JP2017536395A - E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 - Google Patents
E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 Download PDFInfo
- Publication number
- JP2017536395A JP2017536395A JP2017529350A JP2017529350A JP2017536395A JP 2017536395 A JP2017536395 A JP 2017536395A JP 2017529350 A JP2017529350 A JP 2017529350A JP 2017529350 A JP2017529350 A JP 2017529350A JP 2017536395 A JP2017536395 A JP 2017536395A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- compound according
- cells
- groups
- cancer
- 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
Links
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 title abstract description 35
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 title abstract description 35
- 108010024212 E-Selectin Proteins 0.000 title abstract description 32
- 102000015689 E-Selectin Human genes 0.000 title abstract 2
- 239000003112 inhibitor Substances 0.000 title description 26
- 150000001875 compounds Chemical class 0.000 claims abstract description 178
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 78
- 201000011510 cancer Diseases 0.000 claims abstract description 55
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 51
- 238000011282 treatment Methods 0.000 claims abstract description 43
- 201000010099 disease Diseases 0.000 claims abstract description 37
- 239000000203 mixture Substances 0.000 claims abstract description 34
- 210000004369 blood Anatomy 0.000 claims abstract description 27
- 239000008280 blood Substances 0.000 claims abstract description 27
- 230000002265 prevention Effects 0.000 claims abstract description 15
- 230000014759 maintenance of location Effects 0.000 claims abstract description 11
- 238000013508 migration Methods 0.000 claims abstract description 11
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 10
- 230000012292 cell migration Effects 0.000 claims abstract description 6
- 230000001737 promoting effect Effects 0.000 claims abstract description 6
- 230000021164 cell adhesion Effects 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 125000000304 alkynyl group Chemical group 0.000 claims description 23
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 206010027476 Metastases Diseases 0.000 claims description 15
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 15
- 125000006648 (C1-C8) haloalkyl group Chemical group 0.000 claims description 14
- 125000000232 haloalkynyl group Chemical group 0.000 claims description 13
- 239000004615 ingredient Substances 0.000 claims description 13
- 125000005647 linker group Chemical group 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 239000000651 prodrug Substances 0.000 claims description 12
- 229940002612 prodrug Drugs 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 abstract description 108
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 41
- 210000001185 bone marrow Anatomy 0.000 abstract description 27
- 210000000130 stem cell Anatomy 0.000 abstract description 25
- 210000005259 peripheral blood Anatomy 0.000 abstract description 2
- 239000011886 peripheral blood Substances 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 34
- 102100023471 E-selectin Human genes 0.000 description 30
- -1 butadienyl Chemical group 0.000 description 27
- 238000003556 assay Methods 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 22
- 239000000243 solution Substances 0.000 description 19
- 208000035475 disorder Diseases 0.000 description 17
- 210000000988 bone and bone Anatomy 0.000 description 14
- 238000002512 chemotherapy Methods 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 13
- 230000027455 binding Effects 0.000 description 13
- 125000004122 cyclic group Chemical group 0.000 description 13
- 230000009401 metastasis Effects 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 239000011734 sodium Substances 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 229940121384 cxc chemokine receptor type 4 (cxcr4) antagonist Drugs 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 125000003710 aryl alkyl group Chemical group 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 125000000623 heterocyclic group Chemical group 0.000 description 8
- 230000003834 intracellular effect Effects 0.000 description 8
- 239000012528 membrane Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 239000000872 buffer Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 6
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 6
- 206010035226 Plasma cell myeloma Diseases 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000002576 chemokine receptor CXCR4 antagonist Substances 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- MDAXKAUIABOHTD-UHFFFAOYSA-N 1,4,8,11-tetraazacyclotetradecane Chemical group C1CNCCNCCCNCCNC1 MDAXKAUIABOHTD-UHFFFAOYSA-N 0.000 description 5
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 5
- 206010060862 Prostate cancer Diseases 0.000 description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 5
- 239000012472 biological sample Substances 0.000 description 5
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
- 229940126142 compound 16 Drugs 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000005012 migration Effects 0.000 description 5
- 201000002528 pancreatic cancer Diseases 0.000 description 5
- 208000008443 pancreatic carcinoma Diseases 0.000 description 5
- 230000000069 prophylactic effect Effects 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 102000006573 Chemokine CXCL12 Human genes 0.000 description 4
- 108010008951 Chemokine CXCL12 Proteins 0.000 description 4
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 108010092694 L-Selectin Proteins 0.000 description 4
- 102000016551 L-selectin Human genes 0.000 description 4
- 108010035766 P-Selectin Proteins 0.000 description 4
- 102100023472 P-selectin Human genes 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 102000030621 adenylate cyclase Human genes 0.000 description 4
- 108060000200 adenylate cyclase Proteins 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 210000000601 blood cell Anatomy 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 230000035605 chemotaxis Effects 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 201000000050 myeloid neoplasm Diseases 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 238000006268 reductive amination reaction Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 125000006850 spacer group Chemical group 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 3
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 3
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 3
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
- UEUPDYPUTTUXLJ-UHFFFAOYSA-N 1-[[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclotetradecane;octahydrochloride Chemical compound Cl.Cl.Cl.Cl.Cl.Cl.Cl.Cl.C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 UEUPDYPUTTUXLJ-UHFFFAOYSA-N 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 3
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 102000003800 Selectins Human genes 0.000 description 3
- 108090000184 Selectins Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000012875 competitive assay Methods 0.000 description 3
- 229940125797 compound 12 Drugs 0.000 description 3
- 229940126543 compound 14 Drugs 0.000 description 3
- 229940125758 compound 15 Drugs 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000003511 endothelial effect Effects 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthene Chemical compound C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 238000004020 luminiscence type Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000002356 single layer Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 125000004001 thioalkyl group Chemical group 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 2
