AU2014334619A1 - Alkyl linked quinolinyl modulators of RORyt - Google Patents
Alkyl linked quinolinyl modulators of RORyt Download PDFInfo
- Publication number
- AU2014334619A1 AU2014334619A1 AU2014334619A AU2014334619A AU2014334619A1 AU 2014334619 A1 AU2014334619 A1 AU 2014334619A1 AU 2014334619 A AU2014334619 A AU 2014334619A AU 2014334619 A AU2014334619 A AU 2014334619A AU 2014334619 A1 AU2014334619 A1 AU 2014334619A1
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- leu
- glu
- ser
- ala
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 125000000217 alkyl group Chemical group 0.000 title claims description 260
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 title claims description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 180
- -1 pyridyl N-oxide Chemical class 0.000 claims description 113
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 101
- 239000000203 mixture Substances 0.000 claims description 80
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 69
- 238000000034 method Methods 0.000 claims description 62
- 125000004076 pyridyl group Chemical group 0.000 claims description 58
- 201000010099 disease Diseases 0.000 claims description 57
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 50
- 229910052801 chlorine Inorganic materials 0.000 claims description 48
- 208000035475 disorder Diseases 0.000 claims description 44
- 229910052731 fluorine Inorganic materials 0.000 claims description 44
- 208000011580 syndromic disease Diseases 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 34
- 125000002883 imidazolyl group Chemical group 0.000 claims description 34
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 34
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 32
- 125000005495 pyridazyl group Chemical group 0.000 claims description 32
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 32
- 125000001425 triazolyl group Chemical group 0.000 claims description 29
- 125000002971 oxazolyl group Chemical group 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 201000006417 multiple sclerosis Diseases 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 25
- 125000000335 thiazolyl group Chemical group 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 201000004681 Psoriasis Diseases 0.000 claims description 23
- 125000002393 azetidinyl group Chemical group 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 21
- 125000001544 thienyl group Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 241000282414 Homo sapiens Species 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- 125000003386 piperidinyl group Chemical group 0.000 claims description 18
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 18
- 208000006673 asthma Diseases 0.000 claims description 16
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 12
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 12
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 12
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 11
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 10
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 10
- 230000001684 chronic effect Effects 0.000 claims description 10
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 9
- 208000019693 Lung disease Diseases 0.000 claims description 8
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 8
- 230000000414 obstructive effect Effects 0.000 claims description 8
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 8
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 7
- 208000011231 Crohn disease Diseases 0.000 claims description 6
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 230000002757 inflammatory effect Effects 0.000 claims description 6
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 6
- 150000003431 steroids Chemical class 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 238000003776 cleavage reaction Methods 0.000 claims description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 230000007017 scission Effects 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 238000002849 thermal shift Methods 0.000 claims description 3
- 108091005804 Peptidases Proteins 0.000 claims description 2
- 239000004365 Protease Substances 0.000 claims description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 238000002648 combination therapy Methods 0.000 claims description 2
- 229940125721 immunosuppressive agent Drugs 0.000 claims description 2
- 239000003018 immunosuppressive agent Substances 0.000 claims description 2
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 2
- WNRZUESNGGDCJX-JYJNAYRXSA-N Glu-Leu-Phe Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O WNRZUESNGGDCJX-JYJNAYRXSA-N 0.000 claims 8
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 claims 6
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 claims 4
- 108010036211 5-HT-moduline Proteins 0.000 claims 3
- ZPXCNXMJEZKRLU-LSJOCFKGSA-N Ala-His-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CN=CN1 ZPXCNXMJEZKRLU-LSJOCFKGSA-N 0.000 claims 3
- MNZHHDPWDWQJCQ-YUMQZZPRSA-N Ala-Leu-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O MNZHHDPWDWQJCQ-YUMQZZPRSA-N 0.000 claims 3
- GMFAGHNRXPSSJS-SRVKXCTJSA-N Arg-Leu-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O GMFAGHNRXPSSJS-SRVKXCTJSA-N 0.000 claims 3
- RPUYTJJZXQBWDT-SRVKXCTJSA-N Asp-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N RPUYTJJZXQBWDT-SRVKXCTJSA-N 0.000 claims 3
- LKHMGNHQULEPFY-ACZMJKKPSA-N Cys-Ser-Glu Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O LKHMGNHQULEPFY-ACZMJKKPSA-N 0.000 claims 3
- JFOKLAPFYCTNHW-SRVKXCTJSA-N Gln-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)N)N JFOKLAPFYCTNHW-SRVKXCTJSA-N 0.000 claims 3
- MAGNEQBFSBREJL-DCAQKATOSA-N Gln-Glu-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N MAGNEQBFSBREJL-DCAQKATOSA-N 0.000 claims 3
- IRDASPPCLZIERZ-XHNCKOQMSA-N Glu-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N IRDASPPCLZIERZ-XHNCKOQMSA-N 0.000 claims 3
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 claims 3
- PMWSGVRIMIFXQH-KKUMJFAQSA-N His-His-Leu Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](N)CC=1NC=NC=1)C1=CN=CN1 PMWSGVRIMIFXQH-KKUMJFAQSA-N 0.000 claims 3
- LJUIEESLIAZSFR-SRVKXCTJSA-N His-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N LJUIEESLIAZSFR-SRVKXCTJSA-N 0.000 claims 3
- BPOHQCZZSFBSON-KKUMJFAQSA-N His-Leu-His Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)Cc1cnc[nH]1)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O BPOHQCZZSFBSON-KKUMJFAQSA-N 0.000 claims 3
- PZAJPILZRFPYJJ-SRVKXCTJSA-N His-Ser-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O PZAJPILZRFPYJJ-SRVKXCTJSA-N 0.000 claims 3
- HTDRTKMNJRRYOJ-SIUGBPQLSA-N Ile-Gln-Tyr Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HTDRTKMNJRRYOJ-SIUGBPQLSA-N 0.000 claims 3
- VOCZPDONPURUHV-QEWYBTABSA-N Ile-Phe-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N VOCZPDONPURUHV-QEWYBTABSA-N 0.000 claims 3
- 241000880493 Leptailurus serval Species 0.000 claims 3
- UCOCBWDBHCUPQP-DCAQKATOSA-N Leu-Arg-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O UCOCBWDBHCUPQP-DCAQKATOSA-N 0.000 claims 3
- QKIBIXAQKAFZGL-GUBZILKMSA-N Leu-Cys-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O QKIBIXAQKAFZGL-GUBZILKMSA-N 0.000 claims 3
- USLNHQZCDQJBOV-ZPFDUUQYSA-N Leu-Ile-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O USLNHQZCDQJBOV-ZPFDUUQYSA-N 0.000 claims 3
