公开(公告)号：EP1797069A2

公开(公告)日：2007-06-20

申请号：EP05794656.8

申请日：2005-09-29

申请人： Tibotec Pharmaceuticals Ltd.

发明人： GUILLEMONT, Jerôme, Emile, Georges ,  HEERES, Jan ,  LEWI, Paulus, Joannes

IPC分类号： C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D413/04 ,  C07D413/14

CPC分类号： C07D405/04 ,  C07D401/04 ,  C07D403/04 ,  C07D409/04 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04

摘要： HIV replication inhibitors of formula (I), N-oxides, pharmaceutically acceptable addition salts, quaternary amines or stereoisomeric forms thereof, wherein -a1=a2-a3=a4- is -CH=CH-CH=CH-, -N=CH-CH=CH-, -N=CH-N=CH-, -N=CH-CH=N-, -N=N-CH=CH-; -b1=b2-b3=b4- is -CH=CH-CH=CH-, -N=CH-CH=CH-, -N=CH-N=CH-, -N=CH-CH=N-, -N=N-CH=CH-; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; optionally substituted C1-6alkyl; C1-6alkyloxycarbonyl; R2 is OH; halo; optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl; substituted carbonyl; carboxyl; CN; nitro; amino; substituted amino; polyhalomethyl; polyhalomethylthio; -S(=O)PR6; C(=NH)R6; R2a is CN; amino; substituted amino; optionally substituted C1-6alkyl; halo; optionally substituted C1-6alkyloxy; substituted carbonyl; -CH=N-NH-C(O)-R16; optionally substituted C1-6alkyloxyC1-6alkyl; substituted C2-6alkenyl or C 2-6 alkynyl; -C(=N-O-R8)-C1-4alkyl; R7 or -X3-R7; X1 is -NR1-, -O-, -C(=O)-, -CH2-, -CHOH-, -S-, -S(=O)P- R3 is CN; amino; C1-6alkyl; halo; optionally substituted C1-6alkyloxy; substituted carbonyl; -CH=N-NH-C(O)-R16; substituted C1-6alkyl; optionally substituted C1-6alkyloxyC1-6alkyl; substituted C2-6alkenyl or C2-6alkynyl; -C(=N-O-R8)-C1-4alkyl; R7; -X3-R7 ; R4 is halo; OH; optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl; C3-7cycloalkyl; C1-6alkyloxy; CN; nitro; polyhaloC1-6alkyl; polyhaloC1-6alkyloxy; substituted carbonyl; formyl; amino; mono- or di(C1-4alkyl)amino or R7; R5 is a 5- or 6-membered completely unsaturated ring system wherein 1 - 4 ring members are nitrogen, oxygen or sulfur; which ring may optionally be substituted and may optionally be annelated with a benzene ring; methods for their preparation and pharmaceutical compositions comprising them. The invention also relates to the use of these compounds for the prevention or the treatment of HIV infection.

公开(公告)号：EP1797048A2

公开(公告)日：2007-06-20

申请号：EP05803358.0

申请日：2005-09-29

申请人： Tibotec Pharmaceuticals Ltd.

发明人： GUILLEMONT, Jerôme, Emile, Georges ,  HEERES, Jan ,  LEWI, Paulus Joannes

IPC分类号： C07D239/48 ,  C07D401/12 ,  C07D417/12 ,  C07D405/12 ,  C07D409/12 ,  C07D403/12 ,  C07D413/14 ,  A61K31/505

CPC分类号： C07D403/12 ,  C07D239/48 ,  C07D239/50 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/14 ,  C07D417/12

