MXPA04011670A - Amidas de 4-alquenil piperidina de indol, azaindol, y relacionadas con heterociclicos. - Google Patents
Amidas de 4-alquenil piperidina de indol, azaindol, y relacionadas con heterociclicos.Info
- Publication number
- MXPA04011670A MXPA04011670A MXPA04011670A MXPA04011670A MXPA04011670A MX PA04011670 A MXPA04011670 A MX PA04011670A MX PA04011670 A MXPA04011670 A MX PA04011670A MX PA04011670 A MXPA04011670 A MX PA04011670A MX PA04011670 A MXPA04011670 A MX PA04011670A
- Authority
- MX
- Mexico
- Prior art keywords
- group
- alkyl
- heteroaryl
- phenyl
- optionally substituted
- Prior art date
Links
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title claims abstract description 26
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title description 73
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 title description 48
- 125000000623 heterocyclic group Chemical group 0.000 title description 47
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title description 37
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title description 37
- 150000001875 compounds Chemical class 0.000 claims abstract description 277
- 238000000034 method Methods 0.000 claims abstract description 232
- 208000030507 AIDS Diseases 0.000 claims abstract description 85
- 230000000840 anti-viral effect Effects 0.000 claims abstract description 25
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- -1 benzoimidazolyl Chemical group 0.000 claims description 235
- 125000001072 heteroaryl group Chemical group 0.000 claims description 186
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 160
- 125000000217 alkyl group Chemical group 0.000 claims description 104
- 229910052736 halogen Inorganic materials 0.000 claims description 80
- 150000002367 halogens Chemical class 0.000 claims description 79
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 76
- 125000001424 substituent group Chemical group 0.000 claims description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims description 50
- 239000001257 hydrogen Substances 0.000 claims description 46
- 208000031886 HIV Infections Diseases 0.000 claims description 45
- 208000037357 HIV infectious disease Diseases 0.000 claims description 43
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 43
- 125000004076 pyridyl group Chemical group 0.000 claims description 42
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 39
- 125000002541 furyl group Chemical group 0.000 claims description 33
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 31
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 31
- 125000001544 thienyl group Chemical group 0.000 claims description 31
- 125000001425 triazolyl group Chemical group 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 29
- 125000002971 oxazolyl group Chemical group 0.000 claims description 28
- 125000002883 imidazolyl group Chemical group 0.000 claims description 27
- 239000003112 inhibitor Substances 0.000 claims description 27
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 27
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 26
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 26
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 26
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 26
- 125000000335 thiazolyl group Chemical group 0.000 claims description 26
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
- 125000004193 piperazinyl group Chemical group 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- 229910052731 fluorine Inorganic materials 0.000 claims description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 15
- 239000011737 fluorine Substances 0.000 claims description 13
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 125000004306 triazinyl group Chemical group 0.000 claims description 11
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 241000700605 Viruses Species 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 230000002924 anti-infective effect Effects 0.000 claims description 7
- 239000003443 antiviral agent Substances 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 6
- 239000002955 immunomodulating agent Substances 0.000 claims description 6
- 229940121354 immunomodulator Drugs 0.000 claims description 6
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 claims description 5
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 4
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 4
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 4
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000005872 benzooxazolyl group Chemical group 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 230000002584 immunomodulator Effects 0.000 claims description 4
