NO313877B1 - Heteroaryl-heksansyreamidderivater, deres fremstilling, deres anvendelse samt farmasöytisk blanding - Google Patents
Heteroaryl-heksansyreamidderivater, deres fremstilling, deres anvendelse samt farmasöytisk blanding Download PDFInfo
- Publication number
- NO313877B1 NO313877B1 NO19994101A NO994101A NO313877B1 NO 313877 B1 NO313877 B1 NO 313877B1 NO 19994101 A NO19994101 A NO 19994101A NO 994101 A NO994101 A NO 994101A NO 313877 B1 NO313877 B1 NO 313877B1
- Authority
- NO
- Norway
- Prior art keywords
- hydroxy
- alkyl
- carboxylic acid
- amide
- methyl
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 10
- 238000002360 preparation method Methods 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 137
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
- 239000001257 hydrogen Substances 0.000 claims abstract description 29
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 11
- 102000004500 CCR1 Receptors Human genes 0.000 claims abstract description 9
- 108010017319 CCR1 Receptors Proteins 0.000 claims abstract description 9
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- -1 tetrahydroquinolyl Chemical group 0.000 claims description 75
- 150000001408 amides Chemical class 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 36
- UPUZGXILYFKSGE-UHFFFAOYSA-N quinoxaline-2-carboxylic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CN=C21 UPUZGXILYFKSGE-UHFFFAOYSA-N 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 230000002265 prevention Effects 0.000 claims description 18
- 150000002431 hydrogen Chemical group 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 230000001684 chronic effect Effects 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 12
- 230000001154 acute effect Effects 0.000 claims description 12
- 150000002367 halogens Chemical group 0.000 claims description 12
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 claims description 10
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 claims description 10
- 206010061218 Inflammation Diseases 0.000 claims description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 230000004054 inflammatory process Effects 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 9
- 206010027654 Allergic conditions Diseases 0.000 claims description 8
- 201000001320 Atherosclerosis Diseases 0.000 claims description 8
- 208000023275 Autoimmune disease Diseases 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- 230000004968 inflammatory condition Effects 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 208000037803 restenosis Diseases 0.000 claims description 8
- 230000003612 virological effect Effects 0.000 claims description 8
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 7
- 208000031886 HIV Infections Diseases 0.000 claims description 6
- 208000037357 HIV infectious disease Diseases 0.000 claims description 6
- 230000003042 antagnostic effect Effects 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 5
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 claims description 5
- 125000005493 quinolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 claims description 3
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 2
- 125000006532 (C3-C5) alkyl group Chemical group 0.000 claims description 2
- UUVDQMYRPUHXPB-UHFFFAOYSA-N 1,3-benzothiazole-2-carboxylic acid Chemical compound C1=CC=C2SC(C(=O)O)=NC2=C1 UUVDQMYRPUHXPB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 2
- 125000005916 2-methylpentyl group Chemical group 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- QKUIXNPZATTWNU-UHFFFAOYSA-N 8-fluoroquinoline-3-carboxylic acid Chemical compound FC1=CC=CC2=CC(C(=O)O)=CN=C21 QKUIXNPZATTWNU-UHFFFAOYSA-N 0.000 claims description 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 2
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 2
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 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 2
