CA2662852A1 - Composes heteroaromatiques presentant une activite biologique agoniste et/ou antagoniste sur le recepteur sphingosine-1-phosphate (s1p) - Google Patents

Composes heteroaromatiques presentant une activite biologique agoniste et/ou antagoniste sur le recepteur sphingosine-1-phosphate (s1p) Download PDF

Info

Publication number: CA2662852A1
Authority: CA; Canada
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

CA002662852A

Other languages

English (en)

Inventor

Richard L. Beard

John E. Donello

Haiqing Yuan

Xiaoxia Liu

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

Individual

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 Individual filed Critical Individual

2008-03-13 Publication of CA2662852A1 publication Critical patent/CA2662852A1/fr

Status Abandoned legal-status Critical Current

Links

230000004071 biological effect Effects 0.000 title description 5
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 5
229940044601 receptor agonist Drugs 0.000 title description 4
239000000018 receptor agonist Substances 0.000 title description 4
239000002464 receptor antagonist Substances 0.000 title description 2
229940044551 receptor antagonist Drugs 0.000 title description 2
150000002390 heteroarenes Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 187
125000000217 alkyl group Chemical group 0.000 claims abstract description 37
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
125000003118 aryl group Chemical group 0.000 claims abstract description 27
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
230000000694 effects Effects 0.000 claims abstract description 10
102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 claims abstract description 4
108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 claims abstract description 4
239000005557 antagonist Substances 0.000 claims abstract description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
125000004076 pyridyl group Chemical group 0.000 claims description 11
125000005843 halogen group Chemical group 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
125000001072 heteroaryl group Chemical group 0.000 claims description 9
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 7
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
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
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 168
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 133
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 99
238000005481 NMR spectroscopy Methods 0.000 description 91
238000000034 method Methods 0.000 description 90
101150041968 CDC13 gene Proteins 0.000 description 75
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 75
LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
239000007787 solid Substances 0.000 description 57
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
239000000243 solution Substances 0.000 description 51
235000019439 ethyl acetate Nutrition 0.000 description 45
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 33
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 32
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
239000000203 mixture Substances 0.000 description 28
239000003921 oil Substances 0.000 description 27
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 26
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
239000000741 silica gel Substances 0.000 description 21
229910002027 silica gel Inorganic materials 0.000 description 21
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 20
238000004440 column chromatography Methods 0.000 description 20
-1 hydrocarbyl radical Chemical class 0.000 description 20
238000006243 chemical reaction Methods 0.000 description 19
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
210000004027 cell Anatomy 0.000 description 16
235000011149 sulphuric acid Nutrition 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000002904 solvent Substances 0.000 description 14
229910019142 PO4 Inorganic materials 0.000 description 13
239000010452 phosphate Substances 0.000 description 13
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 11
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 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
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
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
229910052786 argon Inorganic materials 0.000 description 10
229940079593 drug Drugs 0.000 description 10
239000003814 drug Substances 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
GSZQTIFGANBTNF-UHFFFAOYSA-N (3-aminopropyl)phosphonic acid Chemical compound NCCCP(O)(O)=O GSZQTIFGANBTNF-UHFFFAOYSA-N 0.000 description 9
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
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 8
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 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
239000007832 Na2SO4 Substances 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
239000011734 sodium Substances 0.000 description 7
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 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
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
101000886583 Homo sapiens Gem-associated protein 7 Proteins 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
229910052736 halogen Inorganic materials 0.000 description 6
150000002367 halogens Chemical class 0.000 description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
JYJVVHFRSFVEJM-UHFFFAOYSA-N iodosobenzene Chemical compound O=IC1=CC=CC=C1 JYJVVHFRSFVEJM-UHFFFAOYSA-N 0.000 description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
230000004044 response Effects 0.000 description 6
239000012279 sodium borohydride Substances 0.000 description 6
229910000033 sodium borohydride Inorganic materials 0.000 description 6
229910000104 sodium hydride Inorganic materials 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
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
HVJJYOAPXBPQQV-UHFFFAOYSA-N ethyl 2-azidoacetate Chemical compound CCOC(=O)CN=[N+]=[N-] HVJJYOAPXBPQQV-UHFFFAOYSA-N 0.000 description 5
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 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
238000007912 intraperitoneal administration Methods 0.000 description 5
GNSLYOGEBCFYDE-UHFFFAOYSA-N lithium;ethynylbenzene Chemical compound [Li+].[C-]#CC1=CC=CC=C1 GNSLYOGEBCFYDE-UHFFFAOYSA-N 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
229910000027 potassium carbonate Inorganic materials 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
150000003410 sphingosines Chemical class 0.000 description 5
239000000126 substance Substances 0.000 description 5
229910052717 sulfur Inorganic materials 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
NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-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
GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 4
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
YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 4
DJMOXMNDXFFONV-UHFFFAOYSA-N 1,3-dimethyl-7-[2-(n-methylanilino)ethyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCN(C)C1=CC=CC=C1 DJMOXMNDXFFONV-UHFFFAOYSA-N 0.000 description 4
KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 4
VGHFZQHSVAXZFS-UHFFFAOYSA-N 1-(2-phenylethynyl)-4-(trifluoromethyl)benzene Chemical compound C1=CC(C(F)(F)F)=CC=C1C#CC1=CC=CC=C1 VGHFZQHSVAXZFS-UHFFFAOYSA-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
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BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-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
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
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 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
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
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 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

Landscapes

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

CA002662852A 2006-09-07 2007-09-05 Composes heteroaromatiques presentant une activite biologique agoniste et/ou antagoniste sur le recepteur sphingosine-1-phosphate (s1p) Abandoned CA2662852A1 (fr)

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
CA2662852A1 true CA2662852A1 (fr)	2008-03-13

Family

ID=38961939

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002662852A Abandoned CA2662852A1 (fr)	2006-09-07	2007-09-05	Composes heteroaromatiques presentant une activite biologique agoniste et/ou antagoniste sur le recepteur sphingosine-1-phosphate (s1p)

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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DE102005014271A1 (de) *	2005-03-24	2006-09-28	Rhein Chemie Rheinau Gmbh	Mikrogele in Kombination mit funktionalen Additiven
WO2008141013A1 (fr) *	2007-05-08	2008-11-20	Allergan, Inc.	Inhibiteurs de récepteur s1p3 pour traiter la douleur
SI2326621T1 (sl)	2008-07-23	2016-10-28	Arena Pharmaceuticals, Inc.	Substituirani derivati 1,2,3,4-tetrahidrociklopenta(b)indol-3-il)ocetne kisline, uporabni pri zdravljenju avtoimunskih in vnetnih motenj
NZ591001A (en)	2008-08-27	2012-11-30	Arena Pharm Inc	Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
US8399451B2 (en)	2009-08-07	2013-03-19	Bristol-Myers Squibb Company	Heterocyclic compounds
US8741875B2 (en)	2009-11-24	2014-06-03	Allergan, Inc.	Compounds as receptor modulators with therapeutic utility
JP2013512243A (ja) *	2009-11-24	2013-04-11	アラーガンインコーポレイテッド	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
SG10201500639TA (en)	2010-01-27	2015-03-30	Arena Pharm Inc	Processes for the preparation of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof
CN105503882B (zh)	2010-03-03	2019-07-05	艾尼纳制药公司	制备s1p1受体调节剂及其晶体形式的方法
JP5735634B2 (ja)	2010-04-23	2015-06-17	ブリストル−マイヤーズスクイブカンパニーＢｒｉｓｔｏｌ−ＭｙｅｒｓＳｑｕｉｂｂＣｏｍｐａｎｙ	スフィンゴシン−１−リン酸受容体１アゴニストとしての４−（５−イソオキサゾリルまたは５−ピラゾリル−１，２，４−オキサジアゾール−３−イル）−マンデル酸アミド化合物
EP2569322A1 (fr)	2010-05-14	2013-03-20	Allergan, Inc.	Composés aromatiques ayant une activité de récepteur de sphingosine-1-phosphonate (s1p)
US8513220B2 (en)	2010-05-14	2013-08-20	Allergan, Inc.	Aromatic compounds having sphingosine-1-phosphonate (S1P) receptor activity
JP5869579B2 (ja)	2010-09-24	2016-02-24	ブリストル−マイヤーズスクイブカンパニーＢｒｉｓｔｏｌ−ＭｙｅｒｓＳｑｕｉｂｂＣｏｍｐａｎｙ	置換オキサジアゾール化合物およびそれらのｓ１ｐ１アゴニストとしての使用
US20160311826A1 (en)	2013-12-11	2016-10-27	Ironwood Pharmaceuticals, Inc.	Sgc stimulators
CN116850181A (zh)	2015-01-06	2023-10-10	艾尼纳制药公司	治疗与s1p1受体有关的病症的方法
AU2016284162A1 (en)	2015-06-22	2018-02-01	Arena Pharmaceuticals, Inc.	Crystalline L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid(Compound1) for use in SIP1 receptor-associated disorders
CA3053416A1 (fr)	2017-02-16	2018-08-23	Arena Pharmaceuticals, Inc.	Composes et methodes pour le traitement de maladies inflammatoires chroniques de l'intestin avec manifestations extra-intestinales
AU2018220521A1 (en)	2017-02-16	2019-09-05	Arena Pharmaceuticals, Inc.	Compounds and methods for treatment of primary biliary cholangitis
WO2019236757A1 (fr)	2018-06-06	2019-12-12	Arena Pharmaceuticals, Inc.	MÉTHODES DE TRAITEMENT DE TROUBLES ASSOCIÉS AU RÉCEPTEUR S1P1<sb />
US11555015B2 (en)	2018-09-06	2023-01-17	Arena Pharmaceuticals, Inc.	Compounds useful in the treatment of autoimmune and inflammatory disorders