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 2
- 229940123546 E-selectin antagonist Drugs 0.000 description 2
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000003172 aldehyde group Chemical group 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 238000002617 apheresis Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 238000005415 bioluminescence Methods 0.000 description 2
- 230000029918 bioluminescence Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000010322 bone marrow transplantation Methods 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- WDECIBYCCFPHNR-UHFFFAOYSA-N chrysene Chemical compound C1=CC=CC2=CC=C3C4=CC=CC=C4C=CC3=C21 WDECIBYCCFPHNR-UHFFFAOYSA-N 0.000 description 2
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000007891 compressed tablet Substances 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 230000037041 intracellular level Effects 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 230000001926 lymphatic effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 230000001483 mobilizing effect Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 239000003961 penetration enhancing agent Substances 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229960002169 plerixafor Drugs 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- 210000002303 tibia Anatomy 0.000 description 2
- 239000012049 topical pharmaceutical composition Substances 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 125000004665 trialkylsilyl group Chemical group 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- LGLVVVCSQBZONM-HCCLCSBVSA-N (2r)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentano Chemical compound NC(N)=NCCC[C@@H](NC(=O)C)C(=O)N[C@H](CCCN=C(N)N)C(=O)N[C@H](CCCN=C(N)N)C(=O)N[C@H](CCCN=C(N)N)C(=O)N[C@H](CCCN=C(N)N)C(=O)N[C@H](CCCN=C(N)N)C(=O)N[C@H](CCCN=C(N)N)C(=O)N[C@H](CCCN=C(N)N)C(=O)N[C@H](CCCN=C(N)N)C(N)=O LGLVVVCSQBZONM-HCCLCSBVSA-N 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- UVNPEUJXKZFWSJ-LMTQTHQJSA-N (R)-N-[(4S)-8-[6-amino-5-[(3,3-difluoro-2-oxo-1H-pyrrolo[2,3-b]pyridin-4-yl)sulfanyl]pyrazin-2-yl]-2-oxa-8-azaspiro[4.5]decan-4-yl]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](=O)N[C@@H]1COCC11CCN(CC1)c1cnc(Sc2ccnc3NC(=O)C(F)(F)c23)c(N)n1 UVNPEUJXKZFWSJ-LMTQTHQJSA-N 0.000 description 1
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 1
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 1
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 125000005987 1-oxo-thiomorpholinyl group Chemical group 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- 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 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 1
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical class [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 108010061299 CXCR4 Receptors Proteins 0.000 description 1
- 102000012000 CXCR4 Receptors Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical class [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 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 1
- 241000283086 Equidae Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical class [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 150000000994 L-ascorbates Chemical class 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000893859 Matelea Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- NUGPIZCTELGDOS-QHCPKHFHSA-N N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclopentanecarboxamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CC[C@@H](C=1C=NC=CC=1)NC(=O)C1CCCC1)C NUGPIZCTELGDOS-QHCPKHFHSA-N 0.000 description 1
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 1
- 108010056642 N-alpha-acetyl-nona-D-arginine amide acetate Proteins 0.000 description 1
- 150000001204 N-oxides Chemical group 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical class [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000003076 Osteolysis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical class [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 108010045306 T134 peptide Proteins 0.000 description 1
- 108010033455 T22 peptide Proteins 0.000 description 1
- SLGBZMMZGDRARJ-UHFFFAOYSA-N Triphenylene Natural products C1=CC=C2C3=CC=CC=C3C3=CC=CC=C3C2=C1 SLGBZMMZGDRARJ-UHFFFAOYSA-N 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 239000003875 Wang resin Substances 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 125000004054 acenaphthylenyl group Chemical group C1(=CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- SQFPKRNUGBRTAR-UHFFFAOYSA-N acephenanthrylene Chemical group C1=CC(C=C2)=C3C2=CC2=CC=CC=C2C3=C1 SQFPKRNUGBRTAR-UHFFFAOYSA-N 0.000 description 1
- HXGDTGSAIMULJN-UHFFFAOYSA-N acetnaphthylene Natural products C1=CC(C=C2)=C3C2=CC=CC3=C1 HXGDTGSAIMULJN-UHFFFAOYSA-N 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005107 alkyl diaryl silyl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 150000004982 aromatic amines Chemical group 0.000 description 1
- KNNXFYIMEYKHBZ-UHFFFAOYSA-N as-indacene Chemical compound C1=CC2=CC=CC2=C2C=CC=C21 KNNXFYIMEYKHBZ-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000005875 benzo[b][1,4]dioxepinyl group Chemical group 0.000 description 1
- 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000005878 benzonaphthofuranyl group Chemical group 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 238000013262 cAMP assay Methods 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000004712 cancer cell adhesion Effects 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000005507 decahydroisoquinolyl group Chemical group 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- 125000005105 dialkylarylsilyl group Chemical group 0.000 description 1
- 125000005266 diarylamine group Chemical group 0.000 description 1
- 125000005509 dibenzothiophenyl group Chemical group 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 150000002081 enamines Chemical group 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000004991 fluoroalkenyl group Chemical group 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000003844 furanonyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 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 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 210000002758 humerus Anatomy 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 150000003949 imides Chemical group 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007915 intraurethral administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002825 nitriles Chemical group 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 231100000435 percutaneous penetration Toxicity 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- XDJOIMJURHQYDW-UHFFFAOYSA-N phenalene Chemical compound C1=CC(CC=C2)=C3C2=CC=CC3=C1 XDJOIMJURHQYDW-UHFFFAOYSA-N 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical class [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002952 polymeric resin Substances 0.000 description 1
- 229920001184 polypeptide 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
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- XVSSGIXTKVRGAR-UHFFFAOYSA-N prop-2-enoxycarbonyl prop-2-enyl carbonate Chemical compound C=CCOC(=O)OC(=O)OCC=C XVSSGIXTKVRGAR-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 125000006853 reporter group Chemical group 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- WEMQMWWWCBYPOV-UHFFFAOYSA-N s-indacene Chemical compound C=1C2=CC=CC2=CC2=CC=CC2=1 WEMQMWWWCBYPOV-UHFFFAOYSA-N 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 150000003873 salicylate salts Chemical class 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
