JP4970946B2 - モルホリン化合物 - Google Patents
モルホリン化合物 Download PDFInfo
- Publication number
- JP4970946B2 JP4970946B2 JP2006535186A JP2006535186A JP4970946B2 JP 4970946 B2 JP4970946 B2 JP 4970946B2 JP 2006535186 A JP2006535186 A JP 2006535186A JP 2006535186 A JP2006535186 A JP 2006535186A JP 4970946 B2 JP4970946 B2 JP 4970946B2
- Authority
- JP
- Japan
- Prior art keywords
- substituent
- methyl
- morpholin
- ylthio
- acetamide
- 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
- 150000002780 morpholines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 485
- -1 hydroxy, nitro, amino Chemical group 0.000 claims description 358
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 346
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 300
- 125000001424 substituent group Chemical group 0.000 claims description 284
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 269
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 209
- 125000000217 alkyl group Chemical group 0.000 claims description 122
- 150000003839 salts Chemical class 0.000 claims description 76
- 239000000203 mixture Substances 0.000 claims description 65
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 61
- 239000012453 solvate Substances 0.000 claims description 47
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 38
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 37
- 125000000623 heterocyclic group Chemical group 0.000 claims description 37
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 35
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000005843 halogen group Chemical group 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 229910052717 sulfur Inorganic materials 0.000 claims description 27
- 125000004434 sulfur atom Chemical group 0.000 claims description 27
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 26
- 125000006509 3,4-difluorobenzyl group Chemical group [H]C1=C(F)C(F)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 125000000984 3-chloro-4-fluorobenzyl group Chemical group [H]C1=C(F)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 20
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 19
- 125000004429 atom Chemical group 0.000 claims description 18
- 125000001544 thienyl group Chemical group 0.000 claims description 16
- 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 14
- 125000004442 acylamino group Chemical group 0.000 claims description 14
- 125000002541 furyl group Chemical group 0.000 claims description 14
- 125000000335 thiazolyl group Chemical group 0.000 claims description 14
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 12
- 125000006591 (C2-C6) alkynylene group Chemical group 0.000 claims description 11
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 11
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 11
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 10
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 9
- 230000000172 allergic effect Effects 0.000 claims description 9
- 208000006673 asthma Diseases 0.000 claims description 9
- 208000010668 atopic eczema Diseases 0.000 claims description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 8
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 8
- 208000011231 Crohn disease Diseases 0.000 claims description 8
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 8
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 8
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 8
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 8
- 201000010105 allergic rhinitis Diseases 0.000 claims description 8
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 8
- 201000008937 atopic dermatitis Diseases 0.000 claims description 8
