JP2019531274A5 - - Google Patents
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- Publication number
- JP2019531274A5 JP2019531274A5 JP2019511947A JP2019511947A JP2019531274A5 JP 2019531274 A5 JP2019531274 A5 JP 2019531274A5 JP 2019511947 A JP2019511947 A JP 2019511947A JP 2019511947 A JP2019511947 A JP 2019511947A JP 2019531274 A5 JP2019531274 A5 JP 2019531274A5
- Authority
- JP
- Japan
- Prior art keywords
- bis
- oxy
- biphenyl
- dimethyl
- diyl
- 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.)
- Granted
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- -1 amino, carboxy Chemical group 0.000 claims 187
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 83
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 64
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 52
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 claims 46
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 28
- 235000010290 biphenyl Nutrition 0.000 claims 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 22
- 125000004076 pyridyl group Chemical group 0.000 claims 21
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 20
- 125000005843 halogen group Chemical group 0.000 claims 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 14
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 13
- 150000001875 compounds Chemical class 0.000 claims 12
- 125000003386 piperidinyl group Chemical group 0.000 claims 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 11
- 239000003814 drug Substances 0.000 claims 11
- 229940124597 therapeutic agent Drugs 0.000 claims 11
- 239000004146 Propane-1,2-diol Substances 0.000 claims 10
- 239000001257 hydrogen Substances 0.000 claims 10
- 229910052739 hydrogen Inorganic materials 0.000 claims 10
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 claims 10
- 229960004063 propylene glycol Drugs 0.000 claims 10
- 235000013772 propylene glycol Nutrition 0.000 claims 10
- 150000003839 salts Chemical class 0.000 claims 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 9
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 claims 8
- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 claims 8
- DBXBTMSZEOQQDU-UHFFFAOYSA-N 3-hydroxyisobutyric acid Chemical compound OCC(C)C(O)=O DBXBTMSZEOQQDU-UHFFFAOYSA-N 0.000 claims 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 6
- 125000000217 alkyl group Chemical group 0.000 claims 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 6
- QWGRWMMWNDWRQN-UHFFFAOYSA-N 2-methylpropane-1,3-diol Chemical compound OCC(C)CO QWGRWMMWNDWRQN-UHFFFAOYSA-N 0.000 claims 5
- 239000002253 acid Substances 0.000 claims 5
- 125000003545 alkoxy group Chemical group 0.000 claims 5
- 125000002883 imidazolyl group Chemical group 0.000 claims 5
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 5
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 claims 4
- ALRHLSYJTWAHJZ-UHFFFAOYSA-N 3-hydroxypropionic acid Chemical compound OCCC(O)=O ALRHLSYJTWAHJZ-UHFFFAOYSA-N 0.000 claims 4
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 4
- 125000004450 alkenylene group Chemical group 0.000 claims 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 4
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 3
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 3
- 235000019260 propionic acid Nutrition 0.000 claims 3
- 125000000335 thiazolyl group Chemical group 0.000 claims 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 3
- UXOQCYFKGDPUDV-PLXFJCCSSA-N (2S,4R)-4-hydroxy-1-[3-[3-[3-[3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidine-2-carboxylic acid Chemical compound O[C@@H]1C[C@H](N(C1)CCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C)C(=O)O UXOQCYFKGDPUDV-PLXFJCCSSA-N 0.000 claims 2
