JP2005506949A - ケモカイン受容体の調節剤としてのジアミン - Google Patents
ケモカイン受容体の調節剤としてのジアミン Download PDFInfo
- Publication number
- JP2005506949A JP2005506949A JP2002551518A JP2002551518A JP2005506949A JP 2005506949 A JP2005506949 A JP 2005506949A JP 2002551518 A JP2002551518 A JP 2002551518A JP 2002551518 A JP2002551518 A JP 2002551518A JP 2005506949 A JP2005506949 A JP 2005506949A
- Authority
- JP
- Japan
- Prior art keywords
- amino
- methyl
- crr
- replaced
- trifluoromethyl
- 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.)
- Withdrawn
Links
- 102000009410 Chemokine receptor Human genes 0.000 title claims description 10
- 108050000299 Chemokine receptor Proteins 0.000 title claims description 10
- 150000004985 diamines Chemical class 0.000 title description 10
- 238000011282 treatment Methods 0.000 claims abstract description 88
- 101710155857 C-C motif chemokine 2 Proteins 0.000 claims abstract description 50
- 102100021943 C-C motif chemokine 2 Human genes 0.000 claims abstract description 50
- 239000000126 substance Substances 0.000 claims abstract description 48
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 15
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 15
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 15
- 208000006673 asthma Diseases 0.000 claims abstract description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 780
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 653
- -1 cyclic acetal Chemical class 0.000 claims description 636
- 125000000217 alkyl group Chemical group 0.000 claims description 211
- 125000005842 heteroatom Chemical group 0.000 claims description 180
- 229910052717 sulfur Inorganic materials 0.000 claims description 176
- 229910052760 oxygen Inorganic materials 0.000 claims description 175
- 150000001875 compounds Chemical class 0.000 claims description 166
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 147
- 125000002837 carbocyclic group Chemical group 0.000 claims description 129
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 114
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 111
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 105
- 125000000623 heterocyclic group Chemical group 0.000 claims description 99
- 125000000304 alkynyl group Chemical group 0.000 claims description 97
- 125000003342 alkenyl group Chemical group 0.000 claims description 95
- 125000002981 3-(trifluoromethyl)benzoyl group Chemical group FC(C=1C=C(C(=O)*)C=CC1)(F)F 0.000 claims description 88
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 86
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 84
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 81
- 229910052739 hydrogen Inorganic materials 0.000 claims description 80
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 77
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 73
- 229910052794 bromium Inorganic materials 0.000 claims description 70
- 229910052801 chlorine Inorganic materials 0.000 claims description 70
- 229910052731 fluorine Inorganic materials 0.000 claims description 70
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 69
- 229910052740 iodine Inorganic materials 0.000 claims description 65
- 150000001408 amides Chemical class 0.000 claims description 62
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 61
- 229910052799 carbon Inorganic materials 0.000 claims description 57
- 238000000034 method Methods 0.000 claims description 57
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 50
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 46
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 42
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 40
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 40
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 37
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 35
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 35
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 34
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 33
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 33
- 125000004076 pyridyl group Chemical group 0.000 claims description 30
- 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 claims description 27
- 125000001041 indolyl group Chemical group 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 25
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 22
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 22
- 125000002971 oxazolyl group Chemical group 0.000 claims description 21
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 21
- 125000000335 thiazolyl group Chemical group 0.000 claims description 21
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 20
- 125000002541 furyl group Chemical group 0.000 claims description 20
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 20
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 20
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 20
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 20
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 20
- 125000001544 thienyl group Chemical group 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 19
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 19
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 19
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 19
- 125000002883 imidazolyl group Chemical group 0.000 claims description 19
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 19
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 19
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 19
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 19
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 18
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 17
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 17
- 102000019034 Chemokines Human genes 0.000 claims description 15
- 108010012236 Chemokines Proteins 0.000 claims description 15
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 14
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 14
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 14
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 14
- 125000003386 piperidinyl group Chemical group 0.000 claims description 14
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 14
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 13
- 150000003951 lactams Chemical class 0.000 claims description 13
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 12
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 12
- 102100032366 C-C motif chemokine 7 Human genes 0.000 claims description 11
- 101710155834 C-C motif chemokine 7 Proteins 0.000 claims description 11
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 11
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 claims description 10
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 10
- 150000002596 lactones Chemical class 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 9
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 9
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 9
- 206010015150 Erythema Diseases 0.000 claims description 8
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 8
- 125000005512 benztetrazolyl group Chemical group 0.000 claims description 8
- 206010009887 colitis Diseases 0.000 claims description 8
- 231100000321 erythema Toxicity 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 8
