NO326349B1 - CCR5-antagonister for behandling av AIDS, farmasoytisk preparat inneholdende disse, og deres anvendelse for fremstilling av medisin. - Google Patents
CCR5-antagonister for behandling av AIDS, farmasoytisk preparat inneholdende disse, og deres anvendelse for fremstilling av medisin. Download PDFInfo
- Publication number
- NO326349B1 NO326349B1 NO20034311A NO20034311A NO326349B1 NO 326349 B1 NO326349 B1 NO 326349B1 NO 20034311 A NO20034311 A NO 20034311A NO 20034311 A NO20034311 A NO 20034311A NO 326349 B1 NO326349 B1 NO 326349B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- aryl
- mmol
- heteroaryl
- solution
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 14
- 239000003814 drug Substances 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 title description 16
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 title description 16
- 239000005557 antagonist Substances 0.000 title description 8
- 208000030507 AIDS Diseases 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 68
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 17
- -1 alpha-substituted benzyl Chemical group 0.000 claims abstract description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 2
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 239000007787 solid Substances 0.000 abstract description 12
- 238000006243 chemical reaction Methods 0.000 abstract description 7
- 206010020751 Hypersensitivity Diseases 0.000 abstract description 6
- 230000007815 allergy Effects 0.000 abstract description 6
- 206010012438 Dermatitis atopic Diseases 0.000 abstract description 5
- 208000006673 asthma Diseases 0.000 abstract description 5
- 201000008937 atopic dermatitis Diseases 0.000 abstract description 5
- 201000006417 multiple sclerosis Diseases 0.000 abstract description 4
- 210000000056 organ Anatomy 0.000 abstract description 4
- 238000002054 transplantation Methods 0.000 abstract description 4
- 208000027866 inflammatory disease Diseases 0.000 abstract description 3
- 230000000840 anti-viral effect Effects 0.000 abstract description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract 1
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- 239000003443 antiviral agent Substances 0.000 abstract 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 abstract 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 abstract 1
- 125000003709 fluoroalkyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- 239000000243 solution Substances 0.000 description 67
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- 239000000460 chlorine Substances 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- 239000010410 layer Substances 0.000 description 38
- 239000011734 sodium Substances 0.000 description 27
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- 239000003921 oil Substances 0.000 description 18
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 238000000034 method Methods 0.000 description 16
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 238000003556 assay Methods 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 229910004298 SiO 2 Inorganic materials 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 11
- 238000000746 purification Methods 0.000 description 10
- 239000012964 benzotriazole Substances 0.000 description 9
- 239000012528 membrane Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 239000003446 ligand Substances 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 239000012458 free base Substances 0.000 description 7
- 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 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 102000001327 Chemokine CCL5 Human genes 0.000 description 6
- 108010055166 Chemokine CCL5 Proteins 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000012746 preparative thin layer chromatography Methods 0.000 description 6
- 238000000159 protein binding assay Methods 0.000 description 6