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 2
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 2
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical class C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000004254 isoquinolin-1-yl group Chemical group [H]C1=C([H])C2=C([H])C([H])=C([H])C([H])=C2C(*)=N1 0.000 claims description 2
- 125000004551 isoquinolin-3-yl group Chemical group C1=NC(=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- PWEICEMEPQPTJQ-RNXOBYDBSA-N n-[(2s,3s,5s)-6-amino-5-cyclohexyl-3-hydroxy-6-oxo-1-phenylhexan-2-yl]quinoline-3-carboxamide Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)N)C1CCCCC1)NC(=O)C=1C=C2C=CC=CC2=NC=1)C1=CC=CC=C1 PWEICEMEPQPTJQ-RNXOBYDBSA-N 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 3
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims 2
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims 1
- XPEZLHDRPACKQM-LAQFCMMRSA-N CC(CC1)CCC1([C@@](C[C@@H]([C@H](CC1=CC=CC=C1)NC(C1=NC2=CC=CC=C2N=C1)=O)O)(C(N)=O)O)O Chemical compound CC(CC1)CCC1([C@@](C[C@@H]([C@H](CC1=CC=CC=C1)NC(C1=NC2=CC=CC=C2N=C1)=O)O)(C(N)=O)O)O XPEZLHDRPACKQM-LAQFCMMRSA-N 0.000 claims 1
- 208000026062 Tissue disease Diseases 0.000 claims 1
- 125000005605 benzo group Chemical group 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 1
- WLXHIYCDCMGCRN-JZWVFAODSA-N n-[(2s,3s,5s)-5-(4,4-difluoro-1-hydroxycyclohexyl)-3-hydroxy-6-(hydroxyamino)-6-oxo-1-phenylhexan-2-yl]quinoxaline-2-carboxamide Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)NO)C1(O)CCC(F)(F)CC1)NC(=O)C=1N=C2C=CC=CC2=NC=1)C1=CC=CC=C1 WLXHIYCDCMGCRN-JZWVFAODSA-N 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract description 4
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- 238000000034 method Methods 0.000 description 64
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- 239000000243 solution Substances 0.000 description 38
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
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- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
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- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
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- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- CGJMVNVWQHPASW-UHFFFAOYSA-N quinoxaline-2-carboxamide Chemical compound C1=CC=CC2=NC(C(=O)N)=CN=C21 CGJMVNVWQHPASW-UHFFFAOYSA-N 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 108010026906 renin inhibitory peptide Proteins 0.000 description 1
- KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 description 1
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- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
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- 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
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- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
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- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- LXIKEPCNDFVJKC-QXMHVHEDSA-N tenidap Chemical compound C12=CC(Cl)=CC=C2N(C(=O)N)C(=O)\C1=C(/O)C1=CC=CS1 LXIKEPCNDFVJKC-QXMHVHEDSA-N 0.000 description 1
- 229960003676 tenidap Drugs 0.000 description 1
- YZDUNYUENNWBRE-KBPBESRZSA-N tert-butyl n-[(1s)-1-[(2s)-5-oxooxolan-2-yl]-2-phenylethyl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)[C@H]1OC(=O)CC1)C1=CC=CC=C1 YZDUNYUENNWBRE-KBPBESRZSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- XQKBFQXWZCFNFF-UHFFFAOYSA-K triiodosamarium Chemical compound I[Sm](I)I XQKBFQXWZCFNFF-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011995 wilkinson's catalyst Substances 0.000 description 1
- UTODFRQBVUVYOB-UHFFFAOYSA-P wilkinson's catalyst Chemical compound [Cl-].C1=CC=CC=C1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)[Rh+](P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UTODFRQBVUVYOB-UHFFFAOYSA-P 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