- 206010025135 lupus erythematosus Diseases 0.000 claims description 8
- 201000008383 nephritis Diseases 0.000 claims description 8
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 8
- 230000009885 systemic effect Effects 0.000 claims description 8
- 101710155833 C-C motif chemokine 8 Proteins 0.000 claims description 7
- 102100034871 C-C motif chemokine 8 Human genes 0.000 claims description 7
- 208000027866 inflammatory disease Diseases 0.000 claims description 7
- AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 230000003589 nefrotoxic effect Effects 0.000 claims description 7
- 231100000381 nephrotoxic Toxicity 0.000 claims description 7
- 210000002966 serum Anatomy 0.000 claims description 7
- 206010001889 Alveolitis Diseases 0.000 claims description 6
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 6
- 101000978374 Mus musculus C-C motif chemokine 12 Proteins 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 claims description 6
- 125000000980 1H-indol-3-ylmethyl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[*])C2=C1[H] 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
- 239000005977 Ethylene Substances 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- PAMCRRDMORMCSM-UHFFFAOYSA-N n-(trifluoromethyl)benzamide Chemical compound FC(F)(F)NC(=O)C1=CC=CC=C1 PAMCRRDMORMCSM-UHFFFAOYSA-N 0.000 claims description 5
- 239000001294 propane Substances 0.000 claims description 5
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 5
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- HXOSNKMHCFTABH-FQEVSTJZSA-N 2-amino-n-[2-[[(2s)-3-[(4-bromo-2-methylphenyl)methylamino]-1-(tert-butylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC(Br)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(C(F)(F)F)=CC=C1N HXOSNKMHCFTABH-FQEVSTJZSA-N 0.000 claims description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 4
- 108010017312 CCR2 Receptors Proteins 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 4
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- OBTXHENLXXGGFV-IBGZPJMESA-N methyl (2s)-2-[[2-[[2-amino-5-(trifluoromethyl)benzoyl]amino]acetyl]amino]-3-[(2,4-dimethylphenyl)methylamino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CNC(=O)C=1C(=CC=C(C=1)C(F)(F)F)N)NCC1=CC=C(C)C=C1C OBTXHENLXXGGFV-IBGZPJMESA-N 0.000 claims description 4
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 claims description 4
- JJYNUAMIRAIFBQ-NRFANRHFSA-N 2-amino-n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(C(F)(F)F)=CC=C1N JJYNUAMIRAIFBQ-NRFANRHFSA-N 0.000 claims description 3
- 102000004497 CCR2 Receptors Human genes 0.000 claims description 3
- 125000002393 azetidinyl group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- KWSFFNBRVWJEJK-INIZCTEOSA-N 2-amino-n-[2-[[(2s)-1-amino-3-[(4-bromophenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)N)NC(=O)CNC(=O)C=1C(=CC=C(C=1)C(F)(F)F)N)NCC1=CC=C(Br)C=C1 KWSFFNBRVWJEJK-INIZCTEOSA-N 0.000 claims description 2
- ZEYAHFUIXMLOML-NRFANRHFSA-N 3-amino-n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(N)=CC(C(F)(F)F)=C1 ZEYAHFUIXMLOML-NRFANRHFSA-N 0.000 claims description 2
- 206010065040 AIDS dementia complex Diseases 0.000 claims description 2
- 206010002329 Aneurysm Diseases 0.000 claims description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 2
- 208000031886 HIV Infections Diseases 0.000 claims description 2
- 208000037357 HIV infectious disease Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 206010037660 Pyrexia Diseases 0.000 claims description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- ZXYFWDUOJFDXFE-QHCPKHFHSA-N ethyl n-[3-[[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]-5-(trifluoromethyl)phenyl]carbamate Chemical compound FC(F)(F)C1=CC(NC(=O)OCC)=CC(C(=O)NCC(=O)N[C@@H](CNCC=2C(=CC(C)=CC=2)C)C(=O)NC(C)(C)C)=C1 ZXYFWDUOJFDXFE-QHCPKHFHSA-N 0.000 claims description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 2
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 2
- VFBXQEUUDUQOBO-LJQANCHMSA-N methyl (2r)-3-[(2,4-dimethylphenyl)methylamino]-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound C([C@H](C(=O)OC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C VFBXQEUUDUQOBO-LJQANCHMSA-N 0.000 claims description 2
- ZJPSEVOKBYZNIC-INIZCTEOSA-N methyl (2s)-3-(1,3-benzodioxol-5-ylmethylamino)-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound N([C@@H](CNCC=1C=C2OCOC2=CC=1)C(=O)OC)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZJPSEVOKBYZNIC-INIZCTEOSA-N 0.000 claims description 2
- OXJASFHPELQTQM-QFIPXVFZSA-N methyl (2s)-3-[(2,4-dimethylphenyl)methylamino]-2-[[2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CNC(=O)C=1C(=CC=C(C=1)C(F)(F)F)NC(=O)OC(C)(C)C)NCC1=CC=C(C)C=C1C OXJASFHPELQTQM-QFIPXVFZSA-N 0.000 claims description 2
- VFBXQEUUDUQOBO-IBGZPJMESA-N methyl (2s)-3-[(2,4-dimethylphenyl)methylamino]-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C VFBXQEUUDUQOBO-IBGZPJMESA-N 0.000 claims description 2
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 2
- WBXYZOVCGSOHBB-VWLOTQADSA-N n-[2-[[(2s)-1-(benzylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NCC=1C=CC=CC=1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 WBXYZOVCGSOHBB-VWLOTQADSA-N 0.000 claims description 2
- LIWQUWGNWHRXDR-QFIPXVFZSA-N n-[2-[[(2s)-1-(cyclobutylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC1CCC1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 LIWQUWGNWHRXDR-QFIPXVFZSA-N 0.000 claims description 2
- KLSWMLOBDUZIGN-NRFANRHFSA-N n-[2-[[(2s)-1-(cyclopropylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC1CC1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KLSWMLOBDUZIGN-NRFANRHFSA-N 0.000 claims description 2
- HIKYYHMSDKVHTL-QFIPXVFZSA-N n-[2-[[(2s)-1-(tert-butylamino)-1-oxo-3-[(4-propan-2-ylphenyl)methylamino]propan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(C(C)C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 HIKYYHMSDKVHTL-QFIPXVFZSA-N 0.000 claims description 2
- USLMKTKWYUXICE-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(difluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)F)=C1 USLMKTKWYUXICE-NRFANRHFSA-N 0.000 claims description 2
- SBZAYKSXVNAATR-FQEVSTJZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2-methylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 SBZAYKSXVNAATR-FQEVSTJZSA-N 0.000 claims description 2
- FRNSXNGJDFMFBE-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-cyano-2-methylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C#N)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 FRNSXNGJDFMFBE-NRFANRHFSA-N 0.000 claims description 2
- CCCRXCYCHFZAEL-QFIPXVFZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-ethenyl-2-methylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C=C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 CCCRXCYCHFZAEL-QFIPXVFZSA-N 0.000 claims description 2
- QRPKNKZUXDIPJG-QFIPXVFZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-ethyl-2-methylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(CC)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 QRPKNKZUXDIPJG-QFIPXVFZSA-N 0.000 claims description 2
- JRQLJCVOBYNBHW-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-methoxy-2-methylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(OC)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 JRQLJCVOBYNBHW-NRFANRHFSA-N 0.000 claims description 2