- PKCXYIGMQIXBHG-YOQGVNIDSA-N (3R)-1-[3-[3-[3-[2-[(3R)-3-hydroxypyrrolidin-1-yl]ethyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound O[C@H]1CN(CC1)CCC1OC2=C(OC1)C=CC(=C2)C=1C(=C(OCCCN2C[C@@H](CC2)O)C=CC=1)C PKCXYIGMQIXBHG-YOQGVNIDSA-N 0.000 claims 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 2
- SPJPZSUFBQISRE-UHFFFAOYSA-N 1-[3-[2-methyl-3-(2-methylphenyl)phenoxy]propyl]pyrrolidin-3-ol Chemical compound OC1CN(CC1)CCCOC=1C(=C(C=CC=1)C1=C(C=CC=C1)C)C SPJPZSUFBQISRE-UHFFFAOYSA-N 0.000 claims 2
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 claims 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N 4-hydroxyproline Chemical compound OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 125000002619 bicyclic group Chemical group 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 230000028993 immune response Effects 0.000 claims 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 claims 2
- FGKJLKRYENPLQH-UHFFFAOYSA-N isocaproic acid Chemical compound CC(C)CCC(O)=O FGKJLKRYENPLQH-UHFFFAOYSA-N 0.000 claims 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 2
- BVOCPVIXARZNQN-UHFFFAOYSA-N nipecotamide Chemical compound NC(=O)C1CCCNC1 BVOCPVIXARZNQN-UHFFFAOYSA-N 0.000 claims 2
- BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 claims 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 2
- ZAMUNOUDPJRWIJ-QPPBQGQZSA-N (2S)-2-hydroxy-3-[3-[3-[3-[3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy]-2-methylphenyl]-2-methylphenoxy]propylamino]propanoic acid Chemical compound O[C@H](C(=O)O)CNCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C ZAMUNOUDPJRWIJ-QPPBQGQZSA-N 0.000 claims 1
- SHMLWSKIQITORU-VMPREFPWSA-N (2S)-3-[3-[3-[3-[3-[[(2S)-2,3-dihydroxypropyl]-(2-pyridin-3-ylethyl)amino]propoxy]-2-methylphenyl]-2-methylphenoxy]propylamino]propane-1,2-diol Chemical compound O[C@@H](CN(CCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCNC[C@@H](CO)O)C)C)CCC=1C=NC=CC=1)CO SHMLWSKIQITORU-VMPREFPWSA-N 0.000 claims 1
- XUVCRLNALYWPFO-DFHRPNOPSA-N (2S)-3-hydroxy-2-[3-[3-[3-[3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy]-2-methylphenyl]-2-methylphenoxy]propylamino]-2-methylpropanoic acid Chemical compound OC[C@](C(=O)O)(C)NCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C XUVCRLNALYWPFO-DFHRPNOPSA-N 0.000 claims 1
- IQYCVHPCIZMJIG-JUQKIHQQSA-N (2S,3S)-3-[3-[3-[3-[3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy]-2-methylphenyl]-2-methylphenoxy]propylamino]-3-phenylpropane-1,2-diol Chemical compound O[C@H]1CN(CC1)CCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN[C@H]([C@@H](CO)O)C1=CC=CC=C1)C)C IQYCVHPCIZMJIG-JUQKIHQQSA-N 0.000 claims 1
- SPJPZSUFBQISRE-GOSISDBHSA-N (3R)-1-[3-[2-methyl-3-(2-methylphenyl)phenoxy]propyl]pyrrolidin-3-ol Chemical compound O[C@H]1CN(CC1)CCCOC=1C(=C(C=CC=1)C1=C(C=CC=C1)C)C SPJPZSUFBQISRE-GOSISDBHSA-N 0.000 claims 1
- PJFDIUZZYNDMBT-RUZDIDTESA-N (3R)-1-[3-[2-methyl-3-[2-methyl-3-(3-piperidin-1-ylpropoxy)phenyl]phenoxy]propyl]pyrrolidin-3-ol Chemical compound CC1=C(C=CC=C1OCCCN1C[C@@H](CC1)O)C1=C(C(=CC=C1)OCCCN1CCCCC1)C PJFDIUZZYNDMBT-RUZDIDTESA-N 0.000 claims 1
- UTWZLLUIGZQEHS-XMMISQBUSA-N (3R)-1-[3-[2-methyl-3-[2-methyl-3-[(1-methylpiperidin-3-yl)methoxy]phenyl]phenoxy]propyl]pyrrolidin-3-ol Chemical compound CC1=C(C=CC=C1OCCCN1C[C@@H](CC1)O)C1=C(C(=CC=C1)OCC1CN(CCC1)C)C UTWZLLUIGZQEHS-XMMISQBUSA-N 0.000 claims 1
- AOTXMUNSPVUYKX-RUZDIDTESA-N (3R)-1-[3-[2-methyl-3-[2-methyl-3-[3-(2-pyrazol-1-ylethylamino)propoxy]phenyl]phenoxy]propyl]pyrrolidin-3-ol Chemical compound N1(N=CC=C1)CCNCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C AOTXMUNSPVUYKX-RUZDIDTESA-N 0.000 claims 1
