AU2003237235B2 - Calcium receptor modulating agents - Google Patents
Calcium receptor modulating agents Download PDFInfo
- Publication number
- AU2003237235B2 AU2003237235B2 AU2003237235A AU2003237235A AU2003237235B2 AU 2003237235 B2 AU2003237235 B2 AU 2003237235B2 AU 2003237235 A AU2003237235 A AU 2003237235A AU 2003237235 A AU2003237235 A AU 2003237235A AU 2003237235 B2 AU2003237235 B2 AU 2003237235B2
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- Australia
- Prior art keywords
- alkyl
- compound
- haloalkyl
- aryl
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000003795 chemical substances by application Substances 0.000 title description 7
- 102000013830 Calcium-Sensing Receptors Human genes 0.000 title description 4
- 108010050543 Calcium-Sensing Receptors Proteins 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 116
- 125000000217 alkyl group Chemical group 0.000 claims description 77
- -1 -OCl_6alkyl Chemical group 0.000 claims description 59
- 238000000034 method Methods 0.000 claims description 54
- 125000004429 atom Chemical group 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 43
- 150000001412 amines Chemical class 0.000 claims description 38
- 125000001188 haloalkyl group Chemical group 0.000 claims description 38
- 229910052736 halogen Inorganic materials 0.000 claims description 38
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 150000002367 halogens Chemical class 0.000 claims description 37
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 37
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 36
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 26
- 229910052717 sulfur Inorganic materials 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 125000001624 naphthyl group Chemical group 0.000 claims description 22
- 229920006395 saturated elastomer Polymers 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 20
- 108090000445 Parathyroid hormone Proteins 0.000 claims description 19
- 230000028327 secretion Effects 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 208000020084 Bone disease Diseases 0.000 claims description 10
- 201000002980 Hyperparathyroidism Diseases 0.000 claims description 10
- 208000001132 Osteoporosis Diseases 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
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- 230000008569 process Effects 0.000 claims description 7
- 101150100019 NRDC gene Proteins 0.000 claims description 6
- 229910003827 NRaRb Inorganic materials 0.000 claims description 4
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000000052 comparative effect Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 47
- 239000000203 mixture Substances 0.000 description 38
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- 239000000243 solution Substances 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
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- 239000000651 prodrug Substances 0.000 description 14
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- 238000004440 column chromatography Methods 0.000 description 11
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- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 229910001424 calcium ion Inorganic materials 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 101150041968 CDC13 gene Proteins 0.000 description 8
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 125000003710 aryl alkyl group Chemical group 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
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- 238000002360 preparation method Methods 0.000 description 7
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- 235000011152 sodium sulphate Nutrition 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 6
- 239000002480 mineral oil Substances 0.000 description 6
- 235000010446 mineral oil Nutrition 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 239000005909 Kieselgur Substances 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 5
- 230000000849 parathyroid Effects 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
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- 230000002378 acidificating effect Effects 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 3
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- 241000124008 Mammalia Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
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- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 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
