公开(公告)号：WO2015108490A3

公开(公告)日：2015-11-26

申请号：PCT/SG2015050005

申请日：2015-01-19

Applicant: AGENCY SCIENCE TECH & RES

Inventor： NACRO KASSOUM ,  CHENNAMANENI LOHITHA RAO ,  CHERIAN JOSEPH ,  POULSEN ANDERS

IPC: C07D471/04 ,  A61K31/437 ,  A61K31/44 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/501 ,  A61K31/5025 ,  A61K31/506 ,  A61K31/519 ,  A61P35/00 ,  C07D213/40 ,  C07D213/73 ,  C07D213/74 ,  C07D213/75 ,  C07D213/84 ,  C07D213/85 ,  C07D277/46 ,  C07D401/06 ,  C07D417/06 ,  C07D487/04

CPC classification number: C07D417/06 ,  A61K45/06 ,  C07D401/06 ,  C07D471/04 ,  C07D487/04

Abstract: The present invention relates to certain heteroaryl alkyne compounds of Formula (I) that act as kinase inhibitors. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the prevention and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, autoimmune disease, metabolic diseases, neurodegenerative diseases (e.g., Alzheimer's disease), or neurodevelopmental disorders (e.g., autism)), as well as methods of treating these diseases.

Abstract translation: 本发明涉及作为激酶抑制剂的式（I）的某些杂芳基炔化合物。 本发明还涉及包含这些化合物的药物组合物以及该化合物用于预防和治疗疾病（例如，增殖性疾病（例如癌症），炎性疾病，自身免疫性疾病，代谢疾病，神经变性疾病（例如， ，阿尔茨海默病）或神经发育障碍（例如自闭症））以及治疗这些疾病的方法。

公开(公告)号：EP3052501A4

公开(公告)日：2017-03-29

申请号：EP14851209

申请日：2014-10-03

Applicant: AGENCY SCIENCE TECH & RES

Inventor： NACRO KASSOUM ,  CHENNAMANENI LOHITHA RAO

IPC: C07D487/04 ,  A61K31/437 ,  A61K31/519 ,  A61K31/535 ,  A61P3/10 ,  A61P35/00 ,  C07D471/04

CPC classification number: C07D487/04 ,  C07D471/04 ,  C07D519/00

Abstract: The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazopyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the prevention and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, autoimmune diseases, metabolic diseases, and neurodegenerative diseases (e.g. autism, autism spectrum disorders, Alzheimer's disease)), as well as methods of treating these diseases.

公开(公告)号：EP2831079A4

公开(公告)日：2015-11-18

申请号：EP13768800

申请日：2013-04-01

Applicant: AGENCY SCIENCE TECH & RES

Inventor： NACRO KASSOUM ,  DURAISWAMY ATHISAYAMANI JEYARAJ ,  CHENNAMANENI LOHITHA RAO

IPC: C07D487/04 ,  A61K31/5025 ,  A61K31/519 ,  A61P3/10 ,  A61P35/00 ,  C07D265/06

CPC classification number: C07D487/04 ,  A61K31/4184 ,  A61K31/437 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/5025 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/551 ,  A61K31/553 ,  A61K45/06 ,  A61K2201/094 ,  C07D235/06 ,  C07D471/04 ,  C07D471/10 ,  C07D491/107 ,  C07D519/00 ,  A61K2300/00

Abstract: The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.

Abstract translation: 本发明涉及作为MAP激酶相互作用激酶MNK2a，MNK2b，MNK1a和MNK1b的抑制剂的某些化合物（例如咪唑并吡嗪，咪唑并吡啶，咪唑并嗪和咪唑嘧啶化合物）。 本发明还涉及包含这些化合物的药物组合物，以及该化合物在制备用于预防和治疗疾病（例如增殖性疾病（例如癌症），炎性疾病，阿尔茨海默病））的药物中的用途， 以及治疗这些疾病的方法。

公开(公告)号：SG10201706594PA

公开(公告)日：2017-09-28

申请号：SG10201706594P

申请日：2013-04-01

Applicant: AGENCY SCIENCE TECH & RES

Inventor： NACRO KASSOUM ,  DURAISWAMY ATHISAYAMANI JEYARAJ ,  CHENNAMANENI LOHITHA RAO

Abstract: The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.

