公开(公告)号：EP2822945A1

公开(公告)日：2015-01-14

申请号：EP13707635.2

申请日：2013-03-05

Applicant: Compound Handling B.V. ,  Stichting Katholieke Universiteit

Inventor： HOOIJ, VAN, Onno ,  SCHALKEN, Jacobus Antonius ,  VIËTOR, Hendrik Engelbertus ,  PIET, Dennis Patrick ,  MAAS, Petrus Emmanuel Marie ,  TIJHUIS, Johann Heinrich ,  DEERENBERG, Sirik ,  SPRENKELS, Nanda Elisabeth ,  TANG, Siu Ha

IPC: C07D417/04 ,  C07D417/14 ,  A61K31/4184 ,  A61K31/428 ,  A61K31/4439 ,  A61K31/4436 ,  A61P35/00

CPC classification number: C07D403/04 ,  A61K31/4155 ,  A61K31/4184 ,  A61K31/428 ,  A61K31/454 ,  A61K45/06 ,  C07D417/04 ,  C07D417/14 ,  H05K999/99

Abstract: A compound having the structure according to formula III wherein: X is NH or S; R1 is H or (1C-4C)alkyl; R2 is (1C-4C)alkyl, phenyl or a monocyclic aromatic ring having one or more N-, O- or S-atoms in the ring, which alkyl, phenyl or aromatic ring is optionally substituted with one or more groups selected from (1C-4C)alkyl, (1C-4C)alkyloxy, halo(1C-4C)alkyl, halo(1C-4C)alkyloxy, phenyloxy, phenylthio, halogen, or nitro; R3 and R4 are each independently H, (1C-6C)alkyl, (2C-6C) alkenyl, (2C-6C)alkynyl, cyano, (3C-6C)cycloalkyl, phenyl, a monocyclic aromatic ring having one or more N-, O- or S-atoms in the ring, a monocyclic non-aromatic ring having one or more N-, O- or S-atoms in the ring, each optionally substituted with hydroxyl, (1C-4C)alkoxy, phenyl, cycloalkyl, piperidyl, piperazinyl, furyl, thienyl, pirazinyl, pyrrolyl, 2H-pyrrolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyrrolidonyl, pyrrolinyl, imidazolinyl, imidazolyl, a monocyclic aromatic ring having one or more N-, O- or S-atoms in the ring, whereby each of these optional substituents is optionally further substituted with (1C-4C)alkyl, (1C-4C)alkyloxy, halo(1C-4C)alkyl, halo(1C-4C)alkyloxy, halogen, nitro or (1C-2C)dioxol forming a ring; or R3 and R4 form together pyrrolyl, imidazolyl, pyrazolyl, pyrrolidinyl, pyrrolinylimidazolidinyl, imidazolinyl, piperidyl, piperazinylmorpholinyl, each optionally substituted with (1C-6C)alkyl, phenyl(1C-4C)alkyl, phenylketo(1C-4C)alkyl; R5 is H, Cl, F, Br, Me, NO2, t-butyl, OCF3, OCH3, CF3; R6 is H, (1C-4C)alkyl, (1C-4C)alkyloxy, halo(1C-4C)alkyl, halo(1C-4C)alkyloxy, nitro or halogen; R7 is H, F, Cl, Br, Me, NO2, t-butyl, OCF3, OCH3, CF3; or pharmaceutically acceptable addition salts thereof for use in treatments of carcinoma, in particular to delay, prevent or reverse metastasis in prostate cancer.

Abstract translation: 具有式III结构的化合物，其中：X是NH或S; R1是H或（1C-4C）烷基; R2是（1C-4C）烷基，苯基或在环中具有一个或多个N，O-或S-原子的单环芳环，该烷基，苯基或芳环任选被一个或多个选自（ 1C-4C）烷基，（1C-4C）烷氧基，卤代（1C-4C）烷基，卤代（1C-4C）烷氧基，苯氧基，苯硫基，卤素或硝基; R3和R4各自独立地为H，（1C-6C）烷基，（2C-6C）烯基，（2C-6C）炔基，氰基，（3C-6C）环烷基，苯基，具有一个或多个N- ，环中的O-或S-原子，在环中具有一个或多个N，O-或S-原子的单环非芳族环，各自任选被羟基取代，（1C-4C）烷氧基，苯基，环烷基 哌啶基，呋喃基，噻吩基，吡嗪基，吡咯基，吡咯基，异恶唑基，异噻唑基，吡咯烷酮基，吡咯烷基，咪唑啉基，咪唑基，具有一个或多个N，O-或S-原子的单环芳环 （1C-4C）烷基，卤代（1C-4C）烷基，卤代（1C-4C）烷氧基，卤素，硝基或（1C- 2C）二氧杂环戊烯形成环; 或者R 3和R 4一起形成吡咯基，咪唑基，吡唑基，吡咯烷基，吡咯烷基咪唑烷基，咪唑啉基，哌啶基，哌嗪基吗啉基，各自任选被（1C-6C）烷基取代，苯基（1C-4C）烷基，苯基酮（1C-4C） R5是H，Cl，F，Br，Me，NO2，叔丁基，OCF3，OCH3，CF3; R6为H，（1C-4C）烷基，（1C-4C）烷氧基，卤代（1C-4C）烷基，卤代（1C-4C）烷氧基，硝基或卤素; R 7是H，F，Cl，Br，Me，NO 2，叔丁基，OCF 3，OCH 3，CF 3; 或其药学上可接受的加成盐，用于治疗癌症，特别是延迟，预防或逆转前列腺癌转移。

公开(公告)号：EP2636673A1

公开(公告)日：2013-09-11

申请号：EP12158253.0

申请日：2012-03-06

Applicant: Compound Handling B.V.

