CA2350730A1 - N-ureidoalkyl-piperidines utilisees en tant que modulateurs de l'activite des recepteurs des chimiokines - Google Patents
N-ureidoalkyl-piperidines utilisees en tant que modulateurs de l'activite des recepteurs des chimiokines Download PDFInfo
- Publication number
- CA2350730A1 CA2350730A1 CA002350730A CA2350730A CA2350730A1 CA 2350730 A1 CA2350730 A1 CA 2350730A1 CA 002350730 A CA002350730 A CA 002350730A CA 2350730 A CA2350730 A CA 2350730A CA 2350730 A1 CA2350730 A1 CA 2350730A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- occurrence
- substituted
- cycloalkyl
- piperidinyl
- 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.)
- Abandoned
Links
- 102000009410 Chemokine receptor Human genes 0.000 title claims description 19
- 108050000299 Chemokine receptor Proteins 0.000 title claims description 19
- 230000000694 effects Effects 0.000 title claims description 10
- 150000003839 salts Chemical group 0.000 claims abstract description 38
- 208000006673 asthma Diseases 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 627
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 338
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 324
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 299
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 288
- 229910052794 bromium Inorganic materials 0.000 claims description 213
- 229910052740 iodine Inorganic materials 0.000 claims description 212
- 229910052731 fluorine Inorganic materials 0.000 claims description 208
- 150000001875 compounds Chemical class 0.000 claims description 198
- 239000004202 carbamide Substances 0.000 claims description 191
- 125000002837 carbocyclic group Chemical group 0.000 claims description 177
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 176
- 125000005842 heteroatom Chemical group 0.000 claims description 160
- -1 isothiadiazolyl Chemical group 0.000 claims description 150
- 125000000623 heterocyclic group Chemical group 0.000 claims description 145
- 125000003342 alkenyl group Chemical group 0.000 claims description 142
- 125000000304 alkynyl group Chemical group 0.000 claims description 136
- 229910052717 sulfur Inorganic materials 0.000 claims description 136
- 229910052760 oxygen Inorganic materials 0.000 claims description 135
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 130
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 117
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 111
- 125000003386 piperidinyl group Chemical group 0.000 claims description 107
- 229910052801 chlorine Inorganic materials 0.000 claims description 94
- 238000000034 method Methods 0.000 claims description 85
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 61
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 61
- 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 58
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 58
- 125000001544 thienyl group Chemical group 0.000 claims description 47
- 125000002541 furyl group Chemical group 0.000 claims description 46
- 125000002971 oxazolyl group Chemical group 0.000 claims description 46
- 125000004076 pyridyl group Chemical group 0.000 claims description 46
- 125000000335 thiazolyl group Chemical group 0.000 claims description 46
- 229910052799 carbon Inorganic materials 0.000 claims description 44
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 39
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 38
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 38
- 125000002883 imidazolyl group Chemical group 0.000 claims description 38
- 125000001041 indolyl group Chemical group 0.000 claims description 38
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 38
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 38
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 38
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 37
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 37
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 37
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 37
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 37
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 37
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 37
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 37
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 37
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 32
- 101100439662 Arabidopsis thaliana CHR5 gene Proteins 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 30
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 29
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 25
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 25
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 24
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 22
- NQRYJNQNLNOLGT-UHFFFAOYSA-O Piperidinium(1+) Chemical compound C1CC[NH2+]CC1 NQRYJNQNLNOLGT-UHFFFAOYSA-O 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical group 0.000 claims description 21
- 125000001624 naphthyl group Chemical group 0.000 claims description 21
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 21
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 18
- 101100243950 Arabidopsis thaliana PIE1 gene Proteins 0.000 claims description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-O Pyrrolidinium ion Chemical compound C1CC[NH2+]C1 RWRDLPDLKQPQOW-UHFFFAOYSA-O 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 17
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 17
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 125000004122 cyclic group Chemical group 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 150000001204 N-oxides Chemical class 0.000 claims description 13
- 208000035475 disorder Diseases 0.000 claims description 13
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 208000010668 atopic eczema Diseases 0.000 claims description 7
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 7
- 208000027866 inflammatory disease Diseases 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 101100244083 Arabidopsis thaliana PKL gene Proteins 0.000 claims description 6
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- JSUGTZOUOKXRQN-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound CC(=O)C1=CC=CC(NC(=O)NCCCN2CCC(CC=3C=CC(F)=CC=3)CC2)=C1 JSUGTZOUOKXRQN-UHFFFAOYSA-N 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 206010059447 Allergic colitis Diseases 0.000 claims description 4
- 208000032671 Allergic granulomatous angiitis Diseases 0.000 claims description 4
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 206010010741 Conjunctivitis Diseases 0.000 claims description 4
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 4
- 201000004624 Dermatitis Diseases 0.000 claims description 4
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 4
- 206010014950 Eosinophilia Diseases 0.000 claims description 4
- 206010053776 Eosinophilic cellulitis Diseases 0.000 claims description 4
- 206010014954 Eosinophilic fasciitis Diseases 0.000 claims description 4
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 claims description 4
- 208000031886 HIV Infections Diseases 0.000 claims description 4
- 208000037357 HIV infectious disease Diseases 0.000 claims description 4
- 208000017604 Hodgkin disease Diseases 0.000 claims description 4
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 4
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 208000030852 Parasitic disease Diseases 0.000 claims description 4
- 206010034277 Pemphigoid Diseases 0.000 claims description 4
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 4
- 208000008526 Wells syndrome Diseases 0.000 claims description 4
- 201000010105 allergic rhinitis Diseases 0.000 claims description 4
- 201000008937 atopic dermatitis Diseases 0.000 claims description 4
- 208000000594 bullous pemphigoid Diseases 0.000 claims description 4