摘要： HIV replication inhibitors of formula (I) N-oxides, a pharmaceutically acceptable addition salts, a quaternary amines or a stereoisomeric forms thereof, wherein -a1=a2-a3=a4 - is -CH=CH-CH=CH-, -N=CH-CH=CH-, -N=CH-N=CH-, -N=CH- CH=N-, -N=N-CH=CH-; -b1=b2-b3=b4- is -CH=CH-CH=CH-, -N=CH-CH=CH-, -N=CH-N=CH-, -N=CH-CH=N-, -N=N-CH=CH-; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; optionally subst ituted C1-6alkyl; C1-6alkyloxycarbonyl; R2 is OH; halo; optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl; substituted carbonyl; carboxyl; CN; nitro; amino; substituted amino; polyhalomethyl; polyhalo methylt hio; -S(=O)rR6; C(=NH)R6; R2a is CN; amino; substituted amino; optionally subst ituted C1-6alkyl; halo; optionally substituted C1-6alkyloxy; substituted carbonyl; -CH=N-NH-C(=O)-R16; optionally substituted C1-6alkyloxy C1-6alkyl; substituted C2-6alkenyl or C2-6alkynyl; -C(=N-O-R8)-C1-4alkyl; R7 or -X3-R7; X1 is -NR1-, -O-, -C(=O)-, CH2 , -CHOH-, -S-, -S(=O)r-; R3 is CN; amino; C1-6alkyl; halo; optionally substituted C1-6alkyloxy; substituted carbonyl; -CH=N-NH-C(=O)-R16; substituted C1-6alkyl; optionally substituted C1-6alkyloxy C1-6alkyl; substituted C2-6alkenyl or C2-6alkynyl; -C(=N-O-R8)-C1-4alkyl; R7; -X3-R7; R4 is halo; OH; optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl; C3-7cycloalkyl; C1-6alkyloxy; CN; nitro; polyhalo C1-6alkyl; polyhalo C1-6alkyloxy; substituted carbonyl; formyl; amino; mono- or di(C1-4alkyl)amino or R7; R5 is-Y-CqH2q-L or -CqH2q-Y-CrH2r-L; L is aryl or Het; processes for the preparation of these compounds, pharmaceut ical compositions comprising these compounds as active ingredient and the use of these compounds for the prevention or the treatment of HIV infection.

公开(公告)号：EP1789139A1

公开(公告)日：2007-05-30

申请号：EP05779369.7

申请日：2005-09-02

申请人： JANSSEN PHARMACEUTICA N.V. ,  Tibotec Pharmaceuticals Ltd.

发明人： STEVENS, Paul Theodoor, Janssen Pharmaceutica N.V. ,  PEETERS, Jozef, Janssen Pharmaceutica N.V. ,  VANDECRUYS, Roger P., Janssen Pharmaceutica N.V. ,  STAPPERS, Alfred E., Janssen PharmaceuticaN.V. ,  COPMANS, Alex Herman, Janssen Pharmaceutica N.V.

IPC分类号： A61P31/18 ,  A61K31/505

CPC分类号： C07D239/48 ,  A61K9/2018

摘要： The present invention relates to the fumarate salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile, pharmaceutical compositions comprising as active ingredient said salt and to processes for their preparation.

公开(公告)号：EP1778696A2

公开(公告)日：2007-05-02

申请号：EP05740229.9

申请日：2005-05-04

申请人： Tibotec Pharmaceuticals Ltd.

发明人： TAHRI, Abdellah ,  MICHIELS, Lieve, Emma, Jan ,  VAN ACKER, Koenraad, Lodewijk, August ,  SURLERAUX, Dominique, Louis, Nestor, Ghislain

IPC分类号： C07D498/04 ,  A61K31/538

CPC分类号： A61K31/538 ,  C07D498/04

摘要： The present invention realtes to 5H-pyrazolo[1,5-c][1,3]benzoxazin-5-yl)phenyl methanone derivatives as inhibitors of the viral replication of the HIV virus, processes for their preparation as well as pharmaceutical compositions, their use as medicines, and diagnostic kits comprising them. The present invention also concerns combinations of the present HIV inhibitors with other anti-retroviral agents. It further relates to their use in assays as reference compounds or as reagents. The compounds of the present invention are useful for preventing or treating infection by HIV and for treating AIDS.

公开(公告)号：EP1765337A1

公开(公告)日：2007-03-28

申请号：EP05774136.5

申请日：2005-07-08

申请人： Tibotec Pharmaceuticals Ltd.

发明人： HOETELMANS, Richard, Marinus, Wilhelmus

IPC分类号： A61K31/427 ,  A61K31/7076 ,  A61K31/343 ,  A61P31/18

CPC分类号： A61K31/343 ,  A61K31/427 ,  A61K31/7076 ,  A61K2300/00

摘要： The invention relates to an anti-HIV combination comprising (i) tenofovir or its disoproxil fumarate derivative; (ii) ritonavir; and (iii) TMC 114, useful for the treatment or prevention of HIV infections. It further relates to pharmaceutical formulations containing such combinations.

