公开(公告)号：US20190010156A1

公开(公告)日：2019-01-10

申请号：US16004145

申请日：2018-06-08

Applicant: Hoffmann-La Roche Inc.

Inventor： Bjoern BARTELS ,  Hasane RATNI ,  Karlheinz BAUMANN ,  Guido GALLEY ,  Georg JAESCHKE ,  Roland JAKOB-ROETNE ,  Anja LIMBERG ,  Werner NEIDHART ,  Rosa Maria RODRIGUEZ-SARMIENTO

IPC: C07D487/04 ,  C07D471/04 ,  A61P25/28

CPC classification number: C07D487/04 ,  A61P25/28 ,  C07D471/04

Abstract: The present invention relates to a compound of formula wherein HetAr is a five or six membered hetaryl group, containing one, two or three heteroatoms, selected from N, O or S; R1 is hydrogen, lower alkyl, lower alkyl substituted by halogen, halogen, or lower alkoxy; R2 is lower alkyl substituted by halogen, —CH2—C3-6-cycloalkyl, substituted by one or two substituents, selected from lower alkyl substituted by halogen or halogen, or is lower alkenyl substituted by halogen; R3 is hydrogen, lower alkyl substituted by halogen, lower alkyl, halogen, C3-6-cycloalkyl or lower alkyl substituted by hydroxy; n is 1 or 2; for n=2, R1 can be independent to each other; Y is CH or N; or to a pharmaceutically active acid addition salt thereof, to a racemic mixture or its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

公开(公告)号：US20200031831A1

公开(公告)日：2020-01-30

申请号：US16337348

申请日：2017-09-28

Applicant: Hoffmann-La Roche Inc.

Inventor： Bjoern BARTELS ,  Roland JAKOB-ROETNE ,  Anja LIMBERG ,  Werner NEIDHART ,  Hasane RATNI ,  Michael REUTLINGER ,  Jérôme Charles SARIE ,  Greta VASTAKAITE

IPC: C07D487/04

Abstract: The present invention relates to a compound of formula (I), wherein R1 is hydrogen, lower alkyl, lower alkyl substituted by halogen, halogen, lower alkoxy or lower alkoxy substituted by halogen; R may be the same or different, if n=2 or 3; n is 1, 2 or 3; m is 1, 2 or 3; Ar is a five or six membered heteroaryl group, selected from (II), (III), (IV) or (V) wherein R2 is hydrogen, lower alkyl, lower alkyl substituted by halogen, halogen or lower alkoxy; R3 is hydrogen or halogen; -( ) m - is —(CH2)m— or to pharmaceutically active acid addition salts thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-in-farct dementia, dementia pugilistica or Down syndrome.

公开(公告)号：US20210309653A1

公开(公告)日：2021-10-07

申请号：US16348322

申请日：2017-11-06

Applicant: Hoffmann-La Roche Inc.

Inventor： Bjoern BARTELS ,  Stefan BERCHTOLD ,  Guido GALLEY ,  Annick GOERGLER ,  Roland JAKOB-ROETNE ,  Daniela KRUMMENACHER ,  Anja LIMBERG ,  Werner NEIDHART ,  Hasane RATNI ,  Michael REUTLINGER ,  Rosa Maria RODRIGUEZ SARMIENTO ,  Christian SCHNIDER

IPC: C07D417/14 ,  C07D401/14 ,  C07D413/14 ,  C07D403/14

Abstract: The present invention relates to a compound of formula I, HetAr is a five or six membered heteroaryl group, selected from wherein R1 is hydrogen, halogen, lower alkyl, lower alkoxy or lower alkyl substituted by halogen, and may be the same or different, i-f two R1 occur; R2 is lower alkyl or a mono- or polydeutered derivative thereof, lower alkyl substituted by halogen or lower alkoxy, lower alkenyl unsubstituted or substituted by halogen, cycloalkyl or CH2-cycloalkyl unsubstituted or substituted by halogen, heterocycloalkyl or CH2-heterocycloalkyl unsubstituted or substituted by lower alkyl; R3 is halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy substituted by halogen or S(0)2-lower alkyl; n is 1, 2 or 3; if n is >1, then R3 may be the same or different; or to a pharmaceutically active acid addition salt thereof, to a racemic mixture or to its corresponding enantiomer and/or an optical isomer and/or stereoisomer thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

公开(公告)号：US20190256517A1

公开(公告)日：2019-08-22

申请号：US16231177

申请日：2018-12-21

Applicant: Hoffmann-La Roche Inc.

Inventor： Bjoern BARTELS ,  Roland JAKOB-ROETNE ,  Anja LIMBERG ,  Werner NEIDHART ,  Hasane RATNI ,  Sandra STEINER ,  Michael REUTLINGER

IPC: C07D487/04 ,  C07D471/04 ,  A61P25/28

Abstract: The present invention relates to compounds of formula I, wherein R1 is phenyl, lower alkyl, C3-6-cycloalkyl, —CH2—C3-6-cycloalkyl, or bridged C3-5-cycloalkyl, optionally substituted by one, two or three substituents, selected from halogen, lower alkyl or lower alkyl substituted by halogen; R2 is hydrogen, halogen, lower alkoxy, lower alkyl substituted by halogen or lower alkoxy substituted by halogen; R3 is a five membered heteroaryl group, selected from wherein R6 is hydrogen or lower alkyl; R7 is halogen or lower alkyl; R8 is hydrogen or lower alkyl; R9 is hydrogen or lower alkyl; R4 is lower alkyl or lower alkyl substituted by hydroxy; R5/R5′ is independently from each other hydrogen or lower alkyl; ( )n- is —CH2— or —CH2CH2— for n being 1 or 2; X is CH or N; or to pharmaceutically active acid addition salts thereof, to racemic mixtures or to its corresponding enantiomers and/or optical isomers and/or stereoisomers thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

公开(公告)号：US20190233427A1

公开(公告)日：2019-08-01

申请号：US16339345

申请日：2017-10-02

Applicant: Hoffmann-La Roche Inc.

Inventor： Bjoern BARTELS ,  Roland JAKOB-ROETNE ,  Anja LIMBERG ,  Werner NEIDHART ,  Hasane RATNI ,  Michael REUTLINGER ,  Greta VASTAKAITE

IPC: C07D487/04 ,  A61P25/28

CPC classification number: C07D487/04 ,  A61P25/28

Abstract: The present invention relates to a compound of formula (I), wherein R1 is hydrogen, lower alkyl, lower alkyl substituted by halogen, halogen, lower alkoxy or lower alkoxy substituted by halogen; and R1 may be different if n is 2 or 3; R2 is hydrogen, lower alkyl, lower alkyl substituted by halogen, halogen, CN, lower alkoxy or lower alkoxy substituted by halogen; X is CH or N; m is 1, 2 or 3; -( )m is —(CH2)m—; n is 1, 2 or 3; Ar is a five membered heteroaryl group, selected from formula (A), (B), (C), (D), (E) or (F), wherein R3 is hydrogen, methyl or chloro; R4 is hydrogen or methyl; R5 is F, Cl, CHF2 or CF3; or to pharmaceutically active acid addition salts thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

公开(公告)号：US20200339522A1

公开(公告)日：2020-10-29

申请号：US16811656

申请日：2020-03-06

Applicant: Hoffmann-La Roche Inc.

Inventor： Jerome HERT ,  Daniel HUNZIKER ,  Holger KUEHNE ,  Thomas LUEBBERS ,  Rainer E. MARTIN ,  Patrizio MATTEI ,  Werner NEIDHART ,  Hans RICHTER ,  Markus RUDOLPH ,  Emmanuel PINARD

IPC: C07D249/08 ,  C07D487/04 ,  C07D249/12 ,  C07D409/12 ,  C07D413/12 ,  C07D231/12 ,  C07F7/08 ,  C07D401/12 ,  C07D407/12 ,  C07D407/04 ,  C07D471/04 ,  C07D237/14 ,  C07D403/12 ,  C07D417/12 ,  C07D231/56 ,  A61P27/02 ,  C07B41/04 ,  C07D231/20 ,  C07D249/04

Abstract: The invention provides novel compounds having the general formula (I) wherein RA, RB, RC, RC1 and W are as defined herein, compositions including the compounds and methods of using the compounds.