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- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- 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
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- 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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
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- C07D221/06—Ring systems of three rings
- C07D221/16—Ring systems of three rings containing carbocyclic rings other than six-membered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
-
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
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- C07D237/28—Cinnolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
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- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/44—Benzopyrazines 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 carbon atoms of the hetero ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
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- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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 in position 2
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- C—CHEMISTRY; METALLURGY
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D307/85—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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 carbon atoms of the hetero ring
- C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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 carbon atoms of the hetero ring
- C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US3916997P | 1997-02-26 | 1997-02-26 | |
PCT/US1998/001568 WO1998038167A1 (en) | 1997-02-26 | 1998-02-05 | Heteroaryl-hexanoic acid amide derivatives, their preparation and their use as selective inhibitors of mip-1-alpha binding to its ccr1 receptor |
Publications (3)
Publication Number | Publication Date |
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NO994101L NO994101L (no) | 1999-08-25 |
NO994101D0 NO994101D0 (no) | 1999-08-25 |
NO313877B1 true NO313877B1 (no) | 2002-12-16 |
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Application Number | Title | Priority Date | Filing Date |
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NO19994101A NO313877B1 (no) | 1997-02-26 | 1999-08-25 | Heteroaryl-heksansyreamidderivater, deres fremstilling, deres anvendelse samt farmasöytisk blanding |
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US (1) | US6403587B1 (uk) |
EP (1) | EP0966443B1 (uk) |
JP (1) | JP3771591B2 (uk) |
KR (1) | KR100447553B1 (uk) |
CN (1) | CN1248968A (uk) |
AP (1) | AP1056A (uk) |
AR (1) | AR011168A1 (uk) |
AT (1) | ATE421954T1 (uk) |
AU (1) | AU745687B2 (uk) |
BG (1) | BG103688A (uk) |
BR (1) | BR9807858A (uk) |
CA (1) | CA2282834C (uk) |
DE (1) | DE69840519D1 (uk) |
DK (1) | DK0966443T3 (uk) |
DZ (1) | DZ2439A1 (uk) |
EA (1) | EA002146B1 (uk) |
ES (1) | ES2319700T3 (uk) |
GT (1) | GT199800042A (uk) |
HN (1) | HN1998000035A (uk) |
HR (1) | HRP980103A2 (uk) |
HU (1) | HUP0001319A3 (uk) |
ID (1) | ID23789A (uk) |
IL (1) | IL131163A (uk) |
IS (1) | IS5139A (uk) |
MA (1) | MA24488A1 (uk) |
MY (1) | MY121294A (uk) |
NO (1) | NO313877B1 (uk) |
NZ (1) | NZ336629A (uk) |
OA (1) | OA11090A (uk) |
PA (1) | PA8447801A1 (uk) |
PE (1) | PE59099A1 (uk) |
PL (1) | PL335484A1 (uk) |
SK (1) | SK112899A3 (uk) |
TN (1) | TNSN98036A1 (uk) |
TR (1) | TR199902056T2 (uk) |
UA (1) | UA67735C2 (uk) |
UY (1) | UY24908A1 (uk) |
WO (1) | WO1998038167A1 (uk) |
YU (1) | YU41399A (uk) |
ZA (1) | ZA981602B (uk) |
Families Citing this family (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6207665B1 (en) * | 1997-06-12 | 2001-03-27 | Schering Aktiengesellschaft | Piperazine derivatives and their use as anti-inflammatory agents |