公开(公告)号：EP1370543B1

公开(公告)日：2006-10-25

申请号：EP02729930.4

申请日：2002-02-14

申请人： Tibotec Pharmaceuticals Ltd.

发明人： SURLERAUX, Dominique, Louis, Nestor, Ghislain ,  WIGERINCK, Piet, Tom, Bert, Paul ,  GETMAN, Daniel ,  VERSCHUEREN, Wim, Gaston ,  VENDEVILLE, Sandrine ,  DE BETHUNE, Marie-Pierre ,  DE KERPEL, Jan, Octaaf, Antoon ,  MOORS, Samuel, Leo, Christiaan ,  DE KOCK, Herman, Augustinus ,  VOETS, Marieke, Christiane, Johanna

IPC分类号： C07D277/82

CPC分类号： C07D417/12 ,  C07D277/82

摘要： The present invention concerns the compounds having the formula (I), N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R1 and R8 each are H, optionally substituted C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het?1, Het2; R¿1 may also be a radical of formula (R11aR11b)NC(R10aR10b)CR9-; t is 0, 1 or 2; R2 is H or C1-6alkyl; L is -C(=O)-, -O-C(=O)-, -NR8-C(=O)-, -O-C1-6alkanediyl-C(=O)-, -NR8-C1-6?alkanediyl-C(=O)-, -S(=O)2-, -O-S(=O)2-, -NR8-S(=O)2; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(=O), carboxyl, aminoC(=O), mono- or di(C1-4alkyl)aminoC(=O), C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; A is C1-6alkanediyl, -C(=O)-, -C(=S)-, -S(=O)2-, C1-6alkanediyl-C(=O)-, C1-6alkanediyl-C(=S)- or C1-6alkanediyl-S(=O)2-; R5 is H, OH, C1-6alkyl, Het?1C¿1-6alkyl, Het2C1-6alkyl, optionally substituted aminoC1-6alkyl; R6 is C1-6alkylO, Het?1, Het1O, Het2, Het2¿O, aryl, arylO, C¿1-6?alkyloxycarbonylamino or amino; and in case -A- is other than C1-6alkanediyl then R?6¿ may also be C¿1-6?alkyl, Het?1C¿1-4alkyl, Het1OC1-4alkyl, Het2C1-4alkyl, Het2OC1-4alkyl, arylC1-4alkyl, arylOC1-4alkyl or aminoC1-4alkyl; whereby each of the amino groups in the definition of R6 may optionally be substituted; R5 and -A-R6 taken together with the nitrogen atom to which they are attached may also form Het?1 or Het2¿. It further relates to their use as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. It also concerns combinations thereof with another anti-retroviral agent, and to their use in assays as reference compounds or as reagents.

公开(公告)号：EP1711485A1

公开(公告)日：2006-10-18

申请号：EP04804953.0

申请日：2004-12-20

申请人： Tibotec Pharmaceuticals Ltd.

发明人： BONFANTI, Jean-François ,  ANDRIES, Koenraad, Jozef, Lodewijk ,  JANSSENS, Frans, Eduard ,  SOMMEN, François, Maria ,  GUILLEMONT, Jerôme, Emile, Georges ,  LACRAMPE, Jean, Fernand, Armand

IPC分类号： C07D401/06 ,  A61K31/4184 ,  C07D401/14 ,  C07D405/14 ,  A61P11/00 ,  A61P31/12

CPC分类号： C07D405/14 ,  C07D401/06 ,  C07D401/14

摘要： The present invention concerns amino-benzimidazoles having inhibitory activity on the replication of the respiratory syncytial virus and having the formula (I) their prodrugs, N-oxides, addition salts, quaternary amines, metal complexes and stereochemically isomeric forms wherein Q is Ar1 or C1-6alkyl substituted with one or more substituents selected from trifluoromethyl, C3-7cycloalkyl, Ar2, hydroxy, C1-4alkoxy, C1-4alkylthio, Ar2-oxy-, Ar2-thio-, Ar2(CH2)„oxy, Ar2(CH2)nthio, hydroxycarbonyl, aminocarbonyl, C1-4 alkylcarbonyl, Ar2carbonyl, C1-4alkoxycarbonyl, Ar2(CH2)n carbonyl, aminocarbonyloxy, C1-4 alkylcarbonyloxy, Ar2carbonyloxy, Ar2(CH2)ncarbonyloxy, hydroxy-C2- 4-alkyloxy, C1-4 alkoxycarbonyl(CH2)noxy, mono­or di(C1-4alkyl)-aminocarbonyl, mono- or di(C1-4alkyl)aminocarbonyloxy, aminosulfonyl, mono- or di(C1-4alkyl)aminosulfonyl, dioxolanyl optionally substituted with one or two C1-6alkyl radicals, and a heterocycle selected from pyrrolidinyl, pyrrolyl, dihydropyrrolyl, thiazolidinyl, imidazolyl, triazolyl, piperidinyl, homopiperidinyl, piperazinyl, pyridyl and tetrahydropyridyl, which each may optionally be substituted with oxo or C1-6alkyl; G is a direct bond or optionally substituted C1-10alkanediyl R1 is Ar1 or a monocyclic or bicyclic heterocycle; one of R2a and R3a is C1-6alkyl and the other one of R2a and R3a is hydrogen; in case R2a is different from hydrogen then R2b is hydrogen or C1-6alkyl, and R3b is hydrogen; in case R3a is different from hydrogen then R3b is hydrogen or C 1-6alkyl, and R2b is hydrogen; Ar1 is phenyl or substituted phenyl and Ar2 is phenyl or substituted phenyl. It further concerns their preparation and compositions comprising them, as well as their use as a medicine.

公开(公告)号：EP1648467A1

公开(公告)日：2006-04-26

申请号：EP04766264.8

申请日：2004-07-19

申请人： Tibotec Pharmaceuticals Ltd.

发明人： LAMOUREUX, Gaël ,  COUSIN, Gérard ,  THONÉ , Daniel, Joseph, Christiaan

IPC分类号： A61K31/53 ,  A61P31/18 ,  A61K9/16 ,  A61K9/50

CPC分类号： A61K31/505 ,  A61K9/1676 ,  A61K9/1682 ,  A61K9/5078 ,  A61K9/5089 ,  A61K31/4196 ,  A61K31/53

摘要： A process for preparing a particle comprising a co-precipitate surrounding a neutral hydrophilic carrier, said process comprising spraying an organic solution on a neutral hydrophilic carrier, said solution comprising at least one triazine or pyrimidine active ingredient having HIV inhibiting properties, one surface active agent, and one hydrophilic polymer, wherein the spraying of whole of the solution occurs in at least two separate steps, each of these steps followed by a grinding step of the product obtained at the end of the preceding step.

摘要翻译： 一种用于制备颗粒，其包含周围的中性亲水性载体的共沉淀方法，所述方法的中性亲水性载体上的包含有机溶液的喷雾，所述溶液包含至少一种三嗪或嘧啶的活性成分具有HIV抑制特性，一种表面活性剂 和一种亲水性聚合物，worin整体在溶液的喷洒发生在至少两个分开的步骤中，每个随后在preceding-步骤结束时获得的产物的研磨步骤的合成步骤。

公开(公告)号：EP1485358A1

公开(公告)日：2004-12-15

申请号：EP03714954.9

申请日：2003-03-12

申请人： Tibotec Pharmaceuticals Ltd.

发明人： SURLERAUX, Dominique, Louis, Nestor, Ghislain ,  WIGERINCK, Piet, Tom, Bert, Paul ,  VOETS, Marieke, Christiane, Johanna ,  VENDEVILLE, Sandrine, Marie, Helene ,  DE KOCK, Herman, Augustinus ,  VERGOUWEN, Bernhard, Joanna, Bernard

IPC分类号： C07D235/32 ,  A61K31/415 ,  C07D493/04 ,  C07D235/30 ,  C07D407/12 ,  C07D417/12 ,  C07D413/12 ,  C07D401/12 ,  A61P31/18

CPC分类号： C07D401/12 ,  A61K31/415 ,  C07D235/30 ,  C07D235/32 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D493/04

摘要： The present invention concerns the compounds having the formula (I), wherein N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R1 and R8 each are H, optionally substituted C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het1, Het2; R1 may also be a radical of formula (R11aR11b)NC(R10aRl0b)CR9-; t is 0, 1 or 2; R2 is H or C1-6alkyl; L is -C(=O)-, -O-C(=O)-, -NR8-C(=O)-, -O-C1-6alkanediyl-C(=O)-, -NR8-C1-6alkanediyl-C(=O)-, -S(=O)2-, -O-S(=O)2-, -NR8-S(=O)2 ; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(=O), carboxyl, aminoC(=O), mono- or di(C1-4alkyl)aminoC(=O), C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; A is C1-6alkanediyl, -C(=O)-, -C(=S)-, -S(=O)2-, C1-6alkanediyl-C(=O)-, C1-6 alkanediyl-C(=S)- or C1-6alkanediyl-S(=O)2-; R5 is H, OH, C1-6alkyl, Het1C1-6alkyl, Het2C1-6 alkyl, optionally substituted amino­-C1-6alkyl; R6 is C1-6alkylO, Het1, Het1O, Het2, Het2O, aryl, arylO, C1-6 alkyloxy­carbonylamino or amino; and in case _A- is other than C1-6alkanediyl then R6 may also be C1-6alkyl, Het1C1-4alkyl, Het1OC1-4alkyl, Het2C1-4alkyl, Het2OC1-4alkyl, arylC1-4alkyl, arylOC1-4alkyl or aminoC1-4alkyl; whereby each of the amino groups in the definition of R6 may optionally be substituted; R5 and _A-R6 taken together with the nitrogen atom to which they are attached may also form Het1 or Het2, R12 , is H, - NH2, _NR5AR6, - C1-6alkyl or alkyl-W-R14 , wherein said alkyl is optionally substituted with halogen, hydroxy, aryl, heteroaryl, Het1, Het2, or amino wherein said amino is optionally mono- or di-substituted with C1-4alkyl and R13 is H, C1-6-alkyl, optionally substituted by aryl, Het1, Het2, hydroxy, halogen, amino whereby the amino group may be optionally be mono- or di-substituted with C1-4alkyl.

公开(公告)号：EP1463502A1

公开(公告)日：2004-10-06

申请号：EP02796754.6

申请日：2002-12-20

申请人： Tibotec Pharmaceuticals Ltd.

发明人： VENDEVILLE, Sandrine, Marie, Helene ,  VERSCHUEREN, Wim, Gaston ,  TAHRI, Abdellah ,  MOORS, Samuel, Leo, Christiaan ,  ERRA SOL , Montserrat

IPC分类号： A61K31/4178 ,  A61P31/18 ,  C07D231/12 ,  C07D277/42 ,  C07D263/32 ,  C07D513/04 ,  C07D233/54 ,  C07D233/88 ,  C07D493/04 ,  C07D277/40 ,  C07D417/14 ,  C07D417/12 ,  A61K31/506 ,  A61K31/427 ,  A61K31/425

CPC分类号： C07D231/12 ,  C07C311/18 ,  C07C2603/18 ,  C07D233/64 ,  C07D233/88 ,  C07D263/32 ,  C07D277/40 ,  C07D277/42 ,  C07D277/46 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D493/04 ,  C07D513/04

摘要： The present invention concerns the compounds having the formula (I), N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein Haryl is an aromatic monocyclic, bicyclic or tricyclic heterocycle having 3 to 14 ring members which contains one or more heteroatom ring members selected from nitrogen, oxygen and sulfur and which may optionally be substituted on (i) one or more carbon atoms by C1-6alkyl, halogen, hydroxy, optionally mono- or disubstituted amino, nitro, cyano, haloC1-6alkyl, carboxyl, C3-7cycloalkyl, optionally mono- or disubstituted aminocarbonyl, methylthio, methylsulfonyl, aryl, -(R7a)n-M-R7b, Het1 and Het2; whereby the optional substituents on any amino function are independently selected from R¿5? and -A-R6; and on (ii) a nitrogen atom if present by hydroxy or -A-R6. It further relates to their use as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. It also concerns combinations thereof with another anti-retroviral agent, and to their use in assays as reference compounds or as reagents.