公开(公告)号：TR200102585T2

公开(公告)日：2002-01-21

申请号：TR200102585

申请日：2000-02-28

Applicant: HOFFMANN LA ROCHE

Inventor： BOES MICHAEL ,  GALLEY GUIDO ,  GODEL THIERRY ,  HOFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK ,  STADLER HEINZ

IPC: C07D295/14 ,  A61K31/166 ,  A61K31/167 ,  A61K31/495 ,  A61K31/496 ,  A61P1/04 ,  A61P1/08 ,  A61P11/06 ,  A61P25/24 ,  A61P25/28 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07C41/01 ,  C07C43/174 ,  C07C209/06 ,  C07C209/50 ,  C07C211/29 ,  C07C211/45 ,  C07C217/54 ,  C07C231/02 ,  C07C231/08 ,  C07C233/11 ,  C07C233/15 ,  C07C233/44 ,  C07C233/66 ,  C07C235/42 ,  C07D295/155

Abstract: The invention relates to compounds of the formulawhereinR is hydrogen, lower alkyl, lower alkoxy halogen, amino, -N(R6)2 or trifluoromethyl;R1 is hydrogen lower alkoxy or halogen,R and R1 may be together -CH=CH-CH=CH-;R2 is halogen, lower alkyl or trifluoromethyl;R3 is hydrogen or lower alkyl;R4 is hydrogen or a cyclic tertiary amine, optionally substituted by lower alkyl;R5 is hydrogen, nitro, amino or -N(R6)2;R6 is hydrogen or lower alkyl,X is -C(O)N(R6)-, -(CH2)nO-, (CH2)nN(R6)-, -N(R6)C(O)- or -N(R6)(CH2)n-; andn is 1 or 2;and pharmaceutically acceptable acid addition salts thereof.The compounds of formula I may be used for the treatment of diseases related to the NK-1 receptor.

公开(公告)号：NO20015701L

公开(公告)日：2001-11-22

申请号：NO20015701

申请日：2001-11-22

Applicant: HOFFMANN LA ROCHE

Inventor： BOES MICHAEL ,  GALLEY GUIDO ,  GODEL THIERRY ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK ,  STADLER HEINZ

IPC: A61K31/505 ,  A61K31/506 ,  A61K31/513 ,  A61K31/5377 ,  A61P1/04 ,  A61P1/08 ,  A61P9/00 ,  A61P11/02 ,  A61P11/06 ,  A61P17/02 ,  A61P25/00 ,  A61P25/06 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D213/00 ,  C07D239/00 ,  C07D239/28 ,  C07D239/34 ,  C07D239/38 ,  C07D239/42 ,  C07D239/46 ,  C07D239/48 ,  C07D295/00 ,  C07D401/04

Abstract: Compounds of the general formula are described:whereinR is hydrogen or halogen;R is hydrogen, halogen, lower alkyl or lower alkoxy;R is halogen, trifluoromethyl, lower alkoxy or lower alkyl;R /R are each independently hydrogen or lower alkyl;R is lower alkyl, lower alkoxy, amino, hydroxy, hydroxy-lower alkyl, -(CH2)n-piperazinyl, optionally substituted by lower alkyl, -(CH2)n-morpholinyl, -(CH2)n+1-imidazolyl, -O-(CH2)n+1-morpholinyl, -O-(CH2)n+1-piperidinyl, lower alkyl-sulfanyl, lower alkyl-sulfonyl, benzylamino, -NH-(CH2)n+1N(R )2, -(CH2)n-NH-(CH2)n+1N(R )2, -(CH2)n+1N(R )2, or -O-(CH2)n+1N(R )2, wherein R is hydrogen or lower alkyl;R is hydrogen;R and R or R and R may together be -CH=CH-CH=CH-, wherein R and R or R and R , respectively, together with the two carbon ring atoms to which they are attached form a fused ring, with the proviso that n for R is 1;n is independently 0-2; andX is -C(O)N(R )- or -N(R )C(O)-;and pharmaceutically acceptable acid addition salts thereof.