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 14
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
- 125000004001 thioalkyl group Chemical group 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 23
- 229940079593 drug Drugs 0.000 abstract description 19
- 238000006243 chemical reaction Methods 0.000 description 442
- 238000002360 preparation method Methods 0.000 description 151
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 129
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 122
- 239000000203 mixture Substances 0.000 description 118
- 239000000543 intermediate Substances 0.000 description 112
- 239000000243 solution Substances 0.000 description 88
- 239000002904 solvent Substances 0.000 description 74
- 239000007787 solid Substances 0.000 description 63
- 229910001868 water Inorganic materials 0.000 description 63
- 238000005859 coupling reaction Methods 0.000 description 60
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 59
- 235000019439 ethyl acetate Nutrition 0.000 description 59
- 230000015572 biosynthetic process Effects 0.000 description 57
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 56
- 238000010168 coupling process Methods 0.000 description 56
- 230000008878 coupling Effects 0.000 description 55
- 238000003786 synthesis reaction Methods 0.000 description 55
- 239000002253 acid Substances 0.000 description 52
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 50
- 101150041968 CDC13 gene Proteins 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 41
- 238000007429 general method Methods 0.000 description 40
- 239000003153 chemical reaction reagent Substances 0.000 description 38
- 125000003118 aryl group Chemical group 0.000 description 36
- 238000002953 preparative HPLC Methods 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 150000001299 aldehydes Chemical group 0.000 description 31
- 238000003756 stirring Methods 0.000 description 30
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 30
- 150000001412 amines Chemical class 0.000 description 29
- 239000012044 organic layer Substances 0.000 description 29
- 241000725303 Human immunodeficiency virus Species 0.000 description 28
- 239000012267 brine Substances 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 27
- 229960002555 zidovudine Drugs 0.000 description 27
- 239000000047 product Substances 0.000 description 26
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 23
- 239000002585 base Substances 0.000 description 23
- 238000000746 purification Methods 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000000460 chlorine Substances 0.000 description 20
- 150000002148 esters Chemical class 0.000 description 20
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 150000001408 amides Chemical class 0.000 description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- 230000009466 transformation Effects 0.000 description 18
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 17
- 229910052794 bromium Inorganic materials 0.000 description 17
- 150000002825 nitriles Chemical class 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 17
- 239000002243 precursor Substances 0.000 description 17
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
- 150000002475 indoles Chemical class 0.000 description 16
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 15
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 14
- 150000001204 N-oxides Chemical class 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
- 239000008346 aqueous phase Substances 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
- 239000007832 Na2SO4 Substances 0.000 description 13
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 13
- 239000003054 catalyst Substances 0.000 description 13
- 229910052801 chlorine Inorganic materials 0.000 description 13
- 230000007062 hydrolysis Effects 0.000 description 13
- 238000006460 hydrolysis reaction Methods 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 230000009467 reduction Effects 0.000 description 13
- 238000006722 reduction reaction Methods 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 12
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 12
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 12
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 12
- 229960005141 piperazine Drugs 0.000 description 12
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 12
- 229920002554 vinyl polymer Polymers 0.000 description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 11
