公开(公告)号：US09365776B2

公开(公告)日：2016-06-14

申请号：US13818562

申请日：2011-08-30

申请人： Robertus Hendrikus Venderbosch ,  Agnes Retno Ardiyanti ,  Hero Jan Heeres ,  Vadim Yakovlev ,  Dmitry Ermakov ,  Sofia Khromova ,  Valentin Parmon

发明人： Robertus Hendrikus Venderbosch ,  Agnes Retno Ardiyanti ,  Hero Jan Heeres ,  Vadim Yakovlev ,  Dmitry Ermakov ,  Sofia Khromova ,  Valentin Parmon

IPC分类号： C07C1/00 ,  C10G1/00 ,  B01J23/00 ,  B01J23/755 ,  B01J23/825 ,  B01J23/83 ,  B01J23/86 ,  B01J23/885 ,  B01J23/89 ,  B01J37/02 ,  B01J37/03 ,  B01J37/18 ,  C10G3/00 ,  C10L1/02 ,  B01J23/887 ,  B01J21/04 ,  B01J21/06 ,  B01J21/08 ,  B01J35/10

CPC分类号： C10G1/002 ,  B01J21/04 ,  B01J21/063 ,  B01J21/066 ,  B01J21/08 ,  B01J23/002 ,  B01J23/755 ,  B01J23/825 ,  B01J23/83 ,  B01J23/868 ,  B01J23/885 ,  B01J23/8874 ,  B01J23/892 ,  B01J23/8926 ,  B01J23/898 ,  B01J23/8986 ,  B01J23/8993 ,  B01J35/1014 ,  B01J35/1019 ,  B01J37/0201 ,  B01J37/031 ,  B01J37/18 ,  B01J2523/00 ,  C10G3/45 ,  C10G3/46 ,  C10G3/48 ,  C10G3/50 ,  C10G2300/1014 ,  C10G2300/4006 ,  C10G2300/4012 ,  C10L1/02 ,  Y02E50/13 ,  Y02E50/14 ,  Y02E50/32 ,  Y02P30/20 ,  B01J2523/17 ,  B01J2523/842 ,  B01J2523/847 ,  B01J2523/824 ,  B01J2523/34 ,  B01J2523/32 ,  B01J2523/845 ,  B01J2523/33

摘要： The present invention relates to a process for the hydrotreatment of a vegetal biomass. Specifically, the present invention relates to a process for the hydrotreatment of a vegetal biomass comprising: a) subjecting said vegetal biomass to a hydrotreatment in a first reactor, said hydrotreatment comprises contacting said vegetal biomass in an aqueous medium and a metal oxide, a mixed metal oxide, or a metal-metalloid oxide catalyst comprising at least 35% by weight of metal oxide, mixed metal oxide, or metal-metalloid oxide relative to the total weight of the catalyst, with hydrogen at a pressure in the range of 10 to 400 bar and at a temperature in the range of 50° C. to 300° C. until a predetermined level of the hydrotreatment of said biomass is obtained and wherein the metal oxide, a mixed metal oxide, or a metal-metalloid oxide catalyst comprises nickel. Further, the present invention relates to a metal oxide, mixed metal oxide or metal-metalloid oxide catalyst. Furthermore, the present invention relates to the use of the catalyst.

摘要翻译： 本发明涉及植物生物质的加氢处理方法。 具体而言，本发明涉及植物生物质的加氢处理方法，包括：a）使所述植物生物质在第一反应器中进行加氢处理，所述加氢处理包括使所述植物生物质与水性介质和金属氧化物接触，混合 金属氧化物或金属 - 类金属氧化物催化剂，其包含相对于催化剂总重量为至少35重量％的金属氧化物，混合金属氧化物或金属 - 类金属氧化物，氢气的压力范围为10〜 400巴，并且在50℃至300℃的温度范围内，直到获得所述生物质的预定水平的加氢处理，并且其中所述金属氧化物，混合金属氧化物或金属 - 准金属氧化物催化剂包括 镍。 此外，本发明涉及金属氧化物，混合金属氧化物或金属 - 准金属氧化物催化剂。 此外，本发明涉及催化剂的用途。

公开(公告)号：US09199961B2

公开(公告)日：2015-12-01

申请号：US13699934

申请日：2011-03-23

申请人： Johannes Gerardus De Vries ,  Teddy ,  Pim Huat Phua ,  Ignacio Vladimiro Melián Cabrera ,  Hero Jan Heeres