公开(公告)号：NO20015700D0

公开(公告)日：2001-11-22

申请号：NO20015700

申请日：2001-11-22

Applicant: HOFFMANN LA ROCHE

Inventor： BOES MICHAEL ,  GALLEY GUIDO ,  GODEL THIERRY ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK ,  STADLER HEINZ

IPC: A61K31/496 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5377 ,  A61P1/04 ,  A61P1/08 ,  A61P9/00 ,  A61P11/06 ,  A61P17/02 ,  A61P19/02 ,  A61P25/00 ,  A61P25/06 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/36 ,  A61P27/00 ,  A61P27/02 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D213/00 ,  C07D239/00 ,  C07D239/28 ,  C07D239/32 ,  C07D239/34 ,  C07D239/38 ,  C07D239/42 ,  C07D239/48 ,  C07D295/00 ,  C07D401/04 ,  C07D403/04 ,  C07D

Abstract: The invention provides compounds of the formulawhereinR1 is hydrogen or halogen;R2 is hydrogen, halogen, lower alkyl or lower alkoxy;R1 and R2 may together be -CH=CH-CH=CH-, wherein R1 and R2 together with the two carbon ring atoms to which they are attached form a fused ring;R3 is halogen, trifluoromethyl, lower alkyl or lower alkoxy;R4/R4' are each independently hydrogen or lower alkyl;R5 is lower alkyl, lower alkoxy, amino, phenyl, hydroxy-lower alkyl, cyano-lower alkyl, carbamoyl-lower alkyl, pyridyl, pyrimidyl, -(CH2)n-piperazinyl, which is optionally substituted by one or two lower alkyl groups or by hydroxy-lower alkyl, -(CH2)n-morpholinyl, -(CH2)n-piperidinyl, -(CH2)n+1-imidazolyl, lower alkyl-sulfanyl, lower alkyl-sulfonyl, benzylamino, -NH-(CH2)n+1N(R4'')2, -(CH2)n+1N(R4'')2, -O-(CH2)n+1-morpholinyl, -O-(CH2)n+1-piperidinyl or -O-(CH2)n+1N(R4'')2, wherein R4'' is hydrogen or lower alkyl; andn is 0-2;X is -C(O)N(R4'')- or -N(R4'')C(O)-;and to pharmaceutically acceptable acid addition salts thereof.It has been shown that the compounds have a good affinity to the NK-1 receptor and may therefore used for the treatment of diseases related to this receptor.

公开(公告)号：NO20014098D0

公开(公告)日：2001-08-23

申请号：NO20014098

申请日：2001-08-23

Applicant: HOFFMANN LA ROCHE

Inventor： BOES MICHAEL ,  GALLEY GUIDO ,  GODEL THIERRY ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK ,  STADLER HEINZ

IPC: A61K31/44 ,  A61P25/00 ,  A61P29/00 ,  C07D213/30 ,  C07D213/38 ,  C07D213/75 ,  C07D213/81 ,  C07D401/04 ,  C07D

Abstract: The invention relates to compounds of the formulawhereinR is hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl;R1 is hydrogen or halogen; orR and R1 may be together -CH=CH-CH=CH-;R2 is hydrogen, halogen, trifluoromethyl, lower alkoxy or cyano;R3 is hydrogen, lower alkyl or form a cycloalkyl group;R4 is hydrogen, -N(R5)2, -N(R5)S(O)2-lower alkyl, -N(R5)C(O)R5 or a cyclic tertiary amine of the groupR5 is, independently from each other, hydrogen, C3-6-cycloalkyl, benzyl or lower alkyl;R6 is hydrogen, hydroxy, lower alkyl, -N(R5)CO-lower alkyl, hydroxy-lower alkyl, cyano, -CHO or a 5- or 6 membered heterocyclic group, optionally bonded via an alkylene group,X is -C(O)N(R5)-, -(CH2)mO-, -(CH2)mN(R5)-, -N(R5)C(O)-, or -N(R5)(CH2)m-;n is 0-4; andm is 1 or 2;and to pharmaceutically acceptable acid addition salts thereof.It has been shown that the above mentioned compounds have a good affinity to the NK-1 receptor.