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical class [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005985 thienyl[1,3]dithianyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012745 toughening agent Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005580 triphenylene group Chemical group 0.000 description 1
- 125000005455 trithianyl group Chemical group 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/207—Cyclohexane rings not substituted by nitrogen atoms, e.g. kasugamycins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
- C07H3/06—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
R1は、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、
R2は、−OH、−NH2、−OC(=O)Y1、−NHC(=O)Y1、および−NHC(=O)NHY1基から選択され、ここで、Y1は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、C2〜8ハロアルキニル、C6〜18アリール、およびC1〜13ヘテロアリール基から選択され、
R3は、−CN、−CH2CN、および−C(=O)Y2基から選択され、ここで、Y2は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、−OZ1、−NHOH、−NHOCH3、−NHCN、および−NZ1Z2基から選択され、ここで、Z1およびZ2は、同じでも異なっていてもよく、独立して、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、Z1およびZ2は、一緒になって環を形成していてもよく、
R4は、C3〜8シクロアルキル基から選択され、
R5は、独立して、H、ハロ、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、ただし、少なくとも1つのR5はHでないことを条件とし、
nは、1〜4の範囲の整数から選択され、
Lは、リンカー基から選択される)
のヘテロ二官能性阻害剤、式(I)のプロドラッグ、および前述のもののいずれかの薬学的に許容される塩が開示される。
E−セレクチンおよびCXCR4ケモカイン受容体が役割を果たす疾患を処置するため、ならびに循環血液への放出後の細胞の滞留を促進するための化合物、組成物、および方法が本明細書で開示される。化合物は、in vitroおよびin vivoで様々な使用を有する。
R1は、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、
R2は、−OH、−NH2、−OC(=O)Y1、−NHC(=O)Y1、および−NHC(=O)NHY1基から選択され、ここで、Y1は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、C2〜8ハロアルキニル、C6〜18アリール、およびC1〜13ヘテロアリール基から選択され、
R3は、−CN、−CH2CN、および−C(=O)Y2基から選択され、ここで、Y2は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、−OZ1、−NHOH、−NHOCH3、−NHCN、および−NZ1Z2基から選択され、ここで、Z1およびZ2は、同じでも異なっていてもよく、独立して、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、Z1およびZ2は、一緒になって環を形成していてもよく、
R4は、C3〜8シクロアルキル基から選択され、
各R5は、独立して、H、ハロ、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、ただし、少なくとも1つのR5はHでないことを条件とし、
nは、1〜4の範囲の整数から選択され、
Lは、リンカー基から選択される)
のヘテロ二官能性阻害剤、式(I)のプロドラッグ、および前述のもののいずれかの薬学的に許容される塩が提供される。
定義
化合物合成手順
ヘテロ二官能性化合物を特徴付けるための方法
医薬組成物および医薬組成物を使用する方法
E−セレクチンおよびCXCR4ケモカイン受容体のヘテロ二官能性阻害剤
(化合物9および16)
例示的な式(I)のヘテロ二官能性化合物を、実施例1〜2に記載されているように、および図1に記載されている例示的合成スキームに示されているように合成した。
(実施例2)
SDF−1誘発性化学走性の阻害を評価するCXCR4アッセイ
E−セレクチン活性−結合アッセイ
E−セレクチンのアンタゴニストをスクリーニングし、特徴づける阻害アッセイは競合的結合アッセイであり、このアッセイからIC50値を決定することができる。37℃で2時間のインキュベーションにより、E−セレクチン/Igキメラを96ウェルマイクロタイタープレート内に固定化した。非特異性の結合を減少させるために、ウシ血清アルブミンを各ウェルに添加し、室温で2時間インキュベートした。プレートを洗浄し、ビオチン化した、sLeaポリアクリルアミドのコンジュゲートの存在下、ストレプトアビジン/西洋わさびペルオキシダーゼと共に試験化合物の段階希釈物をウェルに添加し、室温で2時間インキュベートした。
CXCR4アッセイ − 環状AMPの阻害
(実施例5)
腫瘍関連線維芽細胞へのリンパ管および血管内皮移動の阻害
(実施例6)
PDAC細胞のリンパ単層への結合の阻害
(実施例7)
前立腺がんモデル
Claims (31)
- 式(I):
R1は、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、
R2は、−OH、−NH2、−OC(=O)Y1、−NHC(=O)Y1、および−NHC(=O)NHY1基から選択され、ここで、Y1は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、C2〜8ハロアルキニル、C6〜18アリール、およびC1〜13ヘテロアリール基から選択され、
R3は、−CN、−CH2CN、および−C(=O)Y2基から選択され、ここで、Y2は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、−OZ1、−NHOH、−NHOCH3、−NHCN、および−NZ1Z2基から選択され、ここで、Z1およびZ2は、同じでも異なっていてもよく、独立して、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、Z1およびZ2は、一緒になって環を形成していてもよく、
R4は、C3〜8シクロアルキル基から選択され、
各R5は、独立して、H、ハロ、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、ただし、少なくとも1つのR5はHでないことを条件とし、
nは、1〜4の範囲の整数から選択され、
Lは、リンカー基から選択される)
の化合物、式(I)のプロドラッグ、および前述のもののいずれかの薬学的に許容される塩から選択される少なくとも1つの化合物。 - R1が、C1〜8アルキル基から選択される、請求項1に記載の少なくとも1つの化合物。
- R1が、エチルおよびメチルから選択される、請求項2に記載の少なくとも1つの化合物。
- R1がエチルである、請求項3に記載の少なくとも1つの化合物。
- R2が、−OH、−NH2、−OC(=O)Y1、および−NHC(=O)Y1から選択され、ここで、Y1が、C1〜8アルキル、C6〜18アリール、およびC1〜13ヘテロアリール基から選択される、先行する請求項のいずれかに記載の少なくとも1つの化合物。
- R2が、
- R3が、−C(=O)Y2から選択され、ここで、Y2が、−OZ1、−NHOH、−NHOCH3、および−NZ1Z2基から選択され、ここで、Z1およびZ2が、同じでも異なっていてもよく、独立して、H、およびC1〜8アルキルから選択され、Z1およびZ2が、一緒になって環を形成していてもよい、先行する請求項のいずれかに記載の少なくとも1つの化合物。
- R3が−C(=O)OHである、請求項7に記載の少なくとも1つの化合物。
- R4が、
- 少なくとも1つのR5がハロである、先行する請求項のいずれかに記載の少なくとも1つの化合物。
- 少なくとも1つのR5がブロモである、請求項10に記載の少なくとも1つの化合物。
- nが1である、請求項10または11のいずれか一項に記載の少なくとも1つの化合物。
- 式(Ia)の化合物:
- 式(Ib)の化合物:
- 以下の式:
- 以下の式:
- 以下の式:
- 以下の式:
- 前記リンカー基が−C(=O)NH(CH2)2NH−である、請求項1から18のいずれか一項に記載の少なくとも1つの化合物。
- 前記リンカー基が−CH2NHCH2−である、請求項1から18のいずれか一項に記載の少なくとも1つの化合物。
- 前記リンカー基が−C(=O)NHCH2−である、請求項1から18のいずれか一項に記載の少なくとも1つの化合物。
- 以下の式:
- 以下の式:
-
-
- 請求項1から23のいずれか一項に記載の少なくとも1つの化合物および少なくとも1つの追加の薬学的に許容される成分を含む組成物。
- がんの処置および/または予防のための方法であって、ここで、前記がんの細胞は原発部位を離れることができ、前記方法は、がんの処置および/または予防を必要とする対象に、請求項1から25のいずれか一項に記載の少なくとも1つの化合物の有効量および任意選択で少なくとも1つの追加の薬学的に許容される成分を投与するステップを含む方法。
- がん細胞をある部位から血流へ動員し、前記がん細胞を前記血流中に滞留させることが望まれるがんの処置および/または予防のための方法であって、それを必要とする対象に、請求項1から25のいずれか一項に記載の少なくとも1つの化合物の有効量および任意選択で少なくとも1つの追加の薬学的に許容される成分を投与するステップを含む方法。
- 細胞を循環血液に放出し、前記細胞の前記血液中の滞留を促進するための方法であって、それを必要とする対象に、請求項1から25のいずれか一項に記載の少なくとも1つの化合物の有効量および任意選択で少なくとも1つの追加の薬学的に許容される成分を投与するステップを含む方法。
- 腫瘍転移の処置および/または予防のための方法であって、それを必要とする対象に、請求項1から25のいずれか一項に記載の少なくとも1つの化合物の有効量および任意選択で少なくとも1つの追加の薬学的に許容される成分を投与するステップを含む方法。
- 炎症性疾患の処置および/または予防のための方法であって、ここで、細胞の接着または移動が前記疾患において生じており、前記方法は、炎症性疾患の処置および/または予防を必要とする対象に、請求項1から25のいずれか一項に記載の少なくとも1つの化合物の有効量および任意選択で少なくとも1つの追加の薬学的に許容される成分を投与するステップを含む方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462087085P | 2014-12-03 | 2014-12-03 | |
US62/087,085 | 2014-12-03 | ||
PCT/US2015/063191 WO2016089872A1 (en) | 2014-12-03 | 2015-12-01 | Heterobifunctional inhibitors of e-selectins and cxcr4 chemokine receptors |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020044383A Division JP2020090553A (ja) | 2014-12-03 | 2020-03-13 | E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2017536395A true JP2017536395A (ja) | 2017-12-07 |
JP2017536395A5 JP2017536395A5 (ja) | 2018-11-22 |
JP6689854B2 JP6689854B2 (ja) | 2020-04-28 |
Family
ID=56092327
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017529350A Active JP6689854B2 (ja) | 2014-12-03 | 2015-12-01 | E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 |
JP2020044383A Withdrawn JP2020090553A (ja) | 2014-12-03 | 2020-03-13 | E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020044383A Withdrawn JP2020090553A (ja) | 2014-12-03 | 2020-03-13 | E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 |
Country Status (16)
Country | Link |
---|---|
US (1) | US10519181B2 (ja) |
EP (2) | EP3569609A1 (ja) |
JP (2) | JP6689854B2 (ja) |
KR (1) | KR102542750B1 (ja) |
CN (1) | CN107108679B (ja) |
AU (1) | AU2015355136B2 (ja) |
CA (1) | CA2968391C (ja) |
CY (1) | CY1122038T1 (ja) |
DK (1) | DK3227310T3 (ja) |
ES (1) | ES2754549T3 (ja) |
HU (1) | HUE045542T2 (ja) |
LT (1) | LT3227310T (ja) |
PL (1) | PL3227310T3 (ja) |
PT (1) | PT3227310T (ja) |
SI (1) | SI3227310T1 (ja) |
WO (1) | WO2016089872A1 (ja) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SI3227310T1 (sl) | 2014-12-03 | 2019-11-29 | Glycomimetics Inc | Heterobifunkcionalni inhibitorji e-selektinov in receptorjev kemokina CXCR4 |
CN109069486A (zh) | 2015-12-14 | 2018-12-21 | X4 制药有限公司 | 治疗癌症的方法 |
US11291678B2 (en) | 2016-03-02 | 2022-04-05 | Glycomimetics, Inc | Methods for the treatment and/or prevention of cardiovascular disease by inhibition of E-selectin |
JP2019510785A (ja) | 2016-04-08 | 2019-04-18 | エックス4 ファーマシューティカルズ, インコーポレイテッド | 癌を処置する方法 |
WO2018031445A1 (en) * | 2016-08-08 | 2018-02-15 | Glycomimetics, Inc. | Combination of t-cell checkpoint inhibitors with inhibitors of e-selectin or cxcr4, or with heterobifunctional inhibitors of both e-selectin and cxcr4 |
JP7069136B2 (ja) | 2016-10-07 | 2022-05-17 | グリコミメティクス, インコーポレイテッド | 極めて強力な多量体e-セレクチンアンタゴニスト |