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Publication number	Priority date	Publication date	Assignee	Title
FR2665159B1 (fr) *	1990-07-24	1992-11-13	Rhone Poulenc Sante	Nouveaux derives de la pyridine et de la quinoleine, leur preparation et les compositions pharmaceutiques qui les contiennent.
WO1992002513A1 (fr) *	1990-08-06	1992-02-20	Fujisawa Pharmaceutical Co., Ltd.	Composes heterocycliques
WO2005058848A1 (fr) *	2003-12-17	2005-06-30	Merck & Co., Inc.	Carboxylates propanoiques 3,4-disusbstitues utilises en tant qu'agonistes du recepteur s1p (edg)

2007
- 2007-09-05 AU AU2007292347A patent/AU2007292347A1/en not_active Abandoned
- 2007-09-05 JP JP2009527532A patent/JP2010504286A/ja active Pending
- 2007-09-05 CA CA002662852A patent/CA2662852A1/fr not_active Abandoned
- 2007-09-05 EP EP07841853A patent/EP2066633A1/fr not_active Withdrawn
- 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

Also Published As

Publication number	Publication date
BRPI0716815A2 (pt)	2013-11-05
EP2066633A1 (fr)	2009-06-10
WO2008030843A1 (fr)	2008-03-13
AU2007292347A1 (en)	2008-03-13
JP2010504286A (ja)	2010-02-12

Publication	Publication Date	Title
CA2662852A1 (fr)	2008-03-13	Composes heteroaromatiques presentant une activite biologique agoniste et/ou antagoniste sur le recepteur sphingosine-1-phosphate (s1p)
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
JP5792173B2 (ja)	2015-10-07	ｍＧｌｕＲ５ネガティブアロステリックモジュレータとしての置換ヘテロアリールアミド類似体、ならびに、その形成方法および使用方法
US7728014B2 (en)	2010-06-01	Heteroaromatic compounds having sphingosine-1-phosphate (S1P) receptor agonist biological activity
CN102149683B (zh)	2013-10-02	1-（取代苄基）-5-三氟甲基-2-（1h）吡啶酮化合物及其盐，其制备方法及其用途
CN103497114A (zh)	2014-01-08	用于神经保护的nmda受体拮抗剂
EP1748989A2 (fr)	2007-02-07	Sulfonamides aryle
TW517056B (en)	2003-01-11	Substituted vinylpyridine derivatives and the pharmaceutical composition
AU2003285211A1 (en)	2004-06-30	Pyrazine-based tubulin inhibitors
US8507682B2 (en)	2013-08-13	Condensed ring pyridine compounds as subtype-selective modulators of sphingosine-1-phosphate-2 (S1P2) receptors
KR0173311B1 (ko)	1999-02-01	디아미노트리플루오로메틸피리딘 유도체, 그의 제조 방법 및 그를 함유하는 포스폴리파제 a2 억제제
US7935825B2 (en)	2011-05-03	Arylsulfanyl and heteroarylsulfanyl derivatives for treating pain
RU2235095C2 (ru)	2004-08-27	2,3-дизамещенное производное пиридина, способы его получения, содержащая его фармацевтическая композиция и промежуточный продукт для его получения
EP0074091A2 (fr)	1983-03-16	2(1H)-Pyridinones et leur préparation
CA2662850A1 (fr)	2008-03-13	Composes heteroaromatiques ayant une activite biologique d'agoniste de recepteur de sphingosine-1-phosphate (s1p)
US6921767B2 (en)	2005-07-26	Cycloalkyl alkanoic acids as integrin receptor antagonists derivatives
US4599423A (en)	1986-07-08	Preparation of 5-(hydroxy- and/or aminophenyl-6-lower-alkyl)-2(1H)-pyridinones
AU2001276923A1 (en)	2002-05-02	Calcilytic compounds
EP1368318A2 (fr)	2003-12-10	Composes calcilytiques
AU2002348424A1 (en)	2003-07-03	Arylsulfanyl and heteroarylsulfanyl derivatives for treating pain
WO2011008475A1 (fr)	2011-01-20	Composés de 2-(arylméthyl, aryloxy ou arylthio)-n-pyridin-2-yl-arylacétamide ou de 2,2-bis(aryl)-n-pyridin-2-yl-acétamide éventuellement substitués comme médicaments pour le traitement de maladies des yeux
CA2083956A1 (fr)	1991-12-08	Derives pyridylbenzoiques lies a des amines, pour le traitement de maladies associees aux leucotrienes
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
JPS5857362A (ja)	1983-04-05	２（１ｈ）−ピリジノン及びその製法

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2012-09-05	FZDE	Dead