发明人： Johannes Gerardus De Vries ,  Teddy ,  Pim Huat Phua ,  Ignacio Vladimiro Melián Cabrera ,  Hero Jan Heeres

IPC分类号： C07C29/132 ,  C07D201/08 ,  C07D313/04

CPC分类号： C07D313/04 ,  C07C29/132 ,  C07D201/08

摘要： The present invention relates to a method for preparing caprolactone, comprising converting 5-hydroxymethyl-2-furfuraldehyde by hydrogenation into at least one intermediate compound selected from the group of 2,5-tetrahydrofuran-dimethanol, 1,6-hexanediol and 1,2,6-hexanetriol, and preparing caprolactone from said intermediate compound.Further, the invention relates to a method for preparing 1,2,6-hexanetriol comprising preparing 5-hydroxymethyl-2-furfaldehyde from a renewable source, converting 5-hydroxymethyl-2-furfaldehyde into 2,5-tetrahydrofuran-dimethanol and converting 2,5-tetrahydrofuran-dimethanol into 1,2,6-hexanetriol.Further, the invention relates to a method for preparing 1,6-hexanediol from 1,2,6-hexanetriol, wherein 1,2,6-hexanetriol is subjected to a ring closure reaction, thereby forming (tetrahydro-2H-pyran-2-yl)methanol, and the (tetrahydro-2H-pyran-2-yl)methanol is hydrogenated, thereby forming 1,6-hexane diol.

摘要翻译： 本发明涉及一种制备己内酯的方法，包括通过氢化将5-羟甲基-2-糠醛转化为至少一种选自2,5-四氢呋喃 - 二甲醇，1,6-己二醇和1,2 ，6-己烷三醇，并由所述中间体化合物制备己内酯。 此外，本发明涉及一种制备1,2,6-己三醇的方法，包括从可再生来源制备5-羟甲基-2-糠醛，将5-羟甲基-2-糠醛转化为2,5-四氢呋喃 - 二甲醇并将2 ，5-四氢呋喃 - 二甲醇加入到1,2,6-己三醇中。 此外，本发明涉及从1,2,6-己三醇制备1,6-己二醇的方法，其中1,2,6-己三醇进行闭环反应，从而形成（四氢-2H-吡喃-2-基） - 基）甲醇，并将（四氢-2H-吡喃-2-基）甲醇氢化，从而形成1,6-己二醇。

公开(公告)号：US20130137863A1

公开(公告)日：2013-05-30

申请号：US13699934

申请日：2011-03-23

申请人： Johannes Gerardus De Vries ,  Teddy ,  Pim Huat Phua ,  Ignacio Vladimiro Melián Cabrera ,  Hero Jan Heeres

发明人： Johannes Gerardus De Vries ,  Teddy ,  Pim Huat Phua ,  Ignacio Vladimiro Melián Cabrera ,  Hero Jan Heeres

IPC分类号： C07D313/04 ,  C07C29/132 ,  C07D201/08

CPC分类号： C07D313/04 ,  C07C29/132 ,  C07D201/08

摘要： The present invention relates to a method for preparing caprolactone, comprising converting 5-hydroxymethyl-2-furfuraldehyde by hydrogenation into at least one intermediate compound selected from the group of 2,5-tetrahydrofuran-dimethanol, 1,6-hexanediol and 1,2,6-hexanetriol,and preparing caprolactone from said intermediate compound.Further, the invention relates to a method for preparing 1,2,6-hexanetriol comprising preparing 5-hydroxymethyl-2-furfaldehyde from a renewable source, converting 5-hydroxymethyl-2-furfaldehyde into 2,5-tetrahydrofuran-dimethanol and converting 2,5-tetrahydrofuran-dimethanol into 1,2,6-hexanetriol.Further, the invention relates to a method for preparing 1,6-hexanediol from 1,2,6-hexanetriol, wherein 1,2,6-hexanetriol is subjected to a ring closure reaction, thereby forming (tetrahydro-2H-pyran-2-yl)methanol, and the (tetrahydro-2H-pyran-2-yl)methanol is hydrogenated, thereby forming 1,6-hexane diol.