- MSSFMRMRFNNUBX-FQEVSTJZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-methylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 MSSFMRMRFNNUBX-FQEVSTJZSA-N 0.000 claims description 2
- GVPLREAHHSTSJS-FQEVSTJZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-methylsulfanylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(SC)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GVPLREAHHSTSJS-FQEVSTJZSA-N 0.000 claims description 2
- OUQLHEYPUWVFQL-FQEVSTJZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-methylsulfonylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(S(C)(=O)=O)C=C1 OUQLHEYPUWVFQL-FQEVSTJZSA-N 0.000 claims description 2
- SYNQRMWRRDBJSC-SFHVURJKSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(6-methoxypyridin-3-yl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 SYNQRMWRRDBJSC-SFHVURJKSA-N 0.000 claims description 2
- HTFCAKWNQNHBKJ-DEOSSOPVSA-N n-[2-[[(2s)-1-anilino-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC=1C=CC=CC=1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 HTFCAKWNQNHBKJ-DEOSSOPVSA-N 0.000 claims description 2
- JQTQSHYGYDYRLA-FQEVSTJZSA-N n-[2-[[(2s)-3-[(2,4-dimethylphenyl)methylamino]-1-(ethylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NCC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C JQTQSHYGYDYRLA-FQEVSTJZSA-N 0.000 claims description 2
- KNCWDGUPSSDGDF-NRFANRHFSA-N n-[2-[[(2s)-3-[(2,4-dimethylphenyl)methylamino]-1-[(1-hydroxy-2-methylpropan-2-yl)amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)CO)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KNCWDGUPSSDGDF-NRFANRHFSA-N 0.000 claims description 2
- BRRZJXMTXJQZFT-NRFANRHFSA-N n-[2-[[(2s)-3-[(2,4-dimethylphenyl)methylamino]-1-oxo-1-(propan-2-ylamino)propan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NC(C)C)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C BRRZJXMTXJQZFT-NRFANRHFSA-N 0.000 claims description 2
- DSNRPHZPZPKEDF-FQEVSTJZSA-N n-[2-[[(2s)-3-[(4-bromo-2-methylphenyl)methylamino]-1-(tert-butylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(Br)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 DSNRPHZPZPKEDF-FQEVSTJZSA-N 0.000 claims description 2
- SIBIFTUPQFSVBV-IBGZPJMESA-N n-[2-[[(2s)-3-[(4-bromophenyl)methylamino]-1-(tert-butylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(Br)C=C1 SIBIFTUPQFSVBV-IBGZPJMESA-N 0.000 claims description 2
- ASXQCRGLQIGFLC-SFHVURJKSA-N n-[2-[[(2s)-3-[(4-chlorophenyl)methylamino]-1-(ethylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NCC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(Cl)C=C1 ASXQCRGLQIGFLC-SFHVURJKSA-N 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- SVELLKLGRRLVTI-JOCHJYFZSA-N tert-butyl (3r)-4-[(2,4-dimethylphenyl)methylamino]-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]butanoate Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](CC(=O)OC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 SVELLKLGRRLVTI-JOCHJYFZSA-N 0.000 claims description 2
- TWEGKTGMILCJSR-DEOSSOPVSA-N tert-butyl n-[2-[[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(C(F)(F)F)=CC=C1NC(=O)OC(C)(C)C TWEGKTGMILCJSR-DEOSSOPVSA-N 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000000686 lactone group Chemical group 0.000 claims 6
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 2
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims 2
- JQTQSHYGYDYRLA-HXUWFJFHSA-N n-[2-[[(2r)-3-[(2,4-dimethylphenyl)methylamino]-1-(ethylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@H](C(=O)NCC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C JQTQSHYGYDYRLA-HXUWFJFHSA-N 0.000 claims 2
- VOVIAHPOWDMSIW-QHCPKHFHSA-N 2-amino-n-[2-[[(2s)-1-(tert-butylamino)-4-[(2,4-dimethylphenyl)methyl-methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound N([C@@H](CCN(C)CC=1C(=CC(C)=CC=1)C)C(=O)NC(C)(C)C)C(=O)CNC(=O)C1=CC(C(F)(F)F)=CC=C1N VOVIAHPOWDMSIW-QHCPKHFHSA-N 0.000 claims 1
- BVWYRWWDRBIVKJ-QFIPXVFZSA-N 2-amino-n-[2-[[(2s)-1-(tert-butylamino)-4-[(2,4-dimethylphenyl)methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNCC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(C(F)(F)F)=CC=C1N BVWYRWWDRBIVKJ-QFIPXVFZSA-N 0.000 claims 1
- LWEYMQQVLUOWLP-QFIPXVFZSA-N 3-amino-n-[2-[[(2s)-1-(tert-butylamino)-4-[(4-ethylphenyl)methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound C1=CC(CC)=CC=C1CNCC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(N)=CC(C(F)(F)F)=C1 LWEYMQQVLUOWLP-QFIPXVFZSA-N 0.000 claims 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 208000029028 brain injury Diseases 0.000 claims 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- LWOYRAWIPWSLMT-FQEVSTJZSA-N methyl (2s)-4-[(2,4-dimethylphenyl)methylamino]-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]butanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)CNCC1=CC=C(C)C=C1C LWOYRAWIPWSLMT-FQEVSTJZSA-N 0.000 claims 1
- GSINUEDWKBKBBC-HXUWFJFHSA-N n-[2-[[(2r)-2-[(2,4-dimethylphenyl)methylamino]-3-(ethylamino)-3-oxopropyl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@H](C(=O)NCC)NCC=1C(=CC(C)=CC=1)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GSINUEDWKBKBBC-HXUWFJFHSA-N 0.000 claims 1
- KNCWDGUPSSDGDF-OAQYLSRUSA-N n-[2-[[(2r)-3-[(2,4-dimethylphenyl)methylamino]-1-[(1-hydroxy-2-methylpropan-2-yl)amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@H](C(=O)NC(C)(C)CO)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KNCWDGUPSSDGDF-OAQYLSRUSA-N 0.000 claims 1
- QAPFGTQCICZVMD-DEOSSOPVSA-N n-[2-[[(2s)-1-(cyclohexylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC1CCCCC1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 QAPFGTQCICZVMD-DEOSSOPVSA-N 0.000 claims 1
- GKHDPJJGUXXRIQ-QHCPKHFHSA-N n-[2-[[(2s)-1-(cyclopentylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC1CCCC1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GKHDPJJGUXXRIQ-QHCPKHFHSA-N 0.000 claims 1
- MEFKICKCETVIHD-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-(1h-indol-3-ylmethylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H](CNCC=1C2=CC=CC=C2NC=1)C(=O)NC(C)(C)C)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 MEFKICKCETVIHD-NRFANRHFSA-N 0.000 claims 1
- RBTPLFXLAYIKKD-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-ethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(CC)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 RBTPLFXLAYIKKD-NRFANRHFSA-N 0.000 claims 1
- MZOVYGGMQJARQJ-FQEVSTJZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-methoxyphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(OC)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 MZOVYGGMQJARQJ-FQEVSTJZSA-N 0.000 claims 1
- MINWZMLSSYTQMV-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[[4-(dimethylamino)phenyl]methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(N(C)C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 MINWZMLSSYTQMV-NRFANRHFSA-N 0.000 claims 1
- GYWKVWRKXAGCMG-QFIPXVFZSA-N n-[2-[[(2s)-1-(tert-butylamino)-4-[(2,4-dimethylphenyl)methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNCC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GYWKVWRKXAGCMG-QFIPXVFZSA-N 0.000 claims 1
- SVGYEBVMEHPHCS-QFIPXVFZSA-N n-[2-[[(2s)-3-[(2,4-dimethylphenyl)methylamino]-1-(2-methylpropylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NCC(C)C)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C SVGYEBVMEHPHCS-QFIPXVFZSA-N 0.000 claims 1