- 125000003277 amino group Chemical group 0.000 description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
- 244000309464 bull Species 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 150000004820 halides Chemical class 0.000 description 11
- 230000001404 mediated effect Effects 0.000 description 11
- 229910052751 metal Inorganic materials 0.000 description 11
- 239000002184 metal Substances 0.000 description 11
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 11
- 238000000844 transformation Methods 0.000 description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 150000002576 ketones Chemical class 0.000 description 10
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 10
- 230000003647 oxidation Effects 0.000 description 10
- 238000007254 oxidation reaction Methods 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910000080 stannane Inorganic materials 0.000 description 10
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 9
- 230000010933 acylation Effects 0.000 description 9
- 238000005917 acylation reaction Methods 0.000 description 9
- INLLPKCGLOXCIV-UHFFFAOYSA-N bromoethene Chemical class BrC=C INLLPKCGLOXCIV-UHFFFAOYSA-N 0.000 description 9
- AJDPNPAGZMZOMN-UHFFFAOYSA-N diethyl (4-oxo-1,2,3-benzotriazin-3-yl) phosphate Chemical compound C1=CC=C2C(=O)N(OP(=O)(OCC)OCC)N=NC2=C1 AJDPNPAGZMZOMN-UHFFFAOYSA-N 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000005755 formation reaction Methods 0.000 description 9
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 9
- 229910052740 iodine Inorganic materials 0.000 description 9
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 9
- 238000004949 mass spectrometry Methods 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 8
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
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- 229930191512 spiramycin Natural products 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 229940054565 sustiva Drugs 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- RKXKXFBJYQHSSU-UHFFFAOYSA-N tert-butyl 4-[(2,6-dimethoxypyridin-3-yl)-phenylmethylidene]piperidine-1-carboxylate Chemical compound COC1=NC(OC)=CC=C1C(C=1C=CC=CC=1)=C1CCN(C(=O)OC(C)(C)C)CC1 RKXKXFBJYQHSSU-UHFFFAOYSA-N 0.000 description 1
- WLTPVYIFMPTIFB-UHFFFAOYSA-N tert-butyl 4-[[3-(hydroxymethyl)phenyl]-phenylmethylidene]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1=C(C=1C=C(CO)C=CC=1)C1=CC=CC=C1 WLTPVYIFMPTIFB-UHFFFAOYSA-N 0.000 description 1
- BZHZEQNEDKSBLN-UHFFFAOYSA-N tert-butyl 4-[phenyl(1,3-thiazol-2-yl)methylidene]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1=C(C=1C=CC=CC=1)C1=NC=CS1 BZHZEQNEDKSBLN-UHFFFAOYSA-N 0.000 description 1
- WGCUIGIJDHTHHO-UHFFFAOYSA-N tert-butyl 4-[phenyl(pyrazin-2-yl)methylidene]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1=C(C=1N=CC=NC=1)C1=CC=CC=C1 WGCUIGIJDHTHHO-UHFFFAOYSA-N 0.000 description 1
- PDTZMULNKGUIEJ-UHFFFAOYSA-N tert-butyl 4-methylidenepiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=C)CC1 PDTZMULNKGUIEJ-UHFFFAOYSA-N 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-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
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 150000003549 thiazolines Chemical class 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- SUJUHGSWHZTSEU-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(=O)C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)=C(O)C1)CC1=CC=CC=C1 SUJUHGSWHZTSEU-FYBSXPHGSA-N 0.000 description 1
- 229960000838 tipranavir Drugs 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- GTZCVFVGUGFEME-UHFFFAOYSA-N trans-aconitic acid Natural products OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- YOWGRWHKDCHINP-UHFFFAOYSA-N tributyl(1,3-oxazol-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CO1 YOWGRWHKDCHINP-UHFFFAOYSA-N 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 229940111527 trizivir Drugs 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 229940093257 valacyclovir Drugs 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 229940098802 viramune Drugs 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229940087450 zerit Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
-
- 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
- C07D401/02—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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38350902P | 2002-05-28 | 2002-05-28 | |
| PCT/US2003/013324 WO2004043337A2 (en) | 2002-05-28 | 2003-04-30 | Indole, azaindole and related heterocyclic 4-alkenyl piperidine amides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA04011670A true MXPA04011670A (es) | 2005-03-07 |
Family
ID=32312411
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA04011670A MXPA04011670A (es) | 2002-05-28 | 2003-04-30 | Amidas de 4-alquenil piperidina de indol, azaindol, y relacionadas con heterociclicos. |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US20040063744A1 (https=) |
| EP (1) | EP1513832B1 (https=) |
| JP (1) | JP4446889B2 (https=) |
| KR (1) | KR101001811B1 (https=) |
| CN (1) | CN100528866C (https=) |
| AR (1) | AR040230A1 (https=) |
| AU (1) | AU2003301958B2 (https=) |
| BR (2) | BR0311541A (https=) |
| CA (1) | CA2487542C (https=) |
| CL (1) | CL2003001087A1 (https=) |
| CO (1) | CO5631440A2 (https=) |
| DK (1) | DK1513832T3 (https=) |
| ES (1) | ES2460728T3 (https=) |
| GE (1) | GEP20074152B (https=) |
| HR (1) | HRP20041137B1 (https=) |
| IL (1) | IL165200A (https=) |
| IS (1) | IS2945B (https=) |
| MX (1) | MXPA04011670A (https=) |
| MY (1) | MY139058A (https=) |
| NO (1) | NO329691B1 (https=) |
| NZ (1) | NZ536661A (https=) |
| PE (1) | PE20040526A1 (https=) |
| PL (1) | PL216388B1 (https=) |
| PT (1) | PT1513832E (https=) |
| RS (1) | RS53021B (https=) |
| RU (1) | RU2323934C2 (https=) |
| SI (1) | SI1513832T1 (https=) |
| TW (1) | TWI310381B (https=) |
| UA (1) | UA79470C2 (https=) |
| WO (1) | WO2004043337A2 (https=) |
| ZA (1) | ZA200409504B (https=) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6476034B2 (en) * | 2000-02-22 | 2002-11-05 | Bristol-Myers Squibb Company | Antiviral azaindole derivatives |
| US20040110785A1 (en) * | 2001-02-02 | 2004-06-10 | Tao Wang | Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives |
| US20050075364A1 (en) * | 2003-07-01 | 2005-04-07 | Kap-Sun Yeung | Indole, azaindole and related heterocyclic N-substituted piperazine derivatives |
| US20050124623A1 (en) | 2003-11-26 | 2005-06-09 | Bender John A. | Diazaindole-dicarbonyl-piperazinyl antiviral agents |
| US7087610B2 (en) * | 2004-06-03 | 2006-08-08 | Bristol-Myers Squibb Company | Benzothiazole antiviral agents |
| CA2569887A1 (en) | 2004-06-09 | 2005-12-22 | Glaxo Group Limited | Pyrrolopyridine derivatives |
| US20060100209A1 (en) * | 2004-11-09 | 2006-05-11 | Chong-Hui Gu | Formulations of 1-(4-benzoyl-piperazin-1-yl)-2-[4-methoxy-7-(3-methyl-[1,2,4]triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-ethane-1,2-dione |
| US20060100432A1 (en) * | 2004-11-09 | 2006-05-11 | Matiskella John D | Crystalline materials of 1-(4-benzoyl-piperazin-1-yl)-2-[4-methoxy-7-(3-methyl-[1,2,4]triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-ethane-1,2-dione |
| US7601715B2 (en) * | 2005-06-22 | 2009-10-13 | Bristol-Myers Squibb Company | Process for preparing triazole substituted azaindoleoxoacetic piperazine derivatives and novel salt forms produced therein |
| PE20070239A1 (es) * | 2005-08-09 | 2007-04-01 | Glaxo Group Ltd | Derivados de imidazopiridina con actividad sobre los receptores cannabinoides |
| US7851476B2 (en) * | 2005-12-14 | 2010-12-14 | Bristol-Myers Squibb Company | Crystalline forms of 1-benzoyl-4-[2-[4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-YL)-1-[(phosphonooxy)methyl]-1H-pyrrolo[2,3-C]pyridin-3-YL]-1,2-dioxoethyl]-piperazine |
| US7807671B2 (en) | 2006-04-25 | 2010-10-05 | Bristol-Myers Squibb Company | Diketo-piperazine and piperidine derivatives as antiviral agents |
| US7572810B2 (en) * | 2006-06-08 | 2009-08-11 | Bristol-Myers Squibb Company | Alkene piperidine derivatives as antiviral agents |
| US7504399B2 (en) * | 2006-06-08 | 2009-03-17 | Bristol-Meyers Squibb Company | Piperazine enamines as antiviral agents |
| TWI443090B (zh) * | 2007-05-25 | 2014-07-01 | Abbvie Deutschland | 作為代謝性麩胺酸受體２（ｍｇｌｕ２ 受體）之正向調節劑之雜環化合物 |
| WO2009011912A1 (en) * | 2007-07-18 | 2009-01-22 | Bristol-Myers Squibb Company | A composition for treating hiv comprising virus-like particles |
| JP5433691B2 (ja) * | 2008-06-25 | 2014-03-05 | ブリストル−マイヤーズ スクイブ カンパニー | Ｈｉｖ結合阻害剤としてのジケトピペリジン誘導体 |
| JP5433690B2 (ja) | 2008-06-25 | 2014-03-05 | ブリストル−マイヤーズ スクイブ カンパニー | 抗−ｈｉｖ薬としてのジケト縮合アゾロピペリジンおよびアゾロピペラジン |
| WO2010028108A2 (en) * | 2008-09-04 | 2010-03-11 | Bristol-Myers Squibb Company | Stable pharmaceutical composition for optimized delivery of an hiv attachment inhibitor |
| MX2011008988A (es) * | 2009-02-27 | 2011-12-16 | Siga Technologies Inc | Derivados de tienopiridina para el tratamiento y prevencion de infecciones por el virus del dengue. |
| JP5643222B2 (ja) | 2009-04-02 | 2014-12-17 | 塩野義製薬株式会社 | アクリルアミド化合物およびその使用 |
| EP2308866A1 (de) * | 2009-10-09 | 2011-04-13 | Bayer CropScience AG | Phenylpyri(mi)dinylpyrazole und ihre Verwendung als Fungizide |