- YFWBKLCOKIURAV-GDLZYMKVSA-N (3R)-1-[3-[2-methyl-3-[2-methyl-3-[3-[methyl(2-phenylethyl)amino]propoxy]phenyl]phenoxy]propyl]pyrrolidin-3-ol Chemical compound CC1=C(C=CC=C1OCCCN1C[C@@H](CC1)O)C1=C(C(=CC=C1)OCCCN(CCC1=CC=CC=C1)C)C YFWBKLCOKIURAV-GDLZYMKVSA-N 0.000 claims 1
- IUYQJMVGGQCYAW-HHHXNRCGSA-N (3R)-1-[3-[2-methyl-3-[2-methyl-3-[3-[methyl(pyridin-2-ylmethyl)amino]propoxy]phenyl]phenoxy]propyl]pyrrolidin-3-ol Chemical compound CC1=C(C=CC=C1OCCCN1C[C@@H](CC1)O)C1=C(C(=CC=C1)OCCCN(CC1=NC=CC=C1)C)C IUYQJMVGGQCYAW-HHHXNRCGSA-N 0.000 claims 1
- ZMDHASBCNOHLFM-HHHXNRCGSA-N (3R)-1-[3-[2-methyl-3-[2-methyl-3-[3-[methyl(pyridin-4-ylmethyl)amino]propoxy]phenyl]phenoxy]propyl]pyrrolidin-3-ol Chemical compound CC1=C(C=CC=C1OCCCN1C[C@@H](CC1)O)C1=C(C(=CC=C1)OCCCN(CC1=CC=NC=C1)C)C ZMDHASBCNOHLFM-HHHXNRCGSA-N 0.000 claims 1
- JCMVCJJPQVNXSQ-AREMUKBSSA-N (3R)-1-[3-[2-methyl-3-[2-methyl-3-[3-[methyl-[2-[2-(methylamino)ethoxy]ethyl]amino]propoxy]phenyl]phenoxy]propyl]pyrrolidin-3-ol Chemical compound CC1=C(C=CC=C1OCCCN1C[C@@H](CC1)O)C1=C(C(=CC=C1)OCCCN(CCOCCNC)C)C JCMVCJJPQVNXSQ-AREMUKBSSA-N 0.000 claims 1
- UDCOHOFRJVUEGM-AREMUKBSSA-N (3R)-1-[3-[2-methyl-3-[3-(3-phenylpropoxy)phenyl]phenoxy]propyl]pyrrolidin-3-ol Chemical compound CC1=C(C=CC=C1OCCCN1C[C@@H](CC1)O)C1=CC(=CC=C1)OCCCC1=CC=CC=C1 UDCOHOFRJVUEGM-AREMUKBSSA-N 0.000 claims 1
- YHEYJBXAADEELQ-FGZHOGPDSA-N (3R)-1-[3-[3-[2-chloro-3-[3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy]phenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound ClC1=C(C=CC=C1OCCCN1C[C@@H](CC1)O)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C YHEYJBXAADEELQ-FGZHOGPDSA-N 0.000 claims 1
- VSJTZCLPKHRPRH-AREMUKBSSA-N (3R)-1-[3-[3-[3-[3-(3-imidazol-1-ylpropylamino)propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound N1(C=NC=C1)CCCNCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C VSJTZCLPKHRPRH-AREMUKBSSA-N 0.000 claims 1
- ZVPPJPUZOIVUTB-GDLZYMKVSA-N (3R)-1-[3-[3-[3-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound COC=1C=C2CCN(CC2=CC=1OC)CCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C ZVPPJPUZOIVUTB-GDLZYMKVSA-N 0.000 claims 1
- XNPYNCNECHZDJZ-QZWVJJBASA-N (3R)-1-[3-[3-[3-[3-[(2-hydroxy-1-pyridin-4-ylethyl)amino]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound OCC(C1=CC=NC=C1)NCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C XNPYNCNECHZDJZ-QZWVJJBASA-N 0.000 claims 1
- BNNLKLMGJWJKAC-QZWVJJBASA-N (3R)-1-[3-[3-[3-[3-[(2-hydroxy-2-pyridin-3-ylethyl)amino]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound OC(CNCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C)C=1C=NC=CC=1 BNNLKLMGJWJKAC-QZWVJJBASA-N 0.000 claims 1
- FNOQQPWACKVFEW-DNQXCXABSA-N (3R)-1-[3-[3-[3-[3-[(3R)-3-fluoropyrrolidin-1-yl]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound F[C@H]1CN(CC1)CCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C FNOQQPWACKVFEW-DNQXCXABSA-N 0.000 claims 1
- IYMILTTVAXIHRW-JWQCQUIFSA-N (3R)-1-[3-[3-[3-[3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]piperidine-3-carboxylic acid Chemical compound O[C@H]1CN(CC1)CCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CCC1)C(=O)O)C)C IYMILTTVAXIHRW-JWQCQUIFSA-N 0.000 claims 1
- HPXNLRDTKCJCDZ-DNQXCXABSA-N (3R)-1-[3-[3-[3-[3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound CC1=C(C=CC=C1OCCCN1C[C@@H](CC1)O)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C HPXNLRDTKCJCDZ-DNQXCXABSA-N 0.000 claims 1
- IXHPUSSTLKYZHV-DNQXCXABSA-N (3R)-1-[3-[3-[3-[3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy]-2-methylphenyl]-4-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound CC1=C(C=CC=C1OCCCN1C[C@@H](CC1)O)C1=CC(=CC=C1C)OCCCN1C[C@@H](CC1)O IXHPUSSTLKYZHV-DNQXCXABSA-N 0.000 claims 1