Inventor： Van Hooij, Onno ,  Schalken, Jacobus Antonius ,  Viëtor, Hendrik Engelbertus ,  Piet, Dennis Patrick ,  Maas , Petrus Emmanuel Marie ,  Tijhuis, Johann Heinrich ,  Deerenberg, Sirik ,  Sprenkels, Nanda Elisabeth ,  Tang, Siu Ha

IPC: C07D403/04 ,  C07D403/14 ,  C07D417/04 ,  C07D417/14 ,  A61K31/4184 ,  A61K31/428 ,  A61K31/4439 ,  A61K31/4436 ,  A61P35/00

CPC classification number: C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D417/04

Abstract: The invention provides for a compound having the structure according to formula I

wherein:
X is NH or S; R 1 is H or (1C-4C)alkyl; R 2 is (1C-4C)alkyl, phenyl or a monocyclic aromatic ring having one or more N-, O- or S- atoms in the ring, which alkyl, phenyl or aromatic ring is optionally substituted with one or more groups selected from (1C-4C)alkyl, (1C-4C)alkyloxy, halo(1C-4C)alkyl, halo(1C-4C)alkyloxy, phenyloxy , phenylthio, halogen, or nitro; R 3 and R 4 are each independently H, (1C-6C)alkyl, (2C-6C) alkenyl, (2C-6C)alkynyl, cyano, (3C-6C)cycloalkyl, phenyl, a monocyclic aromatic ring having one or more N-, O- or S- atoms in the ring, a monocyclic non-aromatic ring having one or more N-, O- or S- atoms in the ring, each optionally further substituted with hydroxyl, (1C-4C)alkoxy, phenyl, cycloalkyl, piperidyl, piperazinyl, furyl, thienyl, pirazinyl, pyrrolyl, 2H-pyrrolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyrrolidonyl, pyrrolinyl, imidazolinyl, imidazolyl, a monocyclic aromatic ring having one or more N-, O- or S-atoms in the ring, whereby each of these optional substituents is optionally further substituted with (1 C-4C)alkyl, (1 C-4C)alkyloxy, halo(1 C-4C)alkyl, halo(1 C-4C)alkyloxy, halogen, nitro or (1 C-2C)dioxol forming a ring; or R 3 and R 4 form together pyrrolyl, imidazolyl, pyrazolyl, pyrrolidinyl, pyrrolinylimidazolidinyl, imidazolinyl, piperidyl, piperazinylmorpholinyl, each optionally substituted with (1 C-6C)alkyl, phenyl(1 C-4C)alkyl, phenylketo(1C-4C)alkyl; R 5 is H or CF 3 ; R 6 is (1 C-4C)alkyl, (1 C-4C)alkyloxy, halo(1 C-4C)alkyl, halo(1 C-4C)alkyloxy, nitro or halogen; for use in treatments of carcinoma, in particular to delay, prevent or reverse metastasis in prostate cancer.

Abstract translation: 本发明提供具有式I结构的化合物，其中：X是NH或S; R 1为H或（1C-4C）烷基; R 2是（1C-4C）烷基，苯基或在环中具有一个或多个N，O-或S-原子的单环芳环，该烷基，苯基或芳环任选被一个或多个选自 （1C-4C）烷基，（1C-4C）烷氧基，卤代（1C-4C）烷基，卤代（1C-4C）烷氧基，苯氧基，苯硫基，卤素或硝基; R 3和R 4各自独立地为H，（1C-6C）烷基，（2C-6C）烯基，（2C-6C）炔基，氰基，（3C-6C）环烷基，苯基，具有一个或多个 环中的N-，O-或S-原子，在环中具有一个或多个N，O-或S-原子的单环非芳族环，各自任选进一步被羟基，（1C-4C）烷氧基， 苯基，环烷基，哌啶基，哌嗪基，呋喃基，噻吩基，吡嗪基，吡咯基，吡咯基，吡唑基，异恶唑基，异噻唑基，吡咯烷酮基，吡咯烷基，咪唑啉基，咪唑基，具有一个或多个N-，O-或S- 其中每个这些任选的取代基任选进一步被（C 1 -C 4）烷基，（C 1 -C 4）烷氧基，卤代（C 1 -C 4）烷基，卤代（C 1 -C 4）烷氧基， 卤素，硝基或（1C-2C）二氧杂环戊烯; 或者R 3和R 4一起形成吡咯基，咪唑基，吡唑基，吡咯烷基，吡咯烷基咪唑烷基，咪唑啉基，哌啶基，哌嗪基吗啉基，各自任选被（C 1 -C 6）烷基取代，苯基（C 1 -C 4）烷基，苯基酮 ）烷基; R 5为H或CF 3; R 6是（C 1 -C 4）烷基，（C 1 -C 4）烷氧基，卤素（C 1 -C 4）烷基，卤素（C 1 -C 4）烷氧基，硝基或卤素; 用于治疗癌症，特别是延迟，预防或逆转前列腺癌转移。