EP3596096A1 (en) | 2017-03-15 | 2020-01-22 | GlycoMimetics, Inc. | Galactopyranosyl-cyclohexyl derivatives as e-selectin antagonists |
JP7275131B2 (ja) * | 2017-11-30 | 2023-05-17 | グリコミメティクス, インコーポレイテッド | 骨髄浸潤リンパ球を動員する方法、およびその使用 |
CN111566117A (zh) * | 2017-12-29 | 2020-08-21 | 糖模拟物有限公司 | E-选择蛋白和半乳凝素-3的异双功能抑制剂 |
JP7455064B2 (ja) | 2018-03-05 | 2024-03-25 | グリコミメティクス, インコーポレイテッド | 急性骨髄性白血病および関連状態を処置する方法 |
EP3893936A2 (en) | 2018-12-10 | 2021-10-20 | GlycoMimetics, Inc. | Methods of treating hiv and aids and the elimination of latent reservoirs of hiv infection using selectin, galectin, and siglec antagonists |
WO2020139962A1 (en) | 2018-12-27 | 2020-07-02 | Glycomimetics, Inc. | Heterobifunctional inhibitors of e-selectin and galectin-3 |
WO2020150263A1 (en) | 2019-01-14 | 2020-07-23 | Magnani John L | Selectin or galectin antagonists for treating cytokine release syndrome and crs-induced neurotoxicity |
JP2022529806A (ja) | 2019-04-24 | 2022-06-24 | グリコミメティクス, インコーポレイテッド | E-セレクチン、ガレクチン-3、および/またはcxcr4ケモカイン受容体のガラクトース連結型多量体糖模倣性阻害剤 |
CN114341368A (zh) | 2019-07-12 | 2022-04-12 | 糖模拟物有限公司 | 使用基因表达作为多种肿瘤类型的e-选择素抑制剂功效和临床结果的指标的方法 |
EP4003367A1 (en) | 2019-07-31 | 2022-06-01 | GlycoMimetics, Inc. | Use of e-selectin antagonists to enhance the survival of reconstituted, bone marrow-depleted hosts |
WO2021195465A1 (en) * | 2020-03-27 | 2021-09-30 | Magnani John L | Treatment of acute respiratory distress syndrome and related conditions with antagonists of e-selectin |
CN115666584A (zh) | 2020-05-31 | 2023-01-31 | 糖模拟物有限公司 | 用于减少癌细胞负荷和保护正常血细胞生成的化合物和方法 |
EP4164655A1 (en) | 2020-06-14 | 2023-04-19 | GlycoMimetics, Inc. | Compositions and methods for overcoming microenvironment-mediated resistance via e-selectin targeting |
WO2023014690A1 (en) | 2021-08-03 | 2023-02-09 | Glycomimetics, Inc. | Compositions and methods for overcoming microenvironment-mediated resistance via e-selectin targeting |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002543126A (ja) * | 1999-05-03 | 2002-12-17 | スミスクライン・ビーチャム・コーポレイション | Cxcr−4受容体アンタゴニスト−トロンボポエチン模倣物 |
JP2012525393A (ja) * | 2009-05-01 | 2012-10-22 | グリコミメティックス インコーポレイテッド | E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 |
WO2013096926A1 (en) * | 2011-12-22 | 2013-06-27 | Glycomimetics, Inc. | E-selectin antagonist compounds, compositions, and methods of use |
Family Cites Families (236)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL7409399A (nl) | 1973-07-19 | 1975-01-21 | Rhone Poulenc Sa | Werkwijze ter bereiding van thermostabiele har- sen en voorwerpen geheel of gedeeltelijk be- staande uit deze harsen. |
US4471057A (en) | 1981-06-30 | 1984-09-11 | The Wistar Institute | Detection of colorectal carcinoma |
DK17885D0 (da) | 1985-01-14 | 1985-01-14 | Karlsson Karl Anders | Antiviralt middel |
US4876199A (en) | 1985-04-04 | 1989-10-24 | Fred Hutchinson Cancer Research Center | Hybridomas producing monoclonal antibodies to mono-, di-, and trifucosylated type 2 chain |
US4851511A (en) | 1986-01-30 | 1989-07-25 | Fred Hutchinson Cancer Research Center | Monoclonal antibody that specifically binds to disialosyl Lea |
US4925796A (en) | 1986-03-07 | 1990-05-15 | Massachusetts Institute Of Technology | Method for enhancing glycoprotein stability |
ES2058070T3 (es) | 1986-05-09 | 1994-11-01 | Pulverer Gerhard | Utilizacion de monosacaridos especificos para la preparacion de un medicamento para impedir metastasis de tumores malignos. |
US5538724A (en) | 1987-08-11 | 1996-07-23 | The Board Of Trustees For The Leland Stanford Junior Univ. | Method of control leukocyte extravasation |
US5079353A (en) | 1987-12-02 | 1992-01-07 | Chembiomed, Ltd. | Sialic acid glycosides, antigens, immunoadsorbents, and methods for their preparation |
US5632991A (en) | 1988-11-14 | 1997-05-27 | Brigham & Women's Hospital | Antibodies specific for E-selectin and the uses thereof |
EP0381310A1 (en) | 1989-01-30 | 1990-08-08 | The Biomembrane Institute | Monoclonal antibodies directed to tumor-associated gangliosides and fucogangliosides and method for production thereof |
US5464778A (en) | 1989-03-08 | 1995-11-07 | Board Of Regents Of The University Of Oklahoma | Glycoprotein ligand for P-selectin and methods of use thereof |
US5272263A (en) | 1989-04-28 | 1993-12-21 | Biogen, Inc. | DNA sequences encoding vascular cell adhesion molecules (VCAMS) |
EP0408859B1 (en) | 1989-05-23 | 1995-08-09 | Otsuka Pharmaceutical Co., Ltd. | Monoclonal antibodies to activated endothelial cells |
US6033665A (en) | 1989-09-27 | 2000-03-07 | Elan Pharmaceuticals, Inc. | Compositions and methods for modulating leukocyte adhesion to brain endothelial cells |
US6280932B1 (en) | 1990-06-11 | 2001-08-28 | Gilead Sciences, Inc. | High affinity nucleic acid ligands to lectins |
US6001988A (en) | 1990-06-11 | 1999-12-14 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands to lectins |
US5576305A (en) | 1990-06-15 | 1996-11-19 | Cytel Corporation | Intercellular adhesion mediators |
US5753631A (en) | 1990-06-15 | 1998-05-19 | Cytel Corporation | Intercellular adhesion mediators |
AU8007791A (en) | 1990-06-15 | 1992-01-07 | Cytel Corporation | Intercellular adhesion mediators |
US6387884B1 (en) | 1990-06-18 | 2002-05-14 | Stanford University | Leukocyte homing modulation |
US6391857B1 (en) | 1990-06-18 | 2002-05-21 | Stanford University | Methods and compositions for endothelial binding |
ATE224911T1 (de) | 1990-07-17 | 2002-10-15 | Univ Oklahoma | Gmp-140 ligand |
US5211937A (en) | 1990-07-30 | 1993-05-18 | Glycomed Incorporated | Method of determining a site of inflammation utilizing elam-1 ligands |
US5143712A (en) | 1990-07-30 | 1992-09-01 | Glycomed Incorporated | Method of determining a site of inflammation utilizing elam-1 ligands |
US5648344A (en) | 1990-07-30 | 1997-07-15 | Glycomed Incorporated | Methods of treating inflammation using selection binding compounds |
US5789573A (en) | 1990-08-14 | 1998-08-04 | Isis Pharmaceuticals, Inc. | Antisense inhibition of ICAM-1, E-selectin, and CMV IE1/IE2 |
NZ240316A (en) | 1990-10-25 | 1996-12-20 | Univ Michigan | Compound for treating disease mediated by the elaboration of elam-1 on endothelial cells |
IE914075A1 (en) | 1990-11-23 | 1992-06-03 | Gen Hospital Corp | Inhibition of cell adhesion protein-carbohydrate¹interactions |
US5151360A (en) | 1990-12-31 | 1992-09-29 | Biomembrane Institute | Effect of n,n,n-trimethylsphingosine on protein kinase-c activity, melanoma cell growth in vitro, metastatic potential in vivo and human platelet aggregation |
US6309639B1 (en) | 1991-02-05 | 2001-10-30 | The Board Of Regents Of The University Of Oklahoma | Method for inhibiting an inflammatory response using antibodies to P-selectin glycoprotein ligand |
US6124267A (en) | 1991-02-05 | 2000-09-26 | Southpac Trust Internationals, Inc. | O-glycan inhibitors of selectin mediated inflammation derived from PSGL-1 |
US6121233A (en) | 1991-04-19 | 2000-09-19 | John L. Magnani | Methods for the inhibition of cancer metastasis mediated by endothelial adhesion molecules |
JP3859697B2 (ja) | 1991-05-06 | 2006-12-20 | ジェネンテック・インコーポレーテッド | セレクチンリガンド |
US5318890A (en) | 1991-05-06 | 1994-06-07 | The Regents Of The University Of California | Assays for inhibitors of leukocyte adhesion |
US5352670A (en) | 1991-06-10 | 1994-10-04 | Alberta Research Council | Methods for the enzymatic synthesis of alpha-sialylated oligosaccharide glycosides |
US5646123A (en) | 1991-06-10 | 1997-07-08 | Alberta Research Council | Time dependent administration of oligosaccharide glycosides related to blood group determinants having a type I or type II core structure in reducing inflammation in a sensitized mammal arising form exposure to an antigen |