摘要翻译： 本发明涉及一种制备己内酯的方法，包括通过氢化将5-羟甲基-2-糠醛转化为至少一种选自2,5-四氢呋喃 - 二甲醇，1,6-己二醇和1,2 ，6-己烷三醇，并由所述中间体化合物制备己内酯。 此外，本发明涉及一种制备1,2,6-己三醇的方法，包括从可再生来源制备5-羟甲基-2-糠醛，将5-羟甲基-2-糠醛转化为2,5-四氢呋喃 - 二甲醇并将2 ，5-四氢呋喃 - 二甲醇加入到1,2,6-己三醇中。 此外，本发明涉及从1,2,6-己三醇制备1,6-己二醇的方法，其中1,2,6-己三醇进行闭环反应，从而形成（四氢-2H-吡喃-2-基） - 基）甲醇，并将（四氢-2H-吡喃-2-基）甲醇氢化，从而形成1,6-己二醇。

公开(公告)号：US08026245B2

公开(公告)日：2011-09-27

申请号：US10573364

申请日：2004-09-21

申请人： Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts, legal representative ,  Paulus Joannes Lewi ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Hendrik Maarten Vinkers ,  Ruben Gerardus George Leenders ,  Dirk Alfons Leo Vandenput

发明人： Paul Adriaan Jan Janssen ,  Paulus Joannes Lewi ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Hendrik Maarten Vinkers ,  Ruben Gerardus George Leenders ,  Dirk Alfons Leo Vandenput

IPC分类号： C07D473/16 ,  C07D473/18 ,  A61K31/52 ,  A61K31/522 ,  A61P31/18 ,  C07D473/40

CPC分类号： A61K31/52 ,  C07D473/00 ,  C07D473/16 ,  C07D473/18

摘要： The present invention relates to the use of a compound of formula (I) for the manufacture of a medicament for the prevention or the treatment of HIV infection wherein the compound of formula (I) is a compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein A and B each represents a radical of formula and wherein —C-D- represents a bivalent radical of formula —N═CH—NR17—  (c-1); or —NR17—CH═N—  (c-2); provided that when A represents a radical of formula (a) then B represents a radical of formula (b) and when A represents a radical of formula (b) then B represents a radical of formula (a).

摘要翻译： 本发明涉及式（I）化合物在制备用于预防或治疗HIV感染的药物中的用途，其中式（I）化合物为式I化合物，N-氧化物，药学上 其中A和B各自表示式的基团，其中-CD-表示式-N = CH-NR 17 - （c-1）的二价基团; 或-NR17-CH = N-（c-2）; 条件是当A表示式（a）的基团时，B表示式（b）的基团，并且当A表示式（b）的基团时，B表示式（a）的基团。

公开(公告)号：US20100034810A1

公开(公告)日：2010-02-11

申请号：US12567051

申请日：2009-09-25

申请人： Jan HEERES ,  Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts ,  Marc Rene de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desire Daeyaert ,  Hendrik Maarten Vinkers ,  Jerome Emile Georges Gullemont ,  Elisabeth Theresa Jeanne Pasquier

发明人： Jan HEERES ,  Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts ,  Marc Rene de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desire Daeyaert ,  Hendrik Maarten Vinkers ,  Jerome Emile Georges Gullemont ,  Elisabeth Theresa Jeanne Pasquier

IPC分类号： A61K31/506 ,  A61K39/395 ,  A61K38/00 ,  A61K31/551 ,  A61K31/5377 ,  A61K31/505 ,  A61P31/18

CPC分类号： A61K31/513 ,  C07D239/47 ,  C07D239/48 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

摘要： This invention concerns the use of a compound for the manufacture of a medicament for the prevention of HIV infection via sexual intercourse and related intimate contact between partners, wherein the compound is a compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein the ring containing -a1=a2-a3=a4- and -b1=b2-b3=b4- represents phenyl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl; n is 0 to 5; m is 1 to 4; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; C1-6alkyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyloxy; substituted C1-6alkyloxyC1-6alkylcarbonyl; R2 is hydroxy, halo, optionally substituted C1-6alkyl, C3-7cycloalkyl, optionally substituted C2-6alkenyl, optionally substituted C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6, —C(═NH)R6 or a 5-membered heterocycle; X1 is —NR5—, —NH—NH—, —N═N—, —O—, —C(═O)—, C1-4alkanediyl, —CHOH—, —S—, —S(═O)p—, —X2—C1-4alkanediyl- or —C1-4alkanediyl-X2—; R3 is NHR13; NR13R14; —C(═O)—NHR13; —C(═O)—NR13R14; —C(═O)—R15; —CH═N—NH—C(═O)—R16; substituted C1-6alkyl; optionally substituted C1-6alkyloxyC1-6alkyl; substituted C2-6alkenyl; substituted C2-6alkynyl; C1-6alkyl substituted with hydroxy and a second substituent; —C(═N—O—R8)—C1-4alkyl; R7; or —X3—R7; R4 is halo, hydroxy, C1-6alkyl, C3-7cycloalkyl, C1-6alkyloxy, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyl, formyl, amino, mono- or di(C1-4alkyl)amino; and pharmaceutical compositions comprising them.

公开(公告)号：US07563922B2

公开(公告)日：2009-07-21

申请号：US11738688

申请日：2007-04-23

申请人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jérôme Emile Georges Guillemont

发明人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jérôme Emile Georges Guillemont

IPC分类号： C07C255/42 ,  C07C253/30 ,  C07C253/20 ,  C07D239/48 ,  A61K31/505 ,  A61P31/18

CPC分类号： C07D239/48 ,  C07C253/20 ,  C07C253/30 ,  C07C255/42

摘要： Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]amino]benzonitrile of formula (I), a N-oxide, a pharmaceutically acceptable acid addition salt, a quaternary amine or a stereochemically isomeric form thereof are provided, said processes comprise: a) reacting 4-(2-cyanoethenyl)-2,6-dimethylbenzenamine with an intermediate of formula (III)  in the presence of a suitable solvent; b) reacting an intermediate of formula (IV)  with acrylonitrile in the presence of a suitable palladium catalyst, a suitable base and a suitable solvent; c) dehydrating the corresponding amide of the compound of formula (I).

摘要翻译： 用于制备式（I）的4 - [[4 - [[4-（2-氰基乙烯基）-2,6-二甲基苯基] - 氨基] -2-嘧啶基]氨基]苄腈的方法，N-氧化物， 提供药学上可接受的酸加成盐，季胺或其立体化学异构形式，所述方法包括：a）使4-（2-氰基乙烯基）-2,6-二甲基苯胺与式（III）的中间体在 合适的溶剂; b）在合适的钯催化剂，合适的碱和合适的溶剂的存在下使式（Ⅳ）的中间体与丙烯腈反应; c）使相应的式（I）化合物的酰胺脱水。

公开(公告)号：US07531548B2

公开(公告)日：2009-05-12

申请号：US11576068

申请日：2005-09-29

申请人： Jerôme Emile Georges Guillemont ,  Jan Heeres ,  Paulus Joannes Lewi

发明人： Jerôme Emile Georges Guillemont ,  Jan Heeres ,  Paulus Joannes Lewi

IPC分类号： C07D239/48 ,  C07D239/50 ,  C07D239/34 ,  C07D239/38 ,  C07D239/42 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  A61K31/505 ,  A61P31/18

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 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)rR6; C(═NH)R6; R2a is CN; amino; substituted amino; optionally substituted C1-6alkyl; halo; optionally substituted C2-6alkyloxy; 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, pharmaceutical compositions comprising these compounds as active ingredient and the use of these compounds for the prevention or the treatment of HIV infection.