| WO2012019003A1 (en) * | 2010-08-06 | 2012-02-09 | Bristol-Myers Squibb Company | Substituted indole and azaindole oxoacetyl piperazinamide derivatives |
| WO2012075235A1 (en) | 2010-12-02 | 2012-06-07 | Bristol-Myers Squibb Company | Alkyl amides as hiv attachment inhibitors |
| ES2636312T3 (es) | 2011-04-12 | 2017-10-05 | VIIV Healthcare UK (No.5) Limited | Derivados de tioamida, amidoxima y amidrazona como inhibidores de la fijación del VIH |
| EP2751119B1 (en) | 2011-08-29 | 2016-11-23 | VIIV Healthcare UK (No.5) Limited | Fused bicyclic diamine derivatives as hiv attachment inhibitors |
| ES2609579T3 (es) | 2011-08-29 | 2017-04-21 | VIIV Healthcare UK (No.5) Limited | Derivados espiro de diamina bicíclica como inhibidores de la unión del VIH |
| ES2644747T3 (es) * | 2012-02-08 | 2017-11-30 | Viiv Healthcare Uk (No. 4) Limited | Procedimientos de preparación de un compuesto de profármaco de piperazina inhibidor de la fijación del VIH |
| WO2013138436A1 (en) | 2012-03-14 | 2013-09-19 | Bristol-Myers Squibb Company | Cyclolic hydrazine derivatives as hiv attachment inhibitors |
| ES2616492T3 (es) * | 2012-08-09 | 2017-06-13 | VIIV Healthcare UK (No.5) Limited | Derivados de piperidina amida como inhibidores de la fijación del VIH |
| EP2895472B1 (en) * | 2012-08-09 | 2016-11-23 | VIIV Healthcare UK (No.5) Limited | Tricyclic alkene derivatives as HIV attachment inhibitors |
| WO2017112576A1 (en) * | 2015-12-21 | 2017-06-29 | Dow Global Technologies Llc | Methods for external base-free suzuki couplings |
| CN108059611A (zh) * | 2018-01-22 | 2018-05-22 | 济南舜景医药科技有限公司 | 一种用于治疗心率不齐药物中间体的合成方法 |
| CN109053575A (zh) * | 2018-08-24 | 2018-12-21 | 遵义医学院 | 3-环丙基-1-甲基-1h-吡唑-4-甲醛的制备工艺 |
| US20240124444A1 (en) * | 2020-12-28 | 2024-04-18 | Celgene Corporation | Heterocyclic Compounds and Their Use for Parasitic Diseases |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5023265A (en) * | 1990-06-01 | 1991-06-11 | Schering Corporation | Substituted 1-H-pyrrolopyridine-3-carboxamides |
| US5124327A (en) * | 1991-09-06 | 1992-06-23 | Merck & Co., Inc. | HIV reverse transcriptase |
| US5424329A (en) * | 1993-08-18 | 1995-06-13 | Warner-Lambert Company | Indole-2-carboxamides as inhibitors of cell adhesion |
| TW429256B (en) * | 1995-12-27 | 2001-04-11 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4-(benzimidazolyl- and imidazopyridinyl)-piperidine derivatives |
| TW548271B (en) * | 1996-12-20 | 2003-08-21 | Astra Pharma Inc | Novel piperidine derivatives having an exocyclic double bond with analgesic effects |
| WO1998028292A1 (en) * | 1996-12-23 | 1998-07-02 | Smithkline Beecham Corporation | Novel piperidine containing compounds |
| US6469006B1 (en) * | 1999-06-15 | 2002-10-22 | Bristol-Myers Squibb Company | Antiviral indoleoxoacetyl piperazine derivatives |
| US6476034B2 (en) * | 2000-02-22 | 2002-11-05 | Bristol-Myers Squibb Company | Antiviral azaindole derivatives |
| US20020061892A1 (en) * | 2000-02-22 | 2002-05-23 | Tao Wang | Antiviral azaindole derivatives |
| US6573262B2 (en) * | 2000-07-10 | 2003-06-03 | Bristol-Myers Sqibb Company | Composition and antiviral activity of substituted indoleoxoacetic piperazine derivatives |
-
2003
- 2003-04-29 US US10/425,370 patent/US20040063744A1/en not_active Abandoned
- 2003-04-30 UA UA20041210893A patent/UA79470C2/uk unknown
- 2003-04-30 RU RU2004138565/04A patent/RU2323934C2/ru not_active IP Right Cessation
- 2003-04-30 HR HRP20041137AA patent/HRP20041137B1/hr not_active IP Right Cessation
- 2003-04-30 EP EP03811179.5A patent/EP1513832B1/en not_active Expired - Lifetime
- 2003-04-30 BR BRPI0311541-0A patent/BR0311541A/pt not_active IP Right Cessation
- 2003-04-30 BR BRPI0311541-0A patent/BRPI0311541B1/pt unknown
- 2003-04-30 MX MXPA04011670A patent/MXPA04011670A/es active IP Right Grant
- 2003-04-30 WO PCT/US2003/013324 patent/WO2004043337A2/en not_active Ceased
- 2003-04-30 SI SI200332346T patent/SI1513832T1/sl unknown
- 2003-04-30 CN CNB038175657A patent/CN100528866C/zh not_active Expired - Fee Related
- 2003-04-30 GE GEAP8554A patent/GEP20074152B/en unknown
- 2003-04-30 NZ NZ536661A patent/NZ536661A/en not_active IP Right Cessation
- 2003-04-30 ES ES03811179.5T patent/ES2460728T3/es not_active Expired - Lifetime
- 2003-04-30 RS YU101304A patent/RS53021B/sr unknown
- 2003-04-30 PL PL373603A patent/PL216388B1/pl unknown
- 2003-04-30 PT PT38111795T patent/PT1513832E/pt unknown
- 2003-04-30 DK DK03811179.5T patent/DK1513832T3/da active
- 2003-04-30 KR KR1020047019219A patent/KR101001811B1/ko not_active Expired - Fee Related
- 2003-04-30 AU AU2003301958A patent/AU2003301958B2/en not_active Ceased
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