- VKEIRGOCEUAYTA-FQEVSTJZSA-N n-[2-[[(2s)-3-[(3-amino-4-methylphenyl)methylamino]-1-(tert-butylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(N)C(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 VKEIRGOCEUAYTA-FQEVSTJZSA-N 0.000 claims 1
- HHCXTVSNSLXIJU-QFIPXVFZSA-N n-[2-[[(2s)-4-[(2,4-dimethylphenyl)methyl-methylamino]-1-(ethylamino)-1-oxobutan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NCC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)CN(C)CC1=CC=C(C)C=C1C HHCXTVSNSLXIJU-QFIPXVFZSA-N 0.000 claims 1
- IZWURKUUGCCQGO-NRFANRHFSA-N n-[2-[[(2s)-4-[(2,4-dimethylphenyl)methylamino]-1-(ethylamino)-1-oxobutan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NCC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)CNCC1=CC=C(C)C=C1C IZWURKUUGCCQGO-NRFANRHFSA-N 0.000 claims 1
- OYHVXDINLMMECT-VLIAUNLRSA-N n-[2-[[(2s,3r)-3-[(4-bromophenyl)methylamino]-1-(ethylamino)-1-oxobutan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H](C(=O)NCC)[C@@H](C)NCC=1C=CC(Br)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 OYHVXDINLMMECT-VLIAUNLRSA-N 0.000 claims 1
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 claims 1
- IYOCTVFQXVEVKD-SANMLTNESA-N tert-butyl n-[2-[[2-[[(2s)-1-(tert-butylamino)-4-[(2,4-dimethylphenyl)methyl-methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]carbamoyl]-4-(trifluoromethyl)phenyl]carbamate Chemical compound N([C@@H](CCN(C)CC=1C(=CC(C)=CC=1)C)C(=O)NC(C)(C)C)C(=O)CNC(=O)C1=CC(C(F)(F)F)=CC=C1NC(=O)OC(C)(C)C IYOCTVFQXVEVKD-SANMLTNESA-N 0.000 claims 1
- KNVYVYDCIKDXSF-VWLOTQADSA-N tert-butyl n-[2-[[2-[[(2s)-1-(tert-butylamino)-4-[(2,4-dimethylphenyl)methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]carbamoyl]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC1=CC(C)=CC=C1CNCC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(C(F)(F)F)=CC=C1NC(=O)OC(C)(C)C KNVYVYDCIKDXSF-VWLOTQADSA-N 0.000 claims 1
- 230000002265 prevention Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 91
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- 238000006243 chemical reaction Methods 0.000 description 59
- 239000000243 solution Substances 0.000 description 53
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 238000005259 measurement Methods 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 150000001412 amines Chemical class 0.000 description 35
- 235000019439 ethyl acetate Nutrition 0.000 description 34
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 239000002253 acid Substances 0.000 description 27
- 239000011734 sodium Substances 0.000 description 27
- 239000012267 brine Substances 0.000 description 25
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
- 150000002148 esters Chemical class 0.000 description 24
- 229920006395 saturated elastomer Polymers 0.000 description 24
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 23
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 23
- 239000000463 material Substances 0.000 description 22
- 238000003786 synthesis reaction Methods 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- 241001024304 Mino Species 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
- 238000004007 reversed phase HPLC Methods 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- 239000011347 resin Substances 0.000 description 15
- 229920005989 resin Polymers 0.000 description 15
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 14
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 14
- 239000000284 extract Substances 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 12
- 238000004108 freeze drying Methods 0.000 description 12
- 230000003993 interaction Effects 0.000 description 12
- 229940002612 prodrug Drugs 0.000 description 12
- 239000000651 prodrug Substances 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 230000008485 antagonism Effects 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 150000001413 amino acids Chemical group 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 238000005984 hydrogenation reaction Methods 0.000 description 9
- 150000002576 ketones Chemical class 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 102100023702 C-C motif chemokine 13 Human genes 0.000 description 8
- 101710112613 C-C motif chemokine 13 Proteins 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- 150000001540 azides Chemical class 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 150000002825 nitriles Chemical class 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 239000005557 antagonist Substances 0.000 description 7
- 125000002619 bicyclic group Chemical group 0.000 description 7
- 229910002092 carbon dioxide Inorganic materials 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241000725303 Human immunodeficiency virus Species 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 239000002932 luster Substances 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 5
- 108010055166 Chemokine CCL5 Proteins 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- 235000008206 alpha-amino acids Nutrition 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 150000004795 grignard reagents Chemical class 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- KEUFKEFYFXTLDW-SFHVURJKSA-N n-[2-[[(2s)-1-amino-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(N)=O)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KEUFKEFYFXTLDW-SFHVURJKSA-N 0.000 description 5
- 230000002018 overexpression Effects 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 150000003333 secondary alcohols Chemical class 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- SFKKGJIKDGSCQC-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-(trifluoromethyl)benzoic acid Chemical compound CC(C)(C)OC(=O)NC1=CC=C(C(F)(F)F)C=C1C(O)=O SFKKGJIKDGSCQC-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 102000001902 CC Chemokines Human genes 0.000 description 4
- 108010040471 CC Chemokines Proteins 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- 239000007818 Grignard reagent Substances 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 4
- 238000006268 reductive amination reaction Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 3
- GISVICWQYMUPJF-UHFFFAOYSA-N 2,4-Dimethylbenzaldehyde Chemical compound CC1=CC=C(C=O)C(C)=C1 GISVICWQYMUPJF-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 3
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 3
- 108700012434 CCL3 Proteins 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 102000000013 Chemokine CCL3 Human genes 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 229940123313 MCP-1 antagonist Drugs 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 150000001371 alpha-amino acids Chemical class 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 150000001735 carboxylic acids Chemical class 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 210000003979 eosinophil Anatomy 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 125000000160 oxazolidinyl group Chemical group 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000007127 saponification reaction Methods 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- BUZICZZQJDLXJN-GSVOUGTGSA-N (3R)-3-amino-4-hydroxybutanoic acid Chemical compound OC[C@H](N)CC(O)=O BUZICZZQJDLXJN-GSVOUGTGSA-N 0.000 description 2
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 2