摘要翻译： 式（I）的HIV复制抑制剂N-氧化物，药学上可接受的加成盐，季胺或其立体异构形式，其中-a1 = a2-a3 = a4-是-CH-CH-CH-CH-，-N -CH-CH-CH-，-N-CH-N-CH-，-N-CH-CH-N - ，-NN-CH-CH-; -b1 = b2-b3 = b4-是-CH-CH-CH-CH-，-N-CH-CH-CH-，-N-CH-N-CH-，-N-CH-CH-N-， -NN-CH-CH-; R1是氢; 芳基; 甲酰基 C 1-6烷基羰基; 任选取代的C 1-6烷基; C 1-6烷氧基羰基; R2是OH; 光环; 任选取代的C 1-6烷基，C 2-6烯基或C 2-6炔基; 取代的羰基; 羧基; CN; 硝基 氨基; 取代氨基; 多卤甲基 多卤甲硫基 -S（-O）r R 6; C（-NH）R 6; R2a为CN; 氨基; 取代氨基; 任选取代的C 1-6烷基; 光环; 任选取代的C 2-6烷氧基; 取代的羰基; -CH-N-NH-C（-O）-R16; 任选取代的C 1-6烷氧基C 1-6烷基; 取代的C 2-6烯基或C 2-6炔基; -C（-N-O-R 8）-C 1-4烷基; R7或-X3-R7; X 1是-NR 1 - ， - O - ， - C（-O） - ，CH 2，-CHOH - ， - S - ， - S（-O） R3为CN; 氨基; C 1-6烷基; 光环; 任选取代的C 1-6烷氧基; 取代的羰基; -CH-N-NH-C（-O）-R16; 取代的C 1-6烷基; 任选取代的C 1-6烷氧基C 1-6烷基; 取代的C 2-6烯基或C 2-6炔基; -C（-N-O-R 8）-C 1-4烷基; R7; -X3-R7; R4是卤素; 哦; 任选取代的C 1-6烷基，C 2-6烯基或C 2-6炔基; C 3-7环烷基; C 1-6烷氧基; CN; 硝基 多卤代C1-6烷基; 多卤C 1-6烷氧基; 取代的羰基; 甲酰基 氨基; 单或二（C 1-4烷基）氨基或R 7; R5是-Y-CqH2q-L或-CqH2q-Y-CrH2r-L; L是芳基或Het; 制备这些化合物的方法，包含这些化合物作为活性成分的药物组合物以及这些化合物用于预防或治疗HIV感染的用途。

公开(公告)号：US07514445B2

公开(公告)日：2009-04-07

申请号：US10493452

申请日：2002-10-29

申请人： Eddy Jean Edgard Freyne ,  Peter Jacobus Johannes Antonius Buijnsters ,  Marc Willems ,  Werner Constant Johan Embrechts ,  Christopher John Love ,  Paul Adriaan Jan Janssen ,  Paulus Joannes Lewi ,  Jan Heeres ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Koen Jeanne Alfons Van Aken ,  Gaston Stanislas Marcella Diels

发明人： Eddy Jean Edgard Freyne ,  Peter Jacobus Johannes Antonius Buijnsters ,  Marc Willems ,  Werner Constant Johan Embrechts ,  Christopher John Love ,  Paul Adriaan Jan Janssen ,  Paulus Joannes Lewi ,  Jan Heeres ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Koen Jeanne Alfons Van Aken ,  Gaston Stanislas Marcella Diels

IPC分类号： A61K31/506 ,  A61P3/10 ,  A61P25/28 ,  A61P25/02 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14

CPC分类号： C07D213/74 ,  C07D239/42 ,  C07D239/48 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12

摘要： This invention concerns a compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein ring A is a 6-membered heterocycle; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; optionally substituted C1-6alkyl; C1-6alkyloxycarbonyl; optionally substituted C1-6alkyloxyC1-6alkylcarbonyl; X is a direct bond or a linker atom or group; Z is a direct bond or a linker atom or group; R2 is hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, a carbocycle or a heterocycle, each of said groups may optionally be substituted; R3 is hydrogen; hydroxy; halo; optionally substituted C1-6alkyl or C2-6alkenyl or C2-6alkynyl; C1-6alkyloxy; C1-6alkylthio; C1-6alkyloxycarbonyl; C1-6alkylcarbonyloxy; carboxyl; cyano; nitro; amino; mono- or di(C1-6alkyl)amino; polyhaloC1-6alkyl; polyhaloC1-6alkyloxy; polyhaloC1-6alkylthio; R21; R21—C1-6alkyl; R21—O—; R21—S—; R21—C(═O)—; R21—S(═O)p—; R7—S(═O)p—; R7—S(═O)p—NH—; R21—S(═O)p—NH—; R7—C(═O)—; —NHC(═O)H; —C(═O)NHNH2; R7—C(═O)—NH—; R21—C(═O)—NH—; —C(═NH)R7—C(═NH)R21; R4 is an optionally substituted heterocycle provided that —X—R2 and/or R3 is other than hydrogen; their use, pharmaceutical compositions comprising them and processes for their preparation.

摘要翻译： 本发明涉及式的化合物N-氧化物，药学上可接受的加成盐，季胺及其立体化学异构形式，其中环A是6-元杂环; R1是氢; 芳基; 甲酰基 C 1-6烷基羰基; 任选取代的C 1-6烷基; C 1-6烷氧基羰基; 任选取代的C 1-6烷氧基C 1-6烷基羰基; X是直接键或连接原子或基团; Z是直接键或连接原子或基团; R 2是氢，C 1-10烷基，C 2-10烯基，C 2-10炔基，碳环或杂环，所述基团中的每一个可任选被取代; R3是氢; 羟基; 光环; 任选取代的C 1-6烷基或C 2-6烯基或C 2-6炔基; C 1-6烷氧基; C 1-6烷硫基; C 1-6烷氧基羰基; C 1-6烷基羰基氧基; 羧基; 氰基; 硝基 氨基; 单或二（C 1-6烷基）氨基; 多卤代C 1-6烷基; 多卤代C 1-6烷氧基; 多卤代C 1-6烷硫基; R21; R21-C1-6烷基; R21-O-; R21-S-; R21-C（-O） - ; R21-S（-O）p-; R7-S（-O）p-; R7-S（-O）p-NH-; R21-S（-O）p-NH-; R7-C（-O） - ; -NHC（-O）H; -C（-O）NHNH 2; R7-C（-O）-NH-; R 21 -C（-O）-NH-; -C（ - NH）R 7 -C（-NH）R 21; R4是任选取代的杂环，条件是-X-R 2和/或R 3不是氢; 其用途，包含它们的药物组合物及其制备方法。

公开(公告)号：US07399856B2

公开(公告)日：2008-07-15

申请号：US10523753

申请日：2003-08-07

申请人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jérôme Emile Georges Guillemont

发明人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jérôme Emile Georges Guillemont

IPC分类号： C07D239/48 ,  C07C255/42 ,  C07C253/30 ,  C07C253/20 ,  A61K31/505 ,  A61P31/18

CPC分类号： C07D239/48 ,  C07C253/20 ,  C07C253/30 ,  C07C255/42

摘要： Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]amino]benzonitrile of formula (I), a N-oxide, a pharmaceutically acceptable acid addition salt, a quaternary amine or a stereochemically isomeric form thereof are provided, said processes comprise: a) reacting 4-(2-cyanoethenyl)-2,6-dimethylbenzenamine with an intermediate of formula (III)  in the presence of a suitable solvent; b) reacting an intermediate of formula (IV)  with acrylonitrile in the presence of a suitable palladium catalyst, a suitable base and a suitable solvent; c) dehydrating the corresponding amide of the compound of formula (I).

摘要翻译： 用于制备式（I）的4 - [[4 - [[4-（2-氰基乙烯基）-2,6-二甲基苯基] - 氨基] -2-嘧啶基]氨基]苄腈的方法，N-氧化物， 提供药学上可接受的酸加成盐，季胺或其立体化学异构形式，所述方法包括：a）使4-（2-氰基乙烯基）-2,6-二甲基苯胺与式（III）的中间体在 合适的溶剂; b）在合适的钯催化剂，合适的碱和合适的溶剂的存在下使式（Ⅳ）的中间体与丙烯腈反应; c）使相应的式（I）化合物的酰胺脱水。

公开(公告)号：US20080085907A1

公开(公告)日：2008-04-10

申请号：US11718181

申请日：2005-10-27

申请人： Jerome Guillemont ,  Mikael Paugam ,  Bruno Delest ,  Jan Heeres ,  Paulus Lewi ,  Paul Adriaan Janssen ,  Frank Javier Arts

发明人： Jerome Guillemont ,  Mikael Paugam ,  Bruno Delest ,  Jan Heeres ,  Paulus Lewi ,  Paul Adriaan Janssen ,  Frank Javier Arts

IPC分类号： C07D473/36 ,  A61K31/519 ,  A61K31/52 ,  A61P31/18 ,  C07D487/04 ,  C07D239/70 ,  C07D473/32

CPC分类号： C07D487/04 ,  C07D473/00 ,  C07D473/16 ,  C07D473/24 ,  C07D473/34

摘要： HIV replication inhibitors of formula (1) 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—; n and m is 0, 1, 2, 3 and in certain cases also 4; 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 C2-6alkynyl; —C(═N—O—R8)—C1-4 alkyl; R7 or —X—R4; 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)—C1-4 alkyl; R7; —X—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; -A-B— is —CR5═N—, —N═N—, —CH2—CH2—, —CS—NH—, —CO—NH—, —CH═CH—; pharmaceutical compositions comprising these; methods for the preparation of these compounds and compositions; the use of these compounds for the prevention or the treatment of HIV infection.