- XARVANDLQOZMMJ-CHHVJCJISA-N 2-[(z)-[1-(2-amino-1,3-thiazol-4-yl)-2-oxo-2-(2-oxoethylamino)ethylidene]amino]oxy-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)O\N=C(/C(=O)NCC=O)C1=CSC(N)=N1 XARVANDLQOZMMJ-CHHVJCJISA-N 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 201000004681 Psoriasis Diseases 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 230000035605 chemotaxis Effects 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 208000024908 graft versus host disease Diseases 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- XOFLBQFBSOEHOG-UUOKFMHZSA-N γS-GTP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O XOFLBQFBSOEHOG-UUOKFMHZSA-N 0.000 description 3
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- ZGABDPXDUGYGQE-UHFFFAOYSA-N 1-piperidin-1-ylpiperazine Chemical compound C1CCCCN1N1CCNCC1 ZGABDPXDUGYGQE-UHFFFAOYSA-N 0.000 description 2
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000004274 CCR5 Receptors Human genes 0.000 description 2
- 108010017088 CCR5 Receptors Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000009410 Chemokine receptor Human genes 0.000 description 2
- 108050000299 Chemokine receptor Proteins 0.000 description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 101000946926 Homo sapiens C-C chemokine receptor type 5 Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 230000003185 calcium uptake Effects 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 2
- 239000003067 chemokine receptor CCR5 antagonist Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 102000048160 human CCR5 Human genes 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 1
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 1
- QFDISQIDKZUABE-UHFFFAOYSA-N 1,1'-bipiperidine Chemical compound C1CCCCN1N1CCCCC1 QFDISQIDKZUABE-UHFFFAOYSA-N 0.000 description 1
- CTTUQCIBNSCQRH-UHFFFAOYSA-N 2,3,4-trimethylpentan-3-amine Chemical compound CC(C)C(C)(N)C(C)C CTTUQCIBNSCQRH-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- OINWZUJVEXUHCC-UHFFFAOYSA-N 3-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=CC(S(Cl)(=O)=O)=C1 OINWZUJVEXUHCC-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- NWRVHCPZXMWADG-UHFFFAOYSA-N 4,6-dimethyl-2h-pyrimidine-1-carboxylic acid Chemical compound CC1=NCN(C(O)=O)C(C)=C1 NWRVHCPZXMWADG-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical class CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 108091008927 CC chemokine receptors Proteins 0.000 description 1
- 102000005674 CCR Receptors Human genes 0.000 description 1
- 108700011778 CCR5 Proteins 0.000 description 1
- 101150017501 CCR5 gene Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229940124821 NNRTIs Drugs 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 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
- 239000007983 Tris buffer Substances 0.000 description 1
- 108070000030 Viral receptors Proteins 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 238000011225 antiretroviral therapy Methods 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- PFWWSGFPICCWGU-UHFFFAOYSA-N cyclopropanesulfonyl chloride Chemical compound ClS(=O)(=O)C1CC1 PFWWSGFPICCWGU-UHFFFAOYSA-N 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- ZOGHDTBRWUEJDP-UHFFFAOYSA-N diethylalumanylium;cyanide Chemical compound N#[C-].CC[Al+]CC ZOGHDTBRWUEJDP-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 230000005182 global health Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 239000004030 hiv protease inhibitor Substances 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 229910052500 inorganic mineral Chemical class 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NIXOIRLDFIPNLJ-UHFFFAOYSA-M magnesium;benzene;bromide Chemical compound [Mg+2].[Br-].C1=CC=[C-]C=C1 NIXOIRLDFIPNLJ-UHFFFAOYSA-M 0.000 description 1
- DTKMKZYEOXZPQZ-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=C[C-]=C1 DTKMKZYEOXZPQZ-UHFFFAOYSA-M 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Chemical class 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 239000003149 muscarinic antagonist Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- LMRCKXYHPYNEJV-UHFFFAOYSA-N piperazine;piperidine Chemical compound C1CCNCC1.C1CNCCN1 LMRCKXYHPYNEJV-UHFFFAOYSA-N 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000010648 susceptibility to HIV infection Diseases 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 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 1
