公开(公告)号：PL371063A1

公开(公告)日：2005-06-13

申请号：PL37106302

申请日：2002-12-05

Applicant: HOFFMANN LA ROCHE

Inventor： FLOHR ALEXANDER ,  JAKOB-ROETNE ROLAND ,  NORCROSS ROGER DAVID ,  RIEMER CLAUS

IPC: C07D277/82 ,  A61K31/428 ,  A61K31/454 ,  A61K31/4747 ,  A61K31/497 ,  A61K31/5377 ,  A61K31/5386 ,  A61K31/553 ,  A61P9/10 ,  A61P11/06 ,  A61P11/16 ,  A61P25/00 ,  A61P25/04 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/22 ,  A61P25/28 ,  A61P25/36 ,  A61P37/08 ,  A61P43/00 ,  C07D413/14 ,  C07D417/00 ,  C07D417/04 ,  C07D417/12 ,  C07D453/06 ,  C07D471/10 ,  C07D487/08 ,  C07D491/08 ,  C07D491/107 ,  C07D498/08

Abstract: A compound of formula I and a method of treatment of diseases, related to modulation of the adenosine A 2 receptor system comprising administering a compound of formula to a person in need of such treatment.

公开(公告)号：ZA200403817B

公开(公告)日：2005-05-23

申请号：ZA200403817

申请日：2004-05-18

Applicant: HOFFMANN LA ROCHE

Inventor： FLOHR ALEXANDER ,  NORCROSS ROGER DAVID ,  JAKOB-ROETNE ROLAND ,  RIEMER CLAUS

IPC: A61K31/4439 ,  A61K31/5377 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P25/00 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/32 ,  A61P25/34 ,  A61P25/36 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D417/12 ,  C07D417/14 ,  A61K ,  C07D

Abstract: The present invention relates to compounds of the formulawherein R1, A and R are as described within. The compounds of the present invention have been found to be adenosine receptor ligands. Specifically, the compounds of the present invention have an affinity to the A2A-receptor and are therefore useful in the treatment of diseases related to this receptor.

公开(公告)号：HU0402600A2

公开(公告)日：2005-03-29

申请号：HU0402600

申请日：2002-12-06

Applicant: HOFFMANN LA ROCHE

Inventor： HUWYLER JOERG ,  JAKOB-ROETNE ROLAND ,  POLI SONIA MARIA

IPC: A61K31/401 ,  A61K31/407 ,  A61P3/10 ,  A61P25/28 ,  A61P43/00 ,  C07D207/16 ,  C07D498/14

Abstract: The invention relates to compounds of formulae wherein R 1 and R 2 are independently from each other and signify lower alkoxy, lower alkenyloxy, benzyloxy, hydroxy, ۥOCH(CH 3 )OC(O)-lower alkyl or ۥOCH 2 C(O)N(R 3 )(R 4 ), with the proviso that only one of R 1 or R 2 may be hydroxy; R 3 and R 4 are independently from each other and signify hydrogen, lower alkyl, lower alkenyl or cycloalkyl; or R 1 and R 2 form together with the carbon atom, to which they are attached the linking group X, wherein X is ۥO(CH 2 ) n CH=CH(CH 2 ) n O- or -O(CH 2 ) m O-; n is 1, 2 or 3; and m is 4-8. as well as pharmaceutically acceptable salts of said compounds. Compounds of the present invention can be used for the treatment of diseases where Serum Amyloid P Component depletion has a beneficial effect, in particular in the treatment or prevention of all forms of central and systemic amyloidosis.

