CA3042684A1 - Azole amides and amines as .alpha.v integrin inhibitors - Google Patents
Azole amides and amines as .alpha.v integrin inhibitors Download PDFInfo
- Publication number
- CA3042684A1 CA3042684A1 CA3042684A CA3042684A CA3042684A1 CA 3042684 A1 CA3042684 A1 CA 3042684A1 CA 3042684 A CA3042684 A CA 3042684A CA 3042684 A CA3042684 A CA 3042684A CA 3042684 A1 CA3042684 A1 CA 3042684A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- aryl
- heteroaryl
- alkoxy
- halo
- 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
- -1 Azole amides Chemical class 0.000 title claims description 241
- 102000006495 integrins Human genes 0.000 title abstract description 30
- 108010044426 integrins Proteins 0.000 title abstract description 30
- 239000003112 inhibitor Substances 0.000 title abstract description 21
- 150000001412 amines Chemical class 0.000 title description 8
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title description 7
- 238000000034 method Methods 0.000 claims abstract description 327
- 150000001875 compounds Chemical class 0.000 claims abstract description 144
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 19
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 17
- 230000004761 fibrosis Effects 0.000 claims abstract description 17
- 201000011510 cancer Diseases 0.000 claims abstract description 13
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 9
- 230000001575 pathological effect Effects 0.000 claims abstract description 7
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 3
- 206010052779 Transplant rejections Diseases 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims description 131
- 125000000623 heterocyclic group Chemical group 0.000 claims description 89
- 125000003118 aryl group Chemical group 0.000 claims description 86
- 125000003545 alkoxy group Chemical group 0.000 claims description 75
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 73
- 125000005843 halogen group Chemical group 0.000 claims description 64
- 125000001072 heteroaryl group Chemical group 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 62
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 57
- 239000001257 hydrogen Substances 0.000 claims description 54
- 125000001188 haloalkyl group Chemical group 0.000 claims description 49
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 47
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims description 43
- 229910003827 NRaRb Inorganic materials 0.000 claims description 42
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 42
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 38
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 38
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 38
- 125000004429 atom Chemical group 0.000 claims description 36
- 229940124530 sulfonamide Drugs 0.000 claims description 34
- 150000003456 sulfonamides Chemical group 0.000 claims description 34
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 29
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical group NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 28
- 125000003368 amide group Chemical group 0.000 claims description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 27
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 24
- 239000004475 Arginine Substances 0.000 claims description 24
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 20
- 125000004043 oxo group Chemical group O=* 0.000 claims description 19
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 15
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- 239000003937 drug carrier Substances 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 8
- 210000004185 liver Anatomy 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
- 201000009594 Systemic Scleroderma Diseases 0.000 claims description 6
- 206010042953 Systemic sclerosis Diseases 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 125000005884 carbocyclylalkyl group Chemical group 0.000 claims description 6
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 229910052705 radium Inorganic materials 0.000 claims description 5
- 229910052701 rubidium Inorganic materials 0.000 claims description 5
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 4
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 4
- 125000004992 haloalkylamino group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 3
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 208000020832 chronic kidney disease Diseases 0.000 claims description 3
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 210000002784 stomach Anatomy 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
- 230000000747 cardiac effect Effects 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 210000003679 cervix uteri Anatomy 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 230000002500 effect on skin Effects 0.000 claims description 2
- 210000004696 endometrium Anatomy 0.000 claims description 2
- 210000003238 esophagus Anatomy 0.000 claims description 2
- 210000000232 gallbladder Anatomy 0.000 claims description 2
- 210000004392 genitalia Anatomy 0.000 claims description 2
- 210000003128 head Anatomy 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 210000002429 large intestine Anatomy 0.000 claims description 2
- 210000000867 larynx Anatomy 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 210000002200 mouth mucosa Anatomy 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 210000002850 nasal mucosa Anatomy 0.000 claims description 2
- 210000003739 neck Anatomy 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 210000000813 small intestine Anatomy 0.000 claims description 2
- 210000000952 spleen Anatomy 0.000 claims description 2
- 210000001550 testis Anatomy 0.000 claims description 2
- 210000001685 thyroid gland Anatomy 0.000 claims description 2
- 210000003932 urinary bladder Anatomy 0.000 claims description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 53
- 208000035475 disorder Diseases 0.000 abstract description 34
- 239000012453 solvate Substances 0.000 abstract description 23
- 201000010099 disease Diseases 0.000 abstract description 18
- 230000008482 dysregulation Effects 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 description 311
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 279
- 241000282414 Homo sapiens Species 0.000 description 228
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 226
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 166
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 126
- 238000000547 structure data Methods 0.000 description 123
- 239000000203 mixture Substances 0.000 description 122
- 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 description 116
- 235000019260 propionic acid Nutrition 0.000 description 116
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 105
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 105
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 87
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 73
- 238000005481 NMR spectroscopy Methods 0.000 description 73
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 59
- 239000007787 solid Substances 0.000 description 58
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
- 239000002253 acid Substances 0.000 description 54
- 239000003039 volatile agent Substances 0.000 description 53
- 239000005695 Ammonium acetate Substances 0.000 description 51
- 229940043376 ammonium acetate Drugs 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 51
- 238000005160 1H NMR spectroscopy Methods 0.000 description 50
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 49
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 49
- 235000019257 ammonium acetate Nutrition 0.000 description 49
- 238000002953 preparative HPLC Methods 0.000 description 49
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 47
- 239000012043 crude product Substances 0.000 description 47
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 44
- 239000003814 drug Substances 0.000 description 39
- 239000002245 particle Substances 0.000 description 39
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 36
- 239000000460 chlorine Substances 0.000 description 36
- 239000002904 solvent Substances 0.000 description 35
- 239000012044 organic layer Substances 0.000 description 30
- 239000003921 oil Substances 0.000 description 29
- 235000019198 oils Nutrition 0.000 description 29
- 239000000243 solution Substances 0.000 description 29
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
- 235000019341 magnesium sulphate Nutrition 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- 230000001629 suppression Effects 0.000 description 27
- 150000002148 esters Chemical class 0.000 description 26
- 238000001914 filtration Methods 0.000 description 26
- 238000011282 treatment Methods 0.000 description 26
- 239000000706 filtrate Substances 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- 239000000651 prodrug Substances 0.000 description 22
- 229940002612 prodrug Drugs 0.000 description 22
- 229940124597 therapeutic agent Drugs 0.000 description 21
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 20
- 229910000024 caesium carbonate Inorganic materials 0.000 description 18
- 229910052799 carbon Inorganic materials 0.000 description 18
- 125000001424 substituent group Chemical group 0.000 description 18
- 150000001204 N-oxides Chemical class 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 125000005518 carboxamido group Chemical group 0.000 description 15
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 15
- 238000010898 silica gel chromatography Methods 0.000 description 15
- 238000010511 deprotection reaction Methods 0.000 description 14
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- 125000005842 heteroatom Chemical group 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 229930182821 L-proline Natural products 0.000 description 11
- 150000001721 carbon Chemical group 0.000 description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 description 11
- 229960002429 proline Drugs 0.000 description 11
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 11
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
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- 239000006260 foam Substances 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 125000002950 monocyclic group Chemical group 0.000 description 9
- NXMFJCRMSDRXLD-UHFFFAOYSA-N 2-aminopyridine-3-carbaldehyde Chemical compound NC1=NC=CC=C1C=O NXMFJCRMSDRXLD-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 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
- SZLPRRVCSGZARF-UHFFFAOYSA-N 2-(2-bromoethyl)-2-methyl-1,3-dioxolane Chemical compound BrCCC1(C)OCCO1 SZLPRRVCSGZARF-UHFFFAOYSA-N 0.000 description 7
- 101150041968 CDC13 gene Proteins 0.000 description 7
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 7
- 230000029936 alkylation Effects 0.000 description 7
- 238000005804 alkylation reaction Methods 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 125000003367 polycyclic group Polymers 0.000 description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
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- ONGSQPYHCQJKPP-JTQLQIEISA-N ethyl (3s)-3-amino-3-(3-fluoro-4-methoxyphenyl)propanoate Chemical compound CCOC(=O)C[C@H](N)C1=CC=C(OC)C(F)=C1 ONGSQPYHCQJKPP-JTQLQIEISA-N 0.000 description 6
- KACZQOKEFKFNDB-UHFFFAOYSA-N ethyl 1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1 KACZQOKEFKFNDB-UHFFFAOYSA-N 0.000 description 6
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- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 6
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
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- 125000001544 thienyl group Chemical group 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
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- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 5
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
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- 206010023421 Kidney fibrosis Diseases 0.000 description 5
- 235000019502 Orange oil Nutrition 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 230000003042 antagnostic effect Effects 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 150000002430 hydrocarbons Chemical class 0.000 description 5
- 238000004949 mass spectrometry Methods 0.000 description 5
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- 239000011734 sodium Substances 0.000 description 5
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662418838P | 2016-11-08 | 2016-11-08 | |
| US62/418,838 | 2016-11-08 | ||
| PCT/US2017/060390 WO2018089358A1 (en) | 2016-11-08 | 2017-11-07 | Azole amides and amines as alpha v integrin inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3042684A1 true CA3042684A1 (en) | 2018-05-17 |
Family
ID=60409437
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3042684A Abandoned CA3042684A1 (en) | 2016-11-08 | 2017-11-07 | Azole amides and amines as .alpha.v integrin inhibitors |
Country Status (14)
| Country | Link |
|---|---|
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Families Citing this family (13)
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| WO2018049068A1 (en) | 2016-09-07 | 2018-03-15 | Pliant Therapeutics, Inc. | N-acyl amino acid compounds and methods of use |
| RU2019116820A (ru) | 2016-12-29 | 2021-01-29 | Сент-Луис Юниверсити | Антагонисты интегрина |
| BR112019017929A2 (pt) | 2017-02-28 | 2020-05-19 | Morphic Therapeutic Inc | inibidores de integrina (alfa-v)(beta-6) |
| EP4147698A1 (en) | 2017-02-28 | 2023-03-15 | Morphic Therapeutic, Inc. | Inhibitors of (alpha-v)(beta-6) integrin |
| ES3019404T3 (en) | 2018-08-29 | 2025-05-20 | Morphic Therapeutic Inc | Integrin inhibitors |
| US11179383B2 (en) | 2018-10-30 | 2021-11-23 | Gilead Sciences, Inc. | Compounds for inhibition of α4β7 integrin |
| WO2020092375A1 (en) | 2018-10-30 | 2020-05-07 | Gilead Sciences, Inc. | Quinoline derivatives as alpha4beta7 integrin inhibitors |
| ES3013256T3 (en) | 2018-10-30 | 2025-04-11 | Gilead Sciences Inc | Imidazo[1,2-a]pyridine derivatives as alpha4beta7 integrin inhibitors for the treatment of inflammatory diseases |
| CN112996786B (zh) | 2018-10-30 | 2024-08-20 | 吉利德科学公司 | 用于抑制α4β7整合素的化合物 |
| US11578069B2 (en) | 2019-08-14 | 2023-02-14 | Gilead Sciences, Inc. | Compounds for inhibition of α4 β7 integrin |
| GB202010626D0 (en) * | 2020-07-10 | 2020-08-26 | Univ Nottingham | Compound |
| EP4288412A1 (en) * | 2021-02-08 | 2023-12-13 | Rappta Therapeutics Oy | Modulators of protein phosphatase 2a (pp2a) and methods using same |
| WO2022192545A1 (en) * | 2021-03-10 | 2022-09-15 | Dice Molecules Sv, Inc. | Alpha v beta 6 and alpha v beta 1 integrin inhibitors and uses thereof |
Family Cites Families (25)
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| US5849736A (en) * | 1993-11-24 | 1998-12-15 | The Dupont Merck Pharmaceutical Company | Isoxazoline and isoxazole fibrinogen receptor antagonists |
| ZA972195B (en) | 1996-03-15 | 1998-09-14 | Du Pont Merck Pharma | Spirocycle integrin inhibitors |
| JP2001524481A (ja) * | 1997-11-26 | 2001-12-04 | デュポン ファーマシューティカルズ カンパニー | αＶβ３アンタゴニストとしての１，３，４−チアジアゾール類および１，３，４−オキサジアゾール類 |
| JP2002508323A (ja) | 1997-12-17 | 2002-03-19 | メルク エンド カムパニー インコーポレーテッド | インテグリン受容体拮抗薬 |
| WO2000009503A1 (en) | 1998-08-13 | 2000-02-24 | Merck & Co., Inc. | Integrin receptor antagonists |
| EE200100642A (et) * | 1999-06-02 | 2003-02-17 | Merck & Co., Inc. | Alfa-v integriinretseptori antagonistid ja farmatseutiline kompositsioon |
| JP2004511434A (ja) | 2000-06-15 | 2004-04-15 | ファルマシア・コーポレーション | インテグリン受容体アンタゴニストとしてのヘテロアリールアルカン酸 |
| AU2002243692B2 (en) | 2001-01-29 | 2006-06-08 | 3-Dimensional Pharmaceuticals, Inc. | Substituted indoles and their use as integrin antagonists |
| WO2004020435A1 (en) | 2002-08-16 | 2004-03-11 | Janssen Pharmaceutica N.V. | Piperidinyl compounds that selectively bind integrins |
| ES2308227T3 (es) | 2003-10-01 | 2008-12-01 | Merck Patent Gmbh | Antagonistas de integrina alfavbeta3 y alfavbeta6 como agentes antifibroticos. |
| WO2006108040A1 (en) | 2005-04-05 | 2006-10-12 | Janssen Pharmaceutica, N.V. | Substituted indoles and their use as integrin antagonists |
| US20080045521A1 (en) | 2006-06-09 | 2008-02-21 | Astrazeneca Ab | Phenylalanine derivatives |
| WO2008125811A1 (en) | 2007-04-11 | 2008-10-23 | Astrazeneca Ab | N-[HETEROARYLCARBONYL]-S-THIENYL-L-ALANINE DERIVATIVES AS α5β1 ANTAGONISTS |
| ITFI20100019A1 (it) * | 2010-02-12 | 2011-08-13 | Univ Firenze | Inibitori peptidomimetici di integrine basati sull'1,2,3-triazolo per la diagnosi e terapia dei tumori. |
| MX2015004803A (es) | 2012-10-26 | 2015-08-14 | Hoffmann La Roche | Inhibidores de 1h-pirazol 3,4-disubstituida y tiazol 4,5-disubstituida de syk. |
| US9518053B2 (en) * | 2013-02-07 | 2016-12-13 | Scifluor Life Sciences, Inc. | Fluorinated integrin antagonists |
| GB201305668D0 (en) | 2013-03-28 | 2013-05-15 | Glaxosmithkline Ip Dev Ltd | Avs6 Integrin Antagonists |
| TWI667233B (zh) | 2013-12-19 | 2019-08-01 | 德商拜耳製藥公司 | 新穎吲唑羧醯胺，其製備方法、含彼等之醫藥製劑及其製造醫藥之用途 |
| GB201417011D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417002D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| GB201417094D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417018D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| EP3925959A1 (en) | 2015-02-19 | 2021-12-22 | OcuTerra Therapeutics, Inc. | Fluorinated derivatives of 3-(2-oxo-3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)imidazolidin-1-yl)propanoic acid and uses thereof |
| WO2016145258A1 (en) | 2015-03-10 | 2016-09-15 | The Regents Of The University Of California | Anti-alphavbeta1 integrin inhibitors and methods of use |
| ES2925173T3 (es) * | 2016-11-08 | 2022-10-14 | Bristol Myers Squibb Co | Acidos propiónicos sustituidos en la posición 3 como inhibidores de la integrina alfa V |
-
2017
- 2017-11-07 BR BR112019009245A patent/BR112019009245A2/pt not_active Application Discontinuation
- 2017-11-07 AU AU2017359028A patent/AU2017359028A1/en not_active Abandoned
- 2017-11-07 WO PCT/US2017/060390 patent/WO2018089358A1/en not_active Ceased
- 2017-11-07 EA EA201991121A patent/EA201991121A1/ru unknown
- 2017-11-07 EP EP17801235.7A patent/EP3538527B1/en active Active
- 2017-11-07 CN CN201780082144.8A patent/CN110167933B/zh active Active
- 2017-11-07 KR KR1020197016076A patent/KR102510858B1/ko active Active
- 2017-11-07 JP JP2019523847A patent/JP7128811B2/ja active Active
- 2017-11-07 US US16/347,829 patent/US10851098B2/en active Active
- 2017-11-07 MA MA046746A patent/MA46746A/fr unknown
- 2017-11-07 MX MX2019005234A patent/MX2019005234A/es unknown
- 2017-11-07 ES ES17801235T patent/ES2898835T3/es active Active
- 2017-11-07 CA CA3042684A patent/CA3042684A1/en not_active Abandoned
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2019
- 2019-05-06 IL IL266465A patent/IL266465A/en unknown
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|---|---|
| ES2898835T3 (es) | 2022-03-09 |
| EA201991121A1 (ru) | 2019-11-29 |
| AU2017359028A1 (en) | 2019-06-20 |
| IL266465A (en) | 2019-07-31 |
| US10851098B2 (en) | 2020-12-01 |
| US20190256513A1 (en) | 2019-08-22 |
| WO2018089358A1 (en) | 2018-05-17 |
| CN110167933B (zh) | 2022-06-21 |
| JP7128811B2 (ja) | 2022-08-31 |
| MA46746A (fr) | 2019-09-18 |
| EP3538527B1 (en) | 2021-10-13 |
| MX2019005234A (es) | 2019-08-12 |
| JP2019537603A (ja) | 2019-12-26 |
| BR112019009245A2 (pt) | 2019-07-16 |
| KR20190076030A (ko) | 2019-07-01 |
| EP3538527A1 (en) | 2019-09-18 |
| CN110167933A (zh) | 2019-08-23 |
| KR102510858B1 (ko) | 2023-03-15 |
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