公开(公告)号：US08193353B2

公开(公告)日：2012-06-05

申请号：US13169350

申请日：2011-06-27

申请人： Antonio Giordani ,  Stefano Mandelli ,  Ilario Verpilio ,  Simona Zanzola ,  Francesca Tarchino ,  Gianfranco Caselli ,  Tiziana Piepoli ,  Silvio Mazzari ,  Francesco Makovec ,  Lucio Claudio Rovati

发明人： Antonio Giordani ,  Stefano Mandelli ,  Ilario Verpilio ,  Simona Zanzola ,  Francesca Tarchino ,  Gianfranco Caselli ,  Tiziana Piepoli ,  Silvio Mazzari ,  Francesco Makovec ,  Lucio Claudio Rovati

IPC分类号： C07D239/72

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

摘要： The present invention is directed to novel 6-1H-imidazo-2-aryl and 2-heteroaryl quinazoline and quinoline of formula I, corresponding salts and solvates thereof, to a process for their preparation and to the use of this compounds and corresponding pharmaceutical composition for the treatment of pain and inflammatory related disorders. Compounds of the invention have been proven highly effective in the pharmacological treatment of both inflammatory and neuropathic pain, in addition to striking anti-inflammatory properties. Their effectiveness in interfering with COX-2 and inflammatory cytokines expressions and production, highlights them as interesting compounds also for the treatment of cancer in addition to several inflammatory diseases.

摘要翻译： 本发明涉及式I的新颖的6-1H-咪唑-2-芳基和2-杂芳基喹唑啉和喹啉，其相应的盐和溶剂合物，其制备方法和该化合物及相应的药物组合物的用途 用于治疗疼痛和炎症相关疾病。 除了具有显着的抗炎特性之外，本发明的化合物已经被证明在炎性和神经性疼痛的药理学治疗中都是非常有效的。 它们在干扰COX-2和炎性细胞因子表达和产生方面的有效性，也将它们作为有趣的化合物，也用于治疗癌症以及多种炎性疾病。

公开(公告)号：US20090264451A1

公开(公告)日：2009-10-22

申请号：US12376080

申请日：2006-08-03

申请人： Antonio Giordani ,  Stefano Mandelli ,  Ilario Verpilio ,  Simona Zanzola ,  Francesca Tarchino ,  Gianfranco Caselli ,  Tiziana Piepoli ,  Silvio Mazzari ,  Francesco Makovec ,  Lucio Claudio Rovati

发明人： Antonio Giordani ,  Stefano Mandelli ,  Ilario Verpilio ,  Simona Zanzola ,  Francesca Tarchino ,  Gianfranco Caselli ,  Tiziana Piepoli ,  Silvio Mazzari ,  Francesco Makovec ,  Lucio Claudio Rovati

IPC分类号： A61K31/517 ,  C07D403/10 ,  C07D401/10 ,  C07D405/14 ,  C07D413/14 ,  C07D409/14 ,  A61K31/4709 ,  A61P29/00 ,  A61P25/00

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

摘要： The present invention is directed to novel 6-1H-imidazo-2-aryl and 2-heteroaryl quinazoline and quinoline of formula I, corresponding salts and solvates thereof, to a process for their preparation and to the use of this compounds and corresponding pharmaceutical composition for the treatment of pain and inflammatory related disorders. Compounds of the invention have been proven highly effective in the pharmacological treatment of both inflammatory and neuropathic pain, in addition to striking anti-inflammatory properties. Their effectiveness in interfering with COX-2 and inflammatory cytokines expressions and production, highlights them as interesting compounds also for the treatment of cancer in addition to several inflammatory diseases.Formula I:

摘要翻译： 本发明涉及式I的新颖的6-1H-咪唑-2-芳基和2-杂芳基喹唑啉和喹啉，其相应的盐和溶剂合物，其制备方法和该化合物及相应的药物组合物的用途 用于治疗疼痛和炎症相关疾病。 除了具有显着的抗炎特性之外，本发明的化合物已经被证明在炎性和神经性疼痛的药理学治疗中都是非常有效的。 它们在干扰COX-2和炎性细胞因子表达和产生方面的有效性，也将它们作为有趣的化合物，也用于治疗癌症以及多种炎性疾病。 公式I：

公开(公告)号：US20050197331A1

公开(公告)日：2005-09-08

申请号：US11068347

申请日：2005-03-01

申请人： Francesco Makovec ,  Antonio Giordani ,  Roberto Artusi ,  Stefano Mandelli ,  Ilario Verpilio ,  Simona Zanzola ,  Lucio Rovati

发明人： Francesco Makovec ,  Antonio Giordani ,  Roberto Artusi ,  Stefano Mandelli ,  Ilario Verpilio ,  Simona Zanzola ,  Lucio Rovati

IPC分类号： A61K31/343 ,  A61K31/4045 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/428 ,  A61K31/4439 ,  A61K31/47 ,  A61K31/517 ,  A61P1/04 ,  A61P19/02 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00 ,  C07D209/08 ,  C07D215/38 ,  C07D217/02 ,  C07D235/08 ,  C07D235/10 ,  C07D235/12 ,  C07D235/18 ,  C07D237/28 ,  C07D239/74 ,  C07D263/56 ,  C07D263/57 ,  C07D277/64 ,  C07D277/66 ,  C07D307/79 ,  C07D333/54 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D417/04 ,  C07D498/02

CPC分类号： C07D215/06 ,  C07D209/08 ,  C07D217/04 ,  C07D235/08 ,  C07D235/18 ,  C07D239/74 ,  C07D263/57 ,  C07D277/64 ,  C07D277/66 ,  C07D307/79 ,  C07D333/54 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D417/04

摘要： Heterocyclic amidines with anti-inflammatory and analgesic activity that inhibit nitrogen oxide production, of formula (I): in which: G1 and G2 are hydrogen, halogen, hydroxyl, C1-C4 alkoxy, C1-C4 alkyl, and an amidino substituent of formula Q, provided that, for each compound of formula (I), only one of the two substituents G1 or G2 is an amidino substituent of formula Q: and in which the substituents W, Y and X are combined to form 9- or 10-membered bicyclic heteroaromatic derivatives containing up to 2 hetero atoms in the same ring; and Z is an aryl or heteroaryl group, a linear or branched C1-C6 alkyl or alkenyl chain, a C1-C4 alkyl-aryl group or a C1-C4 alkyl-heteroaryl group.

摘要翻译： 具有抑制氮氧化物生成的抗炎和止痛活性的式（I）的杂环脒：其中：G 1和G 2是氢，卤素，羟基， C 1 -C 4烷氧基，C 1 -C 4烷基和式Q的脒基取代基， 条件是对于式（I）的每种化合物，两个取代基G 1或G 2中只有一个是式Q的脒基取代基，并且其中取代基 W，Y和X组合形成在相同环中含有至多2个杂原子的9元或10元双环杂芳族衍生物; Z是芳基或杂芳基，直链或支链C 1 -C 6烷基或烯基链，C 1 -C 3烷基或链烯基， 烷基 - 芳基或C 1 -C 4烷基 - 杂芳基。

公开(公告)号：US20110257209A1

公开(公告)日：2011-10-20

申请号：US13169350

申请日：2011-06-27

申请人： Antonio GIORDANI ,  Stefano MANDELLI ,  Ilario VERPILIO ,  Simona ZANZOLA ,  Francesca TARCHINO ,  Gianfranco CASELLI ,  Tiziana Piepoli ,  Silvio MAZZARI ,  Francesco MAKOVEC ,  Lucio Claudio ROVATI

发明人： Antonio GIORDANI ,  Stefano MANDELLI ,  Ilario VERPILIO ,  Simona ZANZOLA ,  Francesca TARCHINO ,  Gianfranco CASELLI ,  Tiziana Piepoli ,  Silvio MAZZARI ,  Francesco MAKOVEC ,  Lucio Claudio ROVATI

IPC分类号： A61K31/517 ,  A61P25/00 ,  A61K31/4709

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

摘要： The present invention is directed to novel 6-1H-imidazo-2-aryl and 2-heteroaryl quinazoline and quinoline of formula I, corresponding salts and solvates thereof, to a process for their preparation and to the use of this compounds and corresponding pharmaceutical composition for the treatment of pain and inflammatory related disorders. Compounds of the invention have been proven highly effective in the pharmacological treatment of both inflammatory and neuropathic pain, in addition to striking anti-inflammatory properties. Their effectiveness in interfering with COX-2 and inflammatory cytokines expressions and production, highlights them as interesting compounds also for the treatment of cancer in addition to several inflammatory diseases.

摘要翻译： 本发明涉及式I的新颖的6-1H-咪唑-2-芳基和2-杂芳基喹唑啉和喹啉，其相应的盐和溶剂合物，其制备方法和该化合物及相应的药物组合物的用途 用于治疗疼痛和炎症相关疾病。 除了具有显着的抗炎特性之外，本发明的化合物已经被证明在炎性和神经性疼痛的药理学治疗中都是非常有效的。 它们在干扰COX-2和炎性细胞因子表达和产生方面的有效性，也将它们作为有趣的化合物，也用于治疗癌症以及多种炎性疾病。

公开(公告)号：US07994181B2

公开(公告)日：2011-08-09

申请号：US12376080

申请日：2006-08-03

申请人： Antonio Giordani ,  Stefano Mandelli ,  Ilario Verpilio ,  Simona Zanzola ,  Francesca Tarchino ,  Gianfranco Caselli ,  Tiziana Piepoli ,  Silvio Mazzari ,  Francesco Makovec ,  Lucio Claudio Rovati

发明人： Antonio Giordani ,  Stefano Mandelli ,  Ilario Verpilio ,  Simona Zanzola ,  Francesca Tarchino ,  Gianfranco Caselli ,  Tiziana Piepoli ,  Silvio Mazzari ,  Francesco Makovec ,  Lucio Claudio Rovati

