ZA200209904B

ZA200209904B - Novel compounds.

Novel compounds. Download PDF

Info

Publication number: ZA200209904B
Authority: ZA; South Africa
Prior art keywords: phenyl; compound; formula; acetamide; hydroxy
Prior art date: 2000-06-20

Application number

ZA200209904A

Other languages

English (en)

Inventor

Tomas Eriksson

Tesfaledet Mussie

Tomas Klingstedt

Original Assignee

Astrazeneca Ab

Priority date

2000-06-20

Filing date

2002-12-05

Publication date

2004-03-05

2002-12-05 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2004-03-05 Publication of ZA200209904B publication Critical patent/ZA200209904B/en

Links

150000001875 compounds Chemical class 0.000 title claims description 102
-1 nitro, carboxyl Chemical group 0.000 claims description 71
125000000217 alkyl group Chemical group 0.000 claims description 63
239000000203 mixture Substances 0.000 claims description 53
238000000034 method Methods 0.000 claims description 47
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 42
150000003839 salts Chemical class 0.000 claims description 41
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 40
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 40
239000012453 solvate Substances 0.000 claims description 40
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 32
229910052799 carbon Inorganic materials 0.000 claims description 29
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 26
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
201000010099 disease Diseases 0.000 claims description 24
125000003545 alkoxy group Chemical group 0.000 claims description 22
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 20
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 16
125000000623 heterocyclic group Chemical group 0.000 claims description 16
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
229910052757 nitrogen Inorganic materials 0.000 claims description 15
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 15
229920006395 saturated elastomer Polymers 0.000 claims description 15
238000004519 manufacturing process Methods 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 12
239000003814 drug Substances 0.000 claims description 11
125000004414 alkyl thio group Chemical group 0.000 claims description 9
125000004093 cyano group Chemical group *C#N 0.000 claims description 9
125000000753 cycloalkyl group Chemical group 0.000 claims description 9
125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
208000006673 asthma Diseases 0.000 claims description 8
125000001188 haloalkyl group Chemical group 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
230000008569 process Effects 0.000 claims description 8
238000011282 treatment Methods 0.000 claims description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
239000001301 oxygen Substances 0.000 claims description 7
125000001424 substituent group Chemical group 0.000 claims description 7
238000002560 therapeutic procedure Methods 0.000 claims description 7
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
125000006310 cycloalkyl amino group Chemical group 0.000 claims description 6
230000000694 effects Effects 0.000 claims description 6
125000004438 haloalkoxy group Chemical group 0.000 claims description 6
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
239000005864 Sulphur Chemical group 0.000 claims description 5
239000002671 adjuvant Substances 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
208000027866 inflammatory disease Diseases 0.000 claims description 5
125000003386 piperidinyl group Chemical group 0.000 claims description 5
102000009410 Chemokine receptor Human genes 0.000 claims description 4
108050000299 Chemokine receptor Proteins 0.000 claims description 4
229910052792 caesium Inorganic materials 0.000 claims description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
201000006417 multiple sclerosis Diseases 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
ZWHVZEVXTBVHKA-UHFFFAOYSA-N 2-[3-[[1-[(4-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1OCC(O)CNC1CCN(CC=2C=CC(F)=CC=2)CC1 ZWHVZEVXTBVHKA-UHFFFAOYSA-N 0.000 claims description 3
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 3
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000002947 alkylene group Chemical group 0.000 claims description 3
125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
238000002156 mixing Methods 0.000 claims description 3