US5580858A (en) | 1991-06-10 | 1996-12-03 | Alberta Research Council | Immunosuppressive and tolerogenic modified Lewisx compounds |
WO1993005070A1 (en) | 1991-09-10 | 1993-03-18 | Centocor, Inc. | Peptide inhibitors of inflammation mediated by selectins |
US5268364A (en) | 1991-12-12 | 1993-12-07 | The Biomembrane Institute | Method for inhibiting selectin-dependent adhesion of leukocytes and platelets by O-glycosylation modification |
CA2104099A1 (en) | 1991-12-18 | 1993-06-19 | George A. Heavner | Peptide inhibitors of inflammation mediated by selectins |
US5643873A (en) | 1992-05-06 | 1997-07-01 | Affymax Technologies N.V. | Peptides and compounds that bind selectins including endothelial leukocyte adhesion molecule 1 |
US5591835A (en) | 1992-06-29 | 1997-01-07 | Glycomed Incorporated | Substituted lactose derivatives |
CA2100412A1 (en) | 1992-07-15 | 1994-01-16 | Yutaka Yamada | Glycolipid derivatives |
JPH08503694A (ja) | 1992-09-08 | 1996-04-23 | セントコー・インコーポレーテッド | ペプチド系の細胞接着阻害物質 |
US5519008A (en) | 1992-09-10 | 1996-05-21 | Glycomed Incorporated | Derivatives of triterpenoid acids as inhibitors of cell-adhesion molecules ELAM-1 (E-selectin) and LECAM-1 (L-selectin) |
US5695752A (en) | 1992-09-11 | 1997-12-09 | The Regents Of The University Of California | Treating inflammation via the administration of specific sulfatase enzymes and/or sulfation inhibitor |
AU4859793A (en) | 1992-09-11 | 1994-04-12 | Regents Of The University Of California, The | Sulfated ligands for l-selectins and use of chlorates and or sulfatases for the treatment of inflammation |
US6277975B1 (en) | 1992-10-23 | 2001-08-21 | Genetics Institute, Inc. | Fusions of P-selectin ligand protein and polynucleotides encoding same |
US5843707A (en) | 1992-10-23 | 1998-12-01 | Genetics Institute, Inc. | Nucleic acid encoding a novel P-selectin ligand protein |
EP0601417A3 (de) | 1992-12-11 | 1998-07-01 | Hoechst Aktiengesellschaft | Physiologisch verträglicher und physiologisch abbaubarer, Kohlenhydratrezeptorblocker auf Polymerbasis, ein Verfahren zu seiner Herstellung und seine Verwendung |
WO1994014836A1 (en) | 1992-12-18 | 1994-07-07 | Centocor, Inc. | Peptide inhibitors of selectin binding |
WO1994014467A1 (en) | 1992-12-29 | 1994-07-07 | Genentech, Inc. | Treatment of inflammatory bowel disease with ifn-gamma inhibitors |
US5412123A (en) | 1993-02-08 | 1995-05-02 | Glycomed Incorporated | Anthraquinone and anthracene derivatives as inhibitors of the cell-adhesion molecules of the immune system |
JP2716657B2 (ja) | 1993-02-26 | 1998-02-18 | 株式会社ディ・ディ・エス研究所 | 接着分子elam‐1に特異的結合能を有する化合物 |
CA2157489A1 (en) | 1993-03-04 | 1994-09-15 | Masaaki Numata | Lewis-associated compound, process for producing the same, and anti-inflammatory |
US5527890A (en) | 1993-04-16 | 1996-06-18 | Glycomed Incorporated | Derivatives of triterpenoid acids and uses thereof |
AU4236393A (en) | 1993-05-05 | 1994-11-21 | Affymax Technologies N.V. | Peptides and compounds that bind to elam-1 |
US5854218A (en) | 1993-05-14 | 1998-12-29 | Cytel Corporation | Sialyl Lex analogues as inhibitors of cellular adhesion |
US5811404A (en) | 1993-05-14 | 1998-09-22 | Cytel Corporation | Sialyl Lex analogues as inhibitors of cellular adhesion |
JPH08510729A (ja) | 1993-05-14 | 1996-11-12 | サイテル コーポレイション | 細胞接着のインヒビターとしてのシアリルLe▲上x▼類似体 |
SE9301677L (sv) | 1993-05-14 | 1994-11-18 | Kurt G I Nilsson | Syntesmetod |
US5527785A (en) | 1993-05-14 | 1996-06-18 | The Regents Of The University Of California | Selectin receptor modulating compositions |
US5976540A (en) | 1993-05-17 | 1999-11-02 | T Cell Sciences, Inc. | Compositions comprising complement related proteins and carbohydrates, and methods for producing and using said compositions |
SG52383A1 (en) | 1993-05-17 | 1998-09-28 | T Cell Sciences Inc | Compositions comprising complement related proteins and carbohydrates and methods for producing and using said compositions |
US5856300A (en) | 1994-05-12 | 1999-01-05 | T Cell Sciences, Inc. | Compositions comprising complement related proteins and carbohydrates, and methods for producing and using said compositions |
US5646248A (en) | 1993-06-08 | 1997-07-08 | La Jolla Cancer Research Foundation | E-selection binding soluble lamp-1 polypeptide |
US5789385A (en) | 1993-06-16 | 1998-08-04 | Glycomed Incorporated | Sialyl Lewisx mimetics containing phenyl backbones |
US5658880A (en) | 1993-06-16 | 1997-08-19 | Glycomed Incorporated | Sialic acid/fucose based medicaments |
US5837689A (en) | 1993-06-16 | 1998-11-17 | Glycomed Incorporated | Sialyl lewis-x mimetics containing naphthyl backbones |
US5750508A (en) | 1993-06-16 | 1998-05-12 | Glycomed Incorporated | Sialic acid/fucose based medicaments |
US5679321A (en) | 1993-06-17 | 1997-10-21 | Glycomed Incorporated | Sialic acid/fucose based medicaments |
DK76193D0 (da) | 1993-06-25 | 1993-06-25 | Astra Ab | Kulhydratderivater |
US5559103A (en) | 1993-07-21 | 1996-09-24 | Cytel Corporation | Bivalent sialyl X saccharides |
US5508387A (en) | 1993-08-04 | 1996-04-16 | Glycomed Incorporated | Selectin binding glycopeptides |
US5827837A (en) | 1993-08-20 | 1998-10-27 | The Regents Of The University Of California | Polyanion anti-inflammatory agents |
US5464815A (en) | 1993-09-08 | 1995-11-07 | Genentech, Inc. | Inhibition of heparin-binding |
JPH09504522A (ja) | 1993-10-12 | 1997-05-06 | グリコメド・インコーポレイテッド | 細胞接着インヒビターの同定に有用なグリコ−ペプチドのライブラリー |
US5783693A (en) | 1993-11-19 | 1998-07-21 | The Regents Of The University Of California | Methods for synthesizing sulfated disaccharide inhibitors of selectins |
WO1995014787A1 (en) | 1993-11-22 | 1995-06-01 | Centocor, Inc. | Peptide inhibitors of selecting binding |
US5663151A (en) | 1994-03-04 | 1997-09-02 | Bristol-Myers Squibb Company | Sulfated α-glycolipid derivatives as cell adhesion inhibitors |
DE4408248A1 (de) | 1994-03-11 | 1995-09-14 | Hoechst Ag | Physiologisch verträgliche und physiologisch abbaubare Kohlenhydrat-Mimetika, ein Verfahren zur Herstellung und ihre Verwendung |
EP0671409A3 (de) | 1994-03-11 | 1996-06-12 | Hoechst Ag | Malonsäurederivate mit antiadhäsiven Eigenschaften. |
HUT77345A (hu) | 1994-04-29 | 1998-03-30 | Texas Biotechnology Corporation | E-szelektin, P-szelektin vagy L-szelektin szialil-Lewis x-hez vagy szialil-Lewis a-hoz kapcsolódását gátló mannopiranoziloxi-bifenil származékok és ezeket tartalmazó gyógyszerkészítmények |
US5444050A (en) | 1994-04-29 | 1995-08-22 | Texas Biotechnology Corporation | Binding of E-selectin or P-selectin to sialyl Lewisx or sialyl-Lewisa |
US5486536A (en) | 1994-08-15 | 1996-01-23 | The Regents Of The University Of Michigan | Sulfatides as anti-inflammatory compounds |
JPH0899989A (ja) | 1994-09-30 | 1996-04-16 | Akira Hasegawa | 新規糖脂質誘導体およびその製造用中間体 |
DE4436164A1 (de) | 1994-10-10 | 1996-04-11 | Hoechst Ag | Neue Kohlenhydratkonjugate als Inhibitoren der Zelladhäsion |
US5686426A (en) | 1994-11-17 | 1997-11-11 | Bristol-Myers Squibb Company | Dicarboxymethylated glycolipid derivatives as cell adhesion inhibitors |
US6492332B1 (en) | 1995-12-12 | 2002-12-10 | Omeros Corporation | Irrigation solution and methods for inhibition of tumor cell adhesion, pain and inflammation |
US5639734A (en) | 1994-12-20 | 1997-06-17 | Esko; Jeffrey D. | Disaccharide inflammation inhibitors and uses thereof |
MX9704893A (es) | 1994-12-28 | 1997-10-31 | Sumitomo Pharma | Derivados de lewis x y procesos para producir los mismos. |
US20020040008A1 (en) | 1995-01-24 | 2002-04-04 | Wagner Denisa D. | Method for treating and preventing atherosclerosis |
US5527936A (en) | 1995-02-17 | 1996-06-18 | E. I. Du Pont De Nemours And Company | Hydrosilylation of unsaturated compounds |
GB9504065D0 (en) | 1995-03-01 | 1995-04-19 | Pharmacia Spa | Poly-pyrrolecarboxamidonaphthalenic acid derivatives |
US6506770B1 (en) | 1996-06-06 | 2003-01-14 | Anormed, Inc. | Antiviral compounds |
GB9511357D0 (en) | 1995-06-06 | 1995-08-02 | Johnson Matthey Plc | Improved antiviral compounds |
US5736533A (en) | 1995-06-07 | 1998-04-07 | Neose Technologies, Inc. | Bacterial inhibition with an oligosaccharide compound |
AU6155896A (en) | 1995-06-07 | 1996-12-30 | Cytel Corporation | Humanized antibodies to e-selectin |
NZ311686A (en) | 1995-06-29 | 2000-01-28 | Novartis Ag | Diglycosylated 1,2-diols as mimetics of sialyl-lewis x and sialyl-lewis a |
EP0840606B1 (en) | 1995-06-29 | 2000-06-07 | Texas Biotechnology Corporation | Di- and trivalent small molecule selectin inhibitors |
US5876715A (en) | 1995-08-17 | 1999-03-02 | The Biomembrane Institute | Antibodies that bind novel carbohydrate ligands (myelorollins) that cause E-selectin dependent cell rolling, and uses thereof |
DE19532902A1 (de) | 1995-09-06 | 1997-03-13 | Hoechst Ag | Neuartige Glycomimetika als Selektin-Antagonisten und daraus hergestellte entzündungshemmend wirkende Arzneimittel |
DE19537334A1 (de) | 1995-10-09 | 1997-04-10 | Hoechst Ag | Antiadhäsive Piperidin- und Pyrrolidin-Carbonsäuren |
WO1997014707A1 (en) | 1995-10-18 | 1997-04-24 | Cytel Corporation | SIALYL Lex ANALOGUES AS INHIBITORS OF CELLULAR ADHESION |
US5919769A (en) | 1995-10-26 | 1999-07-06 | Kanebo, Ltd | Fucose derivatives, drugs containing the same as active ingredient, and intermediates for producing the same |
US5747463A (en) | 1995-11-13 | 1998-05-05 | Bristol-Myers Squibb Company | Malonate derivatives of glycolipids as cell adhesion inhibitors |
JPH09176047A (ja) | 1995-12-25 | 1997-07-08 | Unitika Ltd | 外用医薬製剤 |
DE19602355A1 (de) | 1996-01-24 | 1997-07-31 | Hoechst Ag | Mehrfach fucosylierte Dicarbonsäuren mit antiadhäsiven Eigenschaften |
US6187754B1 (en) | 1996-01-30 | 2001-02-13 | Glycotech Corp. | Sialyl-Lewisa and sialyl-Lewisx epitode analogues |
AU1542397A (en) | 1996-01-30 | 1997-08-22 | Novartis Ag | Sialyl-lewisa and sialyl-lewisx epitope analogues |
US5710023A (en) | 1996-03-01 | 1998-01-20 | Genetics Institute, Inc. | IL-13 cytokine receptor chain |
ATE217788T1 (de) | 1996-03-01 | 2002-06-15 | Univ California | Hemmung der selectinbindung |
US6344545B1 (en) | 1996-06-14 | 2002-02-05 | Progenics Pharmaceuticals, Inc. | Method for preventing HIV-1 infection of CD4+ cells |
US5654412A (en) | 1996-05-29 | 1997-08-05 | Glycomed Incorporated | Processes for the synthesis of sialyl Lewisx compounds |
CA2197058A1 (en) | 1996-06-05 | 1997-12-06 | Avery B. Nathens | Anti-inflammatory agent |
US5919768A (en) | 1996-06-26 | 1999-07-06 | Texas Biotechnology Corporation | Di- and trivalent small molecule selectin inhibitors |
NZ334048A (en) | 1996-08-08 | 2000-05-26 | Novartis Ag | Mimetics of natural carbohydrate epitotes as ligands for E and P Selectin |
US5830871A (en) | 1996-10-28 | 1998-11-03 | The Scripps Research Institute | Inhibitors of E-, P- and L-selectin binding |
GB9618520D0 (en) | 1996-09-05 | 1996-10-16 | Chiroscience Ltd | Compounds and their therapeutic use |
US6592872B1 (en) | 1996-09-17 | 2003-07-15 | The United States Of America As Represented By The Department Of Health And Human Services | Targeting antigens to the MHC class I processing pathway with an anthrax toxin fusion protein |
EP0951292B1 (en) | 1996-09-27 | 2007-04-04 | The Trustees of Columbia University in the City of New York | Treating an ischemic disorder and improving stroke outcome |
US6110897A (en) | 1996-10-10 | 2000-08-29 | Glycorex Ab | Antiinflammatory cell adhesion inhibitors |
WO1998021334A2 (en) | 1996-11-13 | 1998-05-22 | Morphogenesis, Inc. | Antibody mg1 recognizing a small subset of human hematopoietic cells |
EP1019064A4 (en) | 1997-02-28 | 2006-11-08 | Univ California | INHIBITION OF CELL-CELL BINDINGS BY LIPID COMPOSITIONS |
US6120751A (en) | 1997-03-21 | 2000-09-19 | Imarx Pharmaceutical Corp. | Charged lipids and uses for the same |
SE9701127D0 (sv) | 1997-03-26 | 1997-03-26 | Karolinska Innovations Ab | Antigenic fusionprotein carrying GALal, 3GAL epitopes |
JP3720520B2 (ja) | 1997-03-27 | 2005-11-30 | タカラバイオ株式会社 | 糖と標的物との相互作用の測定方法 |
US6413760B1 (en) | 1997-04-15 | 2002-07-02 | Genetics Institute, Inc. | Highly purified mocarhagin cobra venom protease polynucleotides endcoding same and related proteases and therapeutic uses thereof |
US5916910A (en) | 1997-06-04 | 1999-06-29 | Medinox, Inc. | Conjugates of dithiocarbamates with pharmacologically active agents and uses therefore |
US6193973B1 (en) | 1997-08-22 | 2001-02-27 | B. David Tuttle | Dietary supplement for boosting energy and increasing muscular strength |
US5948628A (en) | 1997-09-05 | 1999-09-07 | The Board Of Regents Of The University Of Oklahoma | Methods of screening for compounds which mimic galectin-1 |
US7018637B2 (en) | 1998-02-23 | 2006-03-28 | Aventis Pasteur, Inc | Multi-oligosaccharide glycoconjugate bacterial meningitis vaccines |
WO1999043356A1 (en) | 1998-02-25 | 1999-09-02 | Hsc Research Development Limited Partnership | Antibiotic-ligand conjugates and methods of use thereof |
WO1999043353A2 (en) | 1998-02-26 | 1999-09-02 | Boehringer Ingelheim Pharmaceuticals, Inc. | Combination anti-selectin and immunosuppressant therapy |
US6458777B1 (en) | 1998-03-13 | 2002-10-01 | Mucosal Therapeutics Llc | Methods and compositions for treating and preventing mucositis |
CA2245224A1 (en) | 1998-08-14 | 2000-02-14 | Jiang-Hong Giong | Chemokine receptor antagonists and chemotherapeutics |
US6265192B1 (en) | 1998-03-20 | 2001-07-24 | The Regents Of The University Of California | Glycosly sulfortransferase-3 |
US6365365B1 (en) | 1998-03-20 | 2002-04-02 | The Regents Of The University Of California | Method of determining whether an agent modulates glycosyl sulfotransferase-3 |
US6037333A (en) | 1998-05-07 | 2000-03-14 | Trustees Of Tufts College | Microbe-inhibiting compositions |
EP1079859B1 (en) | 1998-05-22 | 2010-07-14 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules and therapies based thereon |
US6593459B1 (en) | 1998-06-16 | 2003-07-15 | The Board Of Regents Of The University Of Oklahoma | Synthetic glycosulfopeptides and methods of synthesis thereof |
US6004815A (en) | 1998-08-13 | 1999-12-21 | The Regents Of The University Of California | Bacteria expressing nonsecreted cytolysin as intracellular microbial delivery vehicles to eukaryotic cells |
JP4553488B2 (ja) | 1998-09-21 | 2010-09-29 | 大塚製薬株式会社 | カルボキシメチルガラクトース誘導体 |
US6960566B1 (en) | 1998-11-06 | 2005-11-01 | The Wister Institute of Anatomy and Biology | Compositions and methods for treatment of cancer |
CA2348781A1 (en) | 1998-11-12 | 2000-05-25 | Novolytics Inc. | Compositions and methods for producing vascular occlusion |
GB9904387D0 (en) | 1999-02-25 | 1999-04-21 | Pharmacia & Upjohn Spa | Antitumour synergistic composition |
US6515117B2 (en) | 1999-10-12 | 2003-02-04 | Bristol-Myers Squibb Company | C-aryl glucoside SGLT2 inhibitors and method |
US6887842B1 (en) | 1999-11-19 | 2005-05-03 | The Board Of Trustees Of The Leland Stanford Junior University | Modulating a pharmacokinetic property of a drug by administering a bifunctional molecule containing the drug |
US7204981B2 (en) | 2000-03-28 | 2007-04-17 | Eli Lilly And Company | Methods of treating diseases with activated protein C |
KR101215789B1 (ko) | 2000-03-30 | 2012-12-26 | 화이트헤드 인스티튜트 포 바이오메디칼 리서치 | Rna 간섭의 rna 서열 특이적인 매개체 |
US6683056B2 (en) | 2000-03-30 | 2004-01-27 | Bristol-Myers Squibb Company | O-aryl glucoside SGLT2 inhibitors and method |
DE60118362T2 (de) | 2000-05-19 | 2007-05-24 | The Center for Blood Research, Inc., Boston | VERFAHREN ZUR BEHANDLUNG VON HÄMOSTATISCHEN STÖRUNGEN DURCH LöSLICHES P-SELECTIN |