IPC分类号： A61K31/517

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

摘要： The present invention is directed to novel 6-1H-imidazo-2-aryl and 2-heteroaryl quinazoline and quinoline of formula I, corresponding salts and solvates thereof, to a process for their preparation and to the use of this compounds and corresponding pharmaceutical composition for the treatment of pain and inflammatory related disorders. Compounds of the invention have been proven highly effective in the pharmacological treatment of both inflammatory and neuropathic pain, in addition to striking anti-inflammatory properties. Their effectiveness in interfering with COX-2 and inflammatory cytokines expressions and production, highlights them as interesting compounds also for the treatment of cancer in addition to several inflammatory diseases.Formula I:

摘要翻译： 本发明涉及式I的新颖的6-1H-咪唑-2-芳基和2-杂芳基喹唑啉和喹啉，其相应的盐和溶剂合物，其制备方法和该化合物及相应的药物组合物的用途 用于治疗疼痛和炎症相关疾病。 除了具有显着的抗炎特性之外，本发明的化合物已经被证明在炎性和神经性疼痛的药理学治疗中都是非常有效的。 它们在干扰COX-2和炎性细胞因子表达和产生方面的有效性，也将它们作为有趣的化合物，也用于治疗癌症以及多种炎性疾病。 公式I：

公开(公告)号：US20110003861A1

公开(公告)日：2011-01-06

申请号：US12919141

申请日：2008-03-06

申请人： Antonio Giordani ,  Ilario Verpilio ,  Sabrina Pucci ,  Roberto Artusi ,  Gianfranco Caselli ,  Marco Lanza ,  Laura Mennuni ,  Francesco Makovec ,  Lucio Claudio Rovati

发明人： Antonio Giordani ,  Ilario Verpilio ,  Sabrina Pucci ,  Roberto Artusi ,  Gianfranco Caselli ,  Marco Lanza ,  Laura Mennuni ,  Francesco Makovec ,  Lucio Claudio Rovati

IPC分类号： A61K31/352 ,  C07D311/54 ,  C07D407/10 ,  A61K31/36 ,  C07D405/10 ,  A61K31/4178 ,  C07D311/56 ,  C07D405/04 ,  A61K31/4433 ,  A61P29/00 ,  A61P35/00 ,  A61P19/02

CPC分类号： C07D311/30 ,  C07D401/04 ,  C07D405/10 ,  C07D407/04

摘要： 2-aryl and 2-heteroaryl 4h-1-benzopyran-4-one-6-amidino derivatives of formula (I) useful as pharmacological agents for the treatment of arthritis, cancer and related pain.

摘要翻译： 式（I）的2-芳基和2-杂芳基4h-1-苯并吡喃-4-酮-6-脒基衍生物可用作治疗关节炎，癌症和相关疼痛的药物。

公开(公告)号：US07674809B2

公开(公告)日：2010-03-09

申请号：US11068347

申请日：2005-03-01

申请人： Francesco Makovec ,  Antonio Giordani ,  Roberto Artusi ,  Stefano Mandelli ,  Ilario Verpilio ,  Simona Zanzola ,  Lucio Claudio Rovati

发明人： Francesco Makovec ,  Antonio Giordani ,  Roberto Artusi ,  Stefano Mandelli ,  Ilario Verpilio ,  Simona Zanzola ,  Lucio Claudio Rovati

IPC分类号： A61K31/425 ,  A61P29/02 ,  C07D277/64 ,  C07D277/66 ,  C07D285/14 ,  A61K31/517 ,  C07D239/94

CPC分类号： C07D215/06 ,  C07D209/08 ,  C07D217/04 ,  C07D235/08 ,  C07D235/18 ,  C07D239/74 ,  C07D263/57 ,  C07D277/64 ,  C07D277/66 ,  C07D307/79 ,  C07D333/54 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D417/04

摘要： Heterocyclic amidines with anti-inflammatory and analgesic activity that inhibit nitrogen oxide production, of formula (I): in which: G1 and G2 are hydrogen, halogen, hydroxyl, C1-C4 alkoxy, C1-C4 alkyl, and an amidino substituent of formula Q, provided that, for each compound of formula (I), only one of the two substituents G1 or G2 is an amidino substituent of formula Q: and in which the substituents W, Y and X are combined to form 9- or 10-membered bicyclic heteroaromatic derivatives containing up to 2 hetero atoms in the same ring; and Z is an aryl or heteroaryl group, a linear or branched C1-C6 alkyl or alkenyl chain, a C1-C4 alkyl-aryl group or a C1-C4 alkyl-heteroaryl group.

摘要翻译： 其中：G1和G2是氢，卤素，羟基，C1-C4烷氧基，C1-C4烷基和式（Ⅳ）的脒基取代基，其具有抑制氮氧化物生成的抗炎和止痛活性的杂环脒; Q，条件是对于每种式（I）化合物，两个取代基G1或G2中只有一个是式Q的脒基取代基，其中取代基W，Y和X被结合形成9-或10- 在同一环中含有至多2个杂原子的二元双环杂芳族衍生物; Z是芳基或杂芳基，直链或支链C 1 -C 6烷基或烯基链，C 1 -C 4烷基 - 芳基或C 1 -C 4烷基 - 杂芳基。