- HRTRLSRYZZKPCO-BJDJZHNGSA-N Leu-Ile-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O HRTRLSRYZZKPCO-BJDJZHNGSA-N 0.000 claims 3
- DPURXCQCHSQPAN-AVGNSLFASA-N Leu-Pro-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DPURXCQCHSQPAN-AVGNSLFASA-N 0.000 claims 3
- RGUXWMDNCPMQFB-YUMQZZPRSA-N Leu-Ser-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RGUXWMDNCPMQFB-YUMQZZPRSA-N 0.000 claims 3
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- NKKFVJRLCCUJNA-QWRGUYRKSA-N Lys-Gly-Lys Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN NKKFVJRLCCUJNA-QWRGUYRKSA-N 0.000 claims 3
- IEVXCWPVBYCJRZ-IXOXFDKPSA-N Lys-Thr-His Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 IEVXCWPVBYCJRZ-IXOXFDKPSA-N 0.000 claims 3
- NAOVYENZCWFBDG-BZSNNMDCSA-N Phe-His-His Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CC=CC=C1 NAOVYENZCWFBDG-BZSNNMDCSA-N 0.000 claims 3
- RTUWVJVJSMOGPL-KKUMJFAQSA-N Phe-Met-Glu Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N RTUWVJVJSMOGPL-KKUMJFAQSA-N 0.000 claims 3
- ZJPGOXWRFNKIQL-JYJNAYRXSA-N Phe-Pro-Pro Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=CC=C1 ZJPGOXWRFNKIQL-JYJNAYRXSA-N 0.000 claims 3
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- 229910006074 SO2NH2 Inorganic materials 0.000 claims 3
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- PNQWAUXQDBIJDY-GUBZILKMSA-N Arg-Glu-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PNQWAUXQDBIJDY-GUBZILKMSA-N 0.000 claims 2
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- AMIQZQAAYGYKOP-FXQIFTODSA-N Arg-Ser-Asn Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O AMIQZQAAYGYKOP-FXQIFTODSA-N 0.000 claims 2
- RZVVKNIACROXRM-ZLUOBGJFSA-N Asn-Ala-Asp Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N RZVVKNIACROXRM-ZLUOBGJFSA-N 0.000 claims 2
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229960004540 secukinumab Drugs 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229940001593 sodium carbonate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 1
- WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
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- 239000007858 starting material Substances 0.000 description 1
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- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
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- 230000008685 targeting Effects 0.000 description 1
- 229950002757 teoclate Drugs 0.000 description 1
- DWSJFXCVJDTTCH-UHFFFAOYSA-N tert-butyl 3-[[4-chloro-2-methoxy-3-[[4-(trifluoromethyl)phenyl]methyl]quinolin-6-yl]-hydroxymethyl]azetidine-1-carboxylate Chemical compound COC1=NC2=CC=C(C(O)C3CN(C3)C(=O)OC(C)(C)C)C=C2C(Cl)=C1CC1=CC=C(C(F)(F)F)C=C1 DWSJFXCVJDTTCH-UHFFFAOYSA-N 0.000 description 1
- JVQOZRRUGOADSU-UHFFFAOYSA-N tert-butyl 3-formylazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(C=O)C1 JVQOZRRUGOADSU-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 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
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 229960003824 ustekinumab Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
- A61K31/431—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- 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
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- 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
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361890890P | 2013-10-15 | 2013-10-15 | |
| US61/890,890 | 2013-10-15 | ||
| PCT/US2014/060375 WO2015057629A1 (en) | 2013-10-15 | 2014-10-14 | ALKYL LINKED QUINOLINYL MODULATORS OF RORyt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2014334619A1 true AU2014334619A1 (en) | 2016-04-21 |
Family
ID=52810186
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2014334619A Abandoned AU2014334619A1 (en) | 2013-10-15 | 2014-10-14 | Alkyl linked quinolinyl modulators of RORyt |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US9346782B2 (https=) |
| EP (1) | EP3057421B1 (https=) |
| JP (1) | JP6423423B2 (https=) |
| KR (1) | KR20160070133A (https=) |
| CN (1) | CN105873439A (https=) |
| AU (1) | AU2014334619A1 (https=) |
| BR (1) | BR112016008215A2 (https=) |
| CA (1) | CA2926339A1 (https=) |
| ES (1) | ES2770727T3 (https=) |
| IL (1) | IL244788A0 (https=) |
| WO (1) | WO2015057629A1 (https=) |
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| US9403816B2 (en) | 2013-10-15 | 2016-08-02 | Janssen Pharmaceutica Nv | Phenyl linked quinolinyl modulators of RORγt |
| US10555941B2 (en) | 2013-10-15 | 2020-02-11 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of RORγt |
| ES2742843T3 (es) | 2013-10-15 | 2020-02-17 | Janssen Pharmaceutica Nv | Moduladores de quinolinilo de ROR(gamma)t |
| TWI667230B (zh) * | 2014-10-30 | 2019-08-01 | 比利時商健生藥品公司 | 用作ＲＯＲγｔ調節劑之三氟甲基醇 |
| CN117534655B (zh) * | 2023-11-13 | 2024-08-30 | 复旦大学 | 一种喹诺酮类化合物及其制备方法和用途 |
Family Cites Families (112)
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| US3472859A (en) | 1966-11-01 | 1969-10-14 | Sterling Drug Inc | 1-alkyl-1,4-dihydro-4-oxo-3 quinoline-carboxylic acids and esters |
| JPS4826772Y1 (https=) | 1969-04-04 | 1973-08-06 | ||
| DE3276432D1 (en) | 1981-03-24 | 1987-07-02 | Ciba Geigy Ag | Acyl quinolinone derivatives, processes for their preparation, pharmaceutical compositions containing them and their use |
| US4656283A (en) | 1982-05-25 | 1987-04-07 | American Cyanamid Company | Alkyl esters of substituted 2-methyl-3-quinolinecarboxylic acid and quinoline-2,3-dicarboxylic acid |
| US4910327A (en) | 1982-05-25 | 1990-03-20 | American Cyanamid Company | Alkyl esters of substituted 2-methyl-3-quinolinecarboxylic acid and quinoline-2,3-dicarboxylic acid: dialkyl 3-(substituted)phenylaminobut-2-ene-dioates and methods for the preparation thereof |
| PT79699B (en) | 1983-12-22 | 1986-12-10 | Pfizer | Process for preparing quinolone inotropic agents |
| FR2634483B2 (fr) * | 1987-12-29 | 1994-03-04 | Esteve Labor Dr | Derives des acides 7-(1-azetidinyl)-1,4-dihydro-4-oxoquinoleine-3-carboxyliques, leur preparation et leur application en tant que medicaments |
| CA2002864C (en) | 1988-11-29 | 1999-11-16 | Eddy J. E. Freyne | (1h-azol-1-ylmethyl) substituted quinoline, quinazoline or quinoxaline derivatives |
| US5409930A (en) | 1991-05-10 | 1995-04-25 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| US5478832A (en) | 1992-05-08 | 1995-12-26 | The Green Cross Corporation | Quinoline compounds |
| JPH0826772A (ja) | 1994-07-22 | 1996-01-30 | Sony Corp | 融着用ガラス、その製造方法及び製造装置、並びに磁気ヘッドの製造方法 |
| DE69512495T2 (de) | 1994-10-27 | 2000-02-03 | Asahi Glass Co. Ltd., Tokio/Tokyo | Verfahren zur Herstellung von Chinolin-2-yl-benzoesäure |
| GB9523267D0 (en) | 1995-11-14 | 1996-01-17 | Sandoz Ltd | Organic compounds |
| DE69620445T2 (de) | 1995-12-08 | 2002-12-12 | Janssen Pharmaceutica N.V., Beerse | (imidazol-5-yl)methyl-2-chinolinoderivate als farnesyl protein transferase inhibitoren |
| US6150352A (en) | 1996-05-20 | 2000-11-21 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| CN100525766C (zh) | 1997-06-02 | 2009-08-12 | 詹森药业有限公司 | 用作平滑肌细胞增殖抑制剂的（咪唑-5-基）甲基-2-喹啉酮衍生物 |
| DE69831506T2 (de) | 1997-12-22 | 2006-06-29 | Pharmacia & Upjohn Co. Llc, Kalamazoo | 4-hydroxychinolin-3-carboxamide und hydrazide als antivirale wirkstoffe |
| FR2776388B1 (fr) | 1998-03-20 | 2006-04-28 | Lipha | Utilisation de recepteurs de la famille ror pour le criblage de substances utiles pour le traitement de l'atherosclerose |