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 2
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 2
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 2
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- BLCJBICVQSYOIF-UHFFFAOYSA-N 2,2-diaminobutanoic acid Chemical compound CCC(N)(N)C(O)=O BLCJBICVQSYOIF-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 2
- 125000005986 4-piperidonyl group Chemical group 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 2
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 2
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 2
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 2
- 102100023698 C-C motif chemokine 17 Human genes 0.000 description 2
- 108050006947 CXC Chemokine Proteins 0.000 description 2
- 102000019388 CXC chemokine Human genes 0.000 description 2
- 102000001326 Chemokine CCL4 Human genes 0.000 description 2
- 108010055165 Chemokine CCL4 Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000053763 Cystosoma Species 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 102100023688 Eotaxin Human genes 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108091006027 G proteins Proteins 0.000 description 2
- 102000030782 GTP binding Human genes 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 101000978362 Homo sapiens C-C motif chemokine 17 Proteins 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010042618 Surgical procedure repeated Diseases 0.000 description 2
- BBAWTPDTGRXPDG-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyridine Chemical compound C1=CC=C2SC=NC2=N1 BBAWTPDTGRXPDG-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 150000001370 alpha-amino acid derivatives Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
- 125000004623 carbolinyl group Chemical group 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000003399 chemotactic effect Effects 0.000 description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 2
- 239000000039 congener Substances 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 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 2
- NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical compound C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000003838 furazanyl group Chemical group 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 description 2
- 125000002636 imidazolinyl group Chemical group 0.000 description 2
- 150000003949 imides Chemical class 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- OLNJUISKUQQNIM-UHFFFAOYSA-N indole-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CNC2=C1 OLNJUISKUQQNIM-UHFFFAOYSA-N 0.000 description 2
- 125000004926 indolenyl group Chemical group 0.000 description 2
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 2
- 229940096397 interleukin-8 Drugs 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 2
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 2
- 125000005438 isoindazolyl group Chemical group 0.000 description 2
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 2
- OIGPUPVQQUOVAP-KRWDZBQOSA-N methyl (2s)-3-[(4-bromophenyl)methylamino]-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(Br)C=C1 OIGPUPVQQUOVAP-KRWDZBQOSA-N 0.000 description 2
- 229940050176 methyl chloride Drugs 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- KEUFKEFYFXTLDW-GOSISDBHSA-N n-[2-[[(2r)-1-amino-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@H](C(N)=O)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KEUFKEFYFXTLDW-GOSISDBHSA-N 0.000 description 2
- STJUEHWSZYBOFD-SFHVURJKSA-N n-[2-[[(2s)-1-amino-3-(1h-indol-3-ylmethylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H](CNCC=1C2=CC=CC=C2NC=1)C(=O)N)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 STJUEHWSZYBOFD-SFHVURJKSA-N 0.000 description 2
- VNLQLUZHIIDOHC-INIZCTEOSA-N n-[2-[[(2s)-1-amino-3-[(4-chlorophenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)N)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(Cl)C=C1 VNLQLUZHIIDOHC-INIZCTEOSA-N 0.000 description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 description 2
- QNNHQVPFZIFNFK-UHFFFAOYSA-N oxazolo[4,5-b]pyridine Chemical compound C1=CC=C2OC=NC2=N1 QNNHQVPFZIFNFK-UHFFFAOYSA-N 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 2
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 2
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 2
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 2
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 2
- 125000002755 pyrazolinyl group Chemical group 0.000 description 2
- 125000001422 pyrrolinyl group Chemical group 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 2
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
- OLMBOHVAVKHHTK-UHFFFAOYSA-N (1-carboxy-2,2-dimethylpropyl)azanium;chloride Chemical compound Cl.CC(C)(C)C(N)C(O)=O OLMBOHVAVKHHTK-UHFFFAOYSA-N 0.000 description 1
- ZYJPUMXJBDHSIF-LLVKDONJSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-LLVKDONJSA-N 0.000 description 1
- QUPFKBITVLIQNA-KPKJPENVSA-N (5e)-2-sulfanylidene-5-[[5-[3-(trifluoromethyl)phenyl]furan-2-yl]methylidene]-1,3-thiazolidin-4-one Chemical compound FC(F)(F)C1=CC=CC(C=2OC(\C=C\3C(NC(=S)S/3)=O)=CC=2)=C1 QUPFKBITVLIQNA-KPKJPENVSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- 150000000093 1,3-dioxanes Chemical class 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical class C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
- JUXAVSAMVBLDKO-UHFFFAOYSA-N 1-(1-azabicyclo[2.2.2]octan-3-yl)-3-[3-(1h-indol-3-yl)-1-oxo-1-spiro[1,2-dihydroindene-3,4'-piperidine]-1'-ylpropan-2-yl]urea Chemical compound C1N(CC2)CCC2C1NC(=O)NC(C(=O)N1CCC2(C3=CC=CC=C3CC2)CC1)CC1=CNC2=CC=CC=C12 JUXAVSAMVBLDKO-UHFFFAOYSA-N 0.000 description 1
- HSDSKVWQTONQBJ-UHFFFAOYSA-N 1-(2,4-dimethylphenyl)ethanone Chemical compound CC(=O)C1=CC=C(C)C=C1C HSDSKVWQTONQBJ-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 125000005955 1H-indazolyl group Chemical group 0.000 description 1
- FJJYHTVHBVXEEQ-UHFFFAOYSA-N 2,2-dimethylpropanal Chemical compound CC(C)(C)C=O FJJYHTVHBVXEEQ-UHFFFAOYSA-N 0.000 description 1
- DYGXEDBIPZDZQS-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-pyrido[3,2-b]indole Chemical compound N1C2=CC=CC=C2C2=C1CCCN2 DYGXEDBIPZDZQS-UHFFFAOYSA-N 0.000 description 1
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-Lutidine Substances CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- WIBAVHOUUFYVQH-UHFFFAOYSA-N 2-[tert-butyl-[3-(trifluoromethyl)benzoyl]amino]acetic acid Chemical compound OC(=O)CN(C(C)(C)C)C(=O)C1=CC=CC(C(F)(F)F)=C1 WIBAVHOUUFYVQH-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 1
- FQXQBFUUVCDIRK-UHFFFAOYSA-N 3-trifluoromethylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C(F)(F)F)=C1 FQXQBFUUVCDIRK-UHFFFAOYSA-N 0.000 description 1
- RLRKXZGNQWPXRC-UHFFFAOYSA-N 4,7,7-trimethylbicyclo[2.2.1]heptan-3-one;hydrochloride Chemical compound Cl.C1CC2(C)C(=O)CC1C2(C)C RLRKXZGNQWPXRC-UHFFFAOYSA-N 0.000 description 1
- RCBPVESMGNZMSG-UHFFFAOYSA-N 4-bromo-2-methylbenzaldehyde Chemical compound CC1=CC(Br)=CC=C1C=O RCBPVESMGNZMSG-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- ATYUCXIJDKHOPX-UHFFFAOYSA-N 5-[4-[(9h-fluoren-9-ylmethoxycarbonylamino)methyl]-3,5-dimethoxyphenoxy]pentanoic acid Chemical compound COC1=CC(OCCCCC(O)=O)=CC(OC)=C1CNC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ATYUCXIJDKHOPX-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- 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 1