US20020165178A1 (en) | 2000-06-28 | 2002-11-07 | Christian Schetter | Immunostimulatory nucleic acids for the treatment of anemia, thrombocytopenia, and neutropenia |
AU2000274809A1 (en) | 2000-09-12 | 2002-03-26 | Genetics Institute Llc | Inhibition of stenosis or restenosis by p-selectin antagonists |
JP2004523479A (ja) | 2000-10-18 | 2004-08-05 | マサチューセッツ インスティテュート オブ テクノロジー | 多糖の肺送達に関する方法および産物 |
AU2002219828A1 (en) | 2000-11-14 | 2002-05-27 | The General Hospital Corporation | Blockade of T cell migration into epithelial GVHD target tissues |
US7422733B2 (en) | 2000-11-29 | 2008-09-09 | Bracco International B.V. | Linkable sialyl Lewis X analogs |
US20020132220A1 (en) | 2000-12-27 | 2002-09-19 | Berens Kurt L. | Use of selectin antagonists in organ preservation solutions |
CA2442020C (en) | 2001-03-28 | 2017-03-14 | President And Fellows Of Harvard College | Methods of delivery of exogenous proteins to the cytosol and uses thereof |
US20030198639A1 (en) | 2002-04-16 | 2003-10-23 | Frenette Paul S. | Methods of treating sickle cell disease |
US7087212B2 (en) | 2001-08-17 | 2006-08-08 | Mallinckrodt, Inc | Multicomponent assemblies having enhanced binding properties for diagnosis and therapy |
US20030130174A1 (en) | 2001-10-19 | 2003-07-10 | Cummings Richard D. | Glycosulfopeptide inhibitors of leukocyte rolling and methods of use thereof |
WO2003049684A2 (en) | 2001-12-07 | 2003-06-19 | Centocor, Inc. | Pseudo-antibody constructs |
WO2003055876A1 (en) | 2001-12-21 | 2003-07-10 | Anormed Inc. | Chemokine receptor binding heterocyclic compounds with enhanced efficacy |
US20030186942A1 (en) | 2002-01-16 | 2003-10-02 | Crooks Peter A. | Compounds of use in the treatment of epilepsy, seizure, and electroconvulsive disorders |
US20040072796A1 (en) | 2002-04-18 | 2004-04-15 | Embury Stephen H. | Method and composition for preventing pain in sickle cell patients |
CA2486106C (en) | 2002-05-16 | 2013-07-16 | Glycomimetics, Inc. | Compounds and methods for inhibiting selectin-mediated function |
JP2006502986A (ja) | 2002-07-03 | 2006-01-26 | グリコミメティクス, インコーポレイテッド | 新脈管形成に関与する医学的状態の診断および治療のための組成物および方法 |
US7556806B2 (en) | 2002-10-11 | 2009-07-07 | University Of Maryland Biotechnology Institute | Carbohydrate-based synthetic vaccines for HIV |
CA2511174A1 (en) | 2002-12-20 | 2004-07-15 | Glycomimetics, Inc. | Oligosaccharides and conjugates thereof for the treatement of pseudomonas bacteria infection |
US6844125B2 (en) | 2003-03-20 | 2005-01-18 | Kabushiki Kaisha Toshiba | Combination of developing agents, image forming apparatus, and method for forming image |
US7332334B2 (en) | 2003-04-18 | 2008-02-19 | Oklahoma Medical Research Foundation | Hematopoietic stem cells treated by in vitro fucosylation and methods of use |
US20040219158A1 (en) | 2003-05-02 | 2004-11-04 | Glycomimetics, Inc. | Compositions and methods for diagnosis and therapy of medical conditions involving infection with pseudomonas bacteria |
WO2005016349A1 (en) | 2003-08-14 | 2005-02-24 | Icos Corporation | Methods of inhibiting leukocyte accumulation |
US7041226B2 (en) | 2003-11-04 | 2006-05-09 | Lexmark International, Inc. | Methods for improving flow through fluidic channels |
US20050214283A1 (en) | 2003-11-07 | 2005-09-29 | Robert Sackstein | Antibodies to CD44 glycoforms and uses thereof |
JP2007524658A (ja) | 2003-11-19 | 2007-08-30 | グリコミメティクス, インコーポレイテッド | E−およびp−セレクチンの両方のための糖模倣物アンタゴニスト |
WO2005051920A2 (en) | 2003-11-19 | 2005-06-09 | Glycomimetics, Inc. | Specific antagonist for both e- and p-selectins |
EP1709063B1 (en) | 2003-12-18 | 2008-01-23 | Unibioscreen S.A. | Glycosylated steroid derivatives with anti-migratory activity |
GB0404434D0 (en) | 2004-02-27 | 2004-03-31 | Novartis Ag | Organic compounds |
US7745421B2 (en) | 2004-05-25 | 2010-06-29 | The Johns Hopkins University | Methods and compositions for treating diseases and disorders associated with Siglec-8 expressing cells |
WO2006002382A2 (en) | 2004-06-24 | 2006-01-05 | The Scripps Research Institute | Arrays with cleavable linkers |
WO2006017180A2 (en) | 2004-07-09 | 2006-02-16 | Progenics Pharmaceuticals, Inc. | Glycopeptide dimers and uses thereof |
WO2006022454A1 (ja) | 2004-08-27 | 2006-03-02 | Ono Pharmaceutical Co., Ltd | 塩基性基を含有する化合物およびその用途 |
WO2006062946A2 (en) | 2004-12-06 | 2006-06-15 | University Of Florida Research Foundation, Inc. | Incorporation of bone marrow derived stem cells in tumors |
US8114884B2 (en) | 2005-01-07 | 2012-02-14 | Emory University | CXCR4 antagonists for the treatment of medical disorders |
RU2007130077A (ru) | 2005-01-07 | 2009-02-20 | Эмори Юниверсити (Us) | Антагонисты cxcr4 и их применение для лечения вич-инфекции |
AU2006214190A1 (en) | 2005-02-17 | 2006-08-24 | Icos Corporation | Phosphoinositide 3-kinase inhibitors for inhibiting leukocyte accumulation |
WO2006105019A1 (en) | 2005-03-25 | 2006-10-05 | Wisconsin Alumni Research Foundation | Compounds and methods for treating seizure disorders |
WO2006127906A1 (en) | 2005-05-25 | 2006-11-30 | Glycomimetics, Inc. | Heterobifunctional compounds for selectin inhibition |
US20060287253A1 (en) | 2005-06-17 | 2006-12-21 | Kriegler Steven M | Compounds and methods for treating seizure disorders |
AU2006272780A1 (en) | 2005-07-22 | 2007-02-01 | The Regents Of The University Of California | Heparin compostions and selectin inhibition |
AU2006280101B2 (en) | 2005-08-09 | 2012-06-28 | Glycomimetics, Inc. | Glycomimetic inhibitors of the PA-IL lectin, PA-IIL lectin or both the lectins from Pseudomonas |
WO2007022089A2 (en) | 2005-08-15 | 2007-02-22 | The Scripps Research Institute | Methods to identify therapeutic agents useful for treating and preventing atherosclerosis by counteracting the effect of cholesterol ozonation products |
WO2007022385A2 (en) | 2005-08-18 | 2007-02-22 | Novartis Ag | Use of cxcr4 binding molecules for the treatment of whim syndrome |
AU2006284578B2 (en) | 2005-09-02 | 2011-01-27 | Glycomimetics, Inc. | Heterobifunctional pan-selectin inhibitors |
EP1937308A4 (en) | 2005-09-14 | 2010-09-15 | Univ Maryland Biotech Inst | SYNTHETIC ADDED CARBOHYDRATES AS INGREDIENTS OF MICROBICIDES |
WO2007143052A1 (en) | 2006-06-01 | 2007-12-13 | Glycomimetics, Inc. | Galactosides and thiodigalactosides as inhibitors of pa-il lectin from pseudomonas |
WO2007146188A2 (en) | 2006-06-07 | 2007-12-21 | The Board Of Trustees Of The Leland Stanford Junior University | Anti-leukocyte recruitment therapy for the treatment of seizures and epilepsy |
US20090175792A1 (en) | 2006-06-23 | 2009-07-09 | Glycomimetics, Inc. | Glycomimetic inhibitors of siglec-8 |
WO2008008852A2 (en) | 2006-07-11 | 2008-01-17 | Emory University | Cxcr4 antagonists including heteroatoms for the treatment of medical disorders |
WO2008008854A2 (en) | 2006-07-11 | 2008-01-17 | Emory University | Cxcr4 antagonists including diazine and triazine structures for the treatment of medical disorders |
US20080227799A1 (en) | 2006-07-11 | 2008-09-18 | Liotta Dennis C | CXCR4 Antagonists Including Heteroatoms for the Treatment of Medical Disorders |
US7998740B2 (en) | 2006-07-18 | 2011-08-16 | Robert Sackstein | Cytokine induction of selectin ligands on cells |
JP5298020B2 (ja) | 2006-10-12 | 2013-09-25 | グリコミメティクス, インコーポレイテッド | ヘキソースおよびn−アセチルヘキソサミンの糖模倣体置換 |
US20080306098A1 (en) | 2006-11-06 | 2008-12-11 | Mutz Mitchell W | Pharmacokinetics of protease inhibitors and other drugs |
WO2008087259A1 (en) | 2007-01-18 | 2008-07-24 | Suomen Punainen Risti, Veripalvelu | Novel carbohydrate profile compositions from human cells and methods for analysis and modification thereof |
JP5511390B2 (ja) | 2007-02-09 | 2014-06-04 | グリコミメティクス, インコーポレイテッド | ヘキソースおよびn−アセチルヘキソサミンの置換体を有する糖模倣体の使用方法 |