公开(公告)号：BR0214932A

公开(公告)日：2004-11-30

申请号：BR0214932

申请日：2002-12-06

Applicant: HOFFMANN LA ROCHE

Inventor： HUWYLER JOERG ,  JAKOB-ROETNE ROLAND ,  POLI SONIA MARIA

IPC: A61K31/401 ,  A61K31/407 ,  A61P3/10 ,  A61P25/28 ,  A61P43/00 ,  C07D207/16 ,  C07D498/14

Abstract: The invention relates to compounds of formulae wherein R 1 and R 2 are independently from each other and signify lower alkoxy, lower alkenyloxy, benzyloxy, hydroxy, ۥOCH(CH 3 )OC(O)-lower alkyl or ۥOCH 2 C(O)N(R 3 )(R 4 ), with the proviso that only one of R 1 or R 2 may be hydroxy; R 3 and R 4 are independently from each other and signify hydrogen, lower alkyl, lower alkenyl or cycloalkyl; or R 1 and R 2 form together with the carbon atom, to which they are attached the linking group X, wherein X is ۥO(CH 2 ) n CH=CH(CH 2 ) n O- or -O(CH 2 ) m O-; n is 1, 2 or 3; and m is 4-8. as well as pharmaceutically acceptable salts of said compounds. Compounds of the present invention can be used for the treatment of diseases where Serum Amyloid P Component depletion has a beneficial effect, in particular in the treatment or prevention of all forms of central and systemic amyloidosis.

公开(公告)号：YU13502A

公开(公告)日：2004-11-25

申请号：YUP13502

申请日：2000-08-28

Applicant: HOFFMANN LA ROCHE

Inventor： HUBER TROTTMANN GERDA ,  HUNKELER WALTER ,  JAKOB-ROETNE ROLAND ,  KILPATRICK GAVIN JOHN ,  NETTEKOVEN MATTHIAS HEINRICH ,  RIEMER CLAUS

IPC: C07D213/73 ,  A61K31/437 ,  A61K31/4418 ,  A61K31/444 ,  A61K31/496 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/551 ,  A61K31/635 ,  A61P9/10 ,  A61P11/06 ,  A61P11/16 ,  A61P25/00 ,  A61P25/04 ,  A61P25/08 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P37/08 ,  A61P43/00 ,  C07D409/04 ,  C07D471/04 ,  C07D519/00

Abstract: Pronalazak se odnosi na jedinjenja formule I, naznacena time sto R1 perdstavlja 5-to ili 6-toclanu heteroarilnu grupu, koja sadrzi 1 do 3 heteroatoma, izabrana izmedju N, O ili S, i cije su grupe opciono supstituisane jednim ili sa dva supstituenta, koji su nizi alkil, -(CH2)nOH, halogen ili nizi alkoksi, i naznacena time sto heteroarilne grupe mogu biti opciono vezane za pirazolski prsten preko nekog alkilena ili alkenil grupe ili je to fenil, opciono supstituisan jednim ili sa dva supstituenta, koji su nizi alkil, hidroksi-nizi alkil, halogen, hidroksi ili nizi alkoksi ili je -O(CH2)nfenil, benzofuril, indolil ili benzotiofenil ili je -S-nizi alkil; R2 i R4 su nezavisno jedan od drugog, vodonik, cijano ili -S(O)2-fenil; R3 je vodonik, halogen ili 5-to ili 6-toclana heteroarilna grupa, koja sadrzi 1 do 3 heteroatoma, izabrana izmedju N, O ili S i gde su grupe opciono supstituisane jednim ili sa dva supstituenta, koji su nizi alkil, -(CH2)n-aril, hldroksi, halogen, nizi alkoksi, morfolinil, amino, nizi alkilamino ili -C(O)NR'2, naznaceno time sto je R* nizi alkil ili vodonik ili je fenil, opciono supstituisan jednim ili sa dva supstituenta koji su halogen, nizi alkoksi, amino, di-nizi alkil amino, CF3, -OCF3, -NHC(O)nizi alkil cijano, -C(O)-nizi alkil, -C(O)O-nizi alkil, -S-nizi alkil, -S(O)2NH-fenil, -S(O)2metilpiperazinil; ili je NR'R", naznacen time sto su R' i R", nezavisno jedan od drugog, vodonik, -(CH2)nfenil, koji je opciono supstituisan halogenom ili nizom alkoksi grupom, -CH(nizi alkil)-fenil, indan-1-il, 1,2,3,4-tetrahidro-naftalen ili cikloalkil; ili je O-fenil, ciji je fenilni prsten opciono supstituisan halogenom, nizom alkil ili nizom alkoksi grupom, -O-tetraidronaftalenil ili -O-CH2-6-metil-piridin-2-il; ili je -benzol[1,3]dioksolil, -1H-indol-5-il, naftil, benzofuran-2-il, 1,3,4,9-tetrahidro-b-karbolin-2-il, piperidin-1-il, pirolidin-1-il, piperazin-4-il-metil ili morfolinil; R5 je -NR2, pri cemu R moze ili ne mora biti vodonik, nizi alkil, fenil, benzil, -CO-nizi alkil, -CO-nizi alkoksi, -nizi alkenil, -CO(CH2)n-fenil ili -COO(CH2)n-fenil, naznacen time sto je fenilni prsten opciono supstituisan sa CF3 nizom alkoksi, halogen ili nizom alkil grupom, -CO(CH2)3-NHCO-nizi alkoksi, -(CH2)n-fenil, naznacen time, sto je fenilni prsten opciono supstituisan nizom alkoksi, CF3 ili halogenom ili je 4,5-dihidro-1H-imidazol-2-il-benzojeva kiselina, 1,4,5,6-tetrahidro-pirimidin-2-il-benzojeva kiselina ili 4,5,6,7-tetrahidro-1H-[1,3]diazepin-2-il-benzojeva kiselina; n je 0-4, i njihove farmaceutski prihvatljive soli.