- VTJJWWVIJXQBIQ-DNQXCXABSA-N (3R)-1-[3-[3-[3-[3-[(3R)-3-hydroxypyrrolidin-1-yl]propoxy]-2-methylphenyl]phenoxy]propyl]pyrrolidin-3-ol Chemical compound CC1=C(C=CC=C1OCCCN1C[C@@H](CC1)O)C1=CC(=CC=C1)OCCCN1C[C@@H](CC1)O VTJJWWVIJXQBIQ-DNQXCXABSA-N 0.000 claims 1
- IEZQRFAPDCUVGU-RUZDIDTESA-N (3R)-1-[3-[3-[3-[3-[2-(4-chloropyrazol-1-yl)ethylamino]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound ClC=1C=NN(C=1)CCNCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C IEZQRFAPDCUVGU-RUZDIDTESA-N 0.000 claims 1
- CYNGYKDELPIQQQ-OFSOJUDTSA-N (3R)-1-[3-[3-[3-[3-[[(1R)-2-hydroxy-1-phenylethyl]amino]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound OC[C@@H](C1=CC=CC=C1)NCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C CYNGYKDELPIQQQ-OFSOJUDTSA-N 0.000 claims 1
- CYNGYKDELPIQQQ-POURPWNDSA-N (3R)-1-[3-[3-[3-[3-[[(1S)-2-hydroxy-1-phenylethyl]amino]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound OC[C@H](C1=CC=CC=C1)NCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C CYNGYKDELPIQQQ-POURPWNDSA-N 0.000 claims 1
- CMCZELPZYAAQHT-OFSOJUDTSA-N (3R)-1-[3-[3-[3-[3-[[(2R)-2-hydroxy-2-phenylethyl]amino]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound O[C@@H](CNCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C)C1=CC=CC=C1 CMCZELPZYAAQHT-OFSOJUDTSA-N 0.000 claims 1
- IIPCFTKEDHLOME-FYBSXPHGSA-N (3R)-1-[3-[3-[3-[3-[[(2S)-2-(3-chloro-4-fluorophenyl)-2-hydroxyethyl]amino]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound ClC=1C=C(C=CC=1F)[C@@H](CNCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C)O IIPCFTKEDHLOME-FYBSXPHGSA-N 0.000 claims 1
- CMCZELPZYAAQHT-POURPWNDSA-N (3R)-1-[3-[3-[3-[3-[[(2S)-2-hydroxy-2-phenylethyl]amino]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound O[C@H](CNCCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C)C1=CC=CC=C1 CMCZELPZYAAQHT-POURPWNDSA-N 0.000 claims 1
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- ADSFSZYYGNVUHL-GDLZYMKVSA-N (3R)-1-[3-[3-[3-[3-[benzyl(2-hydroxyethyl)amino]propoxy]-2-methylphenyl]-2-methylphenoxy]propyl]pyrrolidin-3-ol Chemical compound C(C1=CC=CC=C1)N(CCCOC=1C(=C(C=CC=1)C1=C(C(=CC=C1)OCCCN1C[C@@H](CC1)O)C)C)CCO ADSFSZYYGNVUHL-GDLZYMKVSA-N 0.000 claims 1
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Families Citing this family (103)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10745382B2 (en) | 2015-10-15 | 2020-08-18 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| WO2018005374A1 (en) | 2016-06-27 | 2018-01-04 | Chemocentryx, Inc. | Immunomodulator compounds |
| IL265921B2 (en) | 2016-10-14 | 2024-05-01 | Prec Biosciences Inc | Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome |
| JP7106572B2 (ja) | 2016-12-20 | 2022-07-26 | ブリストル－マイヤーズ スクイブ カンパニー | 免疫調節剤として有用な化合物 |
| WO2018124766A2 (ko) | 2016-12-28 | 2018-07-05 | 주식회사 녹십자랩셀 | 키메라 항원 수용체 및 이를 발현하는 자연 살해 세포 |
| EP3564237A4 (en) * | 2016-12-29 | 2020-06-10 | Shenzhen Chipscreen Biosciences Co., Ltd. | UREA COMPOUND AND PRODUCTION METHOD AND USE THEREOF |
| KR20190133714A (ko) | 2017-03-27 | 2019-12-03 | 브리스톨-마이어스 스큅 컴퍼니 | 면역조정제로서 유용한 치환된 이소퀴놀린 유도체 |
| BR102018007822A2 (pt) | 2017-04-20 | 2018-11-06 | Gilead Sciences, Inc. | composto, métodos para inibir pd-1, pd-l1 e/ou interação de pd-1/pd-l1 e para tratamento de câncer, composição farmacêutica, e, kit para tratamento de ou prevenção de câncer ou uma doença ou condição |
| US11130740B2 (en) | 2017-04-25 | 2021-09-28 | Arbutus Biopharma Corporation | Substituted 2,3-dihydro-1H-indene analogs and methods using same |
| WO2019008156A1 (en) * | 2017-07-07 | 2019-01-10 | Rijksuniversiteit Groningen | INHIBITORS OF PROTEIN / PROTEIN INTERACTION PD-1 / PD-L1 |
| AU2018306619B2 (en) | 2017-07-28 | 2022-06-02 | Chemocentryx, Inc. | Immunomodulator compounds |
| CN111225665B (zh) | 2017-08-08 | 2023-12-08 | 凯莫森特里克斯股份有限公司 | 大环免疫调节剂 |
| US12116417B2 (en) | 2017-11-14 | 2024-10-15 | GC Cell Corporation | Anti-HER2 antibody or antigen-binding fragment thereof, and chimeric antigen receptor comprising same |
| US11649294B2 (en) | 2017-11-14 | 2023-05-16 | GC Cell Corporation | Anti-HER2 antibody or antigen-binding fragment thereof, and chimeric antigen receptor comprising same |
| CN111511754B (zh) | 2017-12-20 | 2023-09-12 | 捷克共和国有机化学与生物化学研究所 | 活化sting转接蛋白的具有膦酸酯键的2’3’环状二核苷酸 |
| US10966999B2 (en) | 2017-12-20 | 2021-04-06 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3′3′ cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
| JP7214752B2 (ja) | 2018-01-23 | 2023-01-30 | ブリストル－マイヤーズ スクイブ カンパニー | 免疫調節剤として有用な２，８－ジアシル－２，８－ジアザスピロ［５．５］ウンデカン化合物 |
| TWI707849B (zh) | 2018-02-13 | 2020-10-21 | 美商基利科學股份有限公司 | Pd‐1/pd‐l1抑制劑 |
| JP7387616B2 (ja) | 2018-02-22 | 2023-11-28 | ケモセントリックス，インコーポレイティド | Ｐｄ－ｌ１アンタゴニストとしてのインダン－アミン |
| PL3759109T3 (pl) | 2018-02-26 | 2024-03-04 | Gilead Sciences, Inc. | Podstawione związki pirolizyny jako inhibitory replikacji hbv |
| EP3759093B1 (en) | 2018-03-01 | 2022-11-30 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| US12083118B2 (en) * | 2018-03-29 | 2024-09-10 | Arbutus Biopharma Corporation | Substituted 1,1′-biphenyl compounds, analogues thereof, and methods using same |
| WO2019195181A1 (en) | 2018-04-05 | 2019-10-10 | Gilead Sciences, Inc. | Antibodies and fragments thereof that bind hepatitis b virus protein x |
| TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
| TWI833744B (zh) | 2018-04-06 | 2024-03-01 | 捷克科學院有機化學與生物化學研究所 | 3'3'-環二核苷酸 |
| TW202005654A (zh) | 2018-04-06 | 2020-02-01 | 捷克科學院有機化學與生物化學研究所 | ２，２，─環二核苷酸 |
| TW201945388A (zh) | 2018-04-12 | 2019-12-01 | 美商精密生物科學公司 | 對b型肝炎病毒基因體中之識別序列具有特異性之最佳化之經工程化巨核酸酶 |
| KR102591947B1 (ko) * | 2018-04-19 | 2023-10-25 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| WO2019211799A1 (en) | 2018-05-03 | 2019-11-07 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide |
| EP3810109B1 (en) | 2018-05-31 | 2024-08-07 | Peloton Therapeutics, Inc. | Compounds and compositions for inhibiting cd73 |
| EP3820572B1 (en) | 2018-07-13 | 2023-08-16 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| CN112424185B (zh) * | 2018-07-13 | 2024-05-17 | 广州丹康医药生物有限公司 | 含苯环的化合物、其制备方法及应用 |
| TWI869058B (zh) | 2018-07-27 | 2025-01-01 | 加拿大商愛彼特生物製藥公司 | 經取代四氫環戊[c]吡咯、經取代二氫吡咯，其類似物及使用其之方法 |
| WO2020028097A1 (en) | 2018-08-01 | 2020-02-06 | Gilead Sciences, Inc. | Solid forms of (r)-11-(methoxymethyl)-12-(3-methoxypropoxy)-3,3-dimethyl-8-0x0-2,3,8,13b-tetrahydro-1h-pyrido[2,1-a]pyrrolo[1,2-c] phthalazine-7-c arboxylic acid |
| CN109305934A (zh) * | 2018-08-07 | 2019-02-05 | 成都海博锐药业有限公司 | 苯醚类衍生物及可药用盐、医药上的用途 |
| CN110872275A (zh) * | 2018-08-31 | 2020-03-10 | 深圳微芯生物科技股份有限公司 | 作为免疫调节剂的联苯化合物及其用途 |
| US11236085B2 (en) | 2018-10-24 | 2022-02-01 | Gilead Sciences, Inc. | PD-1/PD-L1 inhibitors |
| TW202136261A (zh) | 2018-10-31 | 2021-10-01 | 美商基利科學股份有限公司 | 經取代之6-氮雜苯并咪唑化合物 |
| TWI721623B (zh) | 2018-10-31 | 2021-03-11 | 美商基利科學股份有限公司 | 經取代之6-氮雜苯并咪唑化合物 |
| KR20210089195A (ko) | 2018-11-02 | 2021-07-15 | 상하이 맥시노벨 파마수티컬스 씨오., 엘티디. | 비페닐계 화합물, 이의 중간체, 제조 방법, 약학 조성물 및 용도 |
| TW202415643A (zh) | 2018-12-12 | 2024-04-16 | 加拿大商愛彼特生物製藥公司 | 經取代之芳基甲基脲類及雜芳基甲基脲類、其類似物及其使用方法 |