公开(公告)号：NO20014096D0

公开(公告)日：2001-08-23

申请号：NO20014096

申请日：2001-08-23

Applicant: HOFFMANN LA ROCHE

Inventor： BOES MICHAEL ,  GALLEY GUIDO ,  GODEL THIERRY ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK ,  STADLER HEINZ

IPC: A61K31/167 ,  C07C211/44 ,  A61K31/44 ,  A61P25/00 ,  A61P29/00 ,  C07C211/54 ,  C07C233/29 ,  C07C233/33 ,  C07C233/44 ,  C07C317/14 ,  C07C317/40 ,  C07C323/41 ,  C07D213/75 ,  C07D213/79 ,  C07D213/81 ,  C07D295/12 ,  C07D295/135 ,  C07D401/04 ,  C07D

Abstract: The present invention is a series of compounds formed from phenyl substituted pyridine or benzene derivatives and their pharmaceutically acceptable salts. These compounds have shown high affinity as antagonists to the NK-1 receptor.

公开(公告)号：EA200000155A3

公开(公告)日：2000-12-25

申请号：EA200000155

申请日：2000-02-23

Applicant: HOFFMANN LA ROCHE

Inventor： BOES MICHAEL ,  GODEL THIERRY ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK ,  GALLEY GUIDO ,  STADLER HEINZ ,  BRANKA KIRIKO

IPC: A61K20060101 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/444 ,  A61K31/455 ,  A61K31/496 ,  A61P1/00 ,  A61P9/00 ,  A61P11/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/28 ,  A61P25/30 ,  A61P27/02 ,  A61P29/00 ,  A61P43/00 ,  C07D20060101 ,  C07D213/30 ,  C07D213/38 ,  C07D213/40 ,  C07D213/63 ,  C07D213/65 ,  C07D213/74 ,  C07D213/75 ,  C07D213/78 ,  C07D213/82 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D413/14

Abstract: Взаявкеописанысоединенияобщейформулывкоторой R обозначаетводород, (низш.)алкил, (низш.)алкокси, галогенилитрифторметил, Rобозначаетводородилигалоген, либо R и Rсовместномогутобразовыватьгруппу -CH=CH-CH=CH-, Rи Rкаждыйнезависимодруготдругаобозначаетводород, галоген, трифторметил, (низш.)алкоксиилицианогруппу, либо Rи Rсовместномогутобразовыватьгруппу -CH=CH-CH=CH-, необязательнозамещеннуюоднимилидвумязаместителями, выбраннымииз (низш.)алкилаи (низш.)алкокси, Rобозначаетводород, (низш.)алкилилиобразуетциклоалкильнуюгруппу, Rобозначаетводород, -N(R), -N(R)(CH)-OH, -N(R)S(O)-(низш.)алкил, -N(R)S(O)-фенил, -N=CHN(R), -N(R)C(O)RилициклическийтретичныйаминовыйрадикалоднойизследующихгруппRвкаждомслучаенезависимообозначаетводород, C-Cциклоалкил, бензилили (низш.)алкил, Rобозначаетводород, гидроксил, (низш.)алкил, -(CH)COO(низш.)алкил, -N(R)CO-(низш.)алкил, гидрокси(низш.)алкил, цианогруппу, -(CH)O(CH)OH, -CHO или 5- или 6-членнуюгетероциклическуюгруппу, необязательносвязаннуюпосредствомалкиленовойгруппы, X обозначает -C(O)N(R)-, -(CH)O-, -(CH)N(R)-, -N(R)C(O)- или -N(R)(CH)-, n обозначает 0-4 и m обозначает 1 или 2, иихфармацевтическиприемлемыекислотно-аддитивныесоли. Соединенияформулы I проявляютвысокоесродствок рецептору NK-1. Онимогутбытьиспользованыдлялечениязаболеваний, которыесвязаныс антагонистамирецептора NK-1.

公开(公告)号：CA2375670A1

公开(公告)日：2000-12-07

申请号：CA2375670

申请日：2000-05-24

Applicant: HOFFMANN LA ROCHE

Inventor： SCHNIDER PATRICK ,  GODEL THIERRY ,  GALLEY GUIDO ,  BOES MICHAEL ,  HUNKELER WALTER ,  HOFFMANN TORSTEN ,  STADLER HEINZ

IPC: A61K31/505 ,  A61K31/506 ,  A61K31/513 ,  A61K31/5377 ,  A61P1/04 ,  A61P1/08 ,  A61P9/00 ,  A61P11/02 ,  A61P11/06 ,  A61P17/02 ,  A61P25/00 ,  A61P25/06 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D213/00 ,  C07D239/00 ,  C07D239/28 ,  C07D239/34 ,  C07D239/38 ,  C07D239/42 ,  C07D239/46 ,  C07D239/48 ,  C07D295/00 ,  C07D401/04

Abstract: The invention relates to compounds of general formula (I) wherein R1 is hydrogen or halogen; R2 is hydrogen, halogen, lower alkyl or lower alkoxy; R 3 is halogen, trifluoromethyl, lower alkoxy or lower alkyl; R4/R4' are independently from each other hydrogen or lower alkyl; R5 is lower alkyl, lower alkoxy, amino, hydroxy, hydroxy-lower alkyl, -(CH2)n-piperazinyl, optionally substituted by lower alkyl, -(CH2)n-morpholinyl, -(CH2)n+1- imidazolyl, -O-(CH2)n+1-morpholinyl, -O-(CH2)n+1-piperidinyl, lower alkyl- sulfanyl, lower alkyl-sulfonyl, benzylamino, -NH-(CH2)n+1N(R4")2, -(CH2)n-NH - (CH2)n+1N(R4")2, -(CH2)n+1N(R4")2, or -O-(CH2)n+1N(R4")2, wherein R4" is hydrogen or lower alkyl; R6 is hydrogen; R2 and R6 or R1 and R6 may be together with the two carbon ring atoms -CH=CH-CH=CH-, with the proviso that n for R1 is 1; n is independently 0 - 2; and X is -C(O)N(R4")- or -N(R4")C(O)- ; and pharmaceutically acceptable acid addition salts thereof. Compounds of formula (I) have a high affinity to the NK-1 receptor. They are therefore useful for the treatment or diseases which relate to this receptor.

公开(公告)号：EA200000155A2

公开(公告)日：2000-08-28

申请号：EA200000155

申请日：2000-02-23

Applicant: HOFFMANN LA ROCHE

Inventor： BOES MICHAEL ,  GODEL THIERRY ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK ,  GALLEY GUIDO ,  STADLER HEINZ ,  BRANKA KIRIKO

IPC: A61K20060101 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/444 ,  A61K31/455 ,  A61K31/496 ,  A61P1/00 ,  A61P9/00 ,  A61P11/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/28 ,  A61P25/30 ,  A61P27/02 ,  A61P29/00 ,  A61P43/00 ,  C07D20060101 ,  C07D213/30 ,  C07D213/38 ,  C07D213/40 ,  C07D213/63 ,  C07D213/65 ,  C07D213/74 ,  C07D213/75 ,  C07D213/78 ,  C07D213/82 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D413/14

Abstract: Взаявкеописанысоединенияобщейформулывкоторой R обозначаетводород, (низш.)алкил, (низш.)алкокси, галогенилитрифторметил, Rобозначаетводородилигалоген, либо R и Rсовместномогутобразовыватьгруппу -CH=CH-CH=CH-, Rи Rкаждыйнезависимодруготдругаобозначаетводород, галоген, трифторметил, (низш.)алкоксиилицианогруппу, либо Rи Rсовместномогутобразовыватьгруппу -CH=CH-CH=CH-, необязательнозамещеннуюоднимилидвумязаместителями, выбраннымииз (низш.)алкилаи (низш.)алкокси, Rобозначаетводород, (низш.)алкилилиобразуетциклоалкильнуюгруппу, Rобозначаетводород, -N(R), -N(R)(CH)-OH, -N(R)S(O)-(низш.)алкил, -N(R)S(O)-фенил, -N=CHN(R), -N(R)C(O)RилициклическийтретичныйаминовыйрадикалоднойизследующихгруппRвкаждомслучаенезависимообозначаетводород, C-Cциклоалкил, бензилили (низш.)алкил, Rобозначаетводород, гидроксил, (низш.)алкил, -(CH)COO(низш.)алкил, -N(R)CO-(низш.)алкил, гидрокси(низш.)алкил, цианогруппу, -(CH)O(CH)OH, -CHO или 5- или 6-членнуюгетероциклическуюгруппу, необязательносвязаннуюпосредствомалкиленовойгруппы, X обозначает -C(O)N(R)-, -(CH)O-, -(CH)N(R)-, -N(R)C(O)- или -N(R)(CH)-, n обозначает 0-4 и m обозначает 1 или 2, иихфармацевтическиприемлемыекислотно-аддитивныесоли. Соединенияформулы I проявляютвысокоесродствок рецептору NK-1. Онимогутбытьиспользованыдлялечениязаболеваний, которыесвязаныс антагонистамирецептора NK-1.

公开(公告)号：HK1022310A1

公开(公告)日：2000-08-04

申请号：HK00101191

申请日：2000-02-28

Applicant: HOFFMANN LA ROCHE

Inventor： BOES MICHAEL ,  HUNKELER WALTER ,  RIEMER CLAUS

IPC: C07C309/30 ,  A61K31/00 ,  A61K31/10 ,  A61K31/135 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/4433 ,  A61K31/4436 ,  A61K31/505 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07C315/04 ,  C07C317/22 ,  C07C317/32 ,  C07C317/36 ,  C07D213/61 ,  C07D213/62 ,  C07D213/71 ,  C07D213/73 ,  C07D213/74 ,  C07D213/84 ,  C07D239/38 ,  C07D401/04 ,  C07D401/14 ,  C07D409/04 ,  C07D ,  C07C ,  A61K

Abstract: The present invention relates to novel compounds of the general formula wherein R is hydrogen; R is hydrogen, trifluoromethyl or lower alkyl; R is hydrogen or amino; or R and R or R and R taken together are -CH=CH-CH=CH-; Z is pyrimidin-4-yl, pyridin-4-yl, pyridin-2-yl or phenyl; R R are each independently hydrogen, lower alkyl, trifluoromethyl, halogen, lower alkoxy, nitrilo, amino, lower alkyl-amino, di-lower alkyl-amino, piperazinyl, morpholinyl, pyrrolidinyl, vinyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, t-buthylethinyl, hydroxyalkylethinyl, phenylethinyl, naphthyl, thiophenyl, or phenyl, which may be substituted by halogen, lower alkoxy, lower alkyl, trifluoromethyl or nitro, or a group -NH(CH2)nNR R , -N(CH3)(CH2)nNR R , -NH(CH2)n-morpholin-4-yl or -NH(CH2)nOH; n is 2-4 R and R are each independently hydrogen or lower alkyl, and to their pharmaceutically acceptable salts. It has been found that the compounds of formula I possess a selective affinity to 5HT-6 receptors.

公开(公告)号：SG71898A1

公开(公告)日：2000-04-18

申请号：SG1999000077

申请日：1999-01-13

Applicant: HOFFMANN LA ROCHE

Inventor： BOES MICHAEL ,  HUNKELER WALTER ,  RIEMER CLAUS

IPC: C07C309/30 ,  A61K31/00 ,  A61K31/10 ,  A61K31/135 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/4433 ,  A61K31/4436 ,  A61K31/505 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07C315/04 ,  C07C317/22 ,  C07C317/32 ,  C07C317/36 ,  C07D213/61 ,  C07D213/62 ,  C07D213/71 ,  C07D213/73 ,  C07D213/74 ,  C07D213/84 ,  C07D239/38 ,  C07D401/04 ,  C07D401/14 ,  C07D409/04

Abstract: The present invention relates to novel compounds of the general formula wherein R is hydrogen; R is hydrogen, trifluoromethyl or lower alkyl; R is hydrogen or amino; or R and R or R and R taken together are -CH=CH-CH=CH-; Z is pyrimidin-4-yl, pyridin-4-yl, pyridin-2-yl or phenyl; R R are each independently hydrogen, lower alkyl, trifluoromethyl, halogen, lower alkoxy, nitrilo, amino, lower alkyl-amino, di-lower alkyl-amino, piperazinyl, morpholinyl, pyrrolidinyl, vinyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, t-buthylethinyl, hydroxyalkylethinyl, phenylethinyl, naphthyl, thiophenyl, or phenyl, which may be substituted by halogen, lower alkoxy, lower alkyl, trifluoromethyl or nitro, or a group -NH(CH2)nNR R , -N(CH3)(CH2)nNR R , -NH(CH2)n-morpholin-4-yl or -NH(CH2)nOH; n is 2-4 R and R are each independently hydrogen or lower alkyl, and to their pharmaceutically acceptable salts. It has been found that the compounds of formula I possess a selective affinity to 5HT-6 receptors.