公开(公告)号：AU2014330089C1

公开(公告)日：2019-06-20

申请号：AU2014330089

申请日：2014-10-03

Applicant: AGENCY SCIENCE TECH & RES

Inventor： NACRO KASSOUM ,  CHENNAMANENI LOHITHA RAO

IPC: C07D487/04 ,  A61K31/437 ,  A61K31/519 ,  A61K31/535 ,  A61P3/10 ,  A61P35/00 ,  C07D471/04

Abstract: The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the prevention and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, autoimmune diseases, metabolic diseases, and neurodegenerative diseases (e.g. autism, autism spectrum disorders, Alzheimer's disease)), as well as methods of treating these diseases

公开(公告)号：PL2831079T3

公开(公告)日：2018-01-31

申请号：PL13768800

申请日：2013-04-01

Applicant: AGENCY SCIENCE TECH & RES

Inventor： NACRO KASSOUM ,  DURAISWAMY ATHISAYAMANI JEYARAJ ,  CHENNAMANENI LOHITHA RAO

IPC: C07D487/04 ,  A61K31/5025 ,  A61K31/519 ,  A61P3/10 ,  A61P35/00 ,  C07D265/06

公开(公告)号：ES2647959T3

公开(公告)日：2017-12-27

申请号：ES13768800

申请日：2013-04-01

Applicant: AGENCY SCIENCE TECH & RES

Inventor： NACRO KASSOUM ,  DURAISWAMY ATHISAYAMANI ,  CHENNAMANENI LOHITHA

IPC: C07D487/04 ,  A61K31/5025 ,  A61K31/519 ,  A61P3/10 ,  A61P35/00 ,  C07D265/06

Abstract: Un compuesto de la fórmula (Ib):**Fórmula** en la que X1, X2, y X3 son independientemente N o C; X4, X5 y X6 son independientemente N o CR4; en la que por lo menos uno de X1, X2, X3, X4, X5 y X6 es N; X7 es N o CH; X8 es N o CH; es un enlace sencillo o doble, como la valencia lo permita; R1 es -C(O)R, en la que R es un sistema de anillos no aromático heterociclilo de 5 a 6 miembros opcionalmente sustituido que tiene átomos de carbono en el anillo y 1-4 heteroátomos en el anillo, en el que cada heteroátomo se selecciona independientemente de nitrógeno, oxígeno, y azufre; en el que el sistema de anillos no aromático heterociclilo de 5 a 6 miembros opcionalmente sustituido es no sustituido o sustituido con halógeno, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -ORaa, -ON(Rbb)2, -N(Rbb)2, -N(Rbb)3+X-, -N(ORcc)Rbb, -SH, - SRaa, -SSRcc, -C(>=O)Raa, -CO2H, -CHO, -C(ORcc)2, -CO2Raa,-OC(>=O)Raa, -OCO2Raa, -C(>=O)N(Rbb)2, -OC(>=O)N(Rbb)2, - NRbbC(>=O)Raa, -NRbbCO2Raa,-NRbbC(>=O)N(Rbb)2, -C(>=NRbb)Raa, -C(>=NRbb)ORaa, -OC(>=NRbb)Raa, -OC(>=NRbb)ORaa,- C(>=NRbb)N(Rbb)2, -OC(>=NRbb)N(Rbb)2, -NRbbC(>=NRbb)N(Rbb)2, -C(>=O)NRbbSO2Raa,-NRbbSO2Raa, -SO2N(Rbb)2, -SO2Raa, - SO2ORaa, -OSO2Raa, -S(>=O)Raa, -OS(>=O)Raa,-Si(Raa)3, -OSi(Raa)3 -C(>=S)N(Rbb)2, -C(>=O)SRaa, -C(>=S)SRaa, -SC(>=S)SRaa, -SC(>=O)SRaa, -OC(>=O)SRaa, -SC(>=O)ORaa, -SC(>=O)Raa, -P(>=O)2Raa, -OP(>=O)2Raa, -P(>=O)(Raa)2,-OP(>=O)(Raa)2, - OP(>=O)(ORcc)2, -P(>=O)2N(Rbb)2, -OP(>=O)2N(Rbb)2, -P(>=O)(NRbb)2,-OP(>=O)(NRbb)2, -NRbbP(>=O)(ORcc)2, - NRbbP(>=O)(NRbb)2, -P(Rcc)2, -P(Rcc)3, -OP(Rcc)2,-OP(Rcc)3, -B(Raa)2, -B(ORcc)2, -BRaa(ORcc), alquilo C1-10, perhaloalquilo C1-10, alquenilo C2-10, alquinilo C2-10, carbociclilo C3-10, heterociclilo de 3-14 miembros, arilo C6-14, y heteroarilo de 5-14 miembros, en el que cada alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo, y heteroarilo se sustituye independientemente con 0, 1, 2, 3, 4, o 5 grupos Rdd; o dos hidrógenos geminales sobre un átomo de carbono se reemplazan con el grupo >=O, >=S, >=NN(Rbb)2, >=NNRbbC(>=O)Raa, >=NNRbbC(>=O)ORaa, >=NNRbbS(>=O)2Raa, >=NRbb, o >=NORcc; cada caso de Raa se selecciona independientemente de alquilo C1-10, perhaloalquilo C1-10, alquenilo C2-10, alquinilo C2-10, carbociclilo C3-10, heterociclilo de 3-14 miembros, arilo C6-14, y heteroarilo de 5-14 miembros, o dos grupos Raa se unen para formar un heterociclilo de 3-14 miembros o anillo heteroarilo de 5-14 miembros, en el que cada alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo, y heteroarilo se sustituye independientemente con 0, 1, 2, 3, 4, o 5 grupos Rdd; cada caso de Rbb se selecciona independientemente de hidrógeno, -OH, -ORaa,-N(Rcc)2, -CN, -C(>=O)Raa, -C(>=O)N(Rcc)2, -CO2Raa, -SO2Raa, -C(>=NRcc)ORaa,-C(>=NRcc)N(Rcc)2, -SO2N(Rcc)2, -SO2Rcc, -SO2ORcc, -SORaa, -C(>=S)N(Rcc)2, - C(>=O)SRcc,-C(>=S)SRcc, -P(>=O)2Raa, -P(>=O)(Raa)2, -P(>=O)2N(Rcc)2, -P(>=O)(NRcc)2, alquilo C1-10, perhaloalquilo C1-10, alquenilo C2-10, alquinilo C2-10, carbociclilo C3-10, heterociclilo de 3-14 miembros, arilo C6-14, y heteroarilo de 5-14 miembros, o dos grupos Rbb se unen para formar un heterociclilo de 3-14 miembros o anillo heteroarilo de 5-14 miembros, en el que cada alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo, y heteroarilo se sustituye independientemente con 0, 1, 2, 3, 4, o 5 grupos Rdd; cada caso de Rcc se selecciona independientemente de hidrógeno, 5 alquilo C1-10, perhaloalquilo C1-10, alquenilo C2-10, alquinilo C2-10, carbociclilo C3-10, heterociclilo de 3-14 miembros, arilo C6-14, y heteroarilo de 5-14 miembros, o dos grupos Rcc se unen para formar un heterociclilo de 3-14 miembros o anillo heteroarilo de 5-14 miembros, en el que cada alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo, y heteroarilo se sustituye independientemente con 0, 1, 2, 3, 4, o 5 grupos Rdd; cada caso de Rdd se selecciona independientemente de halógeno, -CN, -NO2, -N3,-SO2H, -SO3H, -OH, -ORee, -ON(Rff)2, -N(Rff)2, -N(Rff)3 +X-, -N(ORee)Rff, -SH, -SRee,-SSRee, -C(>=O)Ree, -CO2H, -CO2Ree, -OC(>=O)Ree, -OCO2Ree, - C(>=O)N(Rff)2,-OC(>=O)N(Rff)2, -NRffC(>=O)Ree, -NRffCO2Ree, -NRffC(>=O)N(Rff)2, -C(>=NRff)ORee,-OC(>=NRff)Ree, - OC(>=NRff)Ree, -C(>=NRff)N(Rff)2, -OC(>=NRff)N(Rff)2, - NRffC(>=NRff)N(Rff)2,-NRffSO2Ree, -SO2N(Rff)2, -SO2Ree, -SO2ORee, - OSO2Ree, -S(>=O)Ree, -Si(Ree)3, -OSi(Ree)3, -C(>=S)N(Rff)2, -C(>=O)SRee, -C(>=S)SRee, -SC(>=S)SRee, -P(>=O)2Ree, - P(>=O)(Ree)2, -OP(>=O)(Ree)2, -OP(>=O)(ORee)2, alquilo C1-6, perhaloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo C3-10, heterociclilo de 3-10 miembros, arilo C6-10, heteroarilo de 5-10 miembros, en el que cada alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo, y heteroarilo se sustituye independientemente con 0, 1, 2, 3, 4, o 5 grupos Rgg, o dos sustituyentes Rdd gaminales se pueden unir para formar >=O o >=S; cada caso de Ree se selecciona independientemente de alquilo C1-6, perhaloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo C3-10, arilo C6-10, heterociclilo de 3-10 miembros, y heteroarilo de 3-10 miembros, en el que cada alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo, y heteroarilo se sustituye independientemente con 0, 1, 2, 3, 4, o 5 grupos Rgg; cada caso de Rff se selecciona independientemente de hidrógeno, alquilo C1-6, perhaloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo C3-10, heterociclilo de 3-10 miembros, arilo C6-10 y heteroarilo de 5-10 miembros, o dos grupos Rff se unen para formar un heterociclilo de 3-14 miembros o anillo heteroarilo de 5-14 miembros, en el que cada alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo, y heteroarilo se sustituye independientemente con 0, 1, 2, 3, 4, o 5 grupos Rgg; y cada caso de Rgg es, independientemente, halógeno, -CN, -NO2, -N3, -SO2H, -SO3H, - OH, -Oalquilo C1-6, -ON(alquilo C1-6)2, -N(alquilo C1-6)2, -N(alquilo C1-6)3 +X-, -NH(alquilo C1-6)2 +X-, -NH2(alquilo C1-6)+X-, -NH3+X-, -N(Oalquilo C1-6)(alquilo C1-6), -N(OH)(alquilo C1-6), -NH(OH), -SH, -Salquilo C1-6, -SS(alquilo C1-6), -C(>=O)(alquilo C1-6), -CO2H, -CO2(alquilo C1-6), -OC(>=O)(alquilo C1-6), -OCO2(alquilo C1-6), -C(>=O)NH2, -C(>=O)N(alquilo C1-6)2, - OC(>=O)NH(alquilo C1-6), - NHC(>=O)(alquilo C1-6), -N(alquilo C1-6)C(>=O)(alquilo C1-6), - NHCO2(alquilo C1-6), -NHC(>=O)N(alquilo C1-6)2, - NHC(>=O)NH(alquilo C1-6), -NHC(>=O)NH2, -C(>=NH)O(alquilo C1-6),-OC(>=NH)(alquilo C1-6), -OC(>=NH)Oalquilo C1-6, - C(>=NH)N(alquilo C1-6)2, -C(>=NH)NH(alquilo C1-6), -C(>=NH)NH2, -OC(>=NH)N(alquilo C1-6)2, - OC(NH)NH(alquilo C1-6), - 35 OC(NH)NH2, -NHC(NH)N(alquilo C1-6)2, -NHC(>=NH)NH2, - NHSO2(alquilo C1-6), -SO2N(alquilo C1-6)2, -SO2NH(alquilo C1- 6), -SO2NH2,-SO2alquilo C1-6, - SO2Oalquilo C1-6, -OSO2alquilo C1-6, -SOalquilo C1-6, -Si(alquilo C1-6)3, -OSi(alquilo C1-6)3 - C(>=S)N(alquilo C1-6)2, C(>=S)NH(alquilo C1-6), C(>=S)NH2, -C(>=O)S(alquilo C1-6), -C(>=S)Salquilo C1-6, -SC(>=S)Salquilo C1-6, -P(>=O)2(alquilo C1-6), -P(>=O)(alquilo C1-6)2, -OP(>=O)(alquilo C1-6)2, - OP(>=O)(Oalquilo C1-6)2, alquilo C1-6, perhaloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo C3-10, arilo C6-10, heterociclilo de 3-10 miembros, heteroarilo de 5-10 miembros; o dos sustituyentes Rgg geminales se pueden unir para formar >=O o >=S; en los que X- es un contraión; R2, R3, R6 y R7 son independientemente -H, F, Cl, CN, -CH3, -CHF2, -C(O)NH2, -OH, - Oalquilo C1-4, o -OCF3; o R6 y R7 se toman juntos para formar un heterociclilo fusionado de 5-6 meimbros o unidad estructural de heteroarilo; cada R4 es independientemente hidrógeno, o alquilo C1-6.