- 208000030507 AIDS Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000031873 Animal Disease Models Diseases 0.000 description 1
- 101150102415 Apob gene Proteins 0.000 description 1
- 102100029470 Apolipoprotein E Human genes 0.000 description 1
- 101710095339 Apolipoprotein E Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical class CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 102100034065 Atypical chemokine receptor 4 Human genes 0.000 description 1
- 108700036632 Atypical chemokine receptor 4 Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- JXYACYYPACQCDM-UHFFFAOYSA-N Benzyl glycinate Chemical compound NCC(=O)OCC1=CC=CC=C1 JXYACYYPACQCDM-UHFFFAOYSA-N 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010066091 Bronchial Hyperreactivity Diseases 0.000 description 1
- 108050005711 C Chemokine Proteins 0.000 description 1
- 102000017483 C chemokine Human genes 0.000 description 1
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
- 102100031174 C-C chemokine receptor type 10 Human genes 0.000 description 1
- 101710109563 C-C chemokine receptor type 10 Proteins 0.000 description 1
- 102100037853 C-C chemokine receptor type 4 Human genes 0.000 description 1
- 102100036302 C-C chemokine receptor type 6 Human genes 0.000 description 1
- 101710149871 C-C chemokine receptor type 6 Proteins 0.000 description 1
- 101710149872 C-C chemokine receptor type 8 Proteins 0.000 description 1
- 102100036841 C-C motif chemokine 1 Human genes 0.000 description 1
- 102100036848 C-C motif chemokine 20 Human genes 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 102000018213 CC chemokine receptor 2 Human genes 0.000 description 1
- 108010039171 CC cytokine receptor-4 Proteins 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 108010082548 Chemokine CCL11 Proteins 0.000 description 1
- 108010078239 Chemokine CX3CL1 Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 1
- 229930195711 D-Serine Natural products 0.000 description 1
- 108010041986 DNA Vaccines Proteins 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010061819 Disease recurrence Diseases 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
- 101710139422 Eotaxin Proteins 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 102000013818 Fractalkine Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102100034221 Growth-regulated alpha protein Human genes 0.000 description 1
- 101000889953 Homo sapiens Apolipoprotein B-100 Proteins 0.000 description 1
- 101000777564 Homo sapiens C-C chemokine receptor type 1 Proteins 0.000 description 1
- 101000980744 Homo sapiens C-C chemokine receptor type 3 Proteins 0.000 description 1
- 101000946926 Homo sapiens C-C chemokine receptor type 5 Proteins 0.000 description 1
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 1
- 101000713104 Homo sapiens C-C motif chemokine 1 Proteins 0.000 description 1
- 101000713099 Homo sapiens C-C motif chemokine 20 Proteins 0.000 description 1
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 description 1
- 238000006130 Horner-Wadsworth-Emmons olefination reaction Methods 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 102100023487 Lens fiber major intrinsic protein Human genes 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108010047660 Mitochondrial intermediate peptidase Proteins 0.000 description 1
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 1
- 101100490183 Mus musculus Ackr4 gene Proteins 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 241001274216 Naso Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 229940083963 Peptide antagonist Drugs 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
- 101000777393 Rattus norvegicus C-C motif chemokine 2 Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010069363 Traumatic lung injury Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- LUTSRLYCMSCGCS-BWOMAWGNSA-N [(3s,8r,9s,10r,13s)-10,13-dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,16-decahydrocyclopenta[a]phenanthren-3-yl] acetate Chemical compound C([C@@H]12)C[C@]3(C)C(=O)CC=C3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)C)C1 LUTSRLYCMSCGCS-BWOMAWGNSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000011558 animal model by disease Methods 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 150000001509 aspartic acid derivatives Chemical class 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 1
- FHRRJZZGSJXPRQ-UHFFFAOYSA-N benzyl phenylmethoxycarbonyl carbonate Chemical compound C=1C=CC=CC=1COC(=O)OC(=O)OCC1=CC=CC=C1 FHRRJZZGSJXPRQ-UHFFFAOYSA-N 0.000 description 1
- 150000001277 beta hydroxy acids Chemical class 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 150000003997 cyclic ketones Chemical class 0.000 description 1
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 1
- XSYZCZPCBXYQTE-UHFFFAOYSA-N cyclodecylcyclodecane Chemical compound C1CCCCCCCCC1C1CCCCCCCCC1 XSYZCZPCBXYQTE-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 150000001945 cysteines Chemical class 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- PIZLBWGMERQCOC-UHFFFAOYSA-N dibenzyl carbonate Chemical compound C=1C=CC=CC=1COC(=O)OCC1=CC=CC=C1 PIZLBWGMERQCOC-UHFFFAOYSA-N 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- LMBWSYZSUOEYSN-UHFFFAOYSA-N diethyldithiocarbamic acid Chemical compound CCN(CC)C(S)=S LMBWSYZSUOEYSN-UHFFFAOYSA-N 0.000 description 1
- KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229950004394 ditiocarb Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- QPMJENKZJUFOON-PLNGDYQASA-N ethyl (z)-3-chloro-2-cyano-4,4,4-trifluorobut-2-enoate Chemical compound CCOC(=O)C(\C#N)=C(/Cl)C(F)(F)F QPMJENKZJUFOON-PLNGDYQASA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229940083761 high-ceiling diuretics pyrazolone derivative Drugs 0.000 description 1
- 102000052249 human APOB Human genes 0.000 description 1
- XPXMKIXDFWLRAA-UHFFFAOYSA-N hydrazinide Chemical compound [NH-]N XPXMKIXDFWLRAA-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001967 indiganyl group Chemical group [H][In]([H])[*] 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- DQDWATOXYCARFV-UHFFFAOYSA-M magnesium;2-methanidylpropane;bromide Chemical compound [Mg+2].[Br-].CC(C)[CH2-] DQDWATOXYCARFV-UHFFFAOYSA-M 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- QGEFGPVWRJCFQP-UHFFFAOYSA-M magnesium;methanidylbenzene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1=CC=CC=C1 QGEFGPVWRJCFQP-UHFFFAOYSA-M 0.000 description 1
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 108010065176 monocyte chemoattractant protein 1 (9-76) Proteins 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- PPJQDLFXARGOSQ-IBGZPJMESA-N n-[2-[[(2s)-1-amino-4-[(2,4-dimethylphenyl)methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNCC[C@@H](C(N)=O)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 PPJQDLFXARGOSQ-IBGZPJMESA-N 0.000 description 1
- SGFNALWKISCJLN-IBGZPJMESA-N n-[2-[[(2s)-3-[(2,4-dimethylphenyl)methylamino]-1-(methylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C SGFNALWKISCJLN-IBGZPJMESA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- FDSSYPNUQHQSIQ-UHFFFAOYSA-N penta-2,4-dienamide Chemical class NC(=O)C=CC=C FDSSYPNUQHQSIQ-UHFFFAOYSA-N 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 125000005954 phenoxathiinyl group Chemical group 0.000 description 1