- DATRVIMZZZVHMP-QMMMGPOBSA-N tert-butyl (2s)-2-methylpiperazine-1-carboxylate Chemical compound C[C@H]1CNCCN1C(=O)OC(C)(C)C DATRVIMZZZVHMP-QMMMGPOBSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000011269 treatment regimen Methods 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
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P11/06—Antiasthmatics
-
- 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
- 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
- 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
- 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
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Molecular Biology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- AIDS & HIV (AREA)
- Psychiatry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27993801P | 2001-03-29 | 2001-03-29 | |
| PCT/US2002/009491 WO2002079194A1 (en) | 2001-03-29 | 2002-03-27 | Ccr5 antagonists useful for treating aids |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20034311D0 NO20034311D0 (no) | 2003-09-26 |
| NO20034311L NO20034311L (no) | 2003-11-26 |
| NO326349B1 true NO326349B1 (no) | 2008-11-17 |
Family
ID=23070981
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20034311A NO326349B1 (no) | 2001-03-29 | 2003-09-26 | CCR5-antagonister for behandling av AIDS, farmasoytisk preparat inneholdende disse, og deres anvendelse for fremstilling av medisin. |
Country Status (29)
| Country | Link |
|---|---|
| US (5) | US6720325B2 (enExample) |
| EP (2) | EP1591444B1 (enExample) |
| JP (2) | JP4248251B2 (enExample) |
| KR (1) | KR100613528B1 (enExample) |
| CN (1) | CN100519554C (enExample) |
| AR (1) | AR033452A1 (enExample) |
| AT (2) | ATE466009T1 (enExample) |
| AU (1) | AU2002255947B8 (enExample) |
| BR (1) | BR0208398A (enExample) |
| CA (1) | CA2442227C (enExample) |
| CZ (1) | CZ20032636A3 (enExample) |
| DE (2) | DE60204951T2 (enExample) |
| DK (1) | DK1373256T3 (enExample) |
| ES (2) | ES2342942T3 (enExample) |
| HU (1) | HUP0400349A3 (enExample) |
| IL (1) | IL157551A0 (enExample) |
| MX (1) | MXPA03008853A (enExample) |
| MY (1) | MY128609A (enExample) |
| NO (1) | NO326349B1 (enExample) |
| NZ (1) | NZ527768A (enExample) |
| PE (1) | PE20020996A1 (enExample) |
| PL (1) | PL364560A1 (enExample) |
| PT (1) | PT1373256E (enExample) |
| RU (1) | RU2316553C2 (enExample) |
| SI (1) | SI1373256T1 (enExample) |
| SK (1) | SK287521B6 (enExample) |
| TW (1) | TWI237638B (enExample) |
| WO (1) | WO2002079194A1 (enExample) |
| ZA (1) | ZA200307474B (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE466009T1 (de) * | 2001-03-29 | 2010-05-15 | Schering Corp | Ccr5 antagonisten verwendbar für die behandlung von aids |
| DE60209736T2 (de) | 2001-07-02 | 2006-11-02 | Astrazeneca Ab | Piperidinverbindungen, die sich als modulatoren der chemokinrezeptoraktivität eignen |
| SE0200843D0 (sv) | 2002-03-19 | 2002-03-19 | Astrazeneca Ab | Chemical compounds |
| SE0200844D0 (sv) | 2002-03-19 | 2002-03-19 | Astrazeneca Ab | Chemical compounds |
| US7132539B2 (en) * | 2002-10-23 | 2006-11-07 | The Procter & Gamble Company | Melanocortin receptor ligands |
| WO2004055011A1 (en) * | 2002-12-13 | 2004-07-01 | Smithkline Beecham Corporation | Heterocyclic compounds as ccr5 antagonists |
| PE20040769A1 (es) * | 2002-12-18 | 2004-11-06 | Schering Corp | Derivados de piperidina utiles como antagonisas ccr5 |
| SE0300957D0 (sv) | 2003-04-01 | 2003-04-01 | Astrazeneca Ab | Chemical compounds |
| AU2004285051A1 (en) * | 2003-11-03 | 2005-05-12 | Schering Corporation | Bipiperidinyl derivatives useful as inhibitors of chemokine receptors |
| EP1725235B1 (en) * | 2004-02-05 | 2009-04-15 | Schering Corporation | Piperidine derivatives useful as ccr3 antagonists |
| SE0400925D0 (sv) * | 2004-04-06 | 2004-04-06 | Astrazeneca Ab | Chemical compounds |
| ES2431524T3 (es) * | 2004-04-13 | 2013-11-26 | Incyte Corporation | Derivados de piperazinilpiperidina como antagonistas de los receptores de quimiocinas |