- 201000001564 eosinophilic gastroenteritis Diseases 0.000 claims description 4
- 208000004313 familial eosinophilia Diseases 0.000 claims description 4
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 4
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 4
- 201000009732 pulmonary eosinophilia Diseases 0.000 claims description 4
- 229910052701 rubidium Inorganic materials 0.000 claims description 4
- 238000002054 transplantation Methods 0.000 claims description 4
- JLJCTLOBEBJGQV-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[4-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]but-2-ynyl]urea Chemical compound CC(=O)C1=CC=CC(NC(=O)NCC#CCN2CC(CC=3C=CC(F)=CC=3)CCC2)=C1 JLJCTLOBEBJGQV-UHFFFAOYSA-N 0.000 claims description 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 3
- 101100439665 Arabidopsis thaliana SWI2 gene Proteins 0.000 claims description 3
- UWQSNHFXHJIJQG-UHFFFAOYSA-N 1-(1-adamantyl)-3-[4-(4-benzylpiperidin-1-yl)butyl]urea Chemical compound C1C(C2)CC(C3)CC2CC13NC(=O)NCCCCN(CC1)CCC1CC1=CC=CC=C1 UWQSNHFXHJIJQG-UHFFFAOYSA-N 0.000 claims description 2
- WDWSGEFIGUDQLP-UHFFFAOYSA-N 1-(2-fluorophenyl)-3-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCNC(=O)NC=2C(=CC=CC=2)F)CC1 WDWSGEFIGUDQLP-UHFFFAOYSA-N 0.000 claims description 2
- PSTIGTLOMGJZKB-UHFFFAOYSA-N 1-(3,5-diacetylphenyl)-3-[3-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound CC(=O)C1=CC(C(=O)C)=CC(NC(=O)NCCCN2CC(CC=3C=CC(F)=CC=3)CCC2)=C1 PSTIGTLOMGJZKB-UHFFFAOYSA-N 0.000 claims description 2
- BYLFVKNMQPNLJV-UHFFFAOYSA-N 1-(3,5-diacetylphenyl)-3-[4-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]butyl]urea Chemical compound CC(=O)C1=CC(C(=O)C)=CC(NC(=O)NCCCCN2CC(CC=3C=CC(F)=CC=3)CCC2)=C1 BYLFVKNMQPNLJV-UHFFFAOYSA-N 0.000 claims description 2
- OOBRDLYTJIFFAF-NSCUHMNNSA-N 1-(3-acetylphenyl)-3-[(e)-4-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]but-2-enyl]urea Chemical compound CC(=O)C1=CC=CC(NC(=O)NC\C=C\CN2CC(CC=3C=CC(F)=CC=3)CCC2)=C1 OOBRDLYTJIFFAF-NSCUHMNNSA-N 0.000 claims description 2
- OOBRDLYTJIFFAF-IHWYPQMZSA-N 1-(3-acetylphenyl)-3-[(z)-4-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]but-2-enyl]urea Chemical compound CC(=O)C1=CC=CC(NC(=O)NC\C=C/CN2CC(CC=3C=CC(F)=CC=3)CCC2)=C1 OOBRDLYTJIFFAF-IHWYPQMZSA-N 0.000 claims description 2
- FDDSQKZQCHXOJV-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[3-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound CC(=O)C1=CC=CC(NC(=O)NCCCN2CC(CC=3C=CC(F)=CC=3)CCC2)=C1 FDDSQKZQCHXOJV-UHFFFAOYSA-N 0.000 claims description 2
- XLVMKNMUOUEVML-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[3-[3-benzyl-4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound CC(=O)C1=CC=CC(NC(=O)NCCCN2CC(CC=3C=CC=CC=3)C(CC=3C=CC(F)=CC=3)CC2)=C1 XLVMKNMUOUEVML-UHFFFAOYSA-N 0.000 claims description 2
- FACAOYZGDMUDCI-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[4-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]butyl]urea Chemical compound CC(=O)C1=CC=CC(NC(=O)NCCCCN2CC(CC=3C=CC(F)=CC=3)CCC2)=C1 FACAOYZGDMUDCI-UHFFFAOYSA-N 0.000 claims description 2
- NNTAFTUMSNNLKY-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[4-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]butyl]urea Chemical compound CC(=O)C1=CC=CC(NC(=O)NCCCCN2CCC(CC=3C=CC(F)=CC=3)CC2)=C1 NNTAFTUMSNNLKY-UHFFFAOYSA-N 0.000 claims description 2
- AEWGMNWVUZPOJZ-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-cyano-2-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]guanidine Chemical compound CC(=O)C1=CC=CC(NC(NC#N)=NCCCN2CCC(CC=3C=CC(F)=CC=3)CC2)=C1 AEWGMNWVUZPOJZ-UHFFFAOYSA-N 0.000 claims description 2
- MDARSIAWLKIRIV-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCNC(=O)NC=2C=C(Cl)C=CC=2)CC1 MDARSIAWLKIRIV-UHFFFAOYSA-N 0.000 claims description 2
- JVFKBYGIFNFWJA-UPHRSURJSA-N 1-(3-cyanophenyl)-3-[(z)-4-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]but-2-enyl]urea Chemical compound C1=CC(F)=CC=C1CC1CN(C\C=C/CNC(=O)NC=2C=C(C=CC=2)C#N)CCC1 JVFKBYGIFNFWJA-UPHRSURJSA-N 0.000 claims description 2
- KWLPAWJPUXLNRQ-UHFFFAOYSA-N 1-(3-cyanophenyl)-3-[3-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound C1=CC(F)=CC=C1CC1CN(CCCNC(=O)NC=2C=C(C=CC=2)C#N)CCC1 KWLPAWJPUXLNRQ-UHFFFAOYSA-N 0.000 claims description 2
- KOYNBQKVCFQSOA-UHFFFAOYSA-N 1-(3-cyanophenyl)-3-[4-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]butyl]urea Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCCNC(=O)NC=2C=C(C=CC=2)C#N)CC1 KOYNBQKVCFQSOA-UHFFFAOYSA-N 0.000 claims description 2
- RBFWNOQQIXWZBP-UHFFFAOYSA-N 1-(3-fluorophenyl)-3-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCNC(=O)NC=2C=C(F)C=CC=2)CC1 RBFWNOQQIXWZBP-UHFFFAOYSA-N 0.000 claims description 2
- XISNYNIVVDJIEA-UHFFFAOYSA-N 1-(3-methoxyphenyl)-3-[3-[4-[(3-methoxyphenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound COC1=CC=CC(CC2CCN(CCCNC(=O)NC=3C=C(OC)C=CC=3)CC2)=C1 XISNYNIVVDJIEA-UHFFFAOYSA-N 0.000 claims description 2
- RJTCZABUFMJLNH-UHFFFAOYSA-N 1-(4-acetylphenyl)-3-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound C1=CC(C(=O)C)=CC=C1NC(=O)NCCCN1CCC(CC=2C=CC(F)=CC=2)CC1 RJTCZABUFMJLNH-UHFFFAOYSA-N 0.000 claims description 2
- XRVIQHXQUJDIST-UPHRSURJSA-N 1-(4-fluorophenyl)-3-[(z)-4-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]but-2-enyl]urea Chemical compound C1=CC(F)=CC=C1CC1CN(C\C=C/CNC(=O)NC=2C=CC(F)=CC=2)CCC1 XRVIQHXQUJDIST-UPHRSURJSA-N 0.000 claims description 2
- VSIBBEPLUZVVGY-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[3-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound C1=CC(F)=CC=C1CC1CN(CCCNC(=O)NC=2C=CC(F)=CC=2)CCC1 VSIBBEPLUZVVGY-UHFFFAOYSA-N 0.000 claims description 2
- KCJDPOIKFGIHOH-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]urea Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCNC(=O)NC=2C=CC(F)=CC=2)CC1 KCJDPOIKFGIHOH-UHFFFAOYSA-N 0.000 claims description 2
- FRIXBUXIKXKZHL-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[4-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]butyl]urea Chemical compound C1=CC(F)=CC=C1CC1CN(CCCCNC(=O)NC=2C=CC(F)=CC=2)CCC1 FRIXBUXIKXKZHL-UHFFFAOYSA-N 0.000 claims description 2
- IRJQYZHWRKOHKB-NRFANRHFSA-N 1-(5-acetyl-2-methoxyphenyl)-3-cyano-2-[3-[(3s)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]guanidine Chemical compound COC1=CC=C(C(C)=O)C=C1NC(NC#N)=NCCCN1C[C@H](CC=2C=CC(F)=CC=2)CCC1 IRJQYZHWRKOHKB-NRFANRHFSA-N 0.000 claims description 2
- DFMMVTOIQOKHSC-UHFFFAOYSA-N 1-[3-(4-benzylpiperidin-1-yl)propyl]-3-(3-cyanophenyl)urea Chemical compound C=1C=CC(C#N)=CC=1NC(=O)NCCCN(CC1)CCC1CC1=CC=CC=C1 DFMMVTOIQOKHSC-UHFFFAOYSA-N 0.000 claims description 2
- WVFRUIFQEZUUCA-UHFFFAOYSA-N 1-[3-(4-benzylpiperidin-1-yl)propyl]-3-(4-phenylmethoxyphenyl)urea Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1NC(=O)NCCCN(CC1)CCC1CC1=CC=CC=C1 WVFRUIFQEZUUCA-UHFFFAOYSA-N 0.000 claims description 2
- SLOBKPDEROQMJY-UHFFFAOYSA-N 1-[3-(4-benzylpiperidin-1-yl)propyl]-3-[2-(hydroxymethyl)phenyl]urea Chemical compound OCC1=CC=CC=C1NC(=O)NCCCN1CCC(CC=2C=CC=CC=2)CC1 SLOBKPDEROQMJY-UHFFFAOYSA-N 0.000 claims description 2
- SPGPWKNLZJBUIT-UHFFFAOYSA-N 1-[3-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-3-phenylurea Chemical compound C1=CC(F)=CC=C1CC1CN(CCCNC(=O)NC=2C=CC=CC=2)CCC1 SPGPWKNLZJBUIT-UHFFFAOYSA-N 0.000 claims description 2
- AWRZIXYQMNTSBL-UHFFFAOYSA-N 1-[3-[3-benzyl-4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-3-(3-methoxyphenyl)urea Chemical compound COC1=CC=CC(NC(=O)NCCCN2CC(CC=3C=CC=CC=3)C(CC=3C=CC(F)=CC=3)CC2)=C1 AWRZIXYQMNTSBL-UHFFFAOYSA-N 0.000 claims description 2
- VMMGCEFZPGQWPK-UHFFFAOYSA-N 1-[3-[3-benzyl-4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-3-(4-fluorophenyl)urea Chemical compound C1=CC(F)=CC=C1CC1C(CC=2C=CC=CC=2)CN(CCCNC(=O)NC=2C=CC(F)=CC=2)CC1 VMMGCEFZPGQWPK-UHFFFAOYSA-N 0.000 claims description 2
- RRGVESOQRKEVMY-UHFFFAOYSA-N 1-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-3-(2-propan-2-ylphenyl)urea Chemical compound CC(C)C1=CC=CC=C1NC(=O)NCCCN1CCC(CC=2C=CC(F)=CC=2)CC1 RRGVESOQRKEVMY-UHFFFAOYSA-N 0.000 claims description 2
- NYNIGNIZGMSCIO-UHFFFAOYSA-N 1-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-3-[3-(1-hydroxyethyl)phenyl]urea;hydrochloride Chemical compound Cl.CC(O)C1=CC=CC(NC(=O)NCCCN2CCC(CC=3C=CC(F)=CC=3)CC2)=C1 NYNIGNIZGMSCIO-UHFFFAOYSA-N 0.000 claims description 2
- APVMWUNIKUFKIJ-UHFFFAOYSA-N 1-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-3-[3-(trifluoromethyl)phenyl]urea Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCNC(=O)NC=2C=C(C=CC=2)C(F)(F)F)CC1 APVMWUNIKUFKIJ-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004623 carbolinyl group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- KTRFZWJCHOQHMN-UHFFFAOYSA-N chloromethanethioic s-acid Chemical compound SC(Cl)=O KTRFZWJCHOQHMN-UHFFFAOYSA-N 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
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- 238000002425 crystallisation Methods 0.000 description 1
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- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- XSYZCZPCBXYQTE-UHFFFAOYSA-N cyclodecylcyclodecane Chemical compound C1CCCCCCCCC1C1CCCCCCCCC1 XSYZCZPCBXYQTE-UHFFFAOYSA-N 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 150000001945 cysteines Chemical class 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical class NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
- DKWOHBPRFZIUQL-UHFFFAOYSA-N dimethyl-methylidene-oxo-$l^{6}-sulfane Chemical compound C[S+](C)([CH2-])=O DKWOHBPRFZIUQL-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
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- 238000005886 esterification reaction Methods 0.000 description 1
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- QLOJLWADIRKFOP-UHFFFAOYSA-N ethyl 3-[3-(4-benzylpiperidin-1-yl)propylcarbamoylamino]benzoate Chemical compound CCOC(=O)C1=CC=CC(NC(=O)NCCCN2CCC(CC=3C=CC=CC=3)CC2)=C1 QLOJLWADIRKFOP-UHFFFAOYSA-N 0.000 description 1
- PTUJPXJZEGQKFE-UHFFFAOYSA-N ethyl 3-[3-[3-(2-phenylethyl)piperidin-1-yl]propylcarbamoylamino]benzoate Chemical compound CCOC(=O)C1=CC=CC(NC(=O)NCCCN2CC(CCC=3C=CC=CC=3)CCC2)=C1 PTUJPXJZEGQKFE-UHFFFAOYSA-N 0.000 description 1
- UIFUQBFCLAVIIP-UHFFFAOYSA-N ethyl 3-[3-[3-[(4-fluorophenyl)methyl]piperidin-1-yl]propylcarbamoylamino]benzoate Chemical compound CCOC(=O)C1=CC=CC(NC(=O)NCCCN2CC(CC=3C=CC(F)=CC=3)CCC2)=C1 UIFUQBFCLAVIIP-UHFFFAOYSA-N 0.000 description 1
- DSGSHRRALBQIJP-UHFFFAOYSA-N ethyl 4-[3-[4-[(3-methoxyphenyl)methyl]piperidin-1-yl]propylcarbamoylamino]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC(=O)NCCCN1CCC(CC=2C=C(OC)C=CC=2)CC1 DSGSHRRALBQIJP-UHFFFAOYSA-N 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 150000003948 formamides Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 125000005343 heterocyclic alkyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
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- 230000004957 immunoregulator effect Effects 0.000 description 1
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- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
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- 230000002757 inflammatory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
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- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
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- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 238000006138 lithiation reaction Methods 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- PKMBLJNMKINMSK-UHFFFAOYSA-N magnesium;azanide Chemical class [NH2-].[NH2-].[Mg+2] PKMBLJNMKINMSK-UHFFFAOYSA-N 0.000 description 1
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- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical class N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