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 150000008648 triflates Chemical group 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- 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
- 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
- A61P5/20—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of PTH
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (5)
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| US38327002P | 2002-05-23 | 2002-05-23 | |
| US60/383,270 | 2002-05-23 | ||
| US10/444,945 US7176322B2 (en) | 2002-05-23 | 2003-05-22 | Calcium receptor modulating agents |
| US10/444,945 | 2003-05-22 | ||
| PCT/US2003/016384 WO2003099814A1 (en) | 2002-05-23 | 2003-05-23 | Calcium receptor modulating agents |
Publications (2)
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| AU2003237235A1 AU2003237235A1 (en) | 2003-12-12 |
| AU2003237235B2 true AU2003237235B2 (en) | 2007-08-23 |
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| US (1) | US7176322B2 (https=) |
| EP (1) | EP1509518B1 (https=) |
| JP (1) | JP4642461B2 (https=) |
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| AT (1) | ATE544762T1 (https=) |
| AU (1) | AU2003237235B2 (https=) |
| CA (1) | CA2485685C (https=) |
| ES (1) | ES2378759T3 (https=) |
| MX (1) | MXPA04011469A (https=) |
| PL (1) | PL375559A1 (https=) |
| TW (1) | TW200410960A (https=) |
| WO (1) | WO2003099814A1 (https=) |
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| US6908935B2 (en) * | 2002-05-23 | 2005-06-21 | Amgen Inc. | Calcium receptor modulating agents |
| WO2005065050A2 (ja) * | 2003-12-25 | 2005-07-21 | Asahi Kasei Pharma Corporation | ２環化合物 |
| GB0400781D0 (en) * | 2004-01-14 | 2004-02-18 | Novartis Ag | Organic compounds |
| ES2561111T3 (es) | 2004-05-28 | 2016-02-24 | Mitsubishi Tanabe Pharma Corporation | Arilalquilaminas y procedimiento para la producción de las mismas |
| US7361789B1 (en) | 2004-07-28 | 2008-04-22 | Amgen Inc. | Dihydronaphthalene compounds, compositions, uses thereof, and methods for synthesis |
| US7585886B2 (en) | 2005-05-19 | 2009-09-08 | Astellas Pharma Inc. | Pyrrolidine derivative or salt thereof |
| US8486381B2 (en) * | 2005-09-02 | 2013-07-16 | Amgen Inc. | Methods of modulating intestinal fluid balance |
| US20070287707A1 (en) * | 2006-02-28 | 2007-12-13 | Arrington Mark P | Phosphodiesterase 10 inhibitors |
| MX2008012061A (es) * | 2006-03-23 | 2008-12-17 | Amgen Inc | Metodos y composiciones para elaborar y utilizar polimorfos de cinacalcet. |
| EP2010150A2 (en) * | 2006-04-20 | 2009-01-07 | Amgen Inc. | Stable emulsion formulations |
| CA2681582C (en) | 2007-03-30 | 2015-07-14 | Amgen Inc. | Methods of treating bowel disorders |
| ES2476391T3 (es) * | 2007-10-15 | 2014-07-14 | Amgen Inc. | Agentes moduladores de receptor de calcio |
| US20110212053A1 (en) * | 2008-06-19 | 2011-09-01 | Dapeng Qian | Phosphatidylinositol 3 kinase inhibitors |
| WO2010104882A1 (en) | 2009-03-10 | 2010-09-16 | Amgen Inc. | Methods of modulating sperm motility |
| EP2435400A2 (en) | 2009-05-27 | 2012-04-04 | Leo Pharma A/S | Novel calcium sensing receptor modulating compounds and pharmaceutical use thereof |
| US8765676B2 (en) | 2009-05-27 | 2014-07-01 | Leo Pharma A/S | Calcium sensing receptor modulating compounds and pharmaceutical use thereof |
| JP5968881B2 (ja) | 2010-06-30 | 2016-08-10 | レオ ファーマ アクティーゼルスカブ | カルシウム模倣化合物の新規多形 |
| WO2012000498A1 (en) | 2010-06-30 | 2012-01-05 | Leo Pharma A/S | New polymorphic form of a calcimimetic compound |
| JP2014508103A (ja) | 2010-11-26 | 2014-04-03 | レオ ファーマ アクティーゼルスカブ | カルシウム感知受容体活性化合物 |
| WO2012069420A2 (en) | 2010-11-26 | 2012-05-31 | Leo Pharma A/S | Calcium-sensing receptor-active compounds |
| JP2014500882A (ja) | 2010-11-26 | 2014-01-16 | レオ ファーマ アクティーゼルスカブ | カルシウム感知受容体活性化合物 |
| EP2643292A1 (en) | 2010-11-26 | 2013-10-02 | Leo Pharma A/S | Calcium-sensing receptor-active compounds |
| JP2015528462A (ja) * | 2012-08-27 | 2015-09-28 | ルピン・リミテッドＬｕｐｉｎ Ｌｉｍｉｔｅｄ | カルシウム感知受容体モジュレーターとしてのアリールアルキルアミン化合物 |
| GB201217330D0 (en) | 2012-09-28 | 2012-11-14 | Univ Cardiff | Therapeutic for treating inflammatory lung disorders |
| PT2968284T (pt) | 2013-03-14 | 2021-06-28 | Osteoqc Inc | Derivados alquilamina de harmina para promoção de crescimento ósseo |
| AU2019320773B2 (en) | 2018-08-14 | 2024-12-05 | Ossifi Therapeutics Llc | Fluoro β-carboline compounds |
| US10947236B2 (en) | 2018-08-14 | 2021-03-16 | Osteoqc Inc. | Pyrrolo-dipyridine compounds |
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| US143212A (en) * | 1873-09-23 | Improvement in attachments for ladies work-tables | ||
| US444946A (en) * | 1891-01-20 | Method of electric welding | ||
