AU2007292347A1 - Heteroaromatic compounds having sphingosine-1-phosphate (S1P) receptor agonist and/or antagonist biological activity - Google Patents

Heteroaromatic compounds having sphingosine-1-phosphate (S1P) receptor agonist and/or antagonist biological activity Download PDF

Info

Publication number: AU2007292347A1
Authority: AU; Australia
Prior art keywords: compound; mmol; group; phenyl; ethyl
Prior art date: 2006-09-07
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

Application number

AU2007292347A

Other languages

English (en)

Inventor

Richard L. Beard

John E. Donello

Xiaoxia Liu

Haiqing Yuan

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Allergan Inc

Original Assignee

Allergan Inc

Priority date (The priority date 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 date listed.)

2006-09-07

Filing date

2007-09-05

Publication date

2008-03-13

2007-09-05 Application filed by Allergan Inc filed Critical Allergan Inc

2008-03-13 Publication of AU2007292347A1 publication Critical patent/AU2007292347A1/en

Status Abandoned legal-status Critical Current

Links

DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 title description 20
230000004071 biological effect Effects 0.000 title description 5
229940044601 receptor agonist Drugs 0.000 title description 3
239000000018 receptor agonist Substances 0.000 title description 3
150000002390 heteroarenes Chemical class 0.000 title description 2
239000002464 receptor antagonist Substances 0.000 title description 2
229940044551 receptor antagonist Drugs 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 164
125000000217 alkyl group Chemical group 0.000 claims description 34
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
229910052739 hydrogen Inorganic materials 0.000 claims description 29
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
125000003118 aryl group Chemical group 0.000 claims description 25
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
125000004432 carbon atom Chemical group C* 0.000 claims description 11
125000005843 halogen group Chemical group 0.000 claims description 11
125000004076 pyridyl group Chemical group 0.000 claims description 11
230000000694 effects Effects 0.000 claims description 9
125000001072 heteroaryl group Chemical group 0.000 claims description 9
229910052757 nitrogen Inorganic materials 0.000 claims description 9
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 8
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
125000002541 furyl group Chemical group 0.000 claims description 7
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
125000005907 alkyl ester group Chemical group 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
125000006413 ring segment Chemical group 0.000 claims description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000005157 alkyl carboxy group Chemical group 0.000 claims description 4
150000005215 alkyl ethers Chemical class 0.000 claims description 4
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
102000005962 receptors Human genes 0.000 claims description 4
108020003175 receptors Proteins 0.000 claims description 4
239000005557 antagonist Substances 0.000 claims description 3
150000005840 aryl radicals Chemical class 0.000 claims description 3
150000003839 salts Chemical class 0.000 claims description 3
125000004414 alkyl thio group Chemical group 0.000 claims 3
108091008585 IP3 receptors Proteins 0.000 claims 1
102000007640 Inositol 1,4,5-Trisphosphate Receptors Human genes 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 159
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 112
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 93
238000000034 method Methods 0.000 description 72
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
238000005481 NMR spectroscopy Methods 0.000 description 46