公开(公告)号：US20200291034A1

公开(公告)日：2020-09-17

申请号：US16790629

申请日：2020-02-13

Applicant: Hoffmann-La Roche Inc.

Inventor： Bjoern BARTELS ,  Hasane RATNI ,  Karlheinz BAUMANN ,  Guido GALLEY ,  Georg JAESCHKE ,  Roland JAKOB-ROETNE ,  Anja LIMBERG ,  Werner NEIDHART ,  Rosa Maria RODRIGUEZ-SARMIENTO

IPC: C07D487/04 ,  C07D471/04 ,  A61P25/28

Abstract: The present invention relates to a compound of formula wherein HetAr is a five or six membered hetaryl group, containing one, two or three heteroatoms, selected from N, O or S; R1 is hydrogen, lower alkyl, lower alkyl substituted by halogen, halogen, or lower alkoxy; R2 is lower alkyl substituted by halogen, —CH2—C3-6-cycloalkyl, substituted by one or two substituents, selected from lower alkyl substituted by halogen or halogen, or is lower alkenyl substituted by halogen; R3 is hydrogen, lower alkyl substituted by halogen, lower alkyl, halogen, C3-6-cycloalkyl or lower alkyl substituted by hydroxy; n is 1 or 2; for n=2, R1 can be independent to each other; Y is CH or N; or to a pharmaceutically active acid addition salt thereof, to a racemic mixture or its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

公开(公告)号：US20190284191A1

公开(公告)日：2019-09-19

申请号：US16346623

申请日：2017-10-30

Applicant: Hoffmann-La Roche Inc.

Inventor： Bjoern BARTELS ,  Roland JAKOB-ROETNE ,  Anja LIMBERG ,  Werner NEIDHART ,  Hasane RATNI ,  Michael REUTLINGER ,  Jérôme Charles SARIE ,  Greta VASTAKAITE

IPC: C07D487/04

Abstract: The present invention relates to a compound of formula I, 1-1 or 1-2 wherein R1 is hydrogen, lower alkyl, lower alkyl substituted by halogen, halogen, lower alkoxy, or lower alkoxy substituted by halogen; R1 may be different if n=2 or 3 n is 1, 2 or 3 Ar is a six membered heteroaryl group, selected from wherein R2 is hydrogen, lower alkyl, lower alkyl substituted by halogen, halogen or lower alkoxy; R3 is hydrogen or halogen; or to a pharmaceutically active acid addition salt thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

公开(公告)号：US20190194183A1

公开(公告)日：2019-06-27

申请号：US16224507

申请日：2018-12-18

Applicant: Hoffmann-La Roche Inc.

Inventor： Bjoern BARTELS ,  Roland JAKOB-ROETNE ,  Anja LIMBERG ,  Werner NEIDHART ,  Hasane RATNI ,  Rosa Maria RODRIGUEZ SARMIENTO

IPC: C07D451/04 ,  C07D471/04 ,  A61P25/28

CPC classification number: C07D451/04 ,  A61P25/28 ,  C07D471/04

Abstract: The present invention relates to compounds of formula whereinHetAr is a five or six membered hetaryl group, containing one, two or three heteroatoms, selected from N, O or S;R1 is hydrogen, lower alkyl, lower alkyl substituted by halogen, halogen or lower alkoxy;R2 is lower alkyl substituted by halogen;R3 is hydrogen, lower alkyl substituted by halogen, lower alkyl or lower alkyl substituted by hydroxy;Y is R4 is lower alkoxy, lower alkoxy substituted by halogen or CN;or to pharmaceutically active acid addition salts thereof, to racemic mixtures or to its corresponding enantiomers and/or optical isomers and/or stereoisomers thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.