JP2007535554A - アリールフェニルアミノ−、アリールフェニルアミド−、およびアリールフェニルエーテル−スルフィド誘導体 - Google Patents
アリールフェニルアミノ−、アリールフェニルアミド−、およびアリールフェニルエーテル−スルフィド誘導体 Download PDFInfo
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- JP2007535554A JP2007535554A JP2007511000A JP2007511000A JP2007535554A JP 2007535554 A JP2007535554 A JP 2007535554A JP 2007511000 A JP2007511000 A JP 2007511000A JP 2007511000 A JP2007511000 A JP 2007511000A JP 2007535554 A JP2007535554 A JP 2007535554A
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- Prior art keywords
- alkyl
- heterocyclyl
- aryl
- cycloalkyl
- carboxy
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- 238000000034 method Methods 0.000 claims abstract description 256
- 150000001875 compounds Chemical class 0.000 claims abstract description 181
- 150000003839 salts Chemical class 0.000 claims abstract description 45
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 239000000651 prodrug Substances 0.000 claims abstract description 16
- 229940002612 prodrug Drugs 0.000 claims abstract description 16
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 230000004054 inflammatory process Effects 0.000 claims abstract description 12
- 206010061218 Inflammation Diseases 0.000 claims abstract description 11
- 230000028993 immune response Effects 0.000 claims abstract description 8
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 8
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 208000026278 immune system disease Diseases 0.000 claims abstract description 5
- -1 amino, aminothiocarbonyl Chemical group 0.000 claims description 281
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 243
- 125000000623 heterocyclic group Chemical group 0.000 claims description 224
- 125000000217 alkyl group Chemical group 0.000 claims description 201
- 125000003118 aryl group Chemical group 0.000 claims description 200
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 167
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 154
- 150000002148 esters Chemical class 0.000 claims description 146
- 125000003545 alkoxy group Chemical group 0.000 claims description 133
- 125000001424 substituent group Chemical group 0.000 claims description 132
- 150000001408 amides Chemical class 0.000 claims description 130
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 122
- 125000001589 carboacyl group Chemical group 0.000 claims description 121
- 125000003342 alkenyl group Chemical group 0.000 claims description 119
- 125000000304 alkynyl group Chemical group 0.000 claims description 119
- 239000001257 hydrogen Substances 0.000 claims description 117
- 229910052739 hydrogen Inorganic materials 0.000 claims description 117
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 111
- 150000001299 aldehydes Chemical class 0.000 claims description 98
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 97
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 94
- 229910052736 halogen Inorganic materials 0.000 claims description 94
- 150000002367 halogens Chemical class 0.000 claims description 94
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 79
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 76
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 76
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- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 72
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 65
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 62
- 125000004414 alkyl thio group Chemical group 0.000 claims description 58
- 125000005110 aryl thio group Chemical group 0.000 claims description 55
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- 125000004043 oxo group Chemical group O=* 0.000 claims description 49
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 48
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 45
- 239000002253 acid Substances 0.000 claims description 44
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 32
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 28
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 28
- IQZPDFORWZTSKT-UHFFFAOYSA-N nitrosulphonic acid Chemical compound OS(=O)(=O)[N+]([O-])=O IQZPDFORWZTSKT-UHFFFAOYSA-N 0.000 claims description 28
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 23
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 claims description 22
- 230000003993 interaction Effects 0.000 claims description 22
- GZTFUVZVLYUPRG-IZZDOVSWSA-N (e)-3-(4-tert-butylphenyl)-n-(2,3-dihydro-1,4-benzodioxin-6-yl)prop-2-enamide Chemical compound C1=CC(C(C)(C)C)=CC=C1\C=C\C(=O)NC1=CC=C(OCCO2)C2=C1 GZTFUVZVLYUPRG-IZZDOVSWSA-N 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- APEJMQOBVMLION-VOTSOKGWSA-N trans-cinnamamide Chemical compound NC(=O)\C=C\C1=CC=CC=C1 APEJMQOBVMLION-VOTSOKGWSA-N 0.000 claims description 18
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 17
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
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- 239000003112 inhibitor Substances 0.000 claims description 11
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 10