239000007787 solid Substances 0.000 description 46
239000000243 solution Substances 0.000 description 43
235000019439 ethyl acetate Nutrition 0.000 description 38
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
239000000203 mixture Substances 0.000 description 28
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
239000003921 oil Substances 0.000 description 22
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
238000006243 chemical reaction Methods 0.000 description 19
239000000741 silica gel Substances 0.000 description 19
229910002027 silica gel Inorganic materials 0.000 description 19
238000004440 column chromatography Methods 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
210000004027 cell Anatomy 0.000 description 17
-1 hydrocarbyl radical Chemical class 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000011734 sodium Substances 0.000 description 14
239000002904 solvent Substances 0.000 description 13
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 11
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 11
239000012267 brine Substances 0.000 description 11
229940079593 drug Drugs 0.000 description 11
239000003814 drug Substances 0.000 description 11
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 11
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 11
229910052786 argon Inorganic materials 0.000 description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
239000000047 product Substances 0.000 description 10
UDJZTGMLYITLIQ-UHFFFAOYSA-N 1-ethenylpyrrolidine Chemical compound C=CN1CCCC1 UDJZTGMLYITLIQ-UHFFFAOYSA-N 0.000 description 9
208000004454 Hyperalgesia Diseases 0.000 description 9
241000700159 Rattus Species 0.000 description 9
229940127573 compound 38 Drugs 0.000 description 9
PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
150000003408 sphingolipids Chemical class 0.000 description 9
125000001424 substituent group Chemical group 0.000 description 9
GSZQTIFGANBTNF-UHFFFAOYSA-N (3-aminopropyl)phosphonic acid Chemical compound NCCCP(O)(O)=O GSZQTIFGANBTNF-UHFFFAOYSA-N 0.000 description 8
238000005160 1H NMR spectroscopy Methods 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
229910052717 sulfur Inorganic materials 0.000 description 8
IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 7
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
125000003545 alkoxy group Chemical group 0.000 description 7
210000004369 blood Anatomy 0.000 description 7
239000008280 blood Substances 0.000 description 7
229940125807 compound 37 Drugs 0.000 description 7
125000004093 cyano group Chemical group *C#N 0.000 description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 6
HEJNSWMMYRXBQA-UHFFFAOYSA-N 5-(4-ethylphenyl)-6-phenylpyridine-2-carbaldehyde Chemical compound C1=CC(CC)=CC=C1C1=CC=C(C=O)N=C1C1=CC=CC=C1 HEJNSWMMYRXBQA-UHFFFAOYSA-N 0.000 description 6
208000002193 Pain Diseases 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
125000003342 alkenyl group Chemical group 0.000 description 6
125000000304 alkynyl group Chemical group 0.000 description 6
125000001309 chloro group Chemical group Cl* 0.000 description 6
229940125773 compound 10 Drugs 0.000 description 6
229910052736 halogen Inorganic materials 0.000 description 6
150000002367 halogens Chemical class 0.000 description 6
JYJVVHFRSFVEJM-UHFFFAOYSA-N iodosobenzene Chemical compound O=IC1=CC=CC=C1 JYJVVHFRSFVEJM-UHFFFAOYSA-N 0.000 description 6
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 6
230000004044 response Effects 0.000 description 6
WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 6
UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 5
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
239000012981 Hank's balanced salt solution Substances 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
125000002877 alkyl aryl group Chemical group 0.000 description 5
