公开(公告)号：WO2013131931A1

公开(公告)日：2013-09-12

申请号：PCT/EP2013/054449

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

Abstract: A compound having the structure according to formula III 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 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 R 3 and R 4 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; R 5 is H, Cl, F, Br, Me, NO 2 , t-butyl, OCF 3 , OCH 3 , CF 3 ; R 6 is H, (1C-4C)alkyl, (1C-4C)alkyloxy, halo(1C-4C)alkyl, halo(1C-4C)alkyloxy, nitro or halogen;R 7 is H,F, Cl, Br, Me, NO 2 , t-butyl, OCF 3 , OCH 3 , CF 3 ; 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为NH或S; R 1为H或（1C-4C）烷基; R 2为（C 1 -C 4）烷基，苯基或具有一个或多个N-， 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）烷基，（C 1 -C 6）烯基，（C 2 -C 6）炔基，氰基，（C 3 -C 6）烷氧基， 6C）环烷基，苯基，在环中具有一个或多个N，O-或S-原子的单环芳环，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，哌嗪基，呋喃基，噻吩基，吡嗪基，吡咯基，吡咯基，吡唑基，异噻唑基，异噻唑基，吡咯烷酮基，吡咯啉基，咪唑啉基，咪唑基， 环具有一个或多个N-，O-或S-原子 其中每个这些任选的取代基任选进一步被（1C-4C）烷基，（1C-4C）烷氧基，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，或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） 苯基酮（1C-4C）烷基; R5是H，Cl，F，Br，Me，NO2，叔丁基，OCF3，OCH3，CF3; R6是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; R7是H，F，Cl，Br， 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：US10071987B2

公开(公告)日：2018-09-11

申请号：US15729267

申请日：2017-10-10

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

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

IPC: C07D417/04 ,  C07D417/14 ,  C07D403/04 ,  C07D403/14 ,  A61K31/4155 ,  A61K31/4184 ,  A61K31/428 ,  A61K31/454 ,  A61K45/06

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.

公开(公告)号：US09676764B2

公开(公告)日：2017-06-13

申请号：US15216884

申请日：2016-07-22

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

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

IPC: C07D417/04 ,  C07D417/14 ,  A61K31/428 ,  A61K31/454 ,  A61K31/4184 ,  A61K45/06 ,  C07D403/04

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

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.

公开(公告)号：US09453012B2

公开(公告)日：2016-09-27

申请号：US14383083

申请日：2013-03-05

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

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

IPC: A61K31/454 ,  A61K31/428 ,  C07D417/04 ,  C07D417/14

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

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.

公开(公告)号：US20180030035A1

公开(公告)日：2018-02-01

申请号：US15729267

申请日：2017-10-10

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

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

IPC: C07D403/04 ,  A61K31/4184 ,  A61K31/4155

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

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.

公开(公告)号：US20160326152A1

公开(公告)日：2016-11-10

申请号：US15216884

申请日：2016-07-22

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

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

IPC: C07D417/04 ,  A61K31/428 ,  A61K31/454 ,  A61K31/4184 ,  C07D417/14 ,  A61K45/06 ,  C07D403/04

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

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.

公开(公告)号：US20150073019A1

公开(公告)日：2015-03-12

申请号：US14383083

申请日：2013-03-05

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

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

IPC: C07D417/14 ,  C07D417/04 ,  A61K31/454 ,  A61K31/428

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

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.

公开(公告)号：US20170240531A1

公开(公告)日：2017-08-24

申请号：US15590797

申请日：2017-05-09

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

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

IPC: C07D403/04

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

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.

公开(公告)号：US09790205B2

公开(公告)日：2017-10-17

申请号：US15590797

申请日：2017-05-09

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

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

IPC: A61K31/4155 ,  C07D403/04 ,  A61K31/4184

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

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.

公开(公告)号：EP2822945B1

公开(公告)日：2019-06-19

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 ,  C07D403/04 ,  A61K31/454 ,  A61K31/4155