公开(公告)号：AU2017219039A1

公开(公告)日：2017-09-14

申请号：AU2017219039

申请日：2017-08-24

Applicant: AGENCY SCIENCE TECH & RES

Inventor： NACRO KASSOUM ,  DURAISWAMY ATHISAYAMANI JEYARAJ ,  CHENNAMANENI LOHITHA RAO

IPC: C07D487/04 ,  A61K31/5025 ,  A61K31/519 ,  A61P3/10 ,  A61P35/00 ,  C07D265/06

Abstract: BICYCLIC HETEROARYL DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNKl a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.

公开(公告)号：AU2014330089B2

公开(公告)日：2018-12-13

申请号：AU2014330089

申请日：2014-10-03

Applicant: AGENCY SCIENCE TECH & RES

Inventor： NACRO KASSOUM ,  CHENNAMANENI LOHITHA RAO

IPC: C07D487/04 ,  A61K31/437 ,  A61K31/519 ,  A61K31/535 ,  A61P3/10 ,  A61P35/00 ,  C07D471/04

Abstract: The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the prevention and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, autoimmune diseases, metabolic diseases, and neurodegenerative diseases (e.g. autism, autism spectrum disorders, Alzheimer's disease)), as well as methods of treating these diseases

公开(公告)号：AU2013240612B2

公开(公告)日：2017-05-25

申请号：AU2013240612

申请日：2013-04-01

Applicant: AGENCY SCIENCE TECH & RES

Inventor： NACRO KASSOUM ,  DURAISWAMY ATHISAYAMANI JEYARAJ ,  CHENNAMANENI LOHITHA RAO

IPC: C07D487/04 ,  A61K31/5025 ,  A61K31/519 ,  A61P3/10 ,  A61P35/00 ,  C07D265/06

Abstract: The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.