公开(公告)号：BR0214488A

公开(公告)日：2004-10-19

申请号：BR0214488

申请日：2002-11-21

Applicant: HOFFMANN LA ROCHE

Inventor： FLOUHR ALEXANDER ,  JAKOB-ROETNE ROLAND ,  NORCROSS ROGER DAVID ,  RIEMER CLAUS

IPC: A61K31/428 ,  A61K31/5377 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P21/02 ,  A61P25/00 ,  A61P25/02 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/36 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D277/82 ,  C07D417/12

Abstract: The present invention relates to compounds of the formulawherein R and R are as defined herewithin. The compounds of formula I have been found to be adenosine receptor ligands. Specifically, the compounds of the present invention have a good affinity to the A2A-receptor and they are therefore useful in the treatment of diseases, related to this receptor.

公开(公告)号：HRP980572B1

公开(公告)日：2004-06-30

申请号：HRP980572

申请日：1998-10-30

Applicant: HOFFMANN LA ROCHE

Inventor： HERTEL CORNELIA ,  HOFFMANN TORSTEN ,  JAKOB-ROETNE ROLAND ,  NORCROSS ROGER DAVID

IPC: C07K5/078 ,  A61K31/00 ,  A61K31/40 ,  A61K31/401 ,  A61K31/4015 ,  A61K38/08 ,  A61P3/00 ,  A61P3/10 ,  A61P9/04 ,  A61P9/10 ,  A61P25/00 ,  A61P25/28 ,  A61P43/00 ,  C07D207/16 ,  C07D207/22 ,  C07D207/277 ,  C07D401/14 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D419/14 ,  C07D521/00 ,  C07D417/06 ,  C07D413/12 ,  C07D419/12

Abstract: The invention relates to D-prolines of the formula wherein R is SH, benzyl or phenyl, optionally substituted by hydroxy or lower alkoxy or the group R' is hydrogen or halogen; X is -(CH2)n-; -CH(R )(CH2)n-; -CH2O(CH2)n-; -CH2NH-; benzyl, -C(R )=CH-; -CH2CH(OH)-; or thiazol-2,5-diyl; Y is -S-S-; -(CH2)n-; -O-; -NH-; -N(R )-; -CH=CH-; -NHC(O)NH-; - N(R )C(O)N(R )-; -NÄCH2C6H3(OCH3)2Ü-; -N(CHC6H5)-; -N(CH2C6H5)C(O)N(CH2C6H5)-; -N(alkoxyalkyl)-; -N(cycloalkyl-methyl)-; 2,6-pyridyl; 2,5-furanyl; 2,5-thienyl; 1,2-cyclohexyl; 1,3-cyclohexyl; 1,4-cyclohexyl; 1,2-naphthyl; 1,4-naphthyl; 1,5-naphthyl; 1,6-naphthyl; biphenylen; or 1,2-phenylen,1,3-phenylen and 1,4-phenylen, wherein the phenylen groups are optionally substituted by 1 - 4 substituents, selected from halogen, lower alkyl, lower alkoxy, hydroxy, carboxy, -COO-lower alkyl, nitrilo, 5-tetrazol, (2-carboxylic acid-pyrrolidin-1-yl)-2-oxo-ethoxy, N-hydroxycarbamimidoyl, 5-oxo-Ä1,2,4Üoxadiazolyl, 2-oxo-Ä1,2,3,5Üoxathiadiazolyl, 5-thioxo-Ä1,2,4Üoxadiazolyl and 5-tert-butylsulfanyl-Ä1,2,4Üoxadiazolyl; X' is -(CH2)n-; -(CH2)nCH(R )-; -(CH2)nOCH2-; -NHCH2-; benzyl, -CH=C(R )-; -CH(OH)CH2; or thiazol-2,5-diyl; R is lower alkyl, lower alkoxy or benzyl and n is 0-3, and to pharmaceutically acceptable salts and mono- and diesters thereof. The D-prolines of formula I-A and I-B can be used in the treatment or prevention of all forms of central and systemic amyloidosis.

公开(公告)号：PE08212003A1

公开(公告)日：2003-10-04

申请号：PE0011312002

申请日：2002-11-25

Applicant: HOFFMANN LA ROCHE

Inventor： RIEMER CLAUS ,  JAKOB-ROETNE ROLAND ,  NORCROSS ROGER DAVID ,  FLOHR ALEXANDER

IPC: A61K31/428 ,  A61K31/5377 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P21/02 ,  A61P25/00 ,  A61P25/02 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/36 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D277/82 ,  C07D417/12

CPC classification number: C07D277/82

Abstract: SE REFIERE A DERIVADOS DE BENZOTIAZOL DE FORMULA I DONDE R1 ES H, ALQUILO; R2 ES ALQUILO, (CH2)n-O-ALQUILO, CICLOALQUILO, (CH2)n-NR'2; R' ES H, ALQUILO, (CH2)n-O-ALQUILO O JUNTO A N FORMAN PIRROLIDINA; n ES 1-3; SON COMPUESTOS PREFERIDOS 4-[(2-METOXI-ACETILAMINO)-METIL]-N-(4-METOXI-7-MORFOLIN-4-IL-BENZOTIAZOL-2-IL)BENZAMIDA; 4-[(METOXIACETIL-METIL-AMINO)-METIL]-N-(4-METOXI-7-MORFOLIN-4-IL-BENZOTIAZOL-2-IL)BENZAMIDA; 4-[(CICLOPROPANOCARBONIL-AMINO)-METIL]-N-(4-METOXI-7-MORFOLIN-4-IL-BENZOTIAZOL-2-IL)BENZAMIDA; 4-[(DIMETILAMINOACETIL-METIL-AMINO)METIL]-N-(4-METOXI-7-MORFOLIN-4-IL-BENZOTIAZOL-2-IL)BENZAMIDA, ENTRE OTROS; TAMBIEN SE REFIERE A UN PROCEDIMIENTO PARA LA PREPARACION. LOS COMPUESTOS SON LIGANDOS DEL RECEPTOR DE ADENOSINA A2A Y PUEDE SER UTIL PARA EL TRATAMIENTO DE ENFERMEDAD DE ALZHEIMER, PARKINSON, HUNTINGTON, NEUROPROTECCION, ESQUIZOFRENIA, ANSIEDAD, DOLOR, DEFICITS DE RESPIRACION, DEPRESION, ADICCION A DROGAS COMO ANFETAMINA, COCAINA, OPIOIDE, ETANOL, NICOTINA, CANNABINOIDES, ASMA, RESPUESTAS ALERGICAS, HIPOXIA, ISQUEMIA

公开(公告)号：PE20030764A1

公开(公告)日：2003-09-11

申请号：PE2002001184

申请日：2002-12-10

Applicant: HOFFMANN LA ROCHE

Inventor： JAKOB-ROETNE ROLAND ,  POLI SONIA MARIA ,  HUWYLER JOERG

IPC: A61K31/401 ,  A61K31/407 ,  A61P3/10 ,  A61P25/28 ,  A61P43/00 ,  C07D207/16 ,  C07D498/14

Abstract: SE REFIERE A D-PROLINAS DE FORMULA I Y IA DONDE R1, R2 SON ALCOXI, ALQUENILOXI, BENCILOXI, HIDROXI, -CH(CH3)OC(O)-ALQUILO CON LA CONDICION DE QUE SOLAMENTE UNO DE R1 Y R2 PUEDE SER OH; R3 Y R4 SON H, ALQUILO, ALQUENIL, CICLOALQUILO; R1 Y R2 JUNTO A C AL QUE ESTAN UNIDOS FORMAN EL GRUPO DE ENLACE X EN CUYO CASO E ES -C(CH2)nCH=CH(CH2)nO-; n ES 1-3. SON COMPUESTOS PREFERIDOS (R)-1-[6-[(R)-2-CARBAMOILMETOXICARBONIL-PIRROLIDIN-1-IL]-6-OXO-HEXANOIL]-PIRROLIDINA-2-CARBOXILATO DE CARBAMOILMETILO, (R)-1-[6-[(R)-2-ALILCARBAMOILMETOXICARBONILMETOXICARBONIL-PIRROLIDIN-1-IL]-6-OXO-HEXANOIL]-PIRROLIDINA-2-CARBOXILATO DE ALILCARBAMOILMETILO, (R)-1-{6-[(R)-2-(ISOPROPILCARBAMOIL-METOXICARBONIL)-PIRROLIDIN-1-IL]-6-OXO-HEXANOIL]-PIRROLIDINA-2-CARBOXILATO DE ISOPROPILCARBAMOIL-METILO, ENTRE OTROS. LOS COMPUESTOS MENCIONADOS SON UTILES PARA EL TRATAMIENTO DE AMILOIDOSIS CENTRAL O SISTEMICA COMO ALZHEIMER, DIABETES MELLITUS SENIL

公开(公告)号：PE07512003A1

公开(公告)日：2003-09-05

申请号：PE0011892002

申请日：2002-12-10

Applicant: HOFFMANN LA ROCHE

Inventor： FLOHR ALEXANDER ,  RIEMER CLAUS ,  NORCROSS ROGER DAVID ,  JAKOB-ROETNE ROLAND

IPC: C07D277/82 ,  A61K31/428 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/5377 ,  A61P9/10 ,  A61P11/00 ,  A61P21/02 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P43/00 ,  C07D277/84 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

CPC classification number: C07D417/04 ,  C07D277/84 ,  C07D417/12 ,  C07D417/14

Abstract: SE REFIERE A BENZOTIAZOLES DE FORMULA I DONDE R1 ES 3,6-DIHIDRO-2H-PIRAN-4-ILO, 5,6-DIHIDRO-4H-PIRAN-3-ILO, 5,6-DIHIDRO-4H-PIRAN-2-ILO, ENTRE OTROS; R2 ES ALQUILO, PIPERIDIN-1-ILO, FENILO,A LQUILO, MORFOLINILO, PIRIDINILO, ENTRE OTROS; n ES 0-2; R' ES H, ALQUILO. SON COMPUESTOS PREFERIDOS 4-FLUOR-N-[4-METOXI-7-(TETRAHIDROPIRAN-4-IL)-BENZOTIAZOL-2-IL]BENZAMIDA; N-[7-(1-ACETIL-1,2,3,6-TETRAHIDROPIRIDIN-4-IL)-4-METOXI-BENZOTIAZOL-2-IL]-4-FLUORBENZAMIDA; (7-CICLOHEX-1-ENIL-4-METOXI-BENZOTIAZOL-2-IL)CARBAMATO DE METILO, ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDIMIENTO PARA LA PREPARACION. LOS COMPUESTOS SON LIGANDOS DEL RECEPTOR DE ADENOSINA A2A Y PUEDEN SER UTILES PARA EL TRATAMIENTO DE ENFERMEDAD ALZHEIMER, PARKINSON, HUNTINGTON, NEUROPROTECCION, ESQUIZOFRENIA, ANSIEDAD, DOLOR, DEFICIENCIAS RESPIRATORIAS