公开(公告)号：KR840000993B1

公开(公告)日：1984-07-13

申请号：KR800003823

申请日：1980-10-04

Applicant: HOFFMANN LA ROCHE

Inventor： FELY WILLY HAE ,  KYBURZ EMILIO ,  PIERI LORENZO ,  HUNKELER WALTER ,  MOEHLER HANS ,  POLC PETAR

IPC: C07D243/14 ,  C07D265/26 ,  C07D333/42 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  C07D495/22 ,  C07D498/04

公开(公告)号：KR840000991B1

公开(公告)日：1984-07-13

申请号：KR840002837

申请日：1984-05-24

Applicant: HOFFMANN LA ROCHE

Inventor： FELY WILLY HAE ,  KYBURZ EMILIO ,  PIERI LORENZO ,  HUNKELER WALTER ,  MOEHLER HANS ,  POLC PETAR

IPC: C07D495/00 ,  C07D487/04

公开(公告)号：KR840000992B1

公开(公告)日：1984-07-13

申请号：KR840002838

申请日：1984-05-24

Applicant: HOFFMANN LA ROCHE

Inventor： FELY WILLY HAE ,  KYBURZ EMILIO ,  PIERI LORENZO ,  HUNKELER WALTER ,  MOEHLER HANS ,  POLC PETAR

IPC: C07D243/14 ,  C07D265/26 ,  C07D333/42 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  C07D495/22 ,  C07D498/04

公开(公告)号：KR840000990B1

公开(公告)日：1984-07-13

申请号：KR840002836

申请日：1984-05-24

Applicant: HOFFMANN LA ROCHE

Inventor： FELY WILLY HAE ,  KYBURZ EMILIO ,  PIERI LORENZO ,  HUNKELER WALTER ,  MOEHLER HANS ,  POLC PETAR

IPC: C07D243/14 ,  C07D265/26 ,  C07D333/42 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  C07D495/22 ,  C07D498/04

公开(公告)号：KR840000989B1

公开(公告)日：1984-07-13

申请号：KR840002835

申请日：1984-05-24

Applicant: HOFFMANN LA ROCHE

Inventor： FELY WILLY HAE ,  KYBURZ EMILIO ,  PIERI LORENZO ,  HUNKELER WALTER ,  MOEHLER HANS ,  POLC PETAR

IPC: C07D243/14 ,  C07D265/26 ,  C07D333/42 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  C07D495/22 ,  C07D498/04

公开(公告)号：JP2000053635A

公开(公告)日：2000-02-22

申请号：JP741099

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

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful in treating or preventing central nervous system disorders. SOLUTION: This new compound is shown by formula I (R1 is H; R2 is H, trifluoromethyl or the like; R3 is H or amino; Z is pyrimidin-4-yl, pyridin-4-yl, pyridin-2-yl, phenyl or the like; R4 and R5 are each H, a halogen, cyano or the like; (n) is 2-4; R6 and R7 are each H or a lower alkyl; when Z is pyrimidin-4-yl, R4 is different from R5; when Z is pyridin-2-yl, R is not a lower alkyl; when Z is phenyl, one of R4 and R1 to R3 is not H), e.g. [4-(4- aminobenzenesulfonyl)-6-bromopyridin-2-yl]-dimethylamine. The compound of formula I is obtained, for example, by oxidizing the sulfanyl group of a compound of formula II into sulfonyl group through reaction with an oxidizing agent such as NAIO4 or m-chloroperbenzenecarboxylic acid.

公开(公告)号：JP2000247957A

公开(公告)日：2000-09-12

申请号：JP2000047003

申请日：2000-02-24

Applicant: HOFFMANN LA ROCHE

Inventor： BOS 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

Abstract: PROBLEM TO BE SOLVED: To obtain a new 4-phenylpyridine derivative which is a neurokinin 1 receptor antagonist and is useful for pain, headache, Alzheimer's disease, multiple sclerosis, amorphinism relaxation, cardiovascular change, swelling, chronic inflammatory diseases, respiratory diseases, and the like. SOLUTION: A compound of formula I [R is H, a lower alkyl, a lower alkoxy, a halogen or the like; R1 is H or a halogen; R2, R2' are each H, a halogen, trifluoromethyl, a lower alkoxy or cyano, or R and R1, R2 and R2' together form CH=CH-CH=CH which may be substituted by one or more alkyls or the like; R3 is H, a lower alkyl or a cycloalkyl; R4 is H, N(R5)2 (R5 is H, a 3-6C cycloalkyl or the like) or the like; R6 is H, OH, a lower alkyl or the like; X is C(O)N(R5) or the like; (n) is 0-4; (m) is 1 or 2]. For example, N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-4-o-tolyl-nicotinamide. The compound of formula I is obtained, for example, by reacting a compound of formula II with a compound of formula III.

公开(公告)号：WO0050398A3

公开(公告)日：2001-04-05

申请号：PCT/EP0001224

申请日：2000-02-15

Applicant: HOFFMANN LA ROCHE

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

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

CPC classification number: C07D213/75 ,  C07C233/29 ,  C07C233/33 ,  C07C233/44 ,  C07C317/40 ,  C07C323/41 ,  C07D295/135

Abstract: The invention relates to compounds of general formula (I), 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 is hydrogen, halogen, trifluoromethyl, lower alkoxy or cyano; R is independently from each other hydrogen, lower alkyl or form a cycloalkyl group; R is hydrogen, halogen, lower alkyl, lower alkoxy, -N(R )2, -N(R )S(O)2-lower alkyl, -N(R )C(O)R or a cyclic tertiary amine of the group (a); R is, independently from each other, hydrogen, C3-6-cycloalkyl, benzyl or lower alkyl; R is hydrogen, hydroxy, lower alkyl, -N(R )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(R )-, -(CH2)mO-, -(CH2)mN(R )-, -N(R ) C(O)-, C(O)O- or -N(R )(CH2)m-; Y is -(CH2)n-, -O-, -S-, SO2-, -C(O)- or -N(R )-; 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.

Abstract translation: 本发明涉及通式（I）的化合物，其中R是氢，低级烷基，低级烷氧基，卤素或三氟甲基; R 1是氢或卤素; 或R和R 1可以一起是-CH = CH-CH = CH-; R 2是氢，卤素，三氟甲基，低级烷氧基或氰基; R 3彼此独立地为氢，低级烷基或形成环烷基; R 4是氢，卤素，低级烷基，低级烷氧基，-N（R 5）2，-N（R 5）S（O）2-低级烷基，-N（R 5） C（O）R 5或（a）组的环状叔胺; R 5彼此独立地为氢，C 3-6 - 环烷基，苄基或低级烷基; R 6是氢，羟基，低级烷基，-N（R 5）CO-低级烷基，羟基 - 低级烷基，氰基，-CHO或5-或6-元杂环基，任选经由亚烷基键合 ，X是-C（O）N（R 5） - ， - （CH 2）m O - ， - （CH 2）m N（R 5） - ， - N（R 5）C（O） ，C（O）O-或-N（R 5）（CH 2）m - ; Y是 - （CH 2）n - ， - O - ， - S - ，SO 2 - ， - C（O） - 或-N（R 5） Z是= N-，-CH =或-C（C1）=; n为0-4; 是1或2; 及其药学上可接受的酸加成盐。 已经表明式（I）化合物对NK-1受体具有高亲和力。

公开(公告)号：WO0117999A3

公开(公告)日：2001-12-06

申请号：PCT/EP0008372

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

CPC classification number: C07D471/04

Abstract: The invention relates to compounds of formula (I) wherein R is a 5 or 6 membered heteroaryl group, optionally substituted and optionally linked to the pyrazole ring via an alkylene or alkenyle group, or is phenyl, optionally substituted or is -O(CH2)nphenyl, benzofuryl, indolyl or benzothiophenyl, or is -S-lower alkyl; R and R are independently from each other hydrogen, cyano or -S(O)2-phenyl; R is hydrogen, halogen or is heteroaryl or phenyl, optionally substituted -NR'R" or -O-phenyl, or is -benzo[1,3]dioxolyl, -1H-indol-5-yl, naphthyl, benzofuran-2-yl, 1,3,4,9-tetrahydro-b-carbolin-2-yl, piperidin-1-yl, pyrrolidin-1-yl, piperazin-4-yl-methyl or morpholinyl; R is -NR2, n is 0-4 and their pharmaceutically acceptable salts. These compounds are adenosine receptor ligands.

Abstract translation: 本发明涉及式（I）化合物，其中R 1是5或6元杂芳基，任选被取代并任选地通过亚烷基或烯基连接到吡唑环上，或者是苯基，任选被取代或是-O （CH 2）n苯基，苯并呋喃基，吲哚基或苯并噻吩基，或是-S-低级烷基; R 2和R 4彼此独立地为氢，氰基或-S（O）2 - 苯基; R 3是氢，卤素或是杂芳基或苯基，任选取代的-NR'R“或-O-苯基，或是 - 苯并[1,3]二氧杂环戊烯基，-1H-吲哚-5-基，萘基，苯并呋喃 -2-基，1,3,4,9-四氢-b-咔啉-2-基，哌啶-1-基，吡咯烷-1-基，哌嗪-4-基 - 甲基或吗啉基; R 5是 -NR2，n为0-4及其药学上可接受的盐，这些化合物是腺苷受体配体。

公开(公告)号：WO0073278A2

公开(公告)日：2000-12-07

申请号：PCT/EP0004702

申请日：2000-05-24

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

CPC classification number: C07D239/28 ,  C07D239/34 ,  C07D239/42 ,  C07D239/47 ,  C07D239/48

Abstract: The invention relates to compounds of general formula (I) wherein R 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 independently from each other 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 be together with the two carbon ring atoms -CH=CH-CH=CH-, with the proviso that n for R is 1; n is independently 0 - 2; and X is -C(O)N(R )- or -N(R )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.

Abstract translation: 本发明涉及通式（I）的化合物，其中R 1是氢或卤素; R 2是氢，卤素，低级烷基或低级烷氧基; R 3是卤素，三氟甲基，低级烷氧基或低级烷基; R 4 / R 4彼此独立地为氢或低级烷基; - （CH 2）n - 吗啉基， - （CH 2）n + 1-烷基， - （CH 2）n - 咪唑基，-O-（CH 2）n + 1-吗啉基，-O-（CH 2）n + 1-哌啶基，低级烷基 - 硫烷基，低级烷基 - 磺酰基，苄基氨基，-NH-（CH 2）n + 4“>）2， - （CH 2）n -NH-（CH 2）n + 1N（R 4”）2， - （CH 2）n + 1N（R 4“）2或-O- CH 2）n + 1N（R 4“）2，其中R 4是氢或低级烷基; R 6是氢; R 2和R 6或R 1和R” 6>可以与两个碳环原子-CH = CH-CH = CH-一起，条件是R 1的n为1; n独立地为0-2;且X为-C（O）N （R 4） - 或-N（R 4）C（O） - 及其药学上可接受的酸加成盐。式（I）化合物对NK-1受体具有高亲和力 因此可用于与该受体相关的治疗或疾病。