IL135488A0 (en) | 1997-11-18 | 2001-05-20 | Teijin Ltd | Cyclic amine derivatives |
US6673801B1 (en) * | 1998-02-05 | 2004-01-06 | Pfizer Inc. | Dihydroxyhexanoic acid derivatives |
KR20010086166A (ko) * | 1999-01-13 | 2001-09-08 | 로즈 암스트롱, 크리스틴 에이. 트러트웨인 | 케모카인 수용체 조절제로서의 관능화된 헤테로시클 |
CA2360672A1 (en) * | 1999-01-29 | 2000-08-03 | Wayne W. Hancock | Methods for preventing graft rejection and ischemia-reperfusion injury |
US6329510B1 (en) | 1999-01-29 | 2001-12-11 | Millennium Pharmaceuticals, Inc. | Anti-CCR1 antibodies and methods of use therefor |
WO2000044408A2 (en) * | 1999-01-29 | 2000-08-03 | Millennium Pharmaceuticals, Inc. | Method of treating demyelinating inflammatory disease using ccr1 antagonists |
US6361979B1 (en) * | 1999-02-12 | 2002-03-26 | Pfizer Inc. | Microbial conversion of 2-methylquinoxaline |
CN1240699C (zh) | 1999-05-18 | 2006-02-08 | 帝人株式会社 | 与趋化因子有关的疾病的治疗或预防药物 |
CA2378499A1 (en) | 1999-08-04 | 2001-02-15 | Teijin Limited | Cyclic amine ccr3 antagonists |
NZ520075A (en) | 2000-02-04 | 2004-02-27 | Pfizer Prod Inc | Heterocyclic amide derivatives |
EP1498417A1 (en) * | 2000-02-04 | 2005-01-19 | Pfizer Products Inc. | Heterocyclic amide derivatives |
US6737420B2 (en) * | 2000-03-23 | 2004-05-18 | Elan Pharmaceuticals, Inc. | Compounds to treat Alzheimer's disease |
US6410566B1 (en) | 2000-05-16 | 2002-06-25 | Teijin Limited | Cyclic amine derivatives and their use as drugs |
WO2002008189A1 (en) * | 2000-07-24 | 2002-01-31 | The University Of Queensland | Compounds and inhibitors of phospholipases |
US6740636B2 (en) | 2000-07-31 | 2004-05-25 | Schering Aktiengesellschaft | Non-peptide CCR1 receptor antagonists in combination with cyclosporin A for the treatment of heart transplant rejection |
US6693134B2 (en) * | 2001-05-29 | 2004-02-17 | Chemokine Therapeutics Corporation | Bicyclic aromatic chemokine receptor ligands |
HUP0400281A3 (en) | 2001-06-22 | 2009-11-30 | Pfizer Prod Inc | Pharmaceutical compositions of adsorbates of amorphous drug and process for their preparation |
EP1401452A1 (en) * | 2001-06-27 | 2004-03-31 | Elan Pharmaceuticals, Inc. | Beta-hydroxyamine derivatives useful in the treatment of alzheimer's disease |
AR037460A1 (es) * | 2001-11-30 | 2004-11-10 | Smithkline Beecham Plc | Compuesto de hidroxietileno, composicion farmaceutica que lo comprende, uso del mismo para la fabricacion de un medicamento y procedimiento para su preparacion |
JP2005523262A (ja) | 2002-02-01 | 2005-08-04 | ファイザー・プロダクツ・インク | 薬物及び親油性ミクロ相形成物質の非晶質分散物の医薬組成物 |
JP2005530775A (ja) * | 2002-05-14 | 2005-10-13 | ファイザー・プロダクツ・インク | ジヒドロキシヘキサン酸誘導体、それらの中間体、および製法 |
MXPA05001781A (es) * | 2002-08-12 | 2005-04-25 | Pfizer Prod Inc | Formas cristalinas de [4-carbamoil -1-(3- fluorobencil)-2, 7-dihidroxi- 7-metil- octil]-amida del acido quinoxalina-2- carboxilico. |
PL375345A1 (en) | 2002-08-12 | 2005-11-28 | Pfizer Products Inc. | Pharmaceutical compositions of semi-ordered drugs and polymers |
US20040087571A1 (en) * | 2002-10-30 | 2004-05-06 | Pfizer Inc | Methods of using CCR1 antagonists as immunomodulatory agents |
US20040097554A1 (en) * | 2002-10-30 | 2004-05-20 | Pfizer Inc | Heteroaryl-hexanoic acid amide derivatives as immonomodulatory agents |
WO2004054977A1 (en) * | 2002-12-13 | 2004-07-01 | Cytopia Pty Ltd | Nicotinamide-based kinase inhibitors |
AU2003291839B2 (en) * | 2002-12-13 | 2009-01-22 | Ym Biosciences Australia Pty Ltd | Nicotinamide-based kinase inhibitors |
JP4896518B2 (ja) * | 2002-12-13 | 2012-03-14 | ワイエム・バイオサイエンシズ・オーストラリア・ピーティーワイ・リミテッド | ニコチンアミド系キナーゼ阻害薬 |
MXPA06001417A (es) | 2003-08-04 | 2006-05-15 | Pfizer Prod Inc | Composiciones farmaceuticas de adsorbatos de farmacos amorfos y materiales que forman microfases lipofilas. |
EP1682524A1 (en) * | 2003-10-24 | 2006-07-26 | Aventis Pharmaceuticals, Inc. | Novel keto-oxadiazole derivatives as cathepsin inhibitors |
AU2007262004B2 (en) * | 2006-06-23 | 2011-07-07 | Daiichi Sankyo Company, Limited | Cyclic amine compound |