WO2008109154A1 (en) | 2007-03-08 | 2008-09-12 | Altiris Therapeutics, Inc. | Chemokine receptor modulators |
US20090054334A1 (en) | 2007-05-23 | 2009-02-26 | Mutz Mitchell W | Combinatorial improvement of bifunctional drug properties |
US8039442B2 (en) | 2007-07-18 | 2011-10-18 | Glycomimetics, Inc. | Compounds and methods for treatment of sickle cell disease or complications associated therewith |
EP2184349A4 (en) | 2007-08-08 | 2011-10-26 | Kyowa Hakko Kirin Co Ltd | ISOLATED CELL MASS |
EP2211913A4 (en) | 2007-10-12 | 2010-12-22 | Transmolecular Inc | SYSTEMIC ADMINISTRATION OF CHLOROTOXIN AGENTS FOR THE DIAGNOSIS AND TREATMENT OF TUMORS |
FI20070853A0 (fi) | 2007-11-09 | 2007-11-09 | Glykos Finland Oy | Glykaania sitovat monoklonaaliset vasta-aineet |
WO2009073911A1 (en) | 2007-12-10 | 2009-06-18 | Mater Medical Research Institute | Treatment and prophylaxis |
WO2009126556A1 (en) | 2008-04-08 | 2009-10-15 | Glycomimetics, Inc. | Pan-selectin inhibitor with enhanced pharmacokinetic activity |
ES2426784T3 (es) | 2008-06-13 | 2013-10-25 | Glycomimetics, Inc. | Tratamiento de cánceres de la sangre usando compuestos glicomiméticos seleccionados |
US20110245265A1 (en) | 2008-08-29 | 2011-10-06 | Genzyme Corporation | Cxcr4 antagonists for kidney injury |
US20100240773A1 (en) | 2009-03-23 | 2010-09-23 | Kenneth Korzekwa | Multifunctional linkers |
FI20095459A0 (fi) | 2009-04-24 | 2009-04-24 | Suomen Punainen Risti Veripalv | Uusia määritysmenetelmiä |
WO2010132315A1 (en) | 2009-05-13 | 2010-11-18 | Endgenitor Technologies, Inc. | Enhanced hematopoietic stem cell engraftment |
WO2011127179A1 (en) | 2010-04-07 | 2011-10-13 | Glycomimetics, Inc. | Glycomimetic compounds and methods to inhibit infection by hiv |
WO2012037034A1 (en) | 2010-09-14 | 2012-03-22 | Glycomimetics, Inc. | E-selectin antagonists |
US20130261070A1 (en) | 2010-10-04 | 2013-10-03 | John L. Magnani | Anti-epileptogenic agents |
FI20106031A0 (fi) | 2010-10-06 | 2010-10-06 | Suomen Punainen Risti Veripalv | Menetelmä solujen eristämiseksi ja menetelmällä eristetty solupopulaatio |
WO2012061662A1 (en) * | 2010-11-03 | 2012-05-10 | Glycomimetics, Inc. | Glycomimetic-peptidomimetic inhibitors of e-selectins and cxcr4 chemokine receptors |
WO2012151576A1 (en) | 2011-05-05 | 2012-11-08 | Robert Sackstein | Methods of treating complications and disorders associated with g-csf administration |
WO2014070991A2 (en) | 2012-10-31 | 2014-05-08 | Glycomimetics, Inc. | E-selectin antagonist compounds and methods of use |
AU2013355238B2 (en) | 2012-12-07 | 2017-12-14 | Glycomimetics, Inc. | Compounds, compositions and methods using E-selectin antagonists for mobilization of hematopoietic cells |
WO2014149837A1 (en) | 2013-03-15 | 2014-09-25 | Glycomimetics, Inc. | Compounds and methods to enhance the oral availability of glycomimetics |
JP2016531871A (ja) | 2013-09-30 | 2016-10-13 | グリコミメティクス, インコーポレイテッド | 粘膜炎を治療および/または予防するための方法および組成物 |
WO2015109049A1 (en) | 2014-01-17 | 2015-07-23 | Glycomimetics, Inc. | E-selectin antagonists modified by macrocycle formation to the galactose |
SI3227310T1 (sl) | 2014-12-03 | 2019-11-29 | Glycomimetics Inc | Heterobifunkcionalni inhibitorji e-selektinov in receptorjev kemokina CXCR4 |
WO2016164394A1 (en) | 2015-04-08 | 2016-10-13 | Glycomimetics, Inc. | 2-halo-galactose-containing selectin antagonists |
WO2017095904A1 (en) | 2015-12-02 | 2017-06-08 | Glycomimetics, Inc. | Heterobifunctional pan-selectin antagonists having a triazole linker |
-
2015
- 2015-12-01 SI SI201530910T patent/SI3227310T1/sl unknown
- 2015-12-01 ES ES15865762T patent/ES2754549T3/es active Active
- 2015-12-01 PL PL15865762T patent/PL3227310T3/pl unknown
- 2015-12-01 KR KR1020177018135A patent/KR102542750B1/ko active IP Right Grant
- 2015-12-01 EP EP19181063.9A patent/EP3569609A1/en not_active Withdrawn
- 2015-12-01 EP EP15865762.7A patent/EP3227310B1/en active Active
- 2015-12-01 CN CN201580073498.7A patent/CN107108679B/zh active Active
- 2015-12-01 CA CA2968391A patent/CA2968391C/en active Active
- 2015-12-01 WO PCT/US2015/063191 patent/WO2016089872A1/en active Application Filing
- 2015-12-01 HU HUE15865762A patent/HUE045542T2/hu unknown
- 2015-12-01 LT LTEP15865762.7T patent/LT3227310T/lt unknown
- 2015-12-01 JP JP2017529350A patent/JP6689854B2/ja active Active
- 2015-12-01 PT PT158657627T patent/PT3227310T/pt unknown
- 2015-12-01 US US15/531,951 patent/US10519181B2/en not_active Expired - Fee Related
- 2015-12-01 AU AU2015355136A patent/AU2015355136B2/en active Active
- 2015-12-01 DK DK15865762.7T patent/DK3227310T3/da active
-
2019
- 2019-09-17 CY CY20191100971T patent/CY1122038T1/el unknown
-
2020
- 2020-03-13 JP JP2020044383A patent/JP2020090553A/ja not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002543126A (ja) * | 1999-05-03 | 2002-12-17 | スミスクライン・ビーチャム・コーポレイション | Cxcr−4受容体アンタゴニスト−トロンボポエチン模倣物 |
JP2012525393A (ja) * | 2009-05-01 | 2012-10-22 | グリコミメティックス インコーポレイテッド | E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 |
WO2013096926A1 (en) * | 2011-12-22 | 2013-06-27 | Glycomimetics, Inc. | E-selectin antagonist compounds, compositions, and methods of use |
Also Published As
Publication number | Publication date |
---|---|
KR102542750B1 (ko) | 2023-06-12 |
US20170305951A1 (en) | 2017-10-26 |
CN107108679A (zh) | 2017-08-29 |
EP3227310A4 (en) | 2018-07-25 |
EP3227310B1 (en) | 2019-07-31 |
PL3227310T3 (pl) | 2020-02-28 |
WO2016089872A1 (en) | 2016-06-09 |
LT3227310T (lt) | 2019-09-10 |
EP3227310A1 (en) | 2017-10-11 |
CY1122038T1 (el) | 2020-10-14 |
NZ732034A (en) | 2022-03-25 |
PT3227310T (pt) | 2019-11-06 |
HUE045542T2 (hu) | 2019-12-30 |
JP6689854B2 (ja) | 2020-04-28 |
JP2020090553A (ja) | 2020-06-11 |
EP3569609A1 (en) | 2019-11-20 |
CA2968391A1 (en) | 2016-06-09 |
KR20170085594A (ko) | 2017-07-24 |
US10519181B2 (en) | 2019-12-31 |
AU2015355136A1 (en) | 2017-06-08 |
AU2015355136B2 (en) | 2020-06-25 |
SI3227310T1 (sl) | 2019-11-29 |
BR112017011446A2 (pt) | 2018-02-27 |
DK3227310T3 (da) | 2019-09-30 |
ES2754549T3 (es) | 2020-04-20 |
CN107108679B (zh) | 2020-10-23 |
CA2968391C (en) | 2022-04-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6689854B2 (ja) | E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 | |
US9867841B2 (en) | Compounds, compositions and methods using E-selectin antagonists for mobilization of hematopoietic cells | |
DK2794626T3 (en) | E-selectin antagonist compounds | |
US20160243145A1 (en) | Methods and compositions for treating and/or preventing mucositis | |
JP2016501840A (ja) | E−セレクチンアンタゴニスト化合物および使用方法 | |
AU2023204344A1 (en) | Highly potent multimeric E-selectin antagonists | |
UA105764C2 (uk) | Заміщені імідазохіноліни | |
JP2022529806A (ja) | E-セレクチン、ガレクチン-3、および/またはcxcr4ケモカイン受容体のガラクトース連結型多量体糖模倣性阻害剤 | |
BR112017011446B1 (pt) | Composto, composição e uso dos mesmos | |
JP2023524456A (ja) | 担体への組込みに適したcd33リガンド | |
NZ732034B2 (en) | Heterobifunctional inhibitors of e-selectins and cxcr4 chemokine receptors | |
WO2022250976A1 (en) | Galectin-3 inhibiting c-glycoside oximes | |
US20200397901A1 (en) | Photoresponsive smoothened ligand |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181011 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20181011 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190913 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20191211 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200204 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200313 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20200313 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200407 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200408 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6689854 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |