CA3029829A1 - Tetrahydronaphthyridinepentanamide integrin antagonists - Google Patents
Tetrahydronaphthyridinepentanamide integrin antagonists Download PDFInfo
- Publication number
- CA3029829A1 CA3029829A1 CA3029829A CA3029829A CA3029829A1 CA 3029829 A1 CA3029829 A1 CA 3029829A1 CA 3029829 A CA3029829 A CA 3029829A CA 3029829 A CA3029829 A CA 3029829A CA 3029829 A1 CA3029829 A1 CA 3029829A1
- Authority
- CA
- Canada
- Prior art keywords
- compound according
- hydrocarbyl
- chosen
- patient
- naphthyridin
- 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
- 239000005557 antagonist Substances 0.000 title description 7
- 102000006495 integrins Human genes 0.000 title description 5
- 108010044426 integrins Proteins 0.000 title description 5
- MUCAYJCKFRQNOH-UHFFFAOYSA-N 5-(1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl)pentanamide Chemical compound N1C(CCC2=CC=CN=C12)CCCCC(=O)N MUCAYJCKFRQNOH-UHFFFAOYSA-N 0.000 title description 2
- -1 2-Substituted-4-(5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanamido)butanoic acids Chemical class 0.000 claims abstract description 101
- 150000001875 compounds Chemical class 0.000 claims abstract description 81
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 8
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 8
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 6
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims abstract description 5
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims abstract description 5
- 208000017442 Retinal disease Diseases 0.000 claims abstract description 5
- 208000006386 Bone Resorption Diseases 0.000 claims abstract description 4
- 102100033167 Elastin Human genes 0.000 claims abstract description 4
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 4
- 208000009889 Herpes Simplex Diseases 0.000 claims abstract description 4
- 206010027476 Metastases Diseases 0.000 claims abstract description 4
- 206010038910 Retinitis Diseases 0.000 claims abstract description 4
- 208000002220 Supravalvular aortic stenosis Diseases 0.000 claims abstract description 4
- 206010042971 T-cell lymphoma Diseases 0.000 claims abstract description 4
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims abstract description 4
- 206010049644 Williams syndrome Diseases 0.000 claims abstract description 4
- 206010064930 age-related macular degeneration Diseases 0.000 claims abstract description 4
- 230000024279 bone resorption Effects 0.000 claims abstract description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 4
- 230000004761 fibrosis Effects 0.000 claims abstract description 4
- 201000005206 focal segmental glomerulosclerosis Diseases 0.000 claims abstract description 4
- 231100000854 focal segmental glomerulosclerosis Toxicity 0.000 claims abstract description 4
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 4
- 230000009401 metastasis Effects 0.000 claims abstract description 4
- 208000007056 sickle cell anemia Diseases 0.000 claims abstract description 4
- 230000005747 tumor angiogenesis Effects 0.000 claims abstract description 4
- 230000003213 activating effect Effects 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 60
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims description 34
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 25
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000002252 acyl group Chemical group 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 125000005518 carboxamido group Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 12
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 11
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 11
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 10
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 10
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 8
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 4
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006509 3,4-difluorobenzyl group Chemical group [H]C1=C(F)C(F)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 2
- 125000004175 fluorobenzyl group Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000006657 (C1-C10) hydrocarbyl group Chemical group 0.000 claims 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 15
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- 206010012688 Diabetic retinal oedema Diseases 0.000 claims 1
