1
239000006216 vaginal suppository Substances 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
238000005406 washing Methods 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 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
- C07C255/57—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
- 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
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- 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
- C07C255/54—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and etherified hydroxy 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
- C07C255/56—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and doubly-bound oxygen atoms bound to the carbon skeleton

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Physical Education & Sports Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Hematology (AREA)
Immunology (AREA)
Biomedical Technology (AREA)
Obesity (AREA)
Pain & Pain Management (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)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Investigating Or Analysing Biological Materials (AREA)
Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)

SK1098-2001A 1999-02-02 2000-02-02 Kalcilytické zlúčeniny a ich použitie SK10982001A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US11824099P	1999-02-02	1999-02-02
PCT/US2000/002676 WO2000045816A1 (en)	1999-02-02	2000-02-02	Calcilytic compounds

Publications (1)

Publication Number	Publication Date
SK10982001A3 true SK10982001A3 (sk)	2001-12-03

Family

ID=22377367

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1098-2001A SK10982001A3 (sk)	1999-02-02	2000-02-02	Kalcilytické zlúčeniny a ich použitie

Country Status (24)

Country	Link
US (1)	US6417215B1 (zh)
EP (1)	EP1148876A4 (zh)
JP (1)	JP2002536330A (zh)
KR (1)	KR20010093285A (zh)
CN (1)	CN1346269A (zh)
AP (1)	AP2001002220A0 (zh)
AU (1)	AU3480200A (zh)
BG (1)	BG105847A (zh)
BR (1)	BR0007922A (zh)
CA (1)	CA2361589A1 (zh)
CO (1)	CO5251439A1 (zh)
CZ (1)	CZ20012797A3 (zh)
EA (1)	EA200100854A1 (zh)
HK (1)	HK1042036A1 (zh)
HU (1)	HUP0200121A3 (zh)
ID (1)	ID29533A (zh)
IL (1)	IL144470A0 (zh)
MA (1)	MA25379A1 (zh)
NO (1)	NO20013769L (zh)
OA (1)	OA11757A (zh)
PE (1)	PE20001456A1 (zh)
SK (1)	SK10982001A3 (zh)
WO (1)	WO2000045816A1 (zh)
ZA (1)	ZA200106298B (zh)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE60136187D1 (de)	2000-08-11	2008-11-27	Japan Tobacco Inc	Calciumrezeptor-antagonisten
JP2004514659A (ja) *	2000-10-25	2004-05-20	スミスクライン・ビーチャム・コーポレイション	カルシライティック化合物
US6864267B2 (en) *	2001-07-16	2005-03-08	Smithkline Beecham Corporation	Calcilytic compounds
AR042132A1 (es)	2002-11-26	2005-06-08	Smithkline Beecham Corp	Compuesto de 2- hidroxi -3-(2- aril - 1, 1 - dimetiletilamino) propoxifenilo, composicion farmaceutica que lo comprende y uso del mismo para prepararla
US7105537B2 (en)	2003-01-28	2006-09-12	Bristol-Myers Squibb Company	2-substituted cyclic amines as calcium sensing receptor modulators
US7205322B2 (en)	2003-02-12	2007-04-17	Bristol-Myers Squibb Company	Thiazolidine compounds as calcium sensing receptor modulators
EP1619180B1 (en)	2003-04-23	2009-12-16	Japan Tobacco Inc.	CaSR ANTAGONIST
US7265145B2 (en)	2003-05-28	2007-09-04	Bristol-Myers Squibb Company	Substituted piperidines and pyrrolidines as calcium sensing receptor modulators and method
WO2004106280A1 (ja)	2003-05-28	2004-12-09	Japan Tobacco Inc.	ＣａＳＲアンタゴニスト
EP1964548A1 (en) *	2007-03-02	2008-09-03	Novartis AG	Pharmaceutical compositions comprising a calcilytic agent
AU2009255156B2 (en) *	2008-06-05	2013-03-14	Asahi Kasei Pharma Corporation	Sulfonamide compound and application thereof
WO2010103429A1 (en)	2009-03-10	2010-09-16	Pfizer Inc.	1,1-(Dimethyl-Ethylamino)-2-Hydroxy-Propoxy]-Ethyl}-3-Methyl-Biphenyl-4- Carboxylic Acid Derivatives As Calcium Receptor Antagonists
GB201217330D0 (en)	2012-09-28	2012-11-14	Univ Cardiff	Therapeutic for treating inflammatory lung disorders
WO2021029517A1 (en) *	2019-08-13	2021-02-18	Dongguk University Industry-Academic Cooperation Foundation	Pharmaceutical composition for improving or treating post-surgical hypoparathyroidism and treatment method using the same

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PH30484A (en)	1990-02-19	1997-05-28	Ciba Geigy	Acy compounds pharmaceutical composition containing said compound and method of use thereof
DE4102024A1 (de)	1991-01-24	1992-07-30	Thomae Gmbh Dr K	Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
BR9708632A (pt) *	1996-04-09	2000-01-18	Nps Pharma Inc	Composto calcilìticos
UY24949A1 (es) *	1997-04-08	2001-04-30	Smithkline Beecham Corp	Compuestos calcilíticos