| AU2005283326B2 (en) * | 2004-09-13 | 2011-07-21 | Ono Pharmaceutical Co., Ltd. | Nitrogenous heterocyclic derivative and medicine containing the same as an active ingredient |
| US7635698B2 (en) | 2004-12-29 | 2009-12-22 | Millennium Pharmaceuticals, Inc. | Compounds useful as chemokine receptor antagonists |
| WO2006071875A1 (en) | 2004-12-29 | 2006-07-06 | Millennium Pharmaceuticals, Inc. | Compounds useful as chemokine receptor antagonists |
| CN101133048A (zh) * | 2005-01-06 | 2008-02-27 | 先灵公司 | 哌嗪化合物的药用盐制备 |
| WO2006074270A2 (en) * | 2005-01-06 | 2006-07-13 | Schering Corporation | Synthesis of ccr5 receptor antagonists |
| MX2007010257A (es) | 2005-02-23 | 2007-09-11 | Schering Corp | Derivados de piperidinil piperidina utiles como inhibidores de receptores de quimiocinas. |
| KR20070107085A (ko) * | 2005-02-23 | 2007-11-06 | 쉐링 코포레이션 | 케모카인 수용체의 억제제로서 유용한 피페리디닐 피페라진유도체 |
| CA2615650A1 (en) | 2005-07-21 | 2007-01-25 | Astrazeneca Ab | Novel piperidine derivatives |
| US7462485B2 (en) * | 2005-10-07 | 2008-12-09 | Glaser Lawrence F | Modified erythrocytes and uses thereof |
| TW200745087A (en) * | 2006-02-24 | 2007-12-16 | Schering Corp | CCR5 antagonists useful for treating HIV |
| WO2008030853A2 (en) * | 2006-09-06 | 2008-03-13 | Incyte Corporation | Combination therapy for human immunodeficiency virus infection |
| EP2125733A1 (en) * | 2006-12-22 | 2009-12-02 | Schering Corporation | Process for preparing ccr-5 receptor antagonists utilizing 4-substituted 1-cyclopropane-sulfonyl-piperidinyl compounds |
| JP2011513317A (ja) * | 2008-02-29 | 2011-04-28 | シェーリング コーポレイション | Ｈｉｖ感染を防止するための予防薬としてのｃｃｒ５アンタゴニストおよびｈｉｖの伝播を抑制する方法 |
| US11629196B2 (en) | 2020-04-27 | 2023-04-18 | Incelldx, Inc. | Method of treating SARS-CoV-2-associated hypercytokinemia by administering a human monoclonal antibody (PRO-140) that inhibits CCR5/CCL5 binding interactions |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5368854A (en) | 1992-08-20 | 1994-11-29 | Schering Corporation | Use of IL-10 to treat inflammatory bowel disease |
| AU6135294A (en) | 1993-02-12 | 1994-08-29 | Merck & Co., Inc. | Piperazine derivatives as hiv protease inhibitors |
| IL117149A0 (en) | 1995-02-23 | 1996-06-18 | Schering Corp | Muscarinic antagonists |
| US5889006A (en) | 1995-02-23 | 1999-03-30 | Schering Corporation | Muscarinic antagonists |
| DE69623485T2 (de) | 1995-06-07 | 2003-01-09 | Kimberly-Clark Worldwide, Inc. | Inhibierung von exoprotein in absorbierenden produkten |
| NZ321575A (en) | 1995-10-30 | 1999-05-28 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4- substituted piperazine derivatives |
| TW531537B (en) | 1995-12-27 | 2003-05-11 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4-substituted piperidine derivatives |
| US5952349A (en) | 1996-07-10 | 1999-09-14 | Schering Corporation | Muscarinic antagonists for treating memory loss |
| US5977138A (en) | 1996-08-15 | 1999-11-02 | Schering Corporation | Ether muscarinic antagonists |
| EP1003514A4 (en) | 1997-07-25 | 2000-10-11 | Merck & Co Inc | CYCLIC AMINE MODULATORS OF CHEMOKIN RECEPTORS |
| US6066636A (en) | 1998-06-30 | 2000-05-23 | Schering Corporation | Muscarinic antagonists |
| EP1013276A1 (en) * | 1998-12-23 | 2000-06-28 | Pfizer Inc. | Aminoazacycloalkanes as CCR5 modulators |
| SK286641B6 (sk) | 1999-05-04 | 2009-03-05 | Schering Corporation | Piperazínové deriváty užitočné ako CCR5 antagonisty, farmaceutické prípravky s ich obsahom a ich použitie |
| PL203117B1 (pl) * | 1999-05-04 | 2009-08-31 | Schering Corp | Piperydynopiperydynowa pochodna użyteczna jako antagonista CCR5, zawierająca ją kompozycja farmaceutyczna i jej zastosowanie |
| ATE466009T1 (de) * | 2001-03-29 | 2010-05-15 | Schering Corp | Ccr5 antagonisten verwendbar für die behandlung von aids |
-
2002
- 2002-03-27 AT AT05009882T patent/ATE466009T1/de not_active IP Right Cessation
- 2002-03-27 PE PE2002000251A patent/PE20020996A1/es not_active Application Discontinuation
- 2002-03-27 ES ES05009882T patent/ES2342942T3/es not_active Expired - Lifetime
- 2002-03-27 SK SK1196-2003A patent/SK287521B6/sk not_active IP Right Cessation
- 2002-03-27 NZ NZ527768A patent/NZ527768A/en unknown