- 201000011190 diabetic macular edema Diseases 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 129
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 80
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- 239000000243 solution Substances 0.000 description 56
- 239000007787 solid Substances 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 36
- 239000012267 brine Substances 0.000 description 34
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 238000004440 column chromatography Methods 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 29
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 28
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 25
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- 239000007832 Na2SO4 Substances 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- 229910052938 sodium sulfate Inorganic materials 0.000 description 24
- 235000011152 sodium sulphate Nutrition 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 238000003786 synthesis reaction Methods 0.000 description 22
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 18
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- 239000012230 colorless oil Substances 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 15
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- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- BREOKHDXONYFEN-UHFFFAOYSA-N 5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoic acid Chemical compound C1CCNC2=NC(CCCCC(=O)O)=CC=C21 BREOKHDXONYFEN-UHFFFAOYSA-N 0.000 description 13
- 125000000217 alkyl group Chemical group 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 12
- RMHHTJHLXCLWCJ-UHFFFAOYSA-N methyl 2-amino-4-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]butanoate Chemical compound COC(=O)C(N)CCNC(=O)CCCCC1=CC=C2CCCNC2=N1 RMHHTJHLXCLWCJ-UHFFFAOYSA-N 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 239000007821 HATU Substances 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 8
- UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 8
- 125000004414 alkyl thio group Chemical group 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 7
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
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- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 5
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- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- AMLYAMJWYAIXIA-VWNVYAMZSA-N cilengitide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C(C)C)N(C)C(=O)[C@H]1CC1=CC=CC=C1 AMLYAMJWYAIXIA-VWNVYAMZSA-N 0.000 description 5
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- 239000003446 ligand Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
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- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 4
- SQVZMSGXNWZEOP-JOCHJYFZSA-N methyl (2R)-2-(phenylmethoxycarbonylamino)-4-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]butanoate Chemical compound COC(=O)[C@@H](CCNC(=O)CCCCC1=CC=C2CCCNC2=N1)NC(=O)OCC1=CC=CC=C1 SQVZMSGXNWZEOP-JOCHJYFZSA-N 0.000 description 4
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- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical group C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- NGESLMKARBNZQO-UHFFFAOYSA-N 1-hydroxybenzotriazole;dihydrate Chemical compound O.O.C1=CC=C2N(O)N=NC2=C1 NGESLMKARBNZQO-UHFFFAOYSA-N 0.000 description 3
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 3
- OISKFAUXWSTTEN-UHFFFAOYSA-N 2-[(4-methylphenyl)sulfonylamino]-4-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]butanoic acid Chemical compound CC1=CC=C(C=C1)S(=O)(=O)NC(CCNC(=O)CCCCC1=CC=C2CCCNC2=N1)C(O)=O OISKFAUXWSTTEN-UHFFFAOYSA-N 0.000 description 3
- CQDLXXJPIPUBGV-UHFFFAOYSA-N 2-amino-4-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]butanoic acid Chemical compound NC(CCNC(=O)CCCCC1=CC=C2CCCNC2=N1)C(O)=O CQDLXXJPIPUBGV-UHFFFAOYSA-N 0.000 description 3
- CQIUQKLZKFYVSE-UHFFFAOYSA-N 5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoic acid;hydrochloride Chemical compound Cl.C1CCNC2=NC(CCCCC(=O)O)=CC=C21 CQIUQKLZKFYVSE-UHFFFAOYSA-N 0.000 description 3
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