| WO2020144332A1 (en) * | 2019-01-11 | 2020-07-16 | Fundació Institut D'investigació Biomèdica De Bellvitge (Idibell) | Fusion protein with immunosuppressive activity |
| US11766447B2 (en) | 2019-03-07 | 2023-09-26 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3′3′-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| KR102707808B1 (ko) | 2019-03-07 | 2024-09-19 | 인스티튜트 오브 오가닉 케미스트리 앤드 바이오케미스트리 에이에스 씨알 브이.브이.아이. | 2'3'-사이클릭 다이뉴클레오티드 및 이의 프로드럭 |
| EP3935066A1 (en) | 2019-03-07 | 2022-01-12 | Institute of Organic Chemistry and Biochemistry ASCR, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| CN113891748A (zh) | 2019-03-28 | 2022-01-04 | 百时美施贵宝公司 | 治疗肿瘤的方法 |
| KR20210146348A (ko) | 2019-03-28 | 2021-12-03 | 브리스톨-마이어스 스큅 컴퍼니 | 종양을 치료하는 방법 |
| TW202210480A (zh) | 2019-04-17 | 2022-03-16 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TW202212339A (zh) | 2019-04-17 | 2022-04-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| AU2020276277B2 (en) | 2019-05-15 | 2025-03-20 | Chemocentryx, Inc. | Triaryl compounds for treatment of PD-L1 diseases |
| US20220251141A1 (en) * | 2019-05-21 | 2022-08-11 | Bristol-Myers Squibb Company | Immunomodulators |
| US11453681B2 (en) | 2019-05-23 | 2022-09-27 | Gilead Sciences, Inc. | Substituted eneoxindoles and uses thereof |
| JP2022534967A (ja) | 2019-05-30 | 2022-08-04 | ブリストル－マイヤーズ スクイブ カンパニー | 多腫瘍遺伝子シグネチャーおよびその使用 |
| EP3977132A1 (en) | 2019-05-30 | 2022-04-06 | Bristol-Myers Squibb Company | Cell localization signature and combination therapy |
| KR20220016155A (ko) | 2019-05-30 | 2022-02-08 | 브리스톨-마이어스 스큅 컴퍼니 | 면역-종양학 (i-o) 요법에 적합한 대상체를 확인하는 방법 |
| CN112028870B (zh) * | 2019-06-04 | 2021-11-05 | 中国科学院上海药物研究所 | 一种具有苄氧基芳环结构的化合物，其制备方法和用途 |
| SG11202112875UA (en) | 2019-06-20 | 2021-12-30 | Chemocentryx Inc | Compounds for treatment of pd-l1 diseases |
| BR112021025888A2 (pt) | 2019-07-10 | 2022-04-26 | Chemocentryx Inc | Indanos como inibidores de pd-l1 |
| WO2021011891A1 (en) | 2019-07-18 | 2021-01-21 | Gilead Sciences, Inc. | Long-acting formulations of tenofovir alafenamide |
| WO2021034804A1 (en) | 2019-08-19 | 2021-02-25 | Gilead Sciences, Inc. | Pharmaceutical formulations of tenofovir alafenamide |
| CN111909108B (zh) * | 2019-09-02 | 2023-05-02 | 中国药科大学 | 联苯类化合物及其制备方法和医药用途 |
| CA3153777A1 (en) | 2019-09-22 | 2021-03-25 | Bristol-Myers Squibb Company | Quantitative spatial profiling for lag-3 antagonist therapy |
| CN119770638A (zh) | 2019-09-30 | 2025-04-08 | 吉利德科学公司 | Hbv疫苗和治疗hbv的方法 |
| KR20220079893A (ko) * | 2019-10-04 | 2022-06-14 | 브리스톨-마이어스 스큅 컴퍼니 | 면역조정제로서 유용한 화합물 |
| AU2020368393B2 (en) | 2019-10-16 | 2026-01-08 | Chemocentryx, Inc. | Heteroaryl-biphenyl amides for the treatment of PD-L1 diseases |
| CN114555080B (zh) | 2019-10-16 | 2025-10-10 | 凯莫森特里克斯股份有限公司 | 用于治疗pd-l1疾病的杂芳基联苯胺 |
| BR112022008191A2 (pt) | 2019-11-08 | 2022-07-12 | Bristol Myers Squibb Co | Terapia com antagonista de lag-3 para melanoma |
| US12410418B2 (en) | 2019-12-06 | 2025-09-09 | Precision Biosciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome |
| US11718637B2 (en) | 2020-03-20 | 2023-08-08 | Gilead Sciences, Inc. | Prodrugs of 4′-C-substituted-2-halo-2′- deoxyadenosine nucleosides and methods of making and using the same |
| BR112022022335A2 (pt) | 2020-05-05 | 2023-01-10 | Teon Therapeutics Inc | Moduladores de receptor canabinoide tipo 2 (cb2) e usos dos mesmos |
| CN114075123B (zh) | 2020-08-11 | 2023-06-06 | 中国人民解放军军事科学院军事医学研究院 | 苄胺类衍生物及其制备方法与用途 |
| BR112023003427A2 (pt) | 2020-08-28 | 2023-03-21 | Bristol Myers Squibb Co | Terapia com antagonista de lag-3 para carcinoma hepatocelular |
| AU2021334361A1 (en) | 2020-08-31 | 2023-05-11 | Bristol-Myers Squibb Company | Cell localization signature and immunotherapy |