- 201000009890 sinusitis Diseases 0.000 claims description 8
- QBXNXHODSIQDRT-AWEZNQCLSA-N 2-[2-[2-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methylamino]-2-oxoethyl]sulfanyl-1,3-thiazol-4-yl]acetic acid Chemical compound OC(=O)CC1=CSC(SCC(=O)NC[C@@H]2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=N1 QBXNXHODSIQDRT-AWEZNQCLSA-N 0.000 claims description 7
- 208000003926 Myelitis Diseases 0.000 claims description 7
- 150000004677 hydrates Chemical class 0.000 claims description 7
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- SSOJXYMMWRJOKG-YSYXNDDBSA-N N-[[(2S)-3-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-4-pyridin-4-yl-2H-1,3-thiazol-2-yl]sulfanyl]acetamide Chemical compound C(C)(=O)NS[C@@H]1SC=C(N1CC1CN(CCO1)CC1=CC(=C(C=C1)Cl)Cl)C1=CC=NC=C1 SSOJXYMMWRJOKG-YSYXNDDBSA-N 0.000 claims description 5
- AXVSPJDWWCYULK-BIAFCPFJSA-N n-[[(2s)-3-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-4-(3,4-dimethoxyphenyl)-2h-1,3-thiazol-2-yl]sulfanyl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1C1=CS[C@@H](SNC(C)=O)N1CC1OCCN(CC=2C=C(Cl)C(Cl)=CC=2)C1 AXVSPJDWWCYULK-BIAFCPFJSA-N 0.000 claims description 5
- QGONGVRPAFCFAI-SFHVURJKSA-N 2-[[4-(3-aminophenyl)-1,3-thiazol-2-yl]sulfanyl]-n-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]acetamide Chemical compound NC1=CC=CC(C=2N=C(SCC(=O)NC[C@@H]3OCCN(CC=4C=C(Cl)C(Cl)=CC=4)C3)SC=2)=C1 QGONGVRPAFCFAI-SFHVURJKSA-N 0.000 claims description 4
- FRSWNSZEXNWJEF-AWEZNQCLSA-N N-[1-[[(2S)-4-[(3,4-difluorophenyl)methyl]morpholin-2-yl]methyl]-6-oxopyridazin-3-yl]sulfanylacetamide Chemical compound C(C)(=O)NSC1=NN(C(C=C1)=O)C[C@@H]1CN(CCO1)CC1=CC(=C(C=C1)F)F FRSWNSZEXNWJEF-AWEZNQCLSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- XJSQYVGABDQLJE-LBPRGKRZSA-N n-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-2-[[4-(2h-tetrazol-5-yl)-1,3-thiazol-2-yl]sulfanyl]acetamide Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1C[C@H](CNC(=O)CSC=2SC=C(N=2)C2=NNN=N2)OCC1 XJSQYVGABDQLJE-LBPRGKRZSA-N 0.000 claims description 4
- 230000000069 prophylactic effect Effects 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 125000004419 alkynylene group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- NDZYPHLNJZSQJY-QNWVGRARSA-N 1-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-3-[(1r,2s)-2-[[(3s)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]urea Chemical compound CC1=C(C(=O)C)SC(NC(=O)N[C@H]2[C@@H](CCCC2)CN2C[C@H](CC=3C=CC(F)=CC=3)CCC2)=N1 NDZYPHLNJZSQJY-QNWVGRARSA-N 0.000 claims description 2
- MCYBOSMXXTXVNV-MBABXSBOSA-N N-[[(2S)-3-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-4-(5-methyl-1,2,4-oxadiazol-3-yl)-2H-1,3-thiazol-2-yl]sulfanyl]acetamide Chemical compound C(C)(=O)NS[C@@H]1SC=C(N1CC1CN(CCO1)CC1=CC(=C(C=C1)Cl)Cl)C1=NOC(=N1)C MCYBOSMXXTXVNV-MBABXSBOSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 description 440
- 238000003786 synthesis reaction Methods 0.000 description 438
- 239000000047 product Substances 0.000 description 314
- 238000005160 1H NMR spectroscopy Methods 0.000 description 242
- 239000007787 solid Substances 0.000 description 237
- 238000000034 method Methods 0.000 description 204
- 229910052739 hydrogen Inorganic materials 0.000 description 168
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 92
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 239000002904 solvent Substances 0.000 description 88
- 239000012230 colorless oil Substances 0.000 description 61
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 58
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- 238000006243 chemical reaction Methods 0.000 description 50
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 47
- 239000012046 mixed solvent Substances 0.000 description 46