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- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 238000007664 blowing Methods 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
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- YTEZLWCWWMGBAR-FQEVSTJZSA-N methyl (2S)-2-(1,3-benzoxazol-2-ylamino)-4-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]butanoate Chemical compound COC(=O)[C@H](CCNC(=O)CCCCC1=CC=C2CCCNC2=N1)NC1=NC2=C(O1)C=CC=C2 YTEZLWCWWMGBAR-FQEVSTJZSA-N 0.000 description 1
- SQVZMSGXNWZEOP-QFIPXVFZSA-N methyl (2S)-2-(phenylmethoxycarbonylamino)-4-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]butanoate Chemical compound COC(=O)[C@H](CCNC(=O)CCCCC1=CC=C2CCCNC2=N1)NC(=O)OCC1=CC=CC=C1 SQVZMSGXNWZEOP-QFIPXVFZSA-N 0.000 description 1
- CPIQIOZCUNYYJA-DEOSSOPVSA-N methyl (2S)-2-[(5-phenylpyrimidin-2-yl)amino]-4-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]butanoate Chemical compound COC(=O)[C@H](CCNC(=O)CCCCC1=CC=C2CCCNC2=N1)NC1=NC=C(C=N1)C1=CC=CC=C1 CPIQIOZCUNYYJA-DEOSSOPVSA-N 0.000 description 1
- FYAGUOZFQPGKMN-INIZCTEOSA-N methyl (2S)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-2-[(5-phenylpyrimidin-2-yl)amino]butanoate Chemical compound C(C)(C)(C)OC(=O)NCC[C@@H](C(=O)OC)NC1=NC=C(C=N1)C1=CC=CC=C1 FYAGUOZFQPGKMN-INIZCTEOSA-N 0.000 description 1
- LWOHDYABQSVXIE-SSDOTTSWSA-N methyl (2r)-2-amino-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate Chemical compound COC(=O)[C@H](N)CCNC(=O)OC(C)(C)C LWOHDYABQSVXIE-SSDOTTSWSA-N 0.000 description 1
- LWOHDYABQSVXIE-ZETCQYMHSA-N methyl (2s)-2-amino-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate Chemical compound COC(=O)[C@@H](N)CCNC(=O)OC(C)(C)C LWOHDYABQSVXIE-ZETCQYMHSA-N 0.000 description 1
- LEYNRAGKUYDVEB-UHFFFAOYSA-N methyl 2-(1,3-benzoxazol-2-ylamino)-4-[5-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]butanoate Chemical compound O1C(=NC2=C1C=CC=C2)NC(C(=O)OC)CCNC(CCCCC1=NC=2NCCCC=2C=C1C1CC1)=O LEYNRAGKUYDVEB-UHFFFAOYSA-N 0.000 description 1
- LYKLKASYXAFAQH-UHFFFAOYSA-N methyl 4-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(4-phenyltriazol-1-yl)butanoate Chemical compound C(C)(C)(C)OC(=O)NCCC(C(=O)OC)N1N=NC(=C1)C1=CC=CC=C1 LYKLKASYXAFAQH-UHFFFAOYSA-N 0.000 description 1
- MXPZKNZHCNWNMY-UHFFFAOYSA-N methyl 4-amino-2-(phenylmethoxycarbonylamino)butanoate Chemical compound COC(=O)C(CCN)NC(=O)OCC1=CC=CC=C1 MXPZKNZHCNWNMY-UHFFFAOYSA-N 0.000 description 1
- OXTGQSXGROVGAW-UHFFFAOYSA-N methyl 4-amino-2-(phenylmethoxycarbonylamino)butanoate hydrochloride Chemical compound Cl.NCCC(C(=O)OC)NC(=O)OCC1=CC=CC=C1 OXTGQSXGROVGAW-UHFFFAOYSA-N 0.000 description 1
- QTLYBWBLXVVGLF-UHFFFAOYSA-N methyl 4-amino-2-benzylbutanoate hydrochloride Chemical compound Cl.NCCC(C(=O)OC)CC1=CC=CC=C1 QTLYBWBLXVVGLF-UHFFFAOYSA-N 0.000 description 1
- RSENCDQCULGKMU-UHFFFAOYSA-N methyl 4-amino-2-methylbutanoate;hydrochloride Chemical compound Cl.COC(=O)C(C)CCN RSENCDQCULGKMU-UHFFFAOYSA-N 0.000 description 1
- BMZFBGUUHVSOSB-UHFFFAOYSA-N methyl 4-amino-2-phenylbutanoate;hydrochloride Chemical compound Cl.COC(=O)C(CCN)C1=CC=CC=C1 BMZFBGUUHVSOSB-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- HUPQYPMULVBQDL-UHFFFAOYSA-N pentanoic acid Chemical compound CCCCC(O)=O.CCCCC(O)=O HUPQYPMULVBQDL-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 125000005592 polycycloalkyl group Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- MVQJVRJKYYGPAN-UHFFFAOYSA-N tert-butyl 3-cyano-2-(6-phenoxypyridin-3-yl)propanoate Chemical compound C(#N)CC(C(=O)OC(C)(C)C)C=1C=NC(=CC=1)OC1=CC=CC=C1 MVQJVRJKYYGPAN-UHFFFAOYSA-N 0.000 description 1
- PWDOXXVLDZRYBZ-UHFFFAOYSA-N tert-butyl 4-amino-2-quinolin-3-ylbutanoate Chemical compound NCCC(C(=O)OC(C)(C)C)C=1C=NC2=CC=CC=C2C=1 PWDOXXVLDZRYBZ-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- GSQBIOQCECCMOQ-UHFFFAOYSA-N β-alanine ethyl ester Chemical compound CCOC(=O)CCN GSQBIOQCECCMOQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61K31/435—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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662358330P | 2016-07-05 | 2016-07-05 | |
| US62/358,330 | 2016-07-05 | ||
| US201662374234P | 2016-08-12 | 2016-08-12 | |
| US62/374,234 | 2016-08-12 | ||