206010053552 allodynia Diseases 0.000 description 5
229940106189 ceramide Drugs 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
210000002683 foot Anatomy 0.000 description 5
230000006870 function Effects 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
238000007912 intraperitoneal administration Methods 0.000 description 5
239000002207 metabolite Substances 0.000 description 5
229910052760 oxygen Inorganic materials 0.000 description 5
239000001301 oxygen Chemical group 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
150000003410 sphingosines Chemical class 0.000 description 5
239000000126 substance Substances 0.000 description 5
239000011593 sulfur Substances 0.000 description 5
238000001356 surgical procedure Methods 0.000 description 5
239000000725 suspension Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 5
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 5
AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 4
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GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 4
GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 4
IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 4
WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 4
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 4
VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
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OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
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QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 4
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CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
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LINCCPXNUQSLQT-JEZZUBLBSA-N ethyl (2z,4e)-2-azido-5-(4-ethylphenyl)penta-2,4-dienoate Chemical compound CCOC(=O)C(\N=[N+]=[N-])=C\C=C\C1=CC=C(CC)C=C1 LINCCPXNUQSLQT-JEZZUBLBSA-N 0.000 description 1
HVJJYOAPXBPQQV-UHFFFAOYSA-N ethyl 2-azidoacetate Chemical compound CCOC(=O)CN=[N+]=[N-] HVJJYOAPXBPQQV-UHFFFAOYSA-N 0.000 description 1
GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
DMTGCDBJTBYYFD-UHFFFAOYSA-N ethyl 3-ethyl-5-(4-ethylphenyl)-6-phenylpyridine-2-carboxylate Chemical compound C=1C=C(CC)C=CC=1C=1C=C(CC)C(C(=O)OCC)=NC=1C1=CC=CC=C1 DMTGCDBJTBYYFD-UHFFFAOYSA-N 0.000 description 1
MZQVMTSGGKJDGG-UHFFFAOYSA-N ethyl 5-(4-ethylphenyl)-6-[4-(trifluoromethyl)phenyl]pyridine-2-carboxylate Chemical compound C=1C=C(C(F)(F)F)C=CC=1C1=NC(C(=O)OCC)=CC=C1C1=CC=C(CC)C=C1 MZQVMTSGGKJDGG-UHFFFAOYSA-N 0.000 description 1
CVFDCTDEKVQCTR-UHFFFAOYSA-N ethyl 5-(4-ethylphenyl)-6-pyridin-4-ylpyridine-2-carboxylate Chemical compound C=1C=NC=CC=1C1=NC(C(=O)OCC)=CC=C1C1=CC=C(CC)C=C1 CVFDCTDEKVQCTR-UHFFFAOYSA-N 0.000 description 1
LJANWTICFGFJCK-UHFFFAOYSA-N ethyl 5-(4-nonylphenyl)-6-phenyl-1,2,4-triazine-3-carboxylate Chemical compound C1=CC(CCCCCCCCC)=CC=C1C1=NC(C(=O)OCC)=NN=C1C1=CC=CC=C1 LJANWTICFGFJCK-UHFFFAOYSA-N 0.000 description 1
AFFNOJRGQWQRPO-UHFFFAOYSA-N ethyl 5-phenyl-6-[4-(trifluoromethyl)phenyl]-1,2,4-triazine-3-carboxylate Chemical compound C=1C=CC=CC=1C1=NC(C(=O)OCC)=NN=C1C1=CC=C(C(F)(F)F)C=C1 AFFNOJRGQWQRPO-UHFFFAOYSA-N 0.000 description 1
KKCXESMHTNITNC-UHFFFAOYSA-N ethyl 5-phenyl-6-[4-(trifluoromethyl)phenyl]pyridine-2-carboxylate Chemical compound C=1C=C(C(F)(F)F)C=CC=1C1=NC(C(=O)OCC)=CC=C1C1=CC=CC=C1 KKCXESMHTNITNC-UHFFFAOYSA-N 0.000 description 1
FTPPVIANLWFRLC-UHFFFAOYSA-N ethyl 6-(4-methylphenyl)-5-phenyl-1,2,4-triazine-3-carboxylate Chemical compound C=1C=CC=CC=1C1=NC(C(=O)OCC)=NN=C1C1=CC=C(C)C=C1 FTPPVIANLWFRLC-UHFFFAOYSA-N 0.000 description 1
VURNZXPJTCKLNG-UHFFFAOYSA-N ethyl 6-(4-methylphenyl)-5-phenylpyridine-2-carboxylate Chemical compound C=1C=C(C)C=CC=1C1=NC(C(=O)OCC)=CC=C1C1=CC=CC=C1 VURNZXPJTCKLNG-UHFFFAOYSA-N 0.000 description 1
LHPSKRQIZKUCOX-UHFFFAOYSA-N ethyl 6-(4-nonylphenyl)-5-phenyl-1,2,4-triazine-3-carboxylate Chemical compound C1=CC(CCCCCCCCC)=CC=C1C1=NN=C(C(=O)OCC)N=C1C1=CC=CC=C1 LHPSKRQIZKUCOX-UHFFFAOYSA-N 0.000 description 1
MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
238000001914 filtration Methods 0.000 description 1
KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 description 1
229960000556 fingolimod Drugs 0.000 description 1
238000000684 flow cytometry Methods 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
JVZRCNQLWOELDU-UHFFFAOYSA-N gamma-Phenylpyridine Natural products C1=CC=CC=C1C1=CC=NC=C1 JVZRCNQLWOELDU-UHFFFAOYSA-N 0.000 description 1
238000003304 gavage Methods 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
230000036541 health Effects 0.000 description 1
230000009067 heart development Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
230000002489 hematologic effect Effects 0.000 description 1
230000023597 hemostasis Effects 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
239000012456 homogeneous solution Substances 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
208000026278 immune system disease Diseases 0.000 description 1
230000036039 immunity Effects 0.000 description 1
230000001506 immunosuppresive effect Effects 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000000411 inducer Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000003993 interaction Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000011835 investigation Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 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
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
230000000329 lymphopenic effect Effects 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000003550 marker Substances 0.000 description 1
230000035800 maturation Effects 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
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230000037353 metabolic pathway Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
CSJDCSCTVDEHRN-UHFFFAOYSA-N methane;molecular oxygen Chemical compound C.O=O CSJDCSCTVDEHRN-UHFFFAOYSA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
WKHRVPOYSLPHDF-UHFFFAOYSA-N methyl 5,6-diphenyl-1,2,4-triazine-3-carboxylate Chemical compound C=1C=CC=CC=1C1=NC(C(=O)OC)=NN=C1C1=CC=CC=C1 WKHRVPOYSLPHDF-UHFFFAOYSA-N 0.000 description 1
KZLIUCKOXMEOCU-UHFFFAOYSA-N methyl 5-(4-ethylphenyl)-3-methyl-6-phenylpyridine-2-carboxylate Chemical compound C1=CC(CC)=CC=C1C1=CC(C)=C(C(=O)OC)N=C1C1=CC=CC=C1 KZLIUCKOXMEOCU-UHFFFAOYSA-N 0.000 description 1
HOCTYKSTLURCBQ-UHFFFAOYSA-N methyl 5-(4-ethylphenyl)-6-[4-(trifluoromethyl)phenyl]pyridine-2-carboxylate Chemical compound C1=CC(CC)=CC=C1C1=CC=C(C(=O)OC)N=C1C1=CC=C(C(F)(F)F)C=C1 HOCTYKSTLURCBQ-UHFFFAOYSA-N 0.000 description 1
WPBTUBQLQDWZQR-UHFFFAOYSA-N methyl 5-(4-ethylphenyl)-6-phenylpyridine-2-carboxylate Chemical compound C1=CC(CC)=CC=C1C1=CC=C(C(=O)OC)N=C1C1=CC=CC=C1 WPBTUBQLQDWZQR-UHFFFAOYSA-N 0.000 description 1
YFCNSOYLKZQAHN-UHFFFAOYSA-N methyl 5-(4-ethylphenyl)-6-pyridin-4-ylpyridine-2-carboxylate Chemical compound C1=CC(CC)=CC=C1C1=CC=C(C(=O)OC)N=C1C1=CC=NC=C1 YFCNSOYLKZQAHN-UHFFFAOYSA-N 0.000 description 1
HHTJSCIRSQCPEX-UHFFFAOYSA-N methyl 5-(4-methylphenyl)-6-phenylpyridine-2-carboxylate Chemical compound C=1C=CC=CC=1C1=NC(C(=O)OC)=CC=C1C1=CC=C(C)C=C1 HHTJSCIRSQCPEX-UHFFFAOYSA-N 0.000 description 1
KDVGQVZQZMKLBV-UHFFFAOYSA-N methyl 6-(4-methylphenyl)-5-phenylpyrazine-2-carboxylate Chemical compound C=1C=C(C)C=CC=1C1=NC(C(=O)OC)=CN=C1C1=CC=CC=C1 KDVGQVZQZMKLBV-UHFFFAOYSA-N 0.000 description 1
FOKVXZMIIYLNMH-UHFFFAOYSA-N methyl 6-phenyl-5-(4-propan-2-ylphenyl)pyridine-2-carboxylate Chemical compound C=1C=CC=CC=1C1=NC(C(=O)OC)=CC=C1C1=CC=C(C(C)C)C=C1 FOKVXZMIIYLNMH-UHFFFAOYSA-N 0.000 description 1
LSCYWKSKZVSFER-UHFFFAOYSA-N methyl 6-phenyl-5-(4-propylphenyl)pyridine-2-carboxylate Chemical compound C1=CC(CCC)=CC=C1C1=CC=C(C(=O)OC)N=C1C1=CC=CC=C1 LSCYWKSKZVSFER-UHFFFAOYSA-N 0.000 description 1
QDLGVWWODJNOJY-UHFFFAOYSA-N methyl 6-phenyl-5-[4-(trifluoromethyl)phenyl]pyridine-2-carboxylate Chemical compound C=1C=CC=CC=1C1=NC(C(=O)OC)=CC=C1C1=CC=C(C(F)(F)F)C=C1 QDLGVWWODJNOJY-UHFFFAOYSA-N 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000011278 mitosis Effects 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
ZEJPMRKECMRICL-UHFFFAOYSA-N o-ethyl 2-amino-2-oxoethanethioate Chemical compound CCOC(=S)C(N)=O ZEJPMRKECMRICL-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
238000003305 oral gavage Methods 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
230000037361 pathway Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
208000033808 peripheral neuropathy Diseases 0.000 description 1
230000035699 permeability Effects 0.000 description 1
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125000001918 phosphonic acid ester group Chemical group 0.000 description 1
SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 1
239000013641 positive control Substances 0.000 description 1
238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
229960003081 probenecid Drugs 0.000 description 1
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230000035755 proliferation Effects 0.000 description 1
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
108060006633 protein kinase Proteins 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 1
230000004043 responsiveness Effects 0.000 description 1
210000001995 reticulocyte Anatomy 0.000 description 1
238000010242 retro-orbital bleeding Methods 0.000 description 1
OIWNHEPSSHYXTG-UHFFFAOYSA-L ruthenium(2+);triphenylphosphane;dichloride Chemical compound Cl[Ru]Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 OIWNHEPSSHYXTG-UHFFFAOYSA-L 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000035807 sensation Effects 0.000 description 1
230000009919 sequestration Effects 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
230000011664 signaling Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000002002 slurry Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
JLVSPVFPBBFMBE-HXSWCURESA-N sphingosine-1-phosphocholine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP([O-])(=O)OCC[N+](C)(C)C JLVSPVFPBBFMBE-HXSWCURESA-N 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
238000010186 staining Methods 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
INGJYKISFRSCQV-UHFFFAOYSA-N tert-butyl-(4-iodobutoxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCCCI INGJYKISFRSCQV-UHFFFAOYSA-N 0.000 description 1
BQBBPBUGVLGOHG-UHFFFAOYSA-N tert-butyl-[5-[5-(4-ethylphenyl)-6-phenylpyridin-2-yl]pent-4-enoxy]-dimethylsilane Chemical compound C1=CC(CC)=CC=C1C1=CC=C(C=CCCCO[Si](C)(C)C(C)(C)C)N=C1C1=CC=CC=C1 BQBBPBUGVLGOHG-UHFFFAOYSA-N 0.000 description 1
CRZBSCSKPVATSL-UHFFFAOYSA-N tert-butyl-[5-[5-(4-ethylphenyl)-6-phenylpyridin-2-yl]pentoxy]-dimethylsilane Chemical compound C1=CC(CC)=CC=C1C1=CC=C(CCCCCO[Si](C)(C)C(C)(C)C)N=C1C1=CC=CC=C1 CRZBSCSKPVATSL-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
210000000115 thoracic cavity Anatomy 0.000 description 1
230000002446 thrombocytic effect Effects 0.000 description 1
210000003371 toe Anatomy 0.000 description 1
150000003918 triazines Chemical class 0.000 description 1
125000004953 trihalomethyl group Chemical group 0.000 description 1
238000011870 unpaired t-test Methods 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000035899 viability Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
230000029663 wound healing Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
- C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Immunology (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Transplantation (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pyridine Compounds (AREA)