- 125000004932 phenoxathinyl group Chemical group 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 125000004928 piperidonyl group Chemical group 0.000 description 1
- 229940081310 piperonal Drugs 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 125000003367 polycyclic group Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003334 secondary amides Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/36—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Physical Education & Sports Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Crystallography & Structural Chemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25685500P | 2000-12-20 | 2000-12-20 | |
| PCT/US2001/050619 WO2002050019A2 (en) | 2000-12-20 | 2001-12-20 | Diamines as modulators of chemokine receptor activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005506949A true JP2005506949A (ja) | 2005-03-10 |
| JP2005506949A5 JP2005506949A5 (enExample) | 2005-12-22 |
Family
ID=22973869
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002551518A Withdrawn JP2005506949A (ja) | 2000-12-20 | 2001-12-20 | ケモカイン受容体の調節剤としてのジアミン |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US6974836B2 (enExample) |
| EP (1) | EP1351924A2 (enExample) |
| JP (1) | JP2005506949A (enExample) |
| AR (1) | AR035720A1 (enExample) |
| AU (1) | AU2002241724A1 (enExample) |
| CA (1) | CA2432908A1 (enExample) |
| HU (1) | HUP0303540A2 (enExample) |
| WO (1) | WO2002050019A2 (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002241724A1 (en) | 2000-12-20 | 2002-07-01 | Bristol-Myers Squibb Company | Diamines as modulators of chemokine receptor activity |
| WO2002060859A2 (en) * | 2000-12-20 | 2002-08-08 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| WO2003075853A2 (en) | 2002-03-08 | 2003-09-18 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| TW200508224A (en) | 2003-02-12 | 2005-03-01 | Bristol Myers Squibb Co | Cyclic derivatives as modulators of chemokine receptor activity |
| WO2004071449A2 (en) * | 2003-02-12 | 2004-08-26 | Bristol-Myers Squibb Company | Lactams as modulators of chemokine receptor activity |
| JP2006521382A (ja) | 2003-03-28 | 2006-09-21 | イーライ リリー アンド カンパニー | Akt(プロテインキナーゼb)阻害剤 |
| US7291615B2 (en) | 2003-05-01 | 2007-11-06 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| US7230133B2 (en) * | 2003-05-01 | 2007-06-12 | Bristol-Myers Squibb Company | Malonamides and malonamide derivatives as modulators of chemokine receptor activity |
| US7317019B2 (en) * | 2003-08-21 | 2008-01-08 | Bristol Myers Squibb Co. | N-alkylated diaminopropane derivatives as modulators of chemokine receptor activity |
| US7863317B2 (en) * | 2003-08-21 | 2011-01-04 | Bristol-Myers Squibb Company | Lactams of alkylated acyclic diamine derivatives as modulators of chemokine receptor activity |
| US20050043392A1 (en) * | 2003-08-21 | 2005-02-24 | Carter Percy H. | Lactams of alkylated acyclic diamine derivatives as modulators of chemokine receptor activity |
| US7378409B2 (en) | 2003-08-21 | 2008-05-27 | Bristol-Myers Squibb Company | Substituted cycloalkylamine derivatives as modulators of chemokine receptor activity |
| US7163937B2 (en) * | 2003-08-21 | 2007-01-16 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| US20070073064A1 (en) * | 2003-10-08 | 2007-03-29 | Teijin Pharma Limited | Method for producing aminopyrrolidine derivatives and intermediate compounds |
| EP1689719A1 (en) | 2003-11-25 | 2006-08-16 | Eli Lilly And Company | 7-phenyl-isoquinoline-5-sulfonylamino derivatives as inhibitors of akt (proteinkinase b) |
| US7479496B2 (en) | 2004-02-19 | 2009-01-20 | Bristol-Myers Squibb Company | Substituted spiro azabicyclics as modulators of chemokine receptor activity |
| US7381738B2 (en) | 2004-02-19 | 2008-06-03 | Bristol-Myers Squibb Company | Substituted bicycloalkylamine derivatives as modulators of chemokine receptor activity |
| US7288563B2 (en) | 2004-02-19 | 2007-10-30 | Bristol-Myers Squibb Company | Substituted bicycloalkylamine derivatives as modulators of chemokine receptor activity |
| US7230022B2 (en) | 2004-02-19 | 2007-06-12 | Bristol-Myers Squibb Company | Substituted fused bicyclic amines as modulators of chemokine receptor activity |
| SI1771463T1 (sl) * | 2004-07-16 | 2008-06-30 | Lonza Ag | Postopek za sintezo peptidov |
| BRPI0517701A8 (pt) | 2004-11-10 | 2018-01-23 | Genzyme Corp | métodos de tratamento de diabetes mellitus |
| JP2008526861A (ja) * | 2005-01-06 | 2008-07-24 | メルク エンド カムパニー インコーポレーテッド | 炎症性障害を治療するための薬剤併用療法および医薬組成物 |
| ES2546181T3 (es) | 2006-05-09 | 2015-09-21 | Genzyme Corporation | Métodos de tratar la enfermedad del hígado graso mediante inhibición de la síntesis de glucoesfingolípidos |
| US7629351B2 (en) * | 2006-07-28 | 2009-12-08 | Bristol-Myers Squibb Company | N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino) pyrrolidin-1-yl)cyclohexyl)acetamide and other modulators of chemokine receptor activity, crystalline forms and process |
| US7671062B2 (en) * | 2006-07-28 | 2010-03-02 | Bristol-Myers Squibb Company | Modulators of chemokine receptor activity, crystalline forms and process |
| US7687508B2 (en) * | 2006-07-28 | 2010-03-30 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| US20080076120A1 (en) * | 2006-09-14 | 2008-03-27 | Millennium Pharmaceuticals, Inc. | Methods for the identification, evaluation and treatment of patients having CC-Chemokine receptor 2 (CCR-2) mediated disorders |
| EP2594563B1 (en) | 2007-05-31 | 2018-07-18 | Genzyme Corporation | 2-acylaminopropanol-type glucosylceramide synthase inhibitors |
| CA2701649C (en) | 2007-10-05 | 2016-05-24 | Genzyme Corporation | Method of treating polycystic kidney diseases with ceramide derivatives |
| CA2731685A1 (en) | 2008-07-28 | 2010-02-04 | Genzyme Corporation | Glucosylceramide synthase inhibition for the treatment of collapsing glomerulopathy and other glomerular disease |
| CN102271678B (zh) | 2008-10-03 | 2017-06-30 | 简詹姆公司 | 2‑酰胺基丙醇型葡糖神经酰胺合成酶抑制剂 |
| US8383812B2 (en) | 2009-10-13 | 2013-02-26 | Bristol-Myers Squibb Company | N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-A][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide, a dual modulator of chemokine receptor activity, crystalline forms and processes |
Family Cites Families (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US65147A (en) * | 1867-05-28 | winants and john f | ||
| US235835A (en) * | 1880-12-21 | Alfred wilbue | ||
| US110736A (en) * | 1871-01-03 | Improvement in combined cultivators and planters | ||
| US54627A (en) * | 1866-05-08 | Improvement in hay-loaders | ||
| US216434A (en) * | 1879-06-10 | Improvement in machines for making sheet-metal can-bodies | ||
| US186143A (en) * | 1877-01-09 | Improvement in combined wash-stand and bureau | ||
| US235836A (en) * | 1880-12-21 | Lathe-chuck | ||
| US43392A (en) * | 1864-07-05 | Improvement in excavators | ||
| US54626A (en) * | 1866-05-08 | Improvement in spirit-levels | ||
| DE3635907A1 (de) | 1986-10-22 | 1988-04-28 | Merck Patent Gmbh | Hydroxy-aminosaeurederivate |
| JP2867450B2 (ja) | 1989-08-17 | 1999-03-08 | 吉富製薬株式会社 | アルキレンビスアミド化合物 |
| CA2036781A1 (en) * | 1990-02-22 | 1991-08-23 | Fujio Antoku | Triamine derivatives and their acid-addition salts |
| GB9201755D0 (en) | 1992-01-28 | 1992-03-11 | British Bio Technology | Compounds |