- OJBBVTPPCDAKPT-XRIOVQLTSA-N [(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methanamine;dihydrochloride Chemical compound Cl.Cl.C1CO[C@@H](CN)CN1CC1=CC=C(Cl)C(Cl)=C1 OJBBVTPPCDAKPT-XRIOVQLTSA-N 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 239000003921 oil Substances 0.000 description 40
- 235000019198 oils Nutrition 0.000 description 40
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 34
- 239000013078 crystal Substances 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
- 239000002253 acid Substances 0.000 description 30
- 235000019270 ammonium chloride Nutrition 0.000 description 29
- 239000003480 eluent Substances 0.000 description 29
- 238000010898 silica gel chromatography Methods 0.000 description 29
- 239000000843 powder Substances 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- 239000011541 reaction mixture Substances 0.000 description 25
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
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- YNNGZCVDIREDDK-UHFFFAOYSA-N aminocarbamodithioic acid Chemical compound NNC(S)=S YNNGZCVDIREDDK-UHFFFAOYSA-N 0.000 description 19
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- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 14
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
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- WNLLENFSGFJNBQ-VIFPVBQESA-N tert-butyl (2s)-2-[[(2-chloroacetyl)amino]methyl]morpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCO[C@@H](CNC(=O)CCl)C1 WNLLENFSGFJNBQ-VIFPVBQESA-N 0.000 description 1
- MTMBHUYOIZWQAJ-UHFFFAOYSA-N tert-butyl 2-(aminomethyl)morpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOC(CN)C1 MTMBHUYOIZWQAJ-UHFFFAOYSA-N 0.000 description 1
- OSWULUXZFOQIRU-UHFFFAOYSA-N tert-butyl 2-aminoacetate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)CN OSWULUXZFOQIRU-UHFFFAOYSA-N 0.000 description 1
- DOMTZTVJNZKUNX-UHFFFAOYSA-N tert-butyl 3-aminopropanoate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)CCN DOMTZTVJNZKUNX-UHFFFAOYSA-N 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 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
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- ZEMGGZBWXRYJHK-UHFFFAOYSA-N thiouracil Chemical compound O=C1C=CNC(=S)N1 ZEMGGZBWXRYJHK-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 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
- 239000011534 wash buffer Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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
-
- 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
- C07D413/12—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
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/02—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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Otolaryngology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006535186A JP4970946B2 (ja) | 2004-09-08 | 2005-09-08 | モルホリン化合物 |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004261655 | 2004-09-08 | ||
| JP2004261655 | 2004-09-08 | ||
| PCT/JP2005/017002 WO2006028284A1 (ja) | 2004-09-08 | 2005-09-08 | モルホリン化合物 |
| JP2006535186A JP4970946B2 (ja) | 2004-09-08 | 2005-09-08 | モルホリン化合物 |
Publications (2)
| Publication Number | Publication Date |
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| JPWO2006028284A1 JPWO2006028284A1 (ja) | 2008-05-08 |
| JP4970946B2 true JP4970946B2 (ja) | 2012-07-11 |
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| JP2006535186A Expired - Fee Related JP4970946B2 (ja) | 2004-09-08 | 2005-09-08 | モルホリン化合物 |
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Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE398616T1 (de) * | 2005-02-04 | 2008-07-15 | Ctg Pharma S R L | Neue 4-aminochinolinderivate als antimalariamittel |
| KR101562549B1 (ko) | 2005-05-10 | 2015-10-23 | 인사이트 홀딩스 코포레이션 | 인돌아민 2,3-디옥시게나제의 조절제 및 이의 사용방법 |
| TWI382974B (zh) * | 2005-12-20 | 2013-01-21 | Incyte Corp | 作為吲哚胺２，３-二氧化酶調節劑之ｎ-羥基甲脒基雜環化物 |
| TWI399375B (zh) * | 2006-07-11 | 2013-06-21 | Mitsubishi Tanabe Pharma Corp | 嗎啉化合物之鹽 |
| CL2007002650A1 (es) * | 2006-09-19 | 2008-02-08 | Incyte Corp | Compuestos derivados de heterociclo n-hidroxiamino; composicion farmaceutica, util para tratar cancer, infecciones virales y desordenes neurodegenerativos entre otras. |
| US20080146624A1 (en) * | 2006-09-19 | 2008-06-19 | Incyte Corporation | Amidines as modulators of indoleamine 2,3-dioxygenase |
| US20080125470A1 (en) * | 2006-09-19 | 2008-05-29 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
| WO2008058178A1 (en) * | 2006-11-08 | 2008-05-15 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
| US8273766B2 (en) | 2007-04-04 | 2012-09-25 | Kowa Company, Ltd. | Tetrahydroisoquinoline compound |
| PE20110308A1 (es) | 2008-07-08 | 2011-06-10 | Incyte Corp | 1,2,5-oxadiazoles como inhibidores de indolamina 2,3-dioxigenasa |
| WO2015012332A1 (ja) * | 2013-07-24 | 2015-01-29 | 田辺三菱製薬株式会社 | 眼科疾患治療剤 |
| EP3066085B1 (en) | 2013-11-08 | 2020-05-13 | Incyte Holdings Corporation | Process for the synthesis of an indoleamine 2,3-dioxygenase inhibitor |
| WO2020203822A1 (ja) * | 2019-03-29 | 2020-10-08 | 千寿製薬株式会社 | 血管新生を伴う網膜疾患の治療又は予防のための併用医薬 |
| US20220280487A1 (en) * | 2019-08-26 | 2022-09-08 | Stichting Vumc | Inhibition of mycobacterial type vii secretion |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63264467A (ja) * | 1986-04-30 | 1988-11-01 | Dainippon Pharmaceut Co Ltd | ベンズアミド誘導体 |
| JPH03148276A (ja) * | 1989-11-01 | 1991-06-25 | Yoshitomi Pharmaceut Ind Ltd | 光学活性なピリドンカルボン酸化合物 |
| WO2000053600A1 (fr) * | 1999-03-11 | 2000-09-14 | Banyu Pharmaceutical Co., Ltd. | Derives piperidiniques |
| WO2003082294A1 (en) * | 2002-03-28 | 2003-10-09 | Glaxo Group Limited | Morpholine derivatives with a substituted acetamide group in the 2-position for use as ccr-3 antagonists for the treatment of inflammatory diseases |
| WO2004004731A1 (en) * | 2002-07-02 | 2004-01-15 | F. Hoffmann-La Roche Ag | 2, 5-substituted pyrimidine derivatives as ccr-3 receptor antagonists ix |
| JP2004509952A (ja) * | 2000-09-29 | 2004-04-02 | グラクソ グループ リミテッド | 炎症性疾患を処置するためのモルホリン−アセトアミド誘導体 |
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| US4870074A (en) * | 1986-04-30 | 1989-09-26 | Dainippon Pharmaceutical Co., Ltd. | Substituted benzamide derivatives, for enhancing gastrointestinal motility |
| WO1997024325A1 (en) | 1995-12-28 | 1997-07-10 | Takeda Chemical Industries, Ltd. | DIPHENYLMETHANE DERIVATIVES AS MIP-1α/RANTES RECEPTOR ANTAGONISTS |
| CA2259927A1 (en) | 1996-07-12 | 1998-01-22 | Leukosite, Inc. | Chemokine receptor antagonists and methods of use therefor |
| CA2261633A1 (en) | 1996-07-29 | 1998-02-05 | Banyu Pharmaceutical Co., Ltd. | Chemokine receptor antagonists |
| AU5522498A (en) | 1996-12-13 | 1998-07-03 | Merck & Co., Inc. | Substituted aryl piperazines as modulators of chemokine receptor activity |
| CA2329777A1 (en) | 1998-04-27 | 1999-11-04 | Dashyant Dhanak | Ccr-3 receptor antagonists |
| EP1073434A1 (en) | 1998-04-27 | 2001-02-07 | Smithkline Beecham Corporation | Ccr-3 receptor antagonists |
| TR200101397T2 (tr) | 1998-11-20 | 2001-11-21 | F.Hoffmann-La Roche Ag | Piperidin CCR-3 reseptörü antagonistleri |
| WO2000034278A1 (fr) | 1998-12-04 | 2000-06-15 | Toray Industries, Inc. | Derives triazolo, et inhibiteurs de chimiokines contenant ces derives comme ingredient actif |
| CN1344266A (zh) | 1999-03-26 | 2002-04-10 | 阿斯特拉曾尼卡有限公司 | 新的化合物 |