EP2771484A1 (en) | 2011-10-28 | 2014-09-03 | Galderma Research & Development | New leukocyte infiltrate markers for rosacea and uses thereof |
UY36034A (es) | 2014-03-18 | 2015-09-30 | Astrazeneca Ab | Derivados de 3,5-diamino-6-cloro-pirazina-2-carboxamida y sales farmaceuticamente aceptables de estos |
DK3050574T3 (da) | 2015-01-28 | 2020-01-20 | Univ Bordeaux | Anvendelse af plerixafor til behandling og/eller forebyggelse af akutte forværringer af kronisk obstruktiv lungesygdom |
JP2020508436A (ja) | 2016-12-07 | 2020-03-19 | プロジェニティ, インコーポレイテッド | 胃腸管の検出方法、装置およびシステム |
CA3045310A1 (en) | 2016-12-14 | 2018-06-21 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with a chemokine/chemokine receptor inhibitor |
WO2020106750A1 (en) | 2018-11-19 | 2020-05-28 | Progenity, Inc. | Methods and devices for treating a disease with biotherapeutics |
WO2021119482A1 (en) | 2019-12-13 | 2021-06-17 | Progenity, Inc. | Ingestible device for delivery of therapeutic agent to the gastrointestinal tract |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4727060A (en) | 1984-11-13 | 1988-02-23 | Ciba-Geigy Corporation | Novel 5-amino-4-hydroxyvaleryl derivatives |
WO1989001488A1 (en) | 1987-08-07 | 1989-02-23 | The Upjohn Company | Renin inhibiting peptides with nonpeptide linkages |
IL88619A0 (en) * | 1987-12-15 | 1989-07-31 | Pfizer | Non-peptidic renin inhibitors |
US4923864A (en) | 1987-12-15 | 1990-05-08 | Pfizer Inc. | Certain heterocyclic-hexanamides useful for treating hypertension |
EP0374098A3 (de) | 1988-12-15 | 1991-05-02 | Ciba-Geigy Ag | Retrovirale Proteasehemmer |
AU1748792A (en) | 1991-04-04 | 1992-11-02 | Upjohn Company, The | Phosphorus containing compounds as inhibitors of retroviruses |
IE922316A1 (en) | 1991-07-17 | 1993-01-27 | Smithkline Beecham Corp | Retroviral protease inhibitors |
EP0628035A4 (en) | 1992-02-26 | 1995-03-29 | Smithkline Beecham Corp | RETROVIRAL PROTEASE INHIBITORS. |
DE69322269T2 (de) | 1992-05-27 | 1999-04-22 | Conagra, Inc., Omaha, Nebr. | Lebensmittelbehälter und dergleichen mit durch druck aufgetragenen schichten |
IL110898A0 (en) * | 1993-09-10 | 1994-11-28 | Narhex Australia Pty Ltd | Polar-substituted hydrocarbons |
DE69527405T2 (de) | 1994-10-19 | 2003-03-13 | Novartis Ag, Basel | Antivirale Ether von Aspartat-Protease-Substrat-Isosteren |
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- 1998-02-05 WO PCT/US1998/001568 patent/WO1998038167A1/en not_active Application Discontinuation
- 1998-02-05 KR KR10-1999-7007788A patent/KR100447553B1/ko not_active IP Right Cessation
- 1998-02-05 DE DE69840519T patent/DE69840519D1/de not_active Expired - Lifetime
- 1998-02-05 HU HU0001319A patent/HUP0001319A3/hu unknown
- 1998-02-05 CN CN98802888A patent/CN1248968A/zh active Pending
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- 1998-02-05 NZ NZ336629A patent/NZ336629A/xx unknown
- 1998-02-05 US US09/380,269 patent/US6403587B1/en not_active Expired - Fee Related
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- 1998-02-05 EA EA199900678A patent/EA002146B1/ru not_active IP Right Cessation
- 1998-02-05 SK SK1128-99A patent/SK112899A3/sk unknown
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- 1998-02-05 ES ES98906013T patent/ES2319700T3/es not_active Expired - Lifetime
- 1998-02-23 GT GT199800042A patent/GT199800042A/es unknown
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- 1998-02-26 AR ARP980100869A patent/AR011168A1/es unknown
- 1998-02-26 MA MA24983A patent/MA24488A1/fr unknown
- 1998-05-02 UA UA99074134A patent/UA67735C2/uk unknown
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1999
- 1999-07-30 IS IS5139A patent/IS5139A/is unknown
- 1999-08-20 OA OA9900188A patent/OA11090A/en unknown
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- 1999-08-25 NO NO19994101A patent/NO313877B1/no unknown
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