CA2608319C - Substituted spiro-compounds and the use thereof for producing medicaments - Google Patents
Substituted spiro-compounds and the use thereof for producing medicaments Download PDFInfo
- Publication number
- CA2608319C CA2608319C CA2608319A CA2608319A CA2608319C CA 2608319 C CA2608319 C CA 2608319C CA 2608319 A CA2608319 A CA 2608319A CA 2608319 A CA2608319 A CA 2608319A CA 2608319 C CA2608319 C CA 2608319C
- Authority
- CA
- Canada
- Prior art keywords
- butyl
- tert
- oxa
- azaspiro
- dec
- 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.)
- Expired - Fee Related
Links
- 239000003814 drug Substances 0.000 title claims abstract description 64
- 150000003413 spiro compounds Chemical class 0.000 title claims abstract description 40
- 150000001875 compounds Chemical class 0.000 claims abstract description 147
- 238000000034 method Methods 0.000 claims abstract description 20
- 230000008569 process Effects 0.000 claims abstract description 13
- -1 pyridinyl radical Chemical class 0.000 claims description 507
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 274
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 246
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 142
- 150000003254 radicals Chemical group 0.000 claims description 138
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 133
- 239000000203 mixture Substances 0.000 claims description 110
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 110
- 125000001424 substituent group Chemical group 0.000 claims description 88
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 81
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 79
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 79
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 79
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 79
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims description 57
- 229910052731 fluorine Inorganic materials 0.000 claims description 57
- 125000004076 pyridyl group Chemical group 0.000 claims description 52
- 208000002193 Pain Diseases 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 50
- 229910052794 bromium Inorganic materials 0.000 claims description 49
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 44
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 44
- 239000012453 solvate Substances 0.000 claims description 41
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 40
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 39
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 37
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 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
- 229940079593 drug Drugs 0.000 claims description 36
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 36
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 34
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 33
- 150000001408 amides Chemical class 0.000 claims description 32
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 claims description 30
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims description 30
- 125000002541 furyl group Chemical group 0.000 claims description 30
- 229910052740 iodine Inorganic materials 0.000 claims description 30
- 125000000335 thiazolyl group Chemical group 0.000 claims description 28
- 125000001624 naphthyl group Chemical group 0.000 claims description 27
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 26
- 239000002585 base Substances 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 24
- 125000004122 cyclic group Chemical group 0.000 claims description 22
- 208000007848 Alcoholism Diseases 0.000 claims description 21
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical group [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 21
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 21
- 208000011117 substance-related disease Diseases 0.000 claims description 21
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 19
- 125000003386 piperidinyl group Chemical group 0.000 claims description 19
- 239000012429 reaction media Substances 0.000 claims description 19
- 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 claims description 18
- 125000001041 indolyl group Chemical group 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 18
- 238000011321 prophylaxis Methods 0.000 claims description 18
- 108050004388 Transient receptor potential cation channel subfamily V member 1 Proteins 0.000 claims description 17
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 17
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
- 239000005864 Sulphur Substances 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- 229960002504 capsaicin Drugs 0.000 claims description 15
- 235000017663 capsaicin Nutrition 0.000 claims description 15
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 15
- 206010020853 Hypertonic bladder Diseases 0.000 claims description 14
- 208000009722 Overactive Urinary Bladder Diseases 0.000 claims description 14
- 102000003566 TRPV1 Human genes 0.000 claims description 14
- 101150016206 Trpv1 gene Proteins 0.000 claims description 14
- 206010013663 drug dependence Diseases 0.000 claims description 14
- 208000027866 inflammatory disease Diseases 0.000 claims description 14
- 208000020629 overactive bladder Diseases 0.000 claims description 14
- 208000023504 respiratory system disease Diseases 0.000 claims description 14
- OHPSBNXNFPTYFO-UHFFFAOYSA-N 3-phenyl-1-oxa-2-azaspiro[4.5]dec-2-ene-8-carboxylic acid Chemical compound C1CC(C(=O)O)CCC11ON=C(C=2C=CC=CC=2)C1 OHPSBNXNFPTYFO-UHFFFAOYSA-N 0.000 claims description 13
- 238000011161 development Methods 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
- 208000010877 cognitive disease Diseases 0.000 claims description 11
- 208000004296 neuralgia Diseases 0.000 claims description 11
- 230000004770 neurodegeneration Effects 0.000 claims description 11
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 11
- 208000021722 neuropathic pain Diseases 0.000 claims description 11
- 208000000094 Chronic Pain Diseases 0.000 claims description 10
- 206010046543 Urinary incontinence Diseases 0.000 claims description 10
- 208000005298 acute pain Diseases 0.000 claims description 10
- 239000000556 agonist Substances 0.000 claims description 10
- 230000001149 cognitive effect Effects 0.000 claims description 10
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 230000007812 deficiency Effects 0.000 claims description 10
- 230000007794 irritation Effects 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 10
- 206010011224 Cough Diseases 0.000 claims description 9
- 208000030814 Eating disease Diseases 0.000 claims description 9
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 9
- 239000002671 adjuvant Substances 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- 235000014632 disordered eating Nutrition 0.000 claims description 9
- 206010061218 Inflammation Diseases 0.000 claims description 8
- 208000019695 Migraine disease Diseases 0.000 claims description 8
- 206010035664 Pneumonia Diseases 0.000 claims description 8
- 208000006673 asthma Diseases 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 230000004054 inflammatory process Effects 0.000 claims description 8
- 230000000968 intestinal effect Effects 0.000 claims description 8
- 206010027599 migraine Diseases 0.000 claims description 8
- TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 claims description 8
- 208000017520 skin disease Diseases 0.000 claims description 8
- 201000009032 substance abuse Diseases 0.000 claims description 8
- HCAWEHRMIMYHAX-UHFFFAOYSA-N 8-tert-butyl-n-(4-tert-butylphenyl)-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxamide Chemical compound C1CC(C(C)(C)C)CCC11ON=C(C(=O)NC=2C=CC(=CC=2)C(C)(C)C)C1 HCAWEHRMIMYHAX-UHFFFAOYSA-N 0.000 claims description 7
- 206010013654 Drug abuse Diseases 0.000 claims description 7
- 208000023105 Huntington disease Diseases 0.000 claims description 7
- 206010033848 Paramnesia Diseases 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 7
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- 201000006417 multiple sclerosis Diseases 0.000 claims description 7
- 206010012735 Diarrhoea Diseases 0.000 claims description 6
- 208000003251 Pruritus Diseases 0.000 claims description 6
- 210000000748 cardiovascular system Anatomy 0.000 claims description 6
- 206010015037 epilepsy Diseases 0.000 claims description 6
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 6
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 6
- RLWGDRLXZSLGHV-UHFFFAOYSA-N 1-[[4-(2-aminoethoxy)-3-methoxyphenyl]methyl]-3-[(4-tert-butylphenyl)methyl]urea Chemical compound C1=C(OCCN)C(OC)=CC(CNC(=O)NCC=2C=CC(=CC=2)C(C)(C)C)=C1 RLWGDRLXZSLGHV-UHFFFAOYSA-N 0.000 claims description 5
- OUEKLNJUMVZULZ-UHFFFAOYSA-N 2-[4-(2-aminoethoxy)-3-methoxyphenyl]-n-[3-(3,4-dimethylphenyl)propyl]acetamide;hydron;chloride Chemical compound Cl.C1=C(OCCN)C(OC)=CC(CC(=O)NCCCC=2C=C(C)C(C)=CC=2)=C1 OUEKLNJUMVZULZ-UHFFFAOYSA-N 0.000 claims description 5
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- 208000032841 Bulimia Diseases 0.000 claims description 5
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- 206010006895 Cachexia Diseases 0.000 claims description 5
- IKYCZSUNGFRBJS-UHFFFAOYSA-N Euphorbia factor RL9 = U(1) = Resiniferatoxin Natural products COC1=CC(O)=CC(CC(=O)OCC=2CC3(O)C(=O)C(C)=CC3C34C(C)CC5(OC(O4)(CC=4C=CC=CC=4)OC5C3C=2)C(C)=C)=C1 IKYCZSUNGFRBJS-UHFFFAOYSA-N 0.000 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 206010020843 Hyperthermia Diseases 0.000 claims description 5
- OPZKBPQVWDSATI-KHPPLWFESA-N N-Vanillyloleamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 OPZKBPQVWDSATI-KHPPLWFESA-N 0.000 claims description 5
- QVLMCRFQGHWOPM-ZKWNWVNESA-N N-arachidonoyl vanillylamine Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCC1=CC=C(O)C(OC)=C1 QVLMCRFQGHWOPM-ZKWNWVNESA-N 0.000 claims description 5
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- OPZKBPQVWDSATI-UHFFFAOYSA-N oleoyl vanillylamide Natural products CCCCCCCCC=CCCCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 OPZKBPQVWDSATI-UHFFFAOYSA-N 0.000 claims description 5
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- DSDNAKHZNJAGHN-UHFFFAOYSA-N resinferatoxin Natural products C1=C(O)C(OC)=CC(CC(=O)OCC=2CC3(O)C(=O)C(C)=CC3C34C(C)CC5(OC(O4)(CC=4C=CC=CC=4)OC5C3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-UHFFFAOYSA-N 0.000 claims description 5
- DSDNAKHZNJAGHN-MXTYGGKSSA-N resiniferatoxin Chemical compound C1=C(O)C(OC)=CC(CC(=O)OCC=2C[C@]3(O)C(=O)C(C)=C[C@H]3[C@@]34[C@H](C)C[C@@]5(O[C@@](O4)(CC=4C=CC=CC=4)O[C@@H]5[C@@H]3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-MXTYGGKSSA-N 0.000 claims description 5
- 229940073454 resiniferatoxin Drugs 0.000 claims description 5
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 claims description 3
- 125000006017 1-propenyl group Chemical group 0.000 claims description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 claims description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 claims description 3
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- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 3
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- YEMFBPJXUWNDFX-UHFFFAOYSA-N 8-tert-butyl-n-[3-fluoro-4-(methanesulfonamido)phenyl]-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxamide Chemical compound C1CC(C(C)(C)C)CCC11ON=C(C(=O)NC=2C=C(F)C(NS(C)(=O)=O)=CC=2)C1 YEMFBPJXUWNDFX-UHFFFAOYSA-N 0.000 claims description 2
- AVVHGYJXAFZJID-UHFFFAOYSA-N 8-tert-butyl-n-[4-fluoro-3-(methanesulfonamido)phenyl]-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxamide Chemical compound C1CC(C(C)(C)C)CCC11ON=C(C(=O)NC=2C=C(NS(C)(=O)=O)C(F)=CC=2)C1 AVVHGYJXAFZJID-UHFFFAOYSA-N 0.000 claims description 2
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- 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
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- C07D413/12—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 linked by a chain containing hetero atoms as chain links
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| DE102005023779 | 2005-05-19 | ||
| DE102005023779.7 | 2005-05-19 | ||
| DE102005044814.3 | 2005-09-20 | ||
| DE102005044814A DE102005044814A1 (de) | 2005-05-19 | 2005-09-20 | Substituierte Sprio-Verbindungen und deren Verwendung zur Herstellung von Arzneimitteln |
| PCT/EP2006/004653 WO2006136245A1 (de) | 2005-05-19 | 2006-05-17 | Substituierte spiro-verbindungen und deren verwendung zur herstellung von arzneimitteln |
Publications (2)
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| CA2608319A1 CA2608319A1 (en) | 2006-12-28 |
| CA2608319C true CA2608319C (en) | 2014-04-15 |
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| CA2608319A Expired - Fee Related CA2608319C (en) | 2005-05-19 | 2006-05-17 | Substituted spiro-compounds and the use thereof for producing medicaments |
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| Country | Link |
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| US (1) | US7981883B2 (enExample) |
| EP (1) | EP1888542A1 (enExample) |
| JP (1) | JP5376942B2 (enExample) |
| CA (1) | CA2608319C (enExample) |
| DE (1) | DE102005044814A1 (enExample) |
| WO (1) | WO2006136245A1 (enExample) |
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| US20110166124A1 (en) * | 2008-07-23 | 2011-07-07 | Mccormick Kevin D | Tricyclic spirocycle derivatives and methods of use |
| US8232409B2 (en) | 2008-10-15 | 2012-07-31 | Janssen Pharmaceutica N.V. | Heterocyclic benzimidazoles as TRPM8 modulators |
| US8349852B2 (en) | 2009-01-13 | 2013-01-08 | Novartis Ag | Quinazolinone derivatives useful as vanilloid antagonists |
| CA2749856A1 (en) * | 2009-02-04 | 2010-08-12 | N.V. Organon | Isoxazole-3-carboxamide derivatives |
| CN102762572A (zh) | 2010-02-01 | 2012-10-31 | 诺瓦提斯公司 | 作为CRF-1受体拮抗剂的吡唑并[5,1b]*唑衍生物 |
| WO2011092293A2 (en) | 2010-02-01 | 2011-08-04 | Novartis Ag | Cyclohexyl amide derivatives as crf receptor antagonists |
| US8835444B2 (en) | 2010-02-02 | 2014-09-16 | Novartis Ag | Cyclohexyl amide derivatives as CRF receptor antagonists |
| LT3786160T (lt) * | 2017-10-27 | 2022-09-26 | Boehringer Ingelheim International Gmbh | Piridino dariniai ir jų terapinis panaudojimas kaip trpc6 inhibitorių |
Family Cites Families (10)
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| WO1997033887A1 (en) * | 1996-03-15 | 1997-09-18 | Du Pont Pharmaceuticals Company | Spirocycle integrin inhibitors |
| AU6780398A (en) * | 1997-03-28 | 1998-10-22 | Du Pont Merck Pharmaceutical Company, The | Heterocyclic integrin inhibitor prodrugs |
| JP2003505388A (ja) * | 1999-07-21 | 2003-02-12 | アストラゼネカ・アクチエボラーグ | 新規化合物 |
| DE10130020A1 (de) * | 2001-06-25 | 2003-12-04 | Gruenenthal Gmbh | Substituierte 1-Oxa-2,8-diaza-spiro[4.5]dec-2-en-derivate |
| ATE533743T1 (de) * | 2002-05-17 | 2011-12-15 | Janssen Pharmaceutica Nv | Harnstoffderivate von aminotetralin als modulatoren des vanilloid-rezeptors vr1 |
| EP1542692B1 (en) * | 2002-05-22 | 2011-01-05 | Amgen Inc. | Aminopyrimidine derivatives for use as vanilloid receptor ligands for the treatment of pain |
| US7125870B2 (en) * | 2002-11-06 | 2006-10-24 | Bristol-Myers Squibb Company | Isoxazoline derivatives as inhibitors of matrix metalloproteinases and/or TNF-α converting enzyme |
| RU2387646C2 (ru) * | 2003-08-29 | 2010-04-27 | Рэнбакси Лабораториз Лимитед | Ингибиторы фосфодиэстеразы типа-iv |
| US7786141B2 (en) * | 2004-08-19 | 2010-08-31 | Vertex Pharmaceuticals Incorporated | Dihydrospiroindene modulators of muscarinic receptors |
| WO2007103719A2 (en) * | 2006-03-03 | 2007-09-13 | Incyte Corporation | MODULATORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
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2005
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2006
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Also Published As
| Publication number | Publication date |
|---|---|
| JP2008540594A (ja) | 2008-11-20 |
| JP5376942B2 (ja) | 2013-12-25 |
| WO2006136245A1 (de) | 2006-12-28 |
| US20090275628A1 (en) | 2009-11-05 |
| EP1888542A1 (de) | 2008-02-20 |
| US7981883B2 (en) | 2011-07-19 |
| DE102005044814A1 (de) | 2006-11-23 |
| CA2608319A1 (en) | 2006-12-28 |
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| EEER | Examination request | ||
| MKLA | Lapsed |
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