| PT72878B (en) | 1980-04-24 | 1983-03-29 | Merck & Co Inc | Process for preparing mannich-base hydroxamic acid pro-drugs for the improved delivery of non-steroidal anti-inflammatory agents |
| US6031003A (en) * | 1991-08-23 | 2000-02-29 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| ATE313321T1 (de) | 1991-08-23 | 2006-01-15 | Nps Pharma Inc | Kalzium-rezeptor aktive verbindungen |
| US6011068A (en) * | 1991-08-23 | 2000-01-04 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| CN1192011C (zh) | 1991-08-23 | 2005-03-09 | Nps药物有限公司 | 对钙受体具活性的芳烷基胺化合物 |
| US6001884A (en) * | 1991-08-23 | 1999-12-14 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| DE69333527T2 (de) | 1993-02-23 | 2005-06-16 | Brigham & Women's Hospital, Inc., Boston | Calciumrezeptoraktive moleküle |
| AU3414295A (en) | 1994-08-19 | 1996-03-14 | Nps Pharmaceuticals, Inc. | Methods and compounds active at metabotropic glutamate receptors useful for treatment of neurological disorders and diseases |
| WO1996009818A1 (en) | 1994-09-27 | 1996-04-04 | Merck & Co., Inc. | Endothelin receptor antagonists for the treatment of emesis |
| ES2285707T3 (es) * | 1994-10-21 | 2007-11-16 | Nps Pharmaceuticals, Inc. | Compuestos activos frente al receptor de calcio. |
| US5585388A (en) | 1995-04-07 | 1996-12-17 | Sibia Neurosciences, Inc. | Substituted pyridines useful as modulators of acetylcholine receptors |
| ES2308779T3 (es) | 1995-07-26 | 2008-12-01 | Astrazeneca Ab | Receptores quimericos y metodos para identificar compuestos activos en los receptores de glutamato metabotropico y el uso de tales compuestos en el tratamiento de trastornos y enfermedades neurologicas. |
| DE69733649T2 (de) | 1996-04-09 | 2006-05-18 | NPS Pharmaceuticals, Inc., Salt Lake City | Calcylitische verbindungen |
| WO1997041090A1 (en) * | 1996-05-01 | 1997-11-06 | Nps Pharmaceuticals, Inc. | Inorganic ion receptor-active compounds |
| CN1131202C (zh) | 1996-07-08 | 2003-12-17 | 麒麟麦酒株式会社 | 钙受体活性化合物 |
| AU735137B2 (en) | 1997-02-21 | 2001-07-05 | Bayer Intellectual Property Gmbh | Arylsulphonamides and analogues and their use for the treatment and neurovegetative disorders |
| UY24949A1 (es) | 1997-04-08 | 2001-04-30 | Smithkline Beecham Corp | Compuestos calcilíticos |
| AU8181098A (en) | 1997-07-03 | 1999-01-25 | Du Pont Pharmaceuticals Company | Aryl-and arylamino-substituted heterocycles as corticotropin releasing hormone antagonists |
| CA2340341A1 (en) * | 1998-08-12 | 2000-02-24 | Smithkline Beecham Corporation | Calcilytic compounds |
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| KR100437587B1 (ko) * | 1999-02-24 | 2004-06-30 | 에프. 호프만-라 로슈 아게 | 3-페닐피리딘 유도체 및 그의 뉴로키닌-1 수용체길항제로서의 용도 |
| TR200102490T2 (tr) * | 1999-02-24 | 2001-12-21 | F.Hoffmann-La Roche Ag | Fenil ve piridinil türevleri |
| DE60036758T2 (de) | 1999-08-04 | 2008-07-24 | Sumitomo Chemical Co., Ltd. | Verfahren zur Herstellung von optisch aktiver 3,3,3-Trifluor-2-hydroxy-2-methylpropionsäure und deren Salze |
| FR2800735B1 (fr) | 1999-11-09 | 2002-02-01 | Centre Nat Rech Scient | Nouvelles aralkyle-1,2-diamines possedant une activite calcimimetique et leur mode de preparation |
| EP1116711B1 (de) * | 1999-12-18 | 2005-12-14 | Wella Aktiengesellschaft | 2-Aminoalkyl-1,4-diaminobenzol-Derivate und diese Verbindungen enthaltende Färbemittel |
| FR2809396B1 (fr) | 2000-05-24 | 2005-10-14 | Centre Nat Rech Scient | Nouvelles molecules possedant une activite calcimimetique et leur mode de preparation |
| DE10028402A1 (de) | 2000-06-13 | 2001-12-20 | Merck Patent Gmbh | Pyridin-2-yl-aminoalkycarbonylglycyl-beta-alanin und Derivate |
| AU2001269821A1 (en) | 2000-06-15 | 2001-12-24 | Barbara Chen | Cycloalkyl alkanoic acids as integrin receptor antagonists |
| EP1347959A1 (de) | 2000-12-27 | 2003-10-01 | Bayer Aktiengesellschaft | Indol-derivate |
| JP2004536071A (ja) * | 2001-05-25 | 2004-12-02 | クイーンズ ユニバーシティ アット キングストン | 複素環ベータアミノ酸およびそれらの抗癲癇誘発剤としての使用 |
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2003
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| WO2003099814A1 (en) | 2003-12-04 |
| US20040077619A1 (en) | 2004-04-22 |
| JP4642461B2 (ja) | 2011-03-02 |
| EP1509518A1 (en) | 2005-03-02 |
| ES2378759T3 (es) | 2012-04-17 |
| AU2003237235A1 (en) | 2003-12-12 |
| US7176322B2 (en) | 2007-02-13 |
| JP2005530811A (ja) | 2005-10-13 |
| EP1509518B1 (en) | 2012-02-08 |
| CA2485685A1 (en) | 2003-12-04 |
| AR040095A1 (es) | 2005-03-16 |
| ATE544762T1 (de) | 2012-02-15 |
| PL375559A1 (en) | 2005-11-28 |
| TW200410960A (en) | 2004-07-01 |
| MXPA04011469A (es) | 2005-02-14 |
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