| PCT/US2017/040657 WO2018009501A1 (en) | 2016-07-05 | 2017-07-05 | Tetrahydronaphthyridinepentanamide integrin antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3029829A1 true CA3029829A1 (en) | 2018-01-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3029829A Abandoned CA3029829A1 (en) | 2016-07-05 | 2017-07-05 | Tetrahydronaphthyridinepentanamide integrin antagonists |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US11192889B2 (https=) |
| EP (1) | EP3481814B1 (https=) |
| JP (1) | JP2019524702A (https=) |
| KR (1) | KR20190026001A (https=) |
| CN (1) | CN109476632A (https=) |
| AU (1) | AU2017292754B2 (https=) |
| CA (1) | CA3029829A1 (https=) |
| MX (1) | MX2019000043A (https=) |
| WO (1) | WO2018009501A1 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3509590A4 (en) | 2016-09-07 | 2020-12-02 | Pliant Therapeutics, Inc. | N-ACYL AMINO ACID COMPOUNDS AND METHODS OF USE |
| MX394210B (es) | 2017-02-28 | 2025-03-04 | Morphic Therapeutic Inc | INHIBIDORES DE INTEGRINA AVß6. |
| MA52117A (fr) | 2017-02-28 | 2022-04-06 | Morphic Therapeutic Inc | Inhibiteurs de l'intégrine (alpha-v) (bêta-6) |
| FI3761980T3 (fi) * | 2018-03-07 | 2024-02-21 | Pliant Therapeutics Inc | Aminohappoyhdisteitä ja käyttömenetelmiä |
| TWI841573B (zh) | 2018-06-27 | 2024-05-11 | 美商普萊恩醫療公司 | 具有未分支連接子之胺基酸化合物及使用方法 |
| AU2019318538B2 (en) | 2018-08-08 | 2025-02-06 | The General Hospital Corporation | Polypeptide integrin antagonists |
| WO2020047208A1 (en) | 2018-08-29 | 2020-03-05 | Morphic Therapeutic, Inc. | Inhibitors of (alpha-v)(beta-6) integrin |
| WO2020047239A1 (en) | 2018-08-29 | 2020-03-05 | Morphic Therapeutic, Inc. | INHIBITING αV β6 INTEGRIN |
| SI3844162T1 (sl) | 2018-08-29 | 2025-06-30 | Morphic Therapeutic, Inc. | Zaviralci integrina alfa v beta6 |
| TW202028179A (zh) | 2018-10-08 | 2020-08-01 | 美商普萊恩醫療公司 | 胺基酸化合物及使用方法 |
| CN114173803A (zh) * | 2019-04-08 | 2022-03-11 | 普利安特治疗公司 | 氨基酸化合物的剂型和方案 |
| TW202329973A (zh) * | 2021-10-14 | 2023-08-01 | 美商普萊恩醫療公司 | 整合素抑制劑及其與其他藥劑併用之用途 |
| WO2024125634A1 (zh) * | 2022-12-16 | 2024-06-20 | 西藏海思科制药有限公司 | 一种四氢萘啶类化合物及其在医药上的应用 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6048861A (en) * | 1997-12-17 | 2000-04-11 | Merck & Co., Inc. | Integrin receptor antagonists |
| KR20010033248A (ko) * | 1997-12-17 | 2001-04-25 | 폴락 돈나 엘. | 인테그린 수용체 길항제 |
| CN1589145A (zh) * | 1999-06-02 | 2005-03-02 | 麦克公司 | αv整联蛋白受体拮抗剂 |
| FR2808798A1 (fr) | 2000-05-09 | 2001-11-16 | Hoechst Marion Roussel Inc | Nouveaux derives antagonistes du recepteur de la vitronectine |
| AU7793501A (en) * | 2000-07-26 | 2002-02-05 | Merck & Co Inc | Alpha v integrin receptor antagonists |
| EP1389205B1 (en) * | 2001-04-09 | 2005-12-21 | Ortho-McNeil Pharmaceutical Research Inc. | Quinazoline and quinazoline-like compounds for the treatment of integrin-mediated disorders |
| JP2003277340A (ja) * | 2002-03-22 | 2003-10-02 | Toray Ind Inc | 接着分子阻害剤及び新規アミノ酸誘導体 |
| EP2456460A4 (en) | 2009-07-24 | 2013-02-20 | Univ California | METHOD AND COMPOSITIONS FOR TREATING AND PREVENTING DISEASES ASSOCIATED WITH AVB5 INTEGRIN |
| PT2953948T (pt) * | 2013-02-07 | 2017-12-12 | Scifluor Life Sciences Inc | Antagonistas de integrina fluorada |
| US8901144B2 (en) | 2013-02-07 | 2014-12-02 | Scifluor Life Sciences, Llc | Fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives |
-
2017
- 2017-07-05 US US16/315,093 patent/US11192889B2/en active Active
- 2017-07-05 WO PCT/US2017/040657 patent/WO2018009501A1/en not_active Ceased
- 2017-07-05 EP EP17824775.5A patent/EP3481814B1/en not_active Not-in-force
- 2017-07-05 AU AU2017292754A patent/AU2017292754B2/en active Active
- 2017-07-05 KR KR1020197003579A patent/KR20190026001A/ko not_active Ceased
- 2017-07-05 CN CN201780042122.9A patent/CN109476632A/zh active Pending
- 2017-07-05 JP JP2019500301A patent/JP2019524702A/ja active Pending
- 2017-07-05 CA CA3029829A patent/CA3029829A1/en not_active Abandoned
- 2017-07-05 MX MX2019000043A patent/MX2019000043A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20190026001A (ko) | 2019-03-12 |
| EP3481814A4 (en) | 2019-12-04 |
| EP3481814A1 (en) | 2019-05-15 |
| WO2018009501A1 (en) | 2018-01-11 |
| EP3481814B1 (en) | 2022-04-27 |
| JP2019524702A (ja) | 2019-09-05 |
| AU2017292754A1 (en) | 2019-01-24 |
| AU2017292754B2 (en) | 2021-06-17 |
| US11192889B2 (en) | 2021-12-07 |
| CN109476632A (zh) | 2019-03-15 |
| MX2019000043A (es) | 2019-07-04 |
| US20200181138A1 (en) | 2020-06-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20231003 |