| SE9902987D0 (sv) | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
| WO2002018335A1 (fr) | 2000-08-28 | 2002-03-07 | Yamanouchi Pharmaceutical Co., Ltd. | Derives d'amine cyclique |
| IL155092A0 (en) | 2000-09-29 | 2003-10-31 | Glaxo Group Ltd | Compounds useful in the treatment of inflammatory diseases |
| GB0104050D0 (en) | 2001-02-19 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| WO2002088111A1 (fr) | 2001-04-27 | 2002-11-07 | Mitsubishi Pharma Corporation | Nouveaux composes de benzylpiperidine |
| TW200400035A (en) | 2002-03-28 | 2004-01-01 | Glaxo Group Ltd | Novel compounds |
| GB0207439D0 (en) | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
| GB0207436D0 (en) | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
| GB0208158D0 (en) | 2002-03-28 | 2002-05-22 | Glaxo Group Ltd | Novel compounds |
| GB0207445D0 (en) | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
| GB0212355D0 (en) | 2002-05-29 | 2002-07-10 | Glaxo Group Ltd | Novel compounds |
| GB0212357D0 (en) | 2002-05-29 | 2002-07-10 | Glaxo Group Ltd | Novel compounds |
-
2005
- 2005-09-08 ES ES05783689T patent/ES2396419T3/es active Active
- 2005-09-08 KR KR1020077007863A patent/KR101011848B1/ko active IP Right Grant
- 2005-09-08 EP EP05783689.2A patent/EP1801108B9/en active Active
- 2005-09-08 DK DK05783689.2T patent/DK1801108T3/da active
- 2005-09-08 IN IN3493CHN2014 patent/IN2014CN03493A/en unknown
- 2005-09-08 US US11/662,228 patent/US7935700B2/en not_active Expired - Fee Related
- 2005-09-08 JP JP2006535186A patent/JP4970946B2/ja not_active Expired - Fee Related
- 2005-09-08 PT PT57836892T patent/PT1801108E/pt unknown
- 2005-09-08 PL PL05783689T patent/PL1801108T3/pl unknown
- 2005-09-08 WO PCT/JP2005/017002 patent/WO2006028284A1/ja active Application Filing
- 2005-09-08 TW TW094130939A patent/TW200619212A/zh not_active IP Right Cessation
- 2005-09-08 CN CN2005800301370A patent/CN101014580B/zh not_active Expired - Fee Related
- 2005-09-08 CA CA2579207A patent/CA2579207C/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63264467A (ja) * | 1986-04-30 | 1988-11-01 | Dainippon Pharmaceut Co Ltd | ベンズアミド誘導体 |
| JPH03148276A (ja) * | 1989-11-01 | 1991-06-25 | Yoshitomi Pharmaceut Ind Ltd | 光学活性なピリドンカルボン酸化合物 |
| WO2000053600A1 (fr) * | 1999-03-11 | 2000-09-14 | Banyu Pharmaceutical Co., Ltd. | Derives piperidiniques |
| JP2004509952A (ja) * | 2000-09-29 | 2004-04-02 | グラクソ グループ リミテッド | 炎症性疾患を処置するためのモルホリン−アセトアミド誘導体 |
| WO2003082294A1 (en) * | 2002-03-28 | 2003-10-09 | Glaxo Group Limited | Morpholine derivatives with a substituted acetamide group in the 2-position for use as ccr-3 antagonists for the treatment of inflammatory diseases |
| WO2004004731A1 (en) * | 2002-07-02 | 2004-01-15 | F. Hoffmann-La Roche Ag | 2, 5-substituted pyrimidine derivatives as ccr-3 receptor antagonists ix |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2396419T3 (es) | 2013-02-21 |
| KR20070099528A (ko) | 2007-10-09 |
| TW200619212A (en) | 2006-06-16 |
| CN101014580B (zh) | 2011-05-04 |
| US20070265257A1 (en) | 2007-11-15 |
| CA2579207A1 (en) | 2006-03-16 |
| EP1801108A1 (en) | 2007-06-27 |
| CN101014580A (zh) | 2007-08-08 |
| WO2006028284A1 (ja) | 2006-03-16 |
| JPWO2006028284A1 (ja) | 2008-05-08 |
| PT1801108E (pt) | 2012-12-03 |
| TWI367209B (US06903085-20050607-C00131.png) | 2012-07-01 |
| US7935700B2 (en) | 2011-05-03 |
| CA2579207C (en) | 2011-10-18 |
| EP1801108B9 (en) | 2013-11-20 |
| DK1801108T3 (da) | 2013-02-18 |
| PL1801108T3 (pl) | 2013-04-30 |
| EP1801108A4 (en) | 2010-10-13 |
| IN2014CN03493A (US06903085-20050607-C00131.png) | 2015-07-03 |
| KR101011848B1 (ko) | 2011-02-01 |
| EP1801108B1 (en) | 2012-11-14 |
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