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- 238000003328 mesylation reaction Methods 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
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- 235000010755 mineral Nutrition 0.000 description 1
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- 125000002757 morpholinyl group Chemical group 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- RPMXALUWKZHYOV-UHFFFAOYSA-N nitroethene Chemical group [O-][N+](=O)C=C RPMXALUWKZHYOV-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
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- QNNHQVPFZIFNFK-UHFFFAOYSA-N oxazolo[4,5-b]pyridine Chemical compound C1=CC=C2OC=NC2=N1 QNNHQVPFZIFNFK-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000004624 phenarsazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3[As]=C12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
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- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
- 125000003367 polycyclic group Polymers 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 1
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- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- GDPRIIMJONZXBY-UHFFFAOYSA-N pyrrolo[2,3-h][1,2]benzoxazine Chemical class C1=NOC2=C3C=CN=C3C=CC2=C1 GDPRIIMJONZXBY-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
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- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 102220106802 rs139353014 Human genes 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- KKKDGYXNGYJJRX-UHFFFAOYSA-M silver nitrite Chemical compound [Ag+].[O-]N=O KKKDGYXNGYJJRX-UHFFFAOYSA-M 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- SLRCCWJSBJZJBV-AJNGGQMLSA-N sparteine Chemical compound C1N2CCCC[C@H]2[C@@H]2CN3CCCC[C@H]3[C@H]1C2 SLRCCWJSBJZJBV-AJNGGQMLSA-N 0.000 description 1
- 229960001945 sparteine Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 150000003455 sulfinic acids Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- JSPLKZUTYZBBKA-UHFFFAOYSA-N trioxidane Chemical compound OOO JSPLKZUTYZBBKA-UHFFFAOYSA-N 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 101150008351 ycf3 gene Proteins 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- QFDUTPNKBRXHTC-UHFFFAOYSA-N zinc diazide Chemical compound [Zn++].[N-]=[N+]=[N-].[N-]=[N+]=[N-] QFDUTPNKBRXHTC-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D207/04—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 having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—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 having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- 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
- C07D207/04—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 having no double bonds between ring members or between ring members and non-ring members
- C07D207/06—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 having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
-
- 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
- C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom 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
- C07D413/02—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
- 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
- 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
- C07D471/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention concerne des modulateurs de CCR3, de formule (I), ou leurs sels pharmaceutiquement acceptables, utiles dans la prévention de l'asthme et d'autres maladies allergiques.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11271798P | 1998-12-18 | 1998-12-18 | |
US60/112,717 | 1998-12-18 | ||
US16124399P | 1999-10-22 | 1999-10-22 | |
US60/161,243 | 1999-10-22 | ||
PCT/US1999/030332 WO2000035451A1 (fr) | 1998-12-18 | 1999-12-17 | N-ureidoalkyl-piperidines utilisees en tant que modulateurs de l'activite des recepteurs des chimiokines |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2350730A1 true CA2350730A1 (fr) | 2000-06-22 |