| IL106197A (en) | 1992-07-30 | 1999-11-30 | Cor Therapeutics Inc | Agagonists for the rhombin receptors and pharmaceutical preparations containing them |
| US5538997A (en) * | 1993-03-12 | 1996-07-23 | Sandoz Ltd. | 2,4-diamino-3-hydroxycarboxylic acid derivatives |
| IT1270882B (it) | 1993-10-05 | 1997-05-13 | Isagro Srl | Oligopeptidi ad attivita' fungicida |
| US6306840B1 (en) | 1995-01-23 | 2001-10-23 | Biogen, Inc. | Cell adhesion inhibitors |
| EP0731107A1 (en) | 1995-02-13 | 1996-09-11 | Takeda Chemical Industries, Ltd. | Production of aldehyde derivatives |
| EP0824543A1 (en) | 1995-05-10 | 1998-02-25 | Chiroscience Limited | Peptide compounds which inhibit metalloproteinase and tnf liberation, and their therapeutic use |
| US5710171A (en) | 1995-05-24 | 1998-01-20 | Merck & Co., Inc. | Bisphenyl inhibitors of farnesyl-protein transferase |
| TW438591B (en) | 1995-06-07 | 2001-06-07 | Arris Pharm Corp | Reversible cysteine protease inhibitors |
| US5770620A (en) | 1995-06-19 | 1998-06-23 | Ontogen Corporation | Aryl acrylic acid derivatives useful as protein tyrosine phosphatase inhibitors |
| CZ287948B6 (cs) | 1995-06-22 | 2001-03-14 | Novo Nordisk A/S | Peptidový derivát uvolňující růstový hormon, farmaceutický prostředek s jeho obsahem a jejich použití |
| US6100423A (en) | 1995-08-30 | 2000-08-08 | G. D. Searle & Co. | Amino benzenepropanoic acid compounds and derivatives thereof |
| RO118290B1 (ro) | 1995-08-30 | 2003-04-30 | Gdsearle & Co | Derivati de fenilcarboniluree si compozitie farmaceutica |
| US5843904A (en) | 1995-12-20 | 1998-12-01 | Vertex Pharmaceuticals, Inc. | Inhibitors of interleukin-1βconverting enzyme |
| US6011052A (en) | 1996-04-30 | 2000-01-04 | Warner-Lambert Company | Pyrazolone derivatives as MCP-1 antagonists |
| CA2256492C (en) | 1996-05-20 | 2006-04-04 | Teijin Limited | Diarylalkyl cyclic diamine derivatives as chemokine receptor antagonists |
| JP2000516611A (ja) | 1996-08-14 | 2000-12-12 | ワーナー―ランバート・コンパニー | Mcp―1アンタゴニストとしての2―フェニルベンズイミダゾール誘導体 |
| GB9716656D0 (en) * | 1997-08-07 | 1997-10-15 | Zeneca Ltd | Chemical compounds |
| GB9716657D0 (en) | 1997-08-07 | 1997-10-15 | Zeneca Ltd | Chemical compounds |
| US6150378A (en) | 1997-10-07 | 2000-11-21 | Cephalon, Inc. | Peptidyl-containing α-ketoamide cysteine and serine protease inhibitors |
| IL135488A0 (en) | 1997-11-18 | 2001-05-20 | Teijin Ltd | Cyclic amine derivatives |
| US6048861A (en) | 1997-12-17 | 2000-04-11 | Merck & Co., Inc. | Integrin receptor antagonists |
| US6028087A (en) | 1998-01-21 | 2000-02-22 | Smithkline Beecham Corporation | Platelet aggregation inhibiting compounds |
| GB9803228D0 (en) | 1998-02-17 | 1998-04-08 | Zeneca Ltd | Chemical compounds |
| GB9803226D0 (en) | 1998-02-17 | 1998-04-08 | Zeneca Ltd | Chemical compounds |
| US6541208B1 (en) | 1998-03-17 | 2003-04-01 | University Of Maryland Biotechnology Institute | Diagnostic method for distinguishing HIV-associated dementia from other forms of dementia |
| EP2386565A3 (en) | 1999-01-12 | 2013-11-20 | Cambridge Enterprise Ltd. | Compounds and methods to inhibit or augment an inflammatory response |
| GB9902461D0 (en) | 1999-02-05 | 1999-03-24 | Zeneca Ltd | Chemical compounds |
| WO2000069815A1 (en) | 1999-05-13 | 2000-11-23 | Teijin Limited | Ureido-substituted cyclic amine derivatives and their use as drug |
| CA2373607A1 (en) | 1999-05-14 | 2000-11-23 | Bristol-Myers Squibb Pharma Research Labs, Inc. | Cyclic amine derivatives and their uses |
| WO2002060859A2 (en) | 2000-12-20 | 2002-08-08 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| AU2002241724A1 (en) | 2000-12-20 | 2002-07-01 | Bristol-Myers Squibb Company | Diamines as modulators of chemokine receptor activity |
| WO2003075853A2 (en) | 2002-03-08 | 2003-09-18 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| WO2004071449A2 (en) | 2003-02-12 | 2004-08-26 | Bristol-Myers Squibb Company | Lactams as modulators of chemokine receptor activity |
| TW200508224A (en) | 2003-02-12 | 2005-03-01 | Bristol Myers Squibb Co | Cyclic derivatives as modulators of chemokine receptor activity |
| JP3655616B2 (ja) | 2003-03-19 | 2005-06-02 | ファナック株式会社 | 射出成形機 |
| US7291615B2 (en) | 2003-05-01 | 2007-11-06 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| US7230133B2 (en) | 2003-05-01 | 2007-06-12 | Bristol-Myers Squibb Company | Malonamides and malonamide derivatives as modulators of chemokine receptor activity |
| US20050043392A1 (en) | 2003-08-21 | 2005-02-24 | Carter Percy H. | Lactams of alkylated acyclic diamine derivatives as modulators of chemokine receptor activity |
| US7163937B2 (en) | 2003-08-21 | 2007-01-16 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| US7378409B2 (en) | 2003-08-21 | 2008-05-27 | Bristol-Myers Squibb Company | Substituted cycloalkylamine derivatives as modulators of chemokine receptor activity |
| US7317019B2 (en) | 2003-08-21 | 2008-01-08 | Bristol Myers Squibb Co. | N-alkylated diaminopropane derivatives as modulators of chemokine receptor activity |
-
2001
- 2001-12-20 AU AU2002241724A patent/AU2002241724A1/en not_active Abandoned
- 2001-12-20 US US10/027,505 patent/US6974836B2/en not_active Expired - Lifetime
- 2001-12-20 AR ARP010105968A patent/AR035720A1/es unknown
- 2001-12-20 CA CA002432908A patent/CA2432908A1/en not_active Abandoned
- 2001-12-20 WO PCT/US2001/050619 patent/WO2002050019A2/en not_active Ceased
- 2001-12-20 HU HU0303540A patent/HUP0303540A2/hu unknown
- 2001-12-20 EP EP01988415A patent/EP1351924A2/en not_active Withdrawn
- 2001-12-20 JP JP2002551518A patent/JP2005506949A/ja not_active Withdrawn
-
2005
- 2005-07-14 US US11/181,436 patent/US7449493B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA2432908A1 (en) | 2002-06-27 |
| WO2002050019A2 (en) | 2002-06-27 |
| EP1351924A2 (en) | 2003-10-15 |
| US20030060459A1 (en) | 2003-03-27 |
| HUP0303540A2 (hu) | 2004-01-28 |
| AR035720A1 (es) | 2004-07-07 |
| AU2002241724A1 (en) | 2002-07-01 |
| US20050282882A1 (en) | 2005-12-22 |
| US6974836B2 (en) | 2005-12-13 |
| US7449493B2 (en) | 2008-11-11 |
| WO2002050019A3 (en) | 2003-03-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2005506949A (ja) | ケモカイン受容体の調節剤としてのジアミン | |
| US7572813B2 (en) | Cyclic derivatives as modulators of chemokine receptor activity | |
| US7468440B2 (en) | Malonamides and malonamide derivatives as modulators of chemokine receptor activity | |
| US7087604B2 (en) | Cyclic derivatives as modulators of chemokine receptor activity | |
| US7338975B2 (en) | Lactams as modulators of chemokine receptor activity | |
| JP2003512349A (ja) | ケモカイン受容体活性のモジュレーターとしてのベンジルシクロアルキルアミン | |
| US7291615B2 (en) | Cyclic derivatives as modulators of chemokine receptor activity | |
| US7550486B2 (en) | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity | |
| US7288563B2 (en) | Substituted bicycloalkylamine derivatives as modulators of chemokine receptor activity | |
| US7381738B2 (en) | Substituted bicycloalkylamine derivatives as modulators of chemokine receptor activity | |
| US7863317B2 (en) | Lactams of alkylated acyclic diamine derivatives as modulators of chemokine receptor activity | |
| AU2002248244A1 (en) | Cyclic derivatives as modulators of chemokine receptor activity | |
| MX2008009287A (en) | Piperazinyl derivatives as modulators of chemokine receptor activity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20060622 |