AU2007292347A 2006-09-07 2007-09-05 Heteroaromatic compounds having sphingosine-1-phosphate (S1P) receptor agonist and/or antagonist biological activity Abandoned AU2007292347A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US82480706P	2006-09-07	2006-09-07
US60/824,807		2006-09-07
PCT/US2007/077588 WO2008030843A1 (fr)	2006-09-07	2007-09-05	Composés hétéroaromatiques présentant une activité biologique agoniste et/ou antagoniste sur le récepteur sphingosine-1-phosphate (s1p)

Publications (1)

Publication Number	Publication Date
AU2007292347A1 true AU2007292347A1 (en)	2008-03-13

Family

ID=38961939

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU2007292347A Abandoned AU2007292347A1 (en)	2006-09-07	2007-09-05	Heteroaromatic compounds having sphingosine-1-phosphate (S1P) receptor agonist and/or antagonist biological activity

Country Status (6)

Country	Link
EP (1)	EP2066633A1 (fr)
JP (1)	JP2010504286A (fr)
AU (1)	AU2007292347A1 (fr)
BR (1)	BRPI0716815A2 (fr)
CA (1)	CA2662852A1 (fr)
WO (1)	WO2008030843A1 (fr)

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WO2008141013A1 (fr) *	2007-05-08	2008-11-20	Allergan, Inc.	Inhibiteurs de récepteur s1p3 pour traiter la douleur
BRPI0916812B8 (pt)	2008-07-23	2022-10-18	Arena Pharm Inc	Derivados do ácido 1,2,3,4-tetra-hidrociclopenta[b]indol-3-il)acético substituído úteis no tratamento de distúrbios autoimunes e inflamatórios, seu uso, composição farmacêutica que os compreende e processo de preparação
PT2342205T (pt)	2008-08-27	2016-07-28	Arena Pharm Inc	Derivados de ácido tricíclico substituído como agonistas de recetor s1p1 úteis no tratamento de distúrbios autoimunes e inflamatórios
US8399451B2 (en)	2009-08-07	2013-03-19	Bristol-Myers Squibb Company	Heterocyclic compounds
JP5939158B2 (ja) *	2009-11-24	2016-06-22	アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ	治療的有用性を有する受容体調節物質としての新規化合物
US8741875B2 (en)	2009-11-24	2014-06-03	Allergan, Inc.	Compounds as receptor modulators with therapeutic utility
ES2937386T3 (es)	2010-01-27	2023-03-28	Arena Pharm Inc	Procesos para la preparación de ácido (R)-2-(7-(4-ciclopentil-3-(trifluorometil)benciloxi)-1,2,3,4-tetrahidrociclopenta[b]indol-3-il)acético y sales del mismo
CN102884064B (zh)	2010-03-03	2016-01-13	艾尼纳制药公司	制备s1p1受体调节剂及其晶体形式的方法
EP2560969B1 (fr)	2010-04-23	2015-08-12	Bristol-Myers Squibb Company	Amides du 4-(5-isoxazolyl or 5-pyrrazolyl-1,2,4-oxadiazol-3-yl)-acide mandelique comme agonistes du sphingosin-1-phosphate 1 recepteur
US8513220B2 (en)	2010-05-14	2013-08-20	Allergan, Inc.	Aromatic compounds having sphingosine-1-phosphonate (S1P) receptor activity
EP2569322A1 (fr)	2010-05-14	2013-03-20	Allergan, Inc.	Composés aromatiques ayant une activité de récepteur de sphingosine-1-phosphonate (s1p)
ES2548258T3 (es)	2010-09-24	2015-10-15	Bristol-Myers Squibb Company	Compuestos de oxadiazol sustituidos y su uso como agonistas de S1P1
CN106304835A (zh)	2013-12-11	2017-01-04	铁木医药有限公司	sGC刺激剂
UA126268C2 (uk)	2015-01-06	2022-09-14	Арена Фармасьютікалз, Інк.	СПОСОБИ ЛІКУВАННЯ СТАНІВ, ПОВ'ЯЗАНИХ З РЕЦЕПТОРОМ S1P<sub>1 </sub>
MA42807A (fr)	2015-06-22	2018-07-25	Arena Pharm Inc	Sel l-arginine cristallin d'acide (r)-2-(7-(4-cyclopentyl-3-(trifluorométhyl)benzyloxy)-1,2,3,4-tétrahydrocyclo-penta[b]indol-3-yl)acétique (composé 1) pour une utilisation dans des troubles associés au récepteur de s1p1
MA47504A (fr)	2017-02-16	2019-12-25	Arena Pharm Inc	Composés et méthodes de traitement de l'angiocholite biliaire primitive
AU2018222747A1 (en)	2017-02-16	2019-09-05	Arena Pharmaceuticals, Inc.	Compounds and methods for treatment of inflammatory bowel disease with extra-intestinal manifestations
KR102859841B1 (ko)	2018-06-06	2025-09-12	아레나 파마슈티칼스, 인크.	S1p1 수용체와 관련된 병태의 치료 방법
WO2020051378A1 (fr)	2018-09-06	2020-03-12	Arena Pharmaceuticals, Inc.	Composés utiles dans le traitement de troubles auto-immuns et inflammatoires

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2007
- 2007-09-05 CA CA002662852A patent/CA2662852A1/fr not_active Abandoned
- 2007-09-05 BR BRPI0716815-2A2A patent/BRPI0716815A2/pt not_active IP Right Cessation
- 2007-09-05 WO PCT/US2007/077588 patent/WO2008030843A1/fr not_active Ceased
- 2007-09-05 AU AU2007292347A patent/AU2007292347A1/en not_active Abandoned
- 2007-09-05 JP JP2009527532A patent/JP2010504286A/ja active Pending
- 2007-09-05 EP EP07841853A patent/EP2066633A1/fr not_active Withdrawn

Also Published As

Publication number	Publication date
JP2010504286A (ja)	2010-02-12
CA2662852A1 (fr)	2008-03-13
WO2008030843A1 (fr)	2008-03-13
EP2066633A1 (fr)	2009-06-10
BRPI0716815A2 (pt)	2013-11-05

Publication	Publication Date	Title
AU2007292347A1 (en)	2008-03-13	Heteroaromatic compounds having sphingosine-1-phosphate (S1P) receptor agonist and/or antagonist biological activity
US4072746A (en)	1978-02-07	3-Amino-5-(pyridinyl)-2(1H)-pyridinones
CA2726588C (fr)	2019-04-16	Composes et procedes de traitement des troubles inflammatoires et fibrotiques
KR102872871B1 (ko)	2025-10-16	모발 성장을 조절하기 위한 조성물 및 방법
JP5646082B2 (ja)	2014-12-24	Ｈｄｌコレステロール上昇剤としてのオキシム化合物
AU2003285211B8 (en)	2015-04-16	Pyrazine-based tubulin inhibitors
US7728014B2 (en)	2010-06-01	Heteroaromatic compounds having sphingosine-1-phosphate (S1P) receptor agonist biological activity
TW517056B (en)	2003-01-11	Substituted vinylpyridine derivatives and the pharmaceutical composition
US8703797B2 (en)	2014-04-22	Condensed ring pyridine compounds as subtype-selective modulators of sphingosine-1-phosphate-2 (S1P2) receptors
US4465686A (en)	1984-08-14	5-(Hydroxy- and/or amino-phenyl)-6-(lower-alkyl)-2-(1H)-pyridinones, their cardiotonic use and preparation
RU2235095C2 (ru)	2004-08-27	2,3-дизамещенное производное пиридина, способы его получения, содержащая его фармацевтическая композиция и промежуточный продукт для его получения
AU2007292436A1 (en)	2008-03-13	Heteroaromatic compounds having sphingosine-1-phosphate (S1P) receptor agonist biological activity
US4599423A (en)	1986-07-08	Preparation of 5-(hydroxy- and/or aminophenyl-6-lower-alkyl)-2(1H)-pyridinones
US4559352A (en)	1985-12-17	1,2-Dihydro-2-oxo-5-(hydroxy-and/or amino-phenyl)-nicotinonitriles and cardiotonic use thereof
US4515797A (en)	1985-05-07	3-Amino-5-(hydroxy- and/or aminophenyl)-6-(lower-alkyl)-2(1H)-pyridinones and cardiotonic use thereof
US5126357A (en)	1992-06-30	Anti-inflammatory picolyselenobenzamides and salts thereof
CA2771083A1 (fr)	2011-02-17	Antagonistes selectifs des recepteurs de sphingosine-1-phosphate
JPH05170742A (ja)	1993-07-09	ジアミノトリフルオロメチルピリジン誘導体、それらの製造方法及びそれらを含有するホスホリパーゼ▲ａ２▼阻害剤
MXPA96004540A (en)	1998-07-03	Aminostilbazole derivative and medicine
NZ241968A (en)	1994-04-27	Mixed pyridine 2,4- and 2,5-dicarboxamides and pharmaceutical compositions thereof
WO2011028927A1 (fr)	2011-03-10	Antagonistes sélectifs des récepteurs de sphingosine-1-phosphate

Legal Events

Date	Code	Title	Description
2011-09-01	MK1	Application lapsed section 142(2)(a) - no request for examination in relevant period