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims description 9
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 claims description 9
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
- 235000013985 cinnamic acid Nutrition 0.000 claims description 9
- 229930016911 cinnamic acid Natural products 0.000 claims description 9
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
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- 230000001404 mediated effect Effects 0.000 claims description 8
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- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 238000001516 cell proliferation assay Methods 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 4
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 4
- 125000004702 alkoxy alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- IBAHLNWTOIHLKE-UHFFFAOYSA-N cyano cyanate Chemical compound N#COC#N IBAHLNWTOIHLKE-UHFFFAOYSA-N 0.000 claims description 4
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 4
- 125000005182 hydroxyalkylcarbonyl group Chemical group 0.000 claims description 4
- 125000003431 oxalo group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 claims description 3
- 206010037575 Pustular psoriasis Diseases 0.000 claims description 3
- YTDSHPUZEWSEHU-UHFFFAOYSA-N cyano hydrogen carbonate Chemical compound OC(=O)OC#N YTDSHPUZEWSEHU-UHFFFAOYSA-N 0.000 claims description 3
- 150000002170 ethers Chemical class 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 3
- MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 claims description 2
- 206010012455 Dermatitis exfoliative Diseases 0.000 claims description 2
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 2
- 150000003857 carboxamides Chemical class 0.000 claims description 2
- 230000001185 psoriatic effect Effects 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000004963 sulfonylalkyl group Chemical group 0.000 claims description 2
- 125000005942 tetrahydropyridyl group Chemical group 0.000 claims description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 48
- 102100022339 Integrin alpha-L Human genes 0.000 claims 8
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 claims 5
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims 2
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- KCHNRMFPOADKIZ-UHFFFAOYSA-N amino aminooxycarbonyl carbonate Chemical compound NOC(=O)OC(=O)ON KCHNRMFPOADKIZ-UHFFFAOYSA-N 0.000 claims 1
- 125000005243 carbonyl alkyl group Chemical group 0.000 claims 1
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- 239000000126 substance Substances 0.000 abstract description 4
- 239000000047 product Substances 0.000 description 94
- 238000006243 chemical reaction Methods 0.000 description 75
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 71
- 102100025390 Integrin beta-2 Human genes 0.000 description 66
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 59
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 56
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 42
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 37
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
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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 18
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
-
- 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
- A61P17/06—Antipsoriatics
-
- 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
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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| US8809027B1 (en) | 2009-09-27 | 2014-08-19 | Opx Biotechnologies, Inc. | Genetically modified organisms for increased microbial production of 3-hydroxypropionic acid involving an oxaloacetate alpha-decarboxylase |
| CA2775390C (en) | 2009-09-27 | 2021-06-29 | Opx Biotechnologies, Inc. | Method for producing 3-hydroxypropionic acid and other products |
| CN109182238A (zh) | 2012-08-10 | 2019-01-11 | 嘉吉有限公司 | 用于生产脂肪酸和脂肪酸衍生产物的微生物及方法 |
| WO2014145096A1 (en) | 2013-03-15 | 2014-09-18 | Cindy Hoppe | Flash evaporation for production purification and recovery |
| WO2014146026A1 (en) | 2013-03-15 | 2014-09-18 | Opx Biotechnologies, Inc. | Bioproduction of chemicals |
| US11408013B2 (en) | 2013-07-19 | 2022-08-09 | Cargill, Incorporated | Microorganisms and methods for the production of fatty acids and fatty acid derived products |
| JP6603658B2 (ja) | 2013-07-19 | 2019-11-06 | カーギル インコーポレイテッド | 脂肪酸及び脂肪酸誘導体の製造のための微生物及び方法 |
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| CN107406419B (zh) | 2015-01-20 | 2020-09-11 | 诺华股份有限公司 | Pet显像剂 |
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| MXPA06012486A (es) | 2007-03-15 |
| WO2005105770A2 (en) | 2005-11-10 |
| IL178888A0 (en) | 2007-03-08 |
| CA2562176A1 (en) | 2005-11-10 |
| AU2005238534A1 (en) | 2005-11-10 |
| NO20065256L (no) | 2006-11-15 |
| WO2005105770A3 (en) | 2006-03-09 |
| KR20070008708A (ko) | 2007-01-17 |
| EP1740565A2 (en) | 2007-01-10 |
| RU2006141832A (ru) | 2008-06-10 |
| BRPI0510512A (pt) | 2007-10-30 |
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