| US6399629B1 (en) | 1998-06-01 | 2002-06-04 | Microcide Pharmaceuticals, Inc. | Efflux pump inhibitors |
| PL193464B1 (pl) | 1998-07-06 | 2007-02-28 | Janssen Pharmaceutica Nv | Zastosowanie inhibitora białkowej transferazy farnezylowej |
| HRP20000904A2 (en) | 1998-07-06 | 2001-12-31 | Janssen Pharmaceutica Nv | Farnesyl protein transferase inhibitors for treating arthropathies |
| JP2000169451A (ja) | 1998-09-30 | 2000-06-20 | Kyorin Pharmaceut Co Ltd | ６，７―ジ置換キノリンカルボン酸誘導体とその付加塩及びそれらの製造方法 |
| DK1140935T3 (da) | 1998-12-23 | 2003-09-01 | Janssen Pharmaceutica Nv | 1,2-anellerede quinolinderivater |
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| PT1106612E (pt) | 1999-11-30 | 2004-06-30 | Pfizer Prod Inc | Derivados de quinolina uteis para inibir a farnesil-proteina-transferase |
| SI1255537T1 (sl) | 2000-02-04 | 2006-10-31 | Janssen Pharmaceutica Nv | Inhibitorji farnezil protein transferaze za zdravljenje raka dojk |
| ATE375794T1 (de) | 2000-02-24 | 2007-11-15 | Janssen Pharmaceutica Nv | Dosierschema enthaldend farnesyl protein transferase inhibitoren für die behandlung von krebs |
| CA2397690A1 (en) | 2000-02-29 | 2001-09-07 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitor combinations with anti-tumor nucleoside derivatives |
| AU2001244167A1 (en) | 2000-02-29 | 2001-09-12 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitor combinations with anti-tumor anthracycline derivatives |
| EP1265611A2 (en) | 2000-02-29 | 2002-12-18 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitor combinations with taxane compounds |
| US20030027808A1 (en) | 2000-02-29 | 2003-02-06 | Palmer Peter Albert | Farnesyl protein transferase inhibitor combinations with platinum compounds |
| WO2001064196A2 (en) | 2000-02-29 | 2001-09-07 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitor combinations with vinca alkaloids |
| JP2003525245A (ja) | 2000-02-29 | 2003-08-26 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ファルネシルタンパク質トランスフェラーゼ阻害剤組み合わせ剤 |
| EP1261341A2 (en) | 2000-02-29 | 2002-12-04 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitor combinations with camptothecin compounds |
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2014
- 2014-10-14 BR BR112016008215A patent/BR112016008215A2/pt not_active Application Discontinuation
- 2014-10-14 ES ES14853874T patent/ES2770727T3/es active Active
- 2014-10-14 WO PCT/US2014/060375 patent/WO2015057629A1/en not_active Ceased
- 2014-10-14 AU AU2014334619A patent/AU2014334619A1/en not_active Abandoned
- 2014-10-14 CA CA2926339A patent/CA2926339A1/en not_active Abandoned
- 2014-10-14 EP EP14853874.7A patent/EP3057421B1/en active Active
- 2014-10-14 JP JP2016523291A patent/JP6423423B2/ja not_active Expired - Fee Related
- 2014-10-14 US US14/513,455 patent/US9346782B2/en not_active Expired - Fee Related
- 2014-10-14 CN CN201480057018.3A patent/CN105873439A/zh active Pending
- 2014-10-14 KR KR1020167012584A patent/KR20160070133A/ko not_active Withdrawn
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Also Published As
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|---|---|
| EP3057421B1 (en) | 2019-11-20 |
| BR112016008215A2 (pt) | 2017-09-26 |
| ES2770727T3 (es) | 2020-07-02 |
| JP6423423B2 (ja) | 2018-11-14 |
| EP3057421A1 (en) | 2016-08-24 |
| WO2015057629A1 (en) | 2015-04-23 |
| CA2926339A1 (en) | 2015-04-23 |
| IL244788A0 (en) | 2016-04-21 |
| EP3057421A4 (en) | 2017-04-12 |
| US9346782B2 (en) | 2016-05-24 |
| JP2016539917A (ja) | 2016-12-22 |
| CN105873439A (zh) | 2016-08-17 |
| US20150105369A1 (en) | 2015-04-16 |
| KR20160070133A (ko) | 2016-06-17 |
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