OVJRIIXZEYSYCL-UHFFFAOYSA-N n-[2-[3-[[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(C)(O)CNC1CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 OVJRIIXZEYSYCL-UHFFFAOYSA-N 0.000 claims description 3
ROYXRRXTBDPMIB-UHFFFAOYSA-N n-[2-[3-[[1-[(3-chloro-4-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CNC1CCN(CC=2C=C(Cl)C(F)=CC=2)CC1 ROYXRRXTBDPMIB-UHFFFAOYSA-N 0.000 claims description 3
ZHFGLTBMIUEXKD-UHFFFAOYSA-N n-[2-[3-[[1-[(3-chloro-4-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]benzamide Chemical compound C=1C=CC=C(NC(=O)C=2C=CC=CC=2)C=1OCC(O)CNC(CC1)CCN1CC1=CC=C(F)C(Cl)=C1 ZHFGLTBMIUEXKD-UHFFFAOYSA-N 0.000 claims description 3
JNJDANVEPOEXLR-UHFFFAOYSA-N n-[2-[3-[[1-[(3-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]-3,5-dimethyl-1h-pyrrole-2-carboxamide Chemical compound N1C(C)=CC(C)=C1C(=O)NC1=CC=CC=C1OCC(O)CNC1CCN(CC=2C=C(Cl)C=CC=2)CC1 JNJDANVEPOEXLR-UHFFFAOYSA-N 0.000 claims description 3
GIEYOQOEWUNJGM-UHFFFAOYSA-N n-[2-[3-[[1-[(4-bromophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]-3,5-dimethyl-1h-pyrrole-2-carboxamide Chemical compound N1C(C)=CC(C)=C1C(=O)NC1=CC=CC=C1OCC(O)CNC1CCN(CC=2C=CC(Br)=CC=2)CC1 GIEYOQOEWUNJGM-UHFFFAOYSA-N 0.000 claims description 3
FYQVZTPVNNFPST-UHFFFAOYSA-N n-[2-[3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-6-fluorophenyl]acetamide Chemical compound CC(=O)NC1=C(F)C=CC=C1OCC(O)CNC1CCN(CC=2C=CC(Cl)=CC=2)CC1 FYQVZTPVNNFPST-UHFFFAOYSA-N 0.000 claims description 3
125000004043 oxo group Chemical group O=* 0.000 claims description 3
LSBDFXRDZJMBSC-UHFFFAOYSA-N Amide-Phenylacetic acid Natural products NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 claims description 2
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
235000010290 biphenyl Nutrition 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
125000001041 indolyl group Chemical group 0.000 claims description 2
125000000842 isoxazolyl group Chemical group 0.000 claims description 2
UHWWMQGKINJTML-XMMPIXPASA-N n-[2-[(2r)-3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OC[C@](C)(O)CNC1CCN(CC=2C=CC(Cl)=CC=2)CC1 UHWWMQGKINJTML-XMMPIXPASA-N 0.000 claims description 2
LYQPXPOTVRGEDB-UHFFFAOYSA-N n-[2-[3-[[1-[(4-bromophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(C)(O)CNC1CCN(CC=2C=CC(Br)=CC=2)CC1 LYQPXPOTVRGEDB-UHFFFAOYSA-N 0.000 claims description 2
NCRZBMXHPCBDHQ-UHFFFAOYSA-N n-[2-[3-[[1-[(4-bromophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CNC1CCN(CC=2C=CC(Br)=CC=2)CC1 NCRZBMXHPCBDHQ-UHFFFAOYSA-N 0.000 claims description 2
VKAWDNYVQDHWLT-UHFFFAOYSA-N n-[2-[3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]benzamide Chemical compound C=1C=CC=C(NC(=O)C=2C=CC=CC=2)C=1OCC(O)(C)CNC(CC1)CCN1CC1=CC=C(Cl)C=C1 VKAWDNYVQDHWLT-UHFFFAOYSA-N 0.000 claims description 2
JREWIIXZKFBBRF-UHFFFAOYSA-N n-[2-[3-[[1-[(4-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CNC1CCN(CC=2C=CC(F)=CC=2)CC1 JREWIIXZKFBBRF-UHFFFAOYSA-N 0.000 claims description 2
XBGPOFSOBGESNM-NRFANRHFSA-N n-[4-fluoro-2-[(2s)-3-[[1-[(4-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OC[C@@H](O)CNC1CCN(CC=2C=CC(F)=CC=2)CC1 XBGPOFSOBGESNM-NRFANRHFSA-N 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000003226 pyrazolyl group Chemical group 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000000168 pyrrolyl group Chemical group 0.000 claims description 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
125000001425 triazolyl group Chemical group 0.000 claims description 2
239000000126 substance Substances 0.000 claims 23
230000009286 beneficial effect Effects 0.000 claims 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
125000004429 atom Chemical group 0.000 claims 1
XZZCEIOLUHBWLL-NRFANRHFSA-N n-[2-[(2s)-3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-4-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OC[C@@H](O)CNC1CCN(CC=2C=CC(Cl)=CC=2)CC1 XZZCEIOLUHBWLL-NRFANRHFSA-N 0.000 claims 1
FBMVIPOJAIEMEQ-UHFFFAOYSA-N n-[2-[3-[[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-4-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(O)CNC1CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 FBMVIPOJAIEMEQ-UHFFFAOYSA-N 0.000 claims 1
DQKWBTYEFDDBCD-UHFFFAOYSA-N n-[2-[3-[[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]benzamide Chemical compound C=1C=CC=C(NC(=O)C=2C=CC=CC=2)C=1OCC(O)CNC(CC1)CCN1CC1=CC=C(Cl)C(Cl)=C1 DQKWBTYEFDDBCD-UHFFFAOYSA-N 0.000 claims 1
MBQWSRZWBXESPI-UHFFFAOYSA-N n-[2-[3-[[1-[(3,4-difluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(C)(O)CNC1CCN(CC=2C=C(F)C(F)=CC=2)CC1 MBQWSRZWBXESPI-UHFFFAOYSA-N 0.000 claims 1
XVXUQBGLPUEGPD-UHFFFAOYSA-N n-[2-[3-[[1-[(3,4-difluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CNC1CCN(CC=2C=C(F)C(F)=CC=2)CC1 XVXUQBGLPUEGPD-UHFFFAOYSA-N 0.000 claims 1
XXJAJULFILCYBG-UHFFFAOYSA-N n-[2-[3-[[1-[(3-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]-3,5-dimethyl-1h-pyrrole-2-carboxamide Chemical compound N1C(C)=CC(C)=C1C(=O)NC1=CC=CC=C1OCC(O)CNC1CCN(CC=2C=C(F)C=CC=2)CC1 XXJAJULFILCYBG-UHFFFAOYSA-N 0.000 claims 1
UHWWMQGKINJTML-UHFFFAOYSA-N n-[2-[3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(C)(O)CNC1CCN(CC=2C=CC(Cl)=CC=2)CC1 UHWWMQGKINJTML-UHFFFAOYSA-N 0.000 claims 1
IIOAUCXGBIQVDS-UHFFFAOYSA-N n-[3-acetyl-2-[3-[[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC(C(C)=O)=C1OCC(O)CNC1CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 IIOAUCXGBIQVDS-UHFFFAOYSA-N 0.000 claims 1
YILMPRHXSAYTAZ-UHFFFAOYSA-N n-[4-fluoro-2-[3-[[1-[(4-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(C)(O)CNC1CCN(CC=2C=CC(F)=CC=2)CC1 YILMPRHXSAYTAZ-UHFFFAOYSA-N 0.000 claims 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 83
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
239000000243 solution Substances 0.000 description 44
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 23
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
238000005160 1H NMR spectroscopy Methods 0.000 description 20
210000004027 cell Anatomy 0.000 description 20
235000019439 ethyl acetate Nutrition 0.000 description 20
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 18
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 18
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 17
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 17
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 17
150000002118 epoxides Chemical class 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 15
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 14
150000001412 amines Chemical class 0.000 description 14
239000002904 solvent Substances 0.000 description 13
229940093499 ethyl acetate Drugs 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 11
206010039083 rhinitis Diseases 0.000 description 10
239000007787 solid Substances 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
239000000460 chlorine Substances 0.000 description 8
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
XQGVQRPSTODODM-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrrole-2-carboxylic acid Chemical compound CC1=CC(C)=C(C(O)=O)N1 XQGVQRPSTODODM-UHFFFAOYSA-N 0.000 description 7
238000001704 evaporation Methods 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 7
102000019034 Chemokines Human genes 0.000 description 6
108010012236 Chemokines Proteins 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
230000035605 chemotaxis Effects 0.000 description 6
238000003818 flash chromatography Methods 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
239000000377 silicon dioxide Substances 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 5
239000000284 extract Substances 0.000 description 5
239000011737 fluorine Substances 0.000 description 5
229910052731 fluorine Inorganic materials 0.000 description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
OABOXRPGTFRBFZ-IMJSIDKUSA-N Cys-Cys Chemical compound SC[C@H](N)C(=O)N[C@@H](CS)C(O)=O OABOXRPGTFRBFZ-IMJSIDKUSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
239000012267 brine Substances 0.000 description 4
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
229910000024 caesium carbonate Inorganic materials 0.000 description 4
238000001816 cooling Methods 0.000 description 4
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
108010004073 cysteinylcysteine Proteins 0.000 description 4
125000006606 n-butoxy group Chemical group 0.000 description 4
125000006252 n-propylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 4
230000003287 optical effect Effects 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
239000007858 starting material Substances 0.000 description 4
CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
201000004624 Dermatitis Diseases 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 3
238000003556 assay Methods 0.000 description 3
208000010668 atopic eczema Diseases 0.000 description 3
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000002975 chemoattractant Substances 0.000 description 3
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 3
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
239000011630 iodine Substances 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
210000004072 lung Anatomy 0.000 description 3
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 3
208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
239000012071 phase Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
210000003491 skin Anatomy 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
MCGIQVVVGVAMEI-UHFFFAOYSA-N 1-[(3,4-dichlorophenyl)methyl]piperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=C(Cl)C(Cl)=C1 MCGIQVVVGVAMEI-UHFFFAOYSA-N 0.000 description 2
BIMZLZOTBSPLRM-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]piperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=C(Cl)C=C1 BIMZLZOTBSPLRM-UHFFFAOYSA-N 0.000 description 2
ADVGKWPZRIDURE-UHFFFAOYSA-N 2'-Hydroxyacetanilide Chemical compound CC(=O)NC1=CC=CC=C1O ADVGKWPZRIDURE-UHFFFAOYSA-N 0.000 description 2
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
JYNYZGTZSYGZFF-UHFFFAOYSA-N 2-[3-[[1-[(4-bromophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1OCC(O)CNC1CCN(CC=2C=CC(Br)=CC=2)CC1 JYNYZGTZSYGZFF-UHFFFAOYSA-N 0.000 description 2
OSBDKNMYPCZPAJ-UHFFFAOYSA-N 2-[3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1OCC(O)CNC1CCN(CC=2C=CC(Cl)=CC=2)CC1 OSBDKNMYPCZPAJ-UHFFFAOYSA-N 0.000 description 2
QOZLOYKAFDTQNU-UHFFFAOYSA-N 2-amino-3-fluorophenol Chemical compound NC1=C(O)C=CC=C1F QOZLOYKAFDTQNU-UHFFFAOYSA-N 0.000 description 2
BCKXMQIYWWTZDP-UHFFFAOYSA-N 2-hydroxy-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1O BCKXMQIYWWTZDP-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
208000030507 AIDS Diseases 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
201000001320 Atherosclerosis Diseases 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
206010014950 Eosinophilia Diseases 0.000 description 2
102000004890 Interleukin-8 Human genes 0.000 description 2
108090001007 Interleukin-8 Proteins 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
101100366940 Mus musculus Stom gene Proteins 0.000 description 2
241000721454 Pemphigus Species 0.000 description 2
102100036154 Platelet basic protein Human genes 0.000 description 2
239000012980 RPMI-1640 medium Substances 0.000 description 2
YITODUZHQFVOEZ-LLVKDONJSA-N [(2r)-2-methyloxiran-2-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@]1(C)OC1 YITODUZHQFVOEZ-LLVKDONJSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
230000000172 allergic effect Effects 0.000 description 2
WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
229940088710 antibiotic agent Drugs 0.000 description 2
230000001363 autoimmune Effects 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
238000004296 chiral HPLC Methods 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
108010035886 connective tissue-activating peptide Proteins 0.000 description 2
239000013058 crude material Substances 0.000 description 2
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
229960004132 diethyl ether Drugs 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
238000001035 drying Methods 0.000 description 2
239000012894 fetal calf serum Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000012737 fresh medium Substances 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
210000001035 gastrointestinal tract Anatomy 0.000 description 2
210000002216 heart Anatomy 0.000 description 2
XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 2
229940096397 interleukin-8 Drugs 0.000 description 2
229940047889 isobutyramide Drugs 0.000 description 2
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
206010025135 lupus erythematosus Diseases 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
239000002609 medium Substances 0.000 description 2
WWQLYMAILGXGDX-UHFFFAOYSA-N n-(2-fluoro-6-hydroxyphenyl)acetamide Chemical compound CC(=O)NC1=C(O)C=CC=C1F WWQLYMAILGXGDX-UHFFFAOYSA-N 0.000 description 2
UYKVWAQEMQDRGG-UHFFFAOYSA-N n-(2-hydroxyphenyl)benzamide Chemical compound OC1=CC=CC=C1NC(=O)C1=CC=CC=C1 UYKVWAQEMQDRGG-UHFFFAOYSA-N 0.000 description 2
XPODWBQYZVBKMF-UHFFFAOYSA-N n-[2-(oxiran-2-ylmethoxy)phenyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC1=CC=CC=C1OCC1CO1 XPODWBQYZVBKMF-UHFFFAOYSA-N 0.000 description 2
ASMACUZVQOCUAE-UHFFFAOYSA-N n-[2-[(2-methyloxiran-2-yl)methoxy]phenyl]benzamide Chemical compound C=1C=CC=C(NC(=O)C=2C=CC=CC=2)C=1OCC1(C)CO1 ASMACUZVQOCUAE-UHFFFAOYSA-N 0.000 description 2
SFSYBIMGDOACAY-UHFFFAOYSA-N n-[2-[3-[[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-5-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC(F)=CC=C1OCC(O)CNC1CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 SFSYBIMGDOACAY-UHFFFAOYSA-N 0.000 description 2
MNBLPGMJPDFOBA-UHFFFAOYSA-N n-[2-[3-[[1-[(3,4-difluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]benzamide Chemical compound C=1C=CC=C(NC(=O)C=2C=CC=CC=2)C=1OCC(O)CNC(CC1)CCN1CC1=CC=C(F)C(F)=C1 MNBLPGMJPDFOBA-UHFFFAOYSA-N 0.000 description 2
NACXBKZWHYBDEL-UHFFFAOYSA-N n-[2-[3-[[1-[(3-chloro-4-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(C)(O)CNC1CCN(CC=2C=C(Cl)C(F)=CC=2)CC1 NACXBKZWHYBDEL-UHFFFAOYSA-N 0.000 description 2
BEDLBOVTEKQZCR-UHFFFAOYSA-N n-[2-[3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-4-methoxyphenyl]acetamide Chemical compound COC1=CC=C(NC(C)=O)C(OCC(O)CNC2CCN(CC=3C=CC(Cl)=CC=3)CC2)=C1 BEDLBOVTEKQZCR-UHFFFAOYSA-N 0.000 description 2
KPPHYQMDMZRERL-UHFFFAOYSA-N n-[2-[3-[[1-[(4-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-6-methylphenyl]acetamide Chemical compound CC(=O)NC1=C(C)C=CC=C1OCC(O)CNC1CCN(CC=2C=CC(F)=CC=2)CC1 KPPHYQMDMZRERL-UHFFFAOYSA-N 0.000 description 2
210000000440 neutrophil Anatomy 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
239000000843 powder Substances 0.000 description 2
ODNFVADIRXKBCY-UHFFFAOYSA-N pyrrolidin-1-yl carbamate Chemical compound NC(=O)ON1CCCC1 ODNFVADIRXKBCY-UHFFFAOYSA-N 0.000 description 2
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical class [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
238000003756 stirring Methods 0.000 description 2
230000009885 systemic effect Effects 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
125000003944 tolyl group Chemical group 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
AAVHHYWBSVSPPN-UHFFFAOYSA-N (2-methyloxiran-2-yl)methanol Chemical compound OCC1(C)CO1 AAVHHYWBSVSPPN-UHFFFAOYSA-N 0.000 description 1
SMKKEOQDQNCTGL-ZETCQYMHSA-N (2s)-2-[(2-nitrophenoxy)methyl]oxirane Chemical compound [O-][N+](=O)C1=CC=CC=C1OC[C@H]1OC1 SMKKEOQDQNCTGL-ZETCQYMHSA-N 0.000 description 1
GLXIMRGOPABCGC-LLVKDONJSA-N (3r)-1-[(4-chlorophenyl)methyl]pyrrolidin-3-amine Chemical compound C1[C@H](N)CCN1CC1=CC=C(Cl)C=C1 GLXIMRGOPABCGC-LLVKDONJSA-N 0.000 description 1
NBIOUVFLTIZZER-UHFFFAOYSA-N 1,2-dichloro-4-(chloromethyl)benzene;1-[(3,4-dichlorophenyl)methyl]piperidin-4-amine Chemical compound ClCC1=CC=C(Cl)C(Cl)=C1.C1CC(N)CCN1CC1=CC=C(Cl)C(Cl)=C1 NBIOUVFLTIZZER-UHFFFAOYSA-N 0.000 description 1
SSNCMIDZGFCTST-UHFFFAOYSA-N 1,3-difluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=C(F)C=CC=C1F SSNCMIDZGFCTST-UHFFFAOYSA-N 0.000 description 1
WNQXIWMYWRHSNU-UHFFFAOYSA-N 1-[(3,4-difluorophenyl)methyl]piperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=C(F)C(F)=C1 WNQXIWMYWRHSNU-UHFFFAOYSA-N 0.000 description 1
ALGMTGVLDUQQSJ-UHFFFAOYSA-N 1-[(3-chloro-4-fluorophenyl)methyl]piperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=C(F)C(Cl)=C1 ALGMTGVLDUQQSJ-UHFFFAOYSA-N 0.000 description 1
DDPNUBVUABSUEG-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]piperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=C(Br)C=C1 DDPNUBVUABSUEG-UHFFFAOYSA-N 0.000 description 1
DCEXCMVFRCTUOL-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]piperidine Chemical compound C1=CC(Cl)=CC=C1CN1CCCCC1 DCEXCMVFRCTUOL-UHFFFAOYSA-N 0.000 description 1
KRIHULMCWJRKQE-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=C(F)C=C1 KRIHULMCWJRKQE-UHFFFAOYSA-N 0.000 description 1
YUBDLZGUSSWQSS-UHFFFAOYSA-N 1-benzylpiperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=CC=C1 YUBDLZGUSSWQSS-UHFFFAOYSA-N 0.000 description 1
YLRBJYMANQKEAW-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)benzene Chemical compound BrCC1=CC=C(Br)C=C1 YLRBJYMANQKEAW-UHFFFAOYSA-N 0.000 description 1
JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 1
VVHFXJOCUKBZFS-UHFFFAOYSA-N 2-(chloromethyl)-2-methyloxirane Chemical compound ClCC1(C)CO1 VVHFXJOCUKBZFS-UHFFFAOYSA-N 0.000 description 1
PTHRRXYZMDTTOA-UHFFFAOYSA-N 2-[2-(oxiran-2-ylmethoxy)phenyl]acetamide Chemical compound NC(=O)CC1=CC=CC=C1OCC1OC1 PTHRRXYZMDTTOA-UHFFFAOYSA-N 0.000 description 1
CNEBJKQGOODBFD-UHFFFAOYSA-N 2-[3-[[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1OCC(O)CNC1CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 CNEBJKQGOODBFD-UHFFFAOYSA-N 0.000 description 1
FRIBMENBGGCKPD-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)prop-2-enal Chemical compound COC1=CC=CC(C=CC=O)=C1OC FRIBMENBGGCKPD-UHFFFAOYSA-N 0.000 description 1
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
229960000549 4-dimethylaminophenol Drugs 0.000 description 1
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
208000035939 Alveolitis allergic Diseases 0.000 description 1
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
201000008283 Atrophic Rhinitis Diseases 0.000 description 1
102100022718 Atypical chemokine receptor 2 Human genes 0.000 description 1
208000009137 Behcet syndrome Diseases 0.000 description 1
102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 1
101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 1
101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 1
102100037853 C-C chemokine receptor type 4 Human genes 0.000 description 1
101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 1
102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 1
102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 1
102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 1
102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
102100032366 C-C motif chemokine 7 Human genes 0.000 description 1
101710155834 C-C motif chemokine 7 Proteins 0.000 description 1
102100034871 C-C motif chemokine 8 Human genes 0.000 description 1
101710155833 C-C motif chemokine 8 Proteins 0.000 description 1
102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 1
102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 1
102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
102000001902 CC Chemokines Human genes 0.000 description 1
108010040471 CC Chemokines Proteins 0.000 description 1
108050006947 CXC Chemokine Proteins 0.000 description 1
102000019388 CXC chemokine Human genes 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
208000015943 Coeliac disease Diseases 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
206010010744 Conjunctivitis allergic Diseases 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
201000003883 Cystic fibrosis Diseases 0.000 description 1
206010012442 Dermatitis contact Diseases 0.000 description 1
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
102100023688 Eotaxin Human genes 0.000 description 1
101710139422 Eotaxin Proteins 0.000 description 1
BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
206010014989 Epidermolysis bullosa Diseases 0.000 description 1
206010015150 Erythema Diseases 0.000 description 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
208000027445 Farmer Lung Diseases 0.000 description 1
206010016228 Fasciitis Diseases 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
208000005577 Gastroenteritis Diseases 0.000 description 1
239000007821 HATU Substances 0.000 description 1
208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 1
101000777558 Homo sapiens C-C chemokine receptor type 10 Proteins 0.000 description 1
101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 1
101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 1
101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 1
101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 1
101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 1
206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
108010018951 Interleukin-8B Receptors Proteins 0.000 description 1
208000009388 Job Syndrome Diseases 0.000 description 1
206010024227 Lepromatous leprosy Diseases 0.000 description 1
102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 1
108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
102000014962 Monocyte Chemoattractant Proteins Human genes 0.000 description 1
108010064136 Monocyte Chemoattractant Proteins Proteins 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
206010028735 Nasal congestion Diseases 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
206010029164 Nephrotic syndrome Diseases 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
206010036774 Proctitis Diseases 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
201000001263 Psoriatic Arthritis Diseases 0.000 description 1
208000036824 Psoriatic arthropathy Diseases 0.000 description 1
208000033464 Reiter syndrome Diseases 0.000 description 1
206010039088 Rhinitis atrophic Diseases 0.000 description 1
208000036284 Rhinitis seasonal Diseases 0.000 description 1
206010039491 Sarcoma Diseases 0.000 description 1
206010040047 Sepsis Diseases 0.000 description 1
208000009359 Sezary Syndrome Diseases 0.000 description 1
208000021388 Sezary disease Diseases 0.000 description 1
208000021386 Sjogren Syndrome Diseases 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
201000009594 Systemic Scleroderma Diseases 0.000 description 1
206010042953 Systemic sclerosis Diseases 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
208000024780 Urticaria Diseases 0.000 description 1
206010046851 Uveitis Diseases 0.000 description 1
206010047112 Vasculitides Diseases 0.000 description 1
206010047115 Vasculitis Diseases 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000012190 activator Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
208000002205 allergic conjunctivitis Diseases 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
230000007815 allergy Effects 0.000 description 1
208000004631 alopecia areata Diseases 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
230000033115 angiogenesis Effects 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
210000001185 bone marrow Anatomy 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
230000012292 cell migration Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
208000017760 chronic graft versus host disease Diseases 0.000 description 1
201000009151 chronic rhinitis Diseases 0.000 description 1
208000010247 contact dermatitis Diseases 0.000 description 1
210000004087 cornea Anatomy 0.000 description 1
239000012043 crude product Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000004802 cyanophenyl group Chemical group 0.000 description 1
230000006378 damage Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
XEBCWEDRGPSHQH-YUMQZZPRSA-N dipropan-2-yl (2s,3s)-2,3-dihydroxybutanedioate Chemical compound CC(C)OC(=O)[C@@H](O)[C@H](O)C(=O)OC(C)C XEBCWEDRGPSHQH-YUMQZZPRSA-N 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
238000009509 drug development Methods 0.000 description 1
239000000428 dust Substances 0.000 description 1
231100000321 erythema Toxicity 0.000 description 1
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
IZSBSZYFPYIJDI-UHFFFAOYSA-N ethyl 3,5-dimethyl-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C=1NC(C)=CC=1C IZSBSZYFPYIJDI-UHFFFAOYSA-N 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
208000022195 farmer lung disease Diseases 0.000 description 1
235000013305 food Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
206010051040 hyper-IgE syndrome Diseases 0.000 description 1
230000003463 hyperproliferative effect Effects 0.000 description 1
230000004047 hyperresponsiveness Effects 0.000 description 1
230000001969 hypertrophic effect Effects 0.000 description 1
230000028993 immune response Effects 0.000 description 1
208000033065 inborn errors of immunity Diseases 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000028709 inflammatory response Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
208000014674 injury Diseases 0.000 description 1
229940030980 inova Drugs 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000002427 irreversible effect Effects 0.000 description 1
229960004592 isopropanol Drugs 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
239000010410 layer Substances 0.000 description 1
201000010260 leiomyoma Diseases 0.000 description 1
201000011486 lichen planus Diseases 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
208000008585 mastocytosis Diseases 0.000 description 1
AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
206010028417 myasthenia gravis Diseases 0.000 description 1
201000005962 mycosis fungoides Diseases 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
PHOAIOPTKPVQOB-UHFFFAOYSA-N n-(2-hydroxy-4-methoxyphenyl)acetamide Chemical compound COC1=CC=C(NC(C)=O)C(O)=C1 PHOAIOPTKPVQOB-UHFFFAOYSA-N 0.000 description 1
HTVPAACTHAQQAS-UHFFFAOYSA-N n-(2-hydroxy-4-methylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(C)C=C1O HTVPAACTHAQQAS-UHFFFAOYSA-N 0.000 description 1
NEOWELJZRVSZFJ-UHFFFAOYSA-N n-(2-hydroxy-6-methylphenyl)acetamide Chemical compound CC(=O)NC1=C(C)C=CC=C1O NEOWELJZRVSZFJ-UHFFFAOYSA-N 0.000 description 1
SENIMHNFLVMDJV-UHFFFAOYSA-N n-[2-(oxiran-2-ylmethoxy)phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC1OC1 SENIMHNFLVMDJV-UHFFFAOYSA-N 0.000 description 1
UHWWMQGKINJTML-DEOSSOPVSA-N n-[2-[(2s)-3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OC[C@@](C)(O)CNC1CCN(CC=2C=CC(Cl)=CC=2)CC1 UHWWMQGKINJTML-DEOSSOPVSA-N 0.000 description 1
XZZZCTNRNINFIV-NRFANRHFSA-N n-[2-[(2s)-3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OC[C@@H](O)CNC1CCN(CC=2C=CC(Cl)=CC=2)CC1 XZZZCTNRNINFIV-NRFANRHFSA-N 0.000 description 1
VCFZUDKMHJJFCH-UHFFFAOYSA-N n-[2-[3-[[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC=C1OCC(O)CNC1CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 VCFZUDKMHJJFCH-UHFFFAOYSA-N 0.000 description 1
RZZMEDRZZKDEKU-UHFFFAOYSA-N n-[2-[3-[[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-6-methylphenyl]acetamide Chemical compound CC(=O)NC1=C(C)C=CC=C1OCC(O)CNC1CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 RZZMEDRZZKDEKU-UHFFFAOYSA-N 0.000 description 1
CYSCAVXFUNWUFH-UHFFFAOYSA-N n-[2-[3-[[1-[(4-bromophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]benzamide Chemical compound C=1C=CC=C(NC(=O)C=2C=CC=CC=2)C=1OCC(O)(C)CNC(CC1)CCN1CC1=CC=C(Br)C=C1 CYSCAVXFUNWUFH-UHFFFAOYSA-N 0.000 description 1
XZZCEIOLUHBWLL-UHFFFAOYSA-N n-[2-[3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-4-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(O)CNC1CCN(CC=2C=CC(Cl)=CC=2)CC1 XZZCEIOLUHBWLL-UHFFFAOYSA-N 0.000 description 1
YWCRNYCJOLGBBS-UHFFFAOYSA-N n-[2-[3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC=C1OCC(O)CNC1CCN(CC=2C=CC(Cl)=CC=2)CC1 YWCRNYCJOLGBBS-UHFFFAOYSA-N 0.000 description 1
OTSQSUHXXKRRPY-UHFFFAOYSA-N n-[2-[3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]phenyl]benzamide Chemical compound C=1C=CC=C(NC(=O)C=2C=CC=CC=2)C=1OCC(O)CNC(CC1)CCN1CC1=CC=C(Cl)C=C1 OTSQSUHXXKRRPY-UHFFFAOYSA-N 0.000 description 1
JHINGSHMHAREOG-UHFFFAOYSA-N n-[2-[3-[[1-[(4-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(C)(O)CNC1CCN(CC=2C=CC(F)=CC=2)CC1 JHINGSHMHAREOG-UHFFFAOYSA-N 0.000 description 1
AKFLRPNJJJZUED-UHFFFAOYSA-N n-[2-[3-[[1-[(4-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]benzamide Chemical compound C=1C=CC=C(NC(=O)C=2C=CC=CC=2)C=1OCC(O)(C)CNC(CC1)CCN1CC1=CC=C(F)C=C1 AKFLRPNJJJZUED-UHFFFAOYSA-N 0.000 description 1
HNRGYRDDEBEHOH-UHFFFAOYSA-N n-[2-[3-[[1-[(4-fluorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxypropoxy]-4-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C=C1OCC(O)CNC1CCN(CC=2C=CC(F)=CC=2)CC1 HNRGYRDDEBEHOH-UHFFFAOYSA-N 0.000 description 1
OQZXFSZBCFKHMX-UHFFFAOYSA-N n-[2-fluoro-6-(oxiran-2-ylmethoxy)phenyl]acetamide Chemical compound CC(=O)NC1=C(F)C=CC=C1OCC1OC1 OQZXFSZBCFKHMX-UHFFFAOYSA-N 0.000 description 1
ATQSLKHGSWFGIB-UHFFFAOYSA-N n-[4-methoxy-2-(oxiran-2-ylmethoxy)phenyl]acetamide Chemical compound COC1=CC=C(NC(C)=O)C(OCC2OC2)=C1 ATQSLKHGSWFGIB-UHFFFAOYSA-N 0.000 description 1
IYQNZAROPVZDKE-UHFFFAOYSA-N n-[4-methyl-2-(oxiran-2-ylmethoxy)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C=C1OCC1OC1 IYQNZAROPVZDKE-UHFFFAOYSA-N 0.000 description 1
XYNZOQAPGUNBDC-UHFFFAOYSA-N n-methyl-2-(oxiran-2-ylmethoxy)benzamide Chemical compound CNC(=O)C1=CC=CC=C1OCC1OC1 XYNZOQAPGUNBDC-UHFFFAOYSA-N 0.000 description 1
VBWWRHGQADUAFE-UHFFFAOYSA-N n-methyl-2-[(2-methyloxiran-2-yl)methoxy]benzamide Chemical compound CNC(=O)C1=CC=CC=C1OCC1(C)OC1 VBWWRHGQADUAFE-UHFFFAOYSA-N 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000007170 pathology Effects 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
208000028529 primary immunodeficiency disease Diseases 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000000746 purification Methods 0.000 description 1
208000002574 reactive arthritis Diseases 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
201000000306 sarcoidosis Diseases 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000012265 solid product Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
201000005671 spondyloarthropathy Diseases 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
JHYOUOHNCPGQOS-UHFFFAOYSA-N tert-butyl 3-hydroxypiperidine-1-carboxylate;3-(4-chlorophenoxy)piperidine Chemical compound CC(C)(C)OC(=O)N1CCCC(O)C1.C1=CC(Cl)=CC=C1OC1CNCCC1 JHYOUOHNCPGQOS-UHFFFAOYSA-N 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
208000001319 vasomotor rhinitis Diseases 0.000 description 1
201000005539 vernal conjunctivitis Diseases 0.000 description 1