| TW202214568A (zh) | 2020-09-09 | 2022-04-16 | 大陸商廣州再極醫藥科技有限公司 | 芳香乙烯類化合物、其製備方法、中間體、藥物組合物及其應用 |
| US11833209B2 (en) | 2020-09-11 | 2023-12-05 | Nammi Therapeutics, Inc. | Formulated and/or co-formulated liposome compositions containing PD-1 antagonist prodrugs useful in the treatment of cancer and methods thereof |
| WO2022087402A1 (en) | 2020-10-23 | 2022-04-28 | Bristol-Myers Squibb Company | Lag-3 antagonist therapy for lung cancer |
| WO2022120179A1 (en) | 2020-12-03 | 2022-06-09 | Bristol-Myers Squibb Company | Multi-tumor gene signatures and uses thereof |
| US20240181052A1 (en) | 2021-03-29 | 2024-06-06 | Juno Therapeutics, Inc. | Methods for dosing and treatment with a combination of a checkpoint inhibitor therapy and a car t cell therapy |
| CN113135895A (zh) * | 2021-04-30 | 2021-07-20 | 中国药科大学 | 一种新型联苯类衍生物及其制备方法与医药用途 |
| EP4337223A1 (en) | 2021-05-13 | 2024-03-20 | Gilead Sciences, Inc. | Combination of a tlr8 modulating compound and anti-hbv sirna therapeutics |
| JP7673255B2 (ja) | 2021-06-11 | 2025-05-08 | ギリアード サイエンシーズ， インコーポレイテッド | Ｍｃｌ－１阻害剤と抗体薬物コンジュゲートとの組み合わせ |
| TWI910028B (zh) | 2021-06-11 | 2025-12-21 | 美商基利科學股份有限公司 | Mcl-1抑制劑與抗癌劑之組合 |
| WO2022271659A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| CA3222277A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| KR20240005901A (ko) | 2021-06-23 | 2024-01-12 | 길리애드 사이언시즈, 인코포레이티드 | 디아실글리세롤 키나제 조절 화합물 |
| WO2022271677A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| CN115677665B (zh) * | 2021-07-26 | 2024-04-19 | 中国药科大学 | 含联苯类衍生物及其医药用途 |
| WO2023034530A1 (en) | 2021-09-02 | 2023-03-09 | Teon Therapeutics, Inc. | Methods of improving growth and function of immune cells |
| KR20240099362A (ko) | 2021-10-29 | 2024-06-28 | 브리스톨-마이어스 스큅 컴퍼니 | 혈액암에 대한 lag-3 길항제 요법 |
| WO2023081730A1 (en) | 2021-11-03 | 2023-05-11 | Teon Therapeutics, Inc. | 4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide derivatives as cannabinoid cb2 receptor modulators for the treatment of cancer |
| WO2023097211A1 (en) | 2021-11-24 | 2023-06-01 | The University Of Southern California | Methods for enhancing immune checkpoint inhibitor therapy |
| CA3249004A1 (en) | 2022-01-26 | 2023-08-03 | Bristol-Myers Squibb Company | Polytherapy for Hepatocellular Carcinoma |
| US20230326022A1 (en) | 2022-04-08 | 2023-10-12 | Bristol-Myers Squibb Company | Machine Learning Identification, Classification, and Quantification of Tertiary Lymphoid Structures |
| EP4554943A1 (en) | 2022-07-14 | 2025-05-21 | Teon Therapeutics, Inc. | Adenosine receptor antagonists and uses thereof |
| CN120731228A (zh) | 2022-12-21 | 2025-09-30 | 百时美施贵宝公司 | 肺癌的组合疗法 |
| KR20250150141A (ko) | 2023-02-23 | 2025-10-17 | 선샤인 레이크 파르마 컴퍼니 리미티드 | 피리도피리미딘 유도체 및 이의 용도 |
| WO2024196952A1 (en) | 2023-03-20 | 2024-09-26 | Bristol-Myers Squibb Company | Tumor subtype assessment for cancer therapy |
| WO2025240244A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies comprising bulevirtide and lonafarnib for use in the treatment of hepatitis d virus infection |
| WO2025240246A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| US20250345389A1 (en) | 2024-05-13 | 2025-11-13 | Gilead Sciences, Inc. | Combination therapies |
| WO2025240242A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| WO2025245489A1 (en) | 2024-05-24 | 2025-11-27 | Bristol-Myers Squibb Company | Treatment of tumors in subjects having fgl-1 positive samples |
| WO2026035860A1 (en) | 2024-08-07 | 2026-02-12 | Teon Therapeutics, Inc. | Formulations of adenosine receptor antagonist |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LU75628A1 (https=) * | 1976-08-19 | 1978-04-13 | ||
