公开(公告)号：CA2364665A1

公开(公告)日：2000-08-31

申请号：CA2364665

申请日：2000-02-15

Applicant: HOFFMANN LA ROCHE

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

IPC: C07C211/44 ,  A61K31/167 ,  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

Abstract: The invention relates to compounds of general formula (I), wherein R is hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl; R1 is hydrogen or halogen; or R and R1 may be together -CH=CH-CH=CH-; R2 is hydrogen, halogen, trifluoromethyl, lower alkoxy or cyano; R3 is independent ly from each other hydrogen, lower alkyl or form a cycloalkyl group; R4 is hydrogen, halogen, lower alkyl, lower alkoxy, -N(R5)2, -N(R5)S(O)2-lower alkyl, -N(R5)C(O)R5 or a cyclic tertiary amine of the group (a); R5 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, optionall y bonded via an alkylene group, X is -C(O)N(R5)-, -(CH2)mO-, -(CH2)mN(R5)-, - N(R5) C(O)-, C(O)O- or -N(R5)(CH2)m-; Y is -(CH2)n-, -O-, -S-, SO2-, -C(O)- or -N(R5)-; Z is =N-, -CH= or -C(C1)=; n is 0 - 4; and, is 1 or 2; and to pharmaceutically acceptable acid addition salts thereof. It has been shown that the compounds of formula (I) have a high affinity to the NK-1 receptor.

公开(公告)号：CA2364662A1

公开(公告)日：2000-08-31

申请号：CA2364662

申请日：2000-02-15

Applicant: HOFFMANN LA ROCHE

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

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

Abstract: The invention relates to compounds of formula (I) wherein R is hydrogen, low er alkyl, lower alkoxy, halogen or trifluoromethyl; R1 is hydrogen or halogen; or R 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 group (a); R5 is, independentl y 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; and m 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：IS5381A

公开(公告)日：2000-08-25

申请号：IS5381

申请日：2000-02-22

Applicant: HOFFMANN LA ROCHE

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

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 ,  A61K31/442

公开(公告)号：ZA200000894B

公开(公告)日：2000-08-24

申请号：ZA200000894

申请日：2000-02-23

Applicant: HOFFMANN LA ROCHE

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

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 ,  C07D ,  A61K

Abstract: The present invention relates to compounds of the general formula wherein R is hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl; R is hydrogen or halogen; or R and R may be together -CH=CH-CH=CH-; R and R are independently from each other hydrogen, halogen, trifluoromethyl, lower alkoxy or cyano; or R and R may be together -CH=CH-CH=CH-, optionally substituted by one or two substituents selected from lower alkyl or lower alkoxy; R is hydrogen, lower alkyl or form a cycloalkyl group; R is hydrogen, -N(R )2, -N(R )(CH2)nOH, -N(R )S(O)2-lower alkyl, -N(R )S(O)2-phenyl, -N=CH-N(R )2, -N(R )C(O)R or a cyclic tertiary amine of the group R is, independently from each other, hydrogen, C3-6-cycloalkyl, benzyl or lower alkyl; R is hydrogen, hydroxy, lower alkyl, -(CH2)nCOO-lower alkyl, -N(R )CO-lower alkyl, hydroxy-lower alkyl, cyano, -(CH2)nO(CH2)nOH, -CHO or a 5-or 6 membered heterocyclic group, optionally bonded via an alkylene group, X is -C(O)N(R )-, -(CH2)mO-, -(CH2)mN(R )-, -N(R )C(O)-, or -N(R )(CH2)m-; n is 0 - 4; and m is 1 or 2; and to pharmaceutically acceptable acid addition salts thereof. The compounds of formula I show a high affinity to the NK-1 receptor. They may be used for the treatment of diseases, which relate to NK-1 receptor antagonists.

公开(公告)号：NO20000885D0

公开(公告)日：2000-02-23

申请号：NO20000885

申请日：2000-02-23

Applicant: HOFFMANN LA ROCHE

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

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 ,  C07D

Abstract: The present invention relates to compounds of the general formula wherein R is hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl; R is hydrogen or halogen; or R and R may be together -CH=CH-CH=CH-; R and R are independently from each other hydrogen, halogen, trifluoromethyl, lower alkoxy or cyano; or R and R may be together -CH=CH-CH=CH-, optionally substituted by one or two substituents selected from lower alkyl or lower alkoxy; R is hydrogen, lower alkyl or form a cycloalkyl group; R is hydrogen, -N(R )2, -N(R )(CH2)nOH, -N(R )S(O)2-lower alkyl, -N(R )S(O)2-phenyl, -N=CH-N(R )2, -N(R )C(O)R or a cyclic tertiary amine of the group R is, independently from each other, hydrogen, C3-6-cycloalkyl, benzyl or lower alkyl; R is hydrogen, hydroxy, lower alkyl, -(CH2)nCOO-lower alkyl, -N(R )CO-lower alkyl, hydroxy-lower alkyl, cyano, -(CH2)nO(CH2)nOH, -CHO or a 5-or 6 membered heterocyclic group, optionally bonded via an alkylene group, X is -C(O)N(R )-, -(CH2)mO-, -(CH2)mN(R )-, -N(R )C(O)-, or -N(R )(CH2)m-; n is 0 - 4; and m is 1 or 2; and to pharmaceutically acceptable acid addition salts thereof. The compounds of formula I show a high affinity to the NK-1 receptor. They may be used for the treatment of diseases, which relate to NK-1 receptor antagonists.

公开(公告)号：PL330841A1

公开(公告)日：1999-07-19

申请号：PL33084199

申请日：1999-01-14

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 ,  C07C317/34 ,  C07D233/62 ,  C07D213/70

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：NO990187L

公开(公告)日：1999-07-19

申请号：NO990187

申请日：1999-01-15

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.

公开(公告)号：ZA99254B

公开(公告)日：1999-07-16

申请号：ZA99254

申请日：1999-01-14

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 ,  C07C ,  C07D ,  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：CA2258454A1

公开(公告)日：1999-07-16

申请号：CA2258454

申请日：1999-01-13

Applicant: HOFFMANN LA ROCHE

Inventor： RIEMER CLAUS ,  BOES MICHAEL ,  HUNKELER WALTER

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 ,  C07D239/46 ,  A61K31/495 ,  A61K31/535 ,  C07C323/65

Abstract: The present invention relates to novel compounds of the general formula (see formula I) wherein R1 is hydrogen; R2 is hydrogen, trifluoromethyl or lower alkyl; R3 is hydrogen or amino; or R1 and R2 or R3 and R2 taken together are -CH=CH-CH=CH-; Z is pyrimidin-4-yl, pyridin-4-yl, pyridin-2-yl or phenyl; R4, R5 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)n NR6R7, -N(CH3)(CH2)n NR6R7, -NH(CH2)n-morpholin-4-yl or -NH(CH2)n OH; n is 2-4 R6 and R7 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：BG62210B1

公开(公告)日：1999-05-31

申请号：BG9950595

申请日：1995-03-16

Applicant: HOFFMANN LA ROCHE

Inventor： GODEL THIERRY ,  HUNKELER WALTER ,  STADLER HEINZ ,  WIDMER ULRICH

IPC: A61K31/41 ,  A61K31/55 ,  A61K31/5517 ,  A61P21/02 ,  A61P25/08 ,  A61P25/20 ,  A61P43/00 ,  C07D487/02 ,  C07D487/04 ,  C07D495/12 ,  C07D495/14 ,  C07D498/14

Abstract: The imidazodiazepines have the general formulawhere A together with the carbon atoms marked by annd mean some ofthe ressiduesQ is one of the radicalsR1 and R2 means hydrogen, lower alkyl, lower alkenyl, loweralkynyl, lower hydroxyalkyl, lower alkoxy-lower alkyl,(C3-C6)-cycloalkyl, (C3-C6)-cycloalkyl-lower alkyl, amino-loweralkyl, lower alkylamino-lower alkyl, di-lower alkylamino-loweralkyl or aryl-lower alkyl or together with the nitrogen atomforming 5- to 8-member heterocyle, optionally containing anotherheteroatom or condensed benzole ring; R3 is hydrogen and R4 islower alkyl or R3 & R4 together mean di- or trimethylene group; R5& R6 mean hydrogen, halogen, trifluoromethyl, lower alkoxy ornitro, where the - marked carbon atom has S-configuration when R3is different from H, with strongly expressed anxylolithic,anticonvulsive, muscle-relaxing and sedative-hypnotic properties.The imidazodiazepines form very good water-soluble acidic-additivesalts and for this reason they are suitable for the production ofaqeous inoculaation solutions.33 claims