Family
ID=26810265
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CA002350730A Abandoned CA2350730A1 (fr) | 1998-12-18 | 1999-12-17 | N-ureidoalkyl-piperidines utilisees en tant que modulateurs de l'activite des recepteurs des chimiokines |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1140086A4 (fr) |
AU (1) | AU2057200A (fr) |
CA (1) | CA2350730A1 (fr) |
WO (1) | WO2000035451A1 (fr) |
Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
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US6525069B1 (en) | 1998-12-18 | 2003-02-25 | Bristol-Myers Squibb Pharma Co. | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
WO2000069432A1 (fr) | 1999-05-18 | 2000-11-23 | Teijin Limited | Moyens de traitement et de prevention contre les maladies associees a des chimiokines |
US7576117B1 (en) | 1999-08-04 | 2009-08-18 | Teijin Limited | Cyclic amine CCR3 antagonist |
SE9902987D0 (sv) | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
JP2003512349A (ja) | 1999-10-15 | 2003-04-02 | デュポン ファーマシューティカルズ カンパニー | ケモカイン受容体活性のモジュレーターとしてのベンジルシクロアルキルアミン |
US6784200B2 (en) | 2000-10-13 | 2004-08-31 | Bristol-Myers Squibb Pharma Company | Bicyclic and tricyclic amines as modulators of chemokine receptor activity |
CA2386049A1 (fr) | 1999-10-15 | 2001-04-26 | Daniel S. Gardner | Amines bicyliques et tricycliques en tant que modulateurs de l'activite du recepteur de chemokine |
CO5300399A1 (es) | 2000-02-25 | 2003-07-31 | Astrazeneca Ab | Heterocicliocs que contienen nitrogeno, proceso para su preparacion y composiciones farmaceuticas que los contienen |
AR028948A1 (es) | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
AR028947A1 (es) * | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
WO2001098268A2 (fr) | 2000-06-21 | 2001-12-27 | Bristol-Myers Squibb Pharma Company | Amides de piperidine utilises comme modulateurs de l'activite des recepteurs des chimiokines |
IL153123A0 (en) | 2000-06-30 | 2003-06-24 | Bristol Myers Squibb Co | N-ureidoheterocycloalkyl-piperidine derivatives and pharmaceutical compositions containing the same |
CN1678594A (zh) | 2000-09-29 | 2005-10-05 | 葛兰素集团有限公司 | 用于治疗炎性疾病的吗啉-乙酰胺衍生物 |
BR0116352A (pt) | 2000-12-19 | 2003-12-02 | Hoffmann La Roche | Pirrolidinas substituìdas como antagonistas de receptor ccr-3 |
CA2432527A1 (fr) * | 2000-12-22 | 2002-07-04 | Takeda Chemical Industries, Ltd. | Compositions medicinales s'administrant par voie orale |
GB0104050D0 (en) | 2001-02-19 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
AR035230A1 (es) | 2001-03-19 | 2004-05-05 | Astrazeneca Ab | Compuestos de bencimidazol, proceso para su preparacion, composicion farmaceutica, proceso para la preparacion de dicha composicion farmaceutica, y usos de estos compuestos para la elaboracion de medicamentos |
GB0107228D0 (en) | 2001-03-22 | 2001-05-16 | Astrazeneca Ab | Chemical compounds |
SE0101038D0 (sv) | 2001-03-23 | 2001-03-23 | Astrazeneca Ab | Novel compounds |
SE0103818D0 (sv) | 2001-11-15 | 2001-11-15 | Astrazeneca Ab | Chemical compounds |
DE60222015T2 (de) | 2001-11-30 | 2008-06-05 | F. Hoffmann-La Roche Ag | Ccr-3-rezeptorantagonisten vii |
US6977265B2 (en) | 2001-11-30 | 2005-12-20 | Roche Palo Alto Llc | Piperidine CCR-3 receptor antagonists |
RU2004120063A (ru) | 2001-11-30 | 2005-06-10 | Ф.Хоффманн-Ля Рош Аг (Ch) | Производные пиперазина для применения в качестве антагонистов рецетора ccr-3 при лечении астмы |
TW200303304A (en) | 2002-02-18 | 2003-09-01 | Astrazeneca Ab | Chemical compounds |
AU2003275257A1 (en) | 2002-09-26 | 2004-04-19 | Bristol-Myers Squibb Company | N-substituted heterocyclic amines as modulators of chemokine receptor activity |
MXPA05009771A (es) | 2003-03-14 | 2005-10-26 | Ono Pharmaceutical Co | Derivados heterociclicos que contienen nitrogeno y medicamentos que los contienen como el ingrediente activo. |