| CH654286A5 (de) * | 1981-11-04 | 1986-02-14 | Ciba Geigy Ag | Verfahren zur pd-katalysierten arylierung von olefinen mit arylhalogeniden. |
| US6410690B1 (en) | 1995-06-07 | 2002-06-25 | Medarex, Inc. | Therapeutic compounds comprised of anti-Fc receptor antibodies |
| US5811097A (en) | 1995-07-25 | 1998-09-22 | The Regents Of The University Of California | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
| US5977117A (en) | 1996-01-05 | 1999-11-02 | Texas Biotechnology Corporation | Substituted phenyl compounds and derivatives thereof that modulate the activity of endothelin |
| US5922845A (en) | 1996-07-11 | 1999-07-13 | Medarex, Inc. | Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies |
| AU2003281040A1 (en) | 2002-07-10 | 2004-02-02 | Sumitomo Pharmaceuticals Co., Ltd. | Biaryl derivatives |
| EP1603858A2 (en) | 2003-03-11 | 2005-12-14 | NeuroSearch A/S | Kcnq channel modulating compounds and their pharmaceutical use |
| JP2005179281A (ja) | 2003-12-19 | 2005-07-07 | Sumitomo Pharmaceut Co Ltd | ビフェニル化合物 |
| WO2005080367A1 (en) | 2004-02-12 | 2005-09-01 | Pharmagene Laboratories Limited | Ep2 receptor agonists |
| EP1717235A3 (en) | 2005-04-29 | 2007-02-28 | Bioprojet | Phenoxypropylpiperidines and -pyrrolidines and their use as histamine H3-receptor ligands |
| CA2618486A1 (en) | 2005-08-09 | 2007-02-15 | Asterand Uk Limited | Ep2 receptor agonists |
| TW200815377A (en) | 2006-04-24 | 2008-04-01 | Astellas Pharma Inc | Oxadiazolidinedione compound |
| EP2139843B1 (en) | 2007-04-16 | 2013-12-25 | Amgen, Inc | Substituted biphenyl phenoxy-, thiophenyl- and aminophenylpropanoic acid gpr40 modulators |
| TW200932219A (en) * | 2007-10-24 | 2009-08-01 | Astellas Pharma Inc | Oxadiazolidinedione compound |
| TWI444467B (zh) | 2010-05-27 | 2014-07-11 | Angus Chemical | 用於液體碳氫化合物及其他燃料與油之標記物化合物 |
| JP6417419B2 (ja) | 2013-09-04 | 2018-11-07 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 免疫調節剤として有用な化合物 |
| US9850225B2 (en) * | 2014-04-14 | 2017-12-26 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| WO2017004233A1 (en) * | 2015-06-29 | 2017-01-05 | Vanderbilt University | Intravenous administration of citrulline during surgery |
| US10745382B2 (en) * | 2015-10-15 | 2020-08-18 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| CN109689640B (zh) | 2016-07-08 | 2022-01-04 | 百时美施贵宝公司 | 可用作免疫调节剂的化合物 |
| AU2017305399A1 (en) * | 2016-08-03 | 2019-01-31 | Arising International, Inc. | Symmetric or semi-symmetric compounds useful as immunomodulators |
-
2017
- 2017-08-29 US US15/689,115 patent/US10144706B2/en active Active
- 2017-08-30 MA MA046091A patent/MA46091A/fr unknown
- 2017-08-30 AR ARP170102407A patent/AR109471A1/es unknown
- 2017-08-30 EA EA201990495A patent/EA201990495A1/ru unknown
- 2017-08-30 BR BR112019004100A patent/BR112019004100A2/pt not_active Application Discontinuation
- 2017-08-30 KR KR1020197008795A patent/KR102497068B1/ko active Active
- 2017-08-30 MX MX2019002356A patent/MX2019002356A/es unknown
- 2017-08-30 WO PCT/US2017/049252 patent/WO2018044963A1/en not_active Ceased
- 2017-08-30 CN CN201780067319.8A patent/CN109863146B/zh active Active
- 2017-08-30 JP JP2019511947A patent/JP7155110B2/ja active Active
- 2017-08-30 ES ES17764981T patent/ES2919298T3/es active Active
- 2017-08-30 TW TW106129492A patent/TW201815764A/zh unknown
- 2017-08-30 CA CA3035697A patent/CA3035697A1/en not_active Abandoned
- 2017-08-30 AU AU2017319323A patent/AU2017319323A1/en not_active Abandoned
- 2017-08-30 SG SG11201901700UA patent/SG11201901700UA/en unknown
- 2017-08-30 EP EP17764981.1A patent/EP3507284B1/en active Active
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