2000
- 2000-02-01 PE PE2000000070A patent/PE20001456A1/es not_active Application Discontinuation
- 2000-02-02 US US09/890,310 patent/US6417215B1/en not_active Expired - Lifetime
- 2000-02-02 BR BR0007922-7A patent/BR0007922A/pt not_active IP Right Cessation
- 2000-02-02 CO CO00006199A patent/CO5251439A1/es unknown
- 2000-02-02 IL IL14447000A patent/IL144470A0/xx unknown
- 2000-02-02 AU AU34802/00A patent/AU3480200A/en not_active Abandoned
- 2000-02-02 AP APAP/P/2001/002220A patent/AP2001002220A0/en unknown
- 2000-02-02 SK SK1098-2001A patent/SK10982001A3/sk unknown
- 2000-02-02 CA CA002361589A patent/CA2361589A1/en not_active Abandoned
- 2000-02-02 HU HU0200121A patent/HUP0200121A3/hu unknown
- 2000-02-02 HK HK02101521.4A patent/HK1042036A1/zh unknown
- 2000-02-02 EP EP00913335A patent/EP1148876A4/en not_active Withdrawn
- 2000-02-02 OA OA1200100199A patent/OA11757A/en unknown
- 2000-02-02 CN CN00805996A patent/CN1346269A/zh active Pending
- 2000-02-02 KR KR1020017009467A patent/KR20010093285A/ko not_active Withdrawn
- 2000-02-02 CZ CZ20012797A patent/CZ20012797A3/cs unknown
- 2000-02-02 ID IDW00200101673A patent/ID29533A/id unknown
- 2000-02-02 WO PCT/US2000/002676 patent/WO2000045816A1/en not_active Ceased
- 2000-02-02 JP JP2000596936A patent/JP2002536330A/ja not_active Withdrawn
- 2000-02-02 EA EA200100854A patent/EA200100854A1/ru unknown
2001
- 2001-07-31 ZA ZA200106298A patent/ZA200106298B/en unknown
- 2001-08-01 NO NO20013769A patent/NO20013769L/no not_active Application Discontinuation
- 2001-08-01 MA MA26283A patent/MA25379A1/fr unknown
- 2001-08-27 BG BG105847A patent/BG105847A/xx unknown

Also Published As

Publication number	Publication date
CN1346269A (zh)	2002-04-24
CA2361589A1 (en)	2000-08-10
ID29533A (id)	2001-09-06
ZA200106298B (en)	2002-10-18
NO20013769L (no)	2001-09-26
BG105847A (en)	2002-04-30
WO2000045816A1 (en)	2000-08-10
PE20001456A1 (es)	2001-01-28
JP2002536330A (ja)	2002-10-29
HK1042036A1 (zh)	2002-08-02
AU3480200A (en)	2000-08-25
CZ20012797A3 (cs)	2002-01-16
CO5251439A1 (es)	2003-02-28
US6417215B1 (en)	2002-07-09
BR0007922A (pt)	2001-11-06
HUP0200121A3 (en)	2002-11-28
NO20013769D0 (no)	2001-08-01
IL144470A0 (en)	2002-05-23
AP2001002220A0 (en)	2001-09-30
EA200100854A1 (ru)	2002-02-28
HUP0200121A2 (hu)	2002-05-29
EP1148876A4 (en)	2003-07-23
MA25379A1 (fr)	2002-04-01
KR20010093285A (ko)	2001-10-27
OA11757A (en)	2005-07-19
EP1148876A1 (en)	2001-10-31

Publication	Publication Date	Title
SK10982001A3 (sk)	2001-12-03	Kalcilytické zlúčeniny a ich použitie
JP2004535365A (ja)	2004-11-25	尿素の新誘導体、それらの製造方法、それらの薬剤としての使用、製薬組成物及び新規な用途
SK14852000A3 (sk)	2001-05-10	Kalcilytické zlúčeniny, farmaceutický prostriedok s ich obsahom a ich použitie
US6335338B1 (en)	2002-01-01	Calcilytic compounds
WO1999051241A1 (en)	1999-10-14	Calcilytic compounds and method of use
WO1998044925A1 (en)	1998-10-15	Calcilytic compounds
EP1368318B1 (en)	2007-12-05	Calcilytic compounds
US20040009980A1 (en)	2004-01-15	Calcilytic compounds
US6291459B1 (en)	2001-09-18	Calcilytic compounds
AU2001276923A1 (en)	2002-05-02	Calcilytic compounds
BG106942A (bg)	2003-01-31	Калцилитични съединения
EP1383511B1 (en)	2006-10-25	Calcilytic compounds
US20080234370A1 (en)	2008-09-25	Calcilytic Compounds
JP2007536239A (ja)	2007-12-13	カルシウム受容体アンタゴニスト化合物
JP2007506751A (ja)	2007-03-22	カルシウム拮抗化合物
US20020052509A1 (en)	2002-05-02	Calcilytic compounds and method of use
MXPA01007800A (en)	2002-03-05	Calcilytic compounds
WO2006042007A2 (en)	2006-04-20	Chromenone compounds as calcilytics