WO2004092169A1 (fr) | 2003-04-18 | 2004-10-28 | Ono Pharmaceutical Co., Ltd. | Compose de spiropiperidine et son utilisation medicinale |
ES2563304T3 (es) | 2003-04-24 | 2016-03-14 | Incyte Holdings Corporation | Derivados azaespiro alcano como inhibidores de metaloproteasas |
SE0301369D0 (sv) | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Chemical compounds |
US7351720B2 (en) | 2003-06-12 | 2008-04-01 | Bristol-Myers Squibb Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
US7291744B2 (en) | 2003-11-13 | 2007-11-06 | Bristol-Myers Squibb Company | N-ureidoalkyl-amino compounds as modulators of chemokine receptor activity |
SE0400208D0 (sv) | 2004-02-02 | 2004-02-02 | Astrazeneca Ab | Chemical compounds |
CN101775013A (zh) | 2004-09-13 | 2010-07-14 | 小野药品工业株式会社 | 含氮杂环衍生物及含有其作为活性成分的药物 |
EP1889622A4 (fr) | 2005-05-31 | 2009-12-23 | Ono Pharmaceutical Co | Compose de spiropiperidine et son utilisation medicinale |
TW200738634A (en) | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
US8318931B2 (en) | 2005-10-28 | 2012-11-27 | Ono Pharmaceutical Co., Ltd. | Chemokine receptor antagonists and use thereof |
PT1961744E (pt) | 2005-11-18 | 2013-05-15 | Ono Pharmaceutical Co | Composto que contém um grupo básico e sua utilização |
EP1995246A4 (fr) | 2006-03-10 | 2010-11-17 | Ono Pharmaceutical Co | Derive heterocyclique azote et agent pharmaceutique comprenant le derive en tant que principe actif |
WO2007132846A1 (fr) | 2006-05-16 | 2007-11-22 | Ono Pharmaceutical Co., Ltd. | Composé ayant un groupe acide qui peut être protégé et utilisation dudit composé |
WO2008016006A1 (fr) | 2006-07-31 | 2008-02-07 | Ono Pharmaceutical Co., Ltd. | Composé auquel un groupe cyclique est lié par une liaison spiro et son utilisation |
WO2010129351A1 (fr) | 2009-04-28 | 2010-11-11 | Schepens Eye Research Institute | Procédé pour identifier et pour traiter une dégénérescence maculaire liée à l'âge |
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Publication number | Priority date | Publication date | Assignee | Title |
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US3988294A (en) * | 1974-03-11 | 1976-10-26 | R. T. Vanderbilt Company, Inc. | Surface coating compositions containing antimicrobic ureas |
JP2826826B2 (ja) * | 1988-04-11 | 1998-11-18 | 日本ケミファ株式会社 | アルキレンジアミン誘導体 |
FR2641278B1 (fr) * | 1989-01-05 | 1991-03-22 | Lipha | Piperidines, procedes de preparation et medicaments les contenant |
IE903957A1 (en) * | 1989-11-06 | 1991-05-08 | Sanofi Sa | Aromatic amine compounds, their method of preparation and¹pharmaceutical compositions in which they are present |
IL99320A (en) * | 1990-09-05 | 1995-07-31 | Sanofi Sa | Arylalkylamines, their preparation and pharmaceutical preparations containing them |
EP0479601B1 (fr) * | 1990-10-05 | 1999-12-15 | Ajinomoto Co., Inc. | Dérivés de la pipéridine et leur application comme agents anti-arrhythmiques |
DK60893D0 (da) * | 1993-05-26 | 1993-05-26 | Novo Nordisk As | Piperidinderivater, deres fremstilling og anvendelse |
US5668151A (en) * | 1995-06-07 | 1997-09-16 | Bristol-Myers Squibb Company | Dihydropyridine NPY antagonists: piperidine derivatives |
GB9523526D0 (en) * | 1995-11-17 | 1996-01-17 | Zeneca Ltd | Therapeutic compounds |
IL125658A0 (en) * | 1997-08-18 | 1999-04-11 | Hoffmann La Roche | Ccr-3 receptor antagonists |
ATE280157T1 (de) * | 1998-11-17 | 2004-11-15 | Hoffmann La Roche | 4-aroyl-piperidin-ccr-3 rezeptor antagonisten iii |
-
1999
- 1999-12-17 AU AU20572/00A patent/AU2057200A/en not_active Abandoned
- 1999-12-17 EP EP99964297A patent/EP1140086A4/fr not_active Withdrawn
- 1999-12-17 CA CA002350730A patent/CA2350730A1/fr not_active Abandoned
- 1999-12-17 WO PCT/US1999/030332 patent/WO2000035451A1/fr not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
AU2057200A (en) | 2000-07-03 |
EP1140086A1 (fr) | 2001-10-10 |
WO2000035451A1 (fr) | 2000-06-22 |
EP1140086A4 (fr) | 2002-04-03 |
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