- 2002-03-27 RU RU2003131879/04A patent/RU2316553C2/ru not_active IP Right Cessation
- 2002-03-27 PT PT02725381T patent/PT1373256E/pt unknown
- 2002-03-27 ES ES02725381T patent/ES2242856T3/es not_active Expired - Lifetime
- 2002-03-27 AR ARP020101142A patent/AR033452A1/es unknown
- 2002-03-27 CN CNB028076540A patent/CN100519554C/zh not_active Expired - Fee Related
- 2002-03-27 AT AT02725381T patent/ATE299139T1/de active
- 2002-03-27 EP EP05009882A patent/EP1591444B1/en not_active Expired - Lifetime
- 2002-03-27 KR KR1020037012565A patent/KR100613528B1/ko not_active Expired - Fee Related
- 2002-03-27 DK DK02725381T patent/DK1373256T3/da active
- 2002-03-27 WO PCT/US2002/009491 patent/WO2002079194A1/en not_active Ceased
- 2002-03-27 MX MXPA03008853A patent/MXPA03008853A/es active IP Right Grant
- 2002-03-27 DE DE60204951T patent/DE60204951T2/de not_active Expired - Lifetime
- 2002-03-27 SI SI200230169T patent/SI1373256T1/sl unknown
- 2002-03-27 HU HU0400349A patent/HUP0400349A3/hu unknown
- 2002-03-27 EP EP02725381A patent/EP1373256B1/en not_active Expired - Lifetime
- 2002-03-27 IL IL15755102A patent/IL157551A0/xx not_active IP Right Cessation
- 2002-03-27 DE DE60236218T patent/DE60236218D1/de not_active Expired - Lifetime
- 2002-03-27 AU AU2002255947A patent/AU2002255947B8/en not_active Ceased
- 2002-03-27 JP JP2002577819A patent/JP4248251B2/ja not_active Expired - Fee Related
- 2002-03-27 PL PL02364560A patent/PL364560A1/xx not_active IP Right Cessation
- 2002-03-27 CA CA002442227A patent/CA2442227C/en not_active Expired - Fee Related
- 2002-03-27 BR BR0208398-1A patent/BR0208398A/pt not_active IP Right Cessation
- 2002-03-27 CZ CZ20032636A patent/CZ20032636A3/cs unknown
- 2002-03-27 US US10/107,940 patent/US6720325B2/en not_active Expired - Lifetime
- 2002-03-28 TW TW091106166A patent/TWI237638B/zh active
- 2002-03-28 MY MYPI20021140A patent/MY128609A/en unknown
-
2003
- 2003-09-25 ZA ZA200307474A patent/ZA200307474B/en unknown
- 2003-09-26 NO NO20034311A patent/NO326349B1/no not_active IP Right Cessation
-
2004
- 2004-02-06 US US10/773,521 patent/US6900211B2/en not_active Expired - Fee Related
- 2004-10-21 US US10/970,216 patent/US7008946B2/en not_active Expired - Fee Related
-
2005
- 2005-02-17 US US11/059,785 patent/US7060701B2/en not_active Expired - Fee Related
- 2005-10-14 US US11/250,247 patent/US7098213B2/en not_active Expired - Fee Related
-
2007
- 2007-10-26 JP JP2007279663A patent/JP2008074862A/ja not_active Withdrawn
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW454007B (en) | Novel isoxazoline and isozazole fibrinogen receptor antagonists | |
| US8153658B2 (en) | Piperidine derivative or salt thereof | |
| TW201130816A (en) | New CCR2 receptor antagonists and uses thereof | |
| TW200815426A (en) | New pyridine analogues II 333 | |
| CN103140486B (zh) | Ccr3-抑制剂的共结晶体及盐 | |
| TW492960B (en) | Azetidine derivatitives, relevant processes of manufacture and the uses thereof as tachykinin inhibitors | |
| TW200815431A (en) | Azabenzimidazolyl compounds | |
| UA123010C2 (uk) | Модулятори сот та способи їх застосування | |
| WO2004002964A1 (ja) | ジアミノピリミジンカルボキサミド誘導体 | |
| JP2005509032A (ja) | カンナビノイドレセプターリガンド | |
| CZ20013940A3 (cs) | Piperazinové deriváty uľitečné jako CCR5 antagonisté | |
| CA3027495A1 (en) | Cxcr4 inhibitors and uses thereof | |
| WO2009022730A1 (ja) | Ｐ２ｘ４受容体拮抗剤 | |
| CN111163766A (zh) | Ahr抑制剂和其用途 | |
| TW200808707A (en) | Sulfamide and sulfamate derivatives as histone deacetylase inhibitors | |
| TW201326143A (zh) | Ｇ蛋白偶合ｍａｓ受體之調節劑及與其相關病症之治療 | |
| CA2927182A1 (en) | Quinolinyl modulators of ror.gamma.t | |
| US20100324017A1 (en) | Acylguanidine derivative | |
| JP2008531679A (ja) | オキシトシンアンタゴニストとしての１，２，４−トリアゾール誘導体とその使用 | |
| TWI296926B (en) | Interleukin-4 gene expression inhibitors | |
| JP4717815B2 (ja) | イソキノリノンカリウムチャネル阻害剤 | |
| JP2008031180A (ja) | ケモカインレセプターの阻害剤として有用なビピペリジニル誘導体 | |
| EP1303508A1 (en) | Substituted 1-(4-aminophenyl)indoles and their use as anti-inflammatory agents | |
| HU229709B1 (en) | Piperazinyilpiperidine derivatives as chemokine receptor antagonists | |
| TW200800194A (en) | Kinase inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |