公开(公告)号：EA005680B1

公开(公告)日：2005-04-28

申请号：EA200200769

申请日：2001-01-16

Applicant: VERTEX PHARMA

Inventor： CHARIFSON PAUL ,  STAMOS DEAN ,  BADIA MICHAEL ,  GRILLOT ANNE-LAURE ,  RONKIN STEVEN ,  TRUDEAU MARTIN

IPC: C07D231/38 ,  A61K31/4155 ,  A61K31/421 ,  A61K31/422 ,  A61K31/427 ,  A61K31/454 ,  A61K31/5377 ,  A61P1/00 ,  A61P11/00 ,  A61P13/02 ,  A61P13/08 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/08 ,  A61P25/00 ,  A61P31/04 ,  A61P31/06 ,  A61P43/00 ,  C07D403/04 ,  C07D413/04 ,  C07D417/04 ,  C07D417/14

Abstract: Настоящееизобретениеотноситсяк соединениямформулы (I)вкоторыхкольцоА означаеттиазол, оксазол, имидазолилипиразол, азаместителиявляютсятакими, какопределенов описании, ик егофармацевтическиприемлемымсолям. Соединениеингибируетактивностьбактериальнойгиразыи поэтомуиспользуетсядлялечениябактериальныхинфекционныхзаболеваниймлекопитающих.

公开(公告)号：PT1251848E

公开(公告)日：2004-10-29

申请号：PT01903077

申请日：2001-01-16

Applicant: VERTEX PHARMA

Inventor： CHARIFSON PAUL ,  STAMOS DEAN ,  BADIA MICHAEL ,  GRILLOT ANNE-LAURE ,  RONKIN STEVEN ,  TRUDEAU MARTIN

IPC: C07D231/38 ,  A61K31/4155 ,  A61K31/421 ,  A61K31/422 ,  A61K31/427 ,  A61K31/454 ,  A61K31/5377 ,  A61P1/00 ,  A61P11/00 ,  A61P13/02 ,  A61P13/08 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/08 ,  A61P25/00 ,  A61P31/04 ,  A61P31/06 ,  A61P43/00 ,  C07D403/04 ,  C07D413/04 ,  C07D417/04 ,  C07D417/14

Abstract: The present invention relates to compounds of the formula I: where Ring A is a thiazole, oxazole, imidazole or pyrazole and the substituents are as described in the specification, and pharmaceutically acceptable salts thereof. The compounds inhibit bacterial gyrase activity and therefore are useful for treating bacterial infections in mammals.

公开(公告)号：DK1251848T3

公开(公告)日：2004-10-18

申请号：DK01903077

申请日：2001-01-16

Applicant: VERTEX PHARMA

Inventor： RONKIN STEVEN ,  CHARIFSON PAUL ,  STAMOS DEAN ,  BADIA MICHAEL ,  GRILLOT ANNE-LAURE ,  TRUDEAU MARTIN

IPC: C07D231/38 ,  A61K31/4155 ,  A61K31/421 ,  A61K31/422 ,  A61K31/427 ,  A61K31/454 ,  A61K31/5377 ,  A61P1/00 ,  A61P11/00 ,  A61P13/02 ,  A61P13/08 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/08 ,  A61P25/00 ,  A61P31/04 ,  A61P31/06 ,  A61P43/00 ,  C07D403/04 ,  C07D413/04 ,  C07D417/04 ,  C07D417/14

Abstract: The present invention relates to compounds of the formula I: where Ring A is a thiazole, oxazole, imidazole or pyrazole and the substituents are as described in the specification, and pharmaceutically acceptable salts thereof. The compounds inhibit bacterial gyrase activity and therefore are useful for treating bacterial infections in mammals.

公开(公告)号：NZ520628A

公开(公告)日：2004-05-28

申请号：NZ52062801

申请日：2001-01-16

Applicant: VERTEX PHARMA

Inventor： CHARIFSON PAUL ,  STAMOS DEAN ,  BADIA MICHAEL ,  GRILLOT ANNE-LAURE ,  RONKIN STEVEN ,  TRUDEAU MARTIN

IPC: C07D231/38 ,  A61K31/4155 ,  A61K31/421 ,  A61K31/422 ,  A61K31/427 ,  A61K31/454 ,  A61K31/5377 ,  A61P1/00 ,  A61P11/00 ,  A61P13/02 ,  A61P13/08 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/08 ,  A61P25/00 ,  A61P31/04 ,  A61P31/06 ,  A61P43/00 ,  C07D403/04 ,  C07D413/04 ,  C07D417/04 ,  C07D417/14

Abstract: A thiazol-5-yl pyrazole derivative or a pharmaceutically acceptable salt thereof has formula IA wherein: R1 is aliphatic, -C(R4)2(CH2)nNRCOR, -C(R4)=N-OR, -C(R4)=N-OC(=O)-aliphatic, -C(R4)=NNRCO2-aliphatic, -C(R4)=NNRCOR, -C(R4)=NN(R)2, -C(R4)2(CH2)nNRCO2-aliphatic, -CO2-aliphatic, -CON(R)2, -C(R4)2(CH2)nCON(R)2, -C(R4)2(CH2)nSO2N(R)2, -CONH-OR, -SO2N(R)2 or -C(R4)2(CH2)nNRSO2-aliphatic wherein the -CH2- and the aliphatic group can be optionally substituted group; n is 0 or 1; each R is independently hydrogen or an optionally substituted aliphatic group; R2 is hydrogen or, when R1 is -CO2-aliphatic or-CONH-aliphatic, R2 can be -halo, -CN, aliphatic, a three to five-membered heterocyclic, or a five-membered heteroaryl; Ring A is thiazole, oxazole, imidazole or pyrazole, with the imidazole being optionally attached by a C1-3 bridge from an imidazole ring nitrogen to Ar to form a five-to seven membered fused ring; Z is C-R3 or N-R3; R3 is- (CH2)pN(R5)2 or an optionally substituted aliphatic, heterocyclic, heterocyclylalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl; each R4 is independently hydrogen, an optionally substituted aliphatic group, or two R4 taken together with the carbon to which they are attached form a three to six membered aliphatic ring; each R5 is independently hydrogen, an optionally substituted aliphatic group, or two R5 taken together with the nitrogen to which they are attached form a five or six membered heterocyclic ring; p is 0 to 4 when Z is C-R3 or 1 to 4 when Z is N-R3 and Ar is an optionally substituted aryl, heteroaryl, or heterocyclic ring. The compounds are useful in treating bacterial infections.

公开(公告)号：CZ20013349A3

公开(公告)日：2002-03-13

申请号：CZ20013349

申请日：2000-03-17

Applicant: VERTEX PHARMA

Inventor： STAMOS DEAN ,  TRUDEAU MARTIN ,  BETHIEL SCOTT ,  BADIA MICHAEL ,  SAUNDERS JEFFREY

IPC: C07D307/20 ,  A61K31/27 ,  A61K31/275 ,  A61K31/341 ,  A61K31/421 ,  A61K31/422 ,  A61K31/454 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/00 ,  A61P1/18 ,  A61P9/10 ,  A61P11/06 ,  A61P19/02 ,  A61P29/00 ,  A61P31/12 ,  A61P35/00 ,  A61P37/02 ,  A61P43/00 ,  C07C275/40 ,  C07C275/42 ,  C07D263/32 ,  C07D413/12 ,  C07D417/12 ,  C07F9/653 ,  C07F9/143 ,  C07C275/30 ,  C07C275/34 ,  A61K31/17 ,  A61P31/00

Abstract: The present invention relates to compounds which inhibit JMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting JMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of I1VIPDH using the compounds of this invention and related compounds.

公开(公告)号：AU3280901A

公开(公告)日：2001-07-31

申请号：AU3280901

申请日：2001-01-16

Applicant: VERTEX PHARMA

Inventor： CHARIFSON PAUL ,  BELLON STEVE ,  STAMOS DEAN ,  BADIA MICHAEL ,  GRILLOT ANNE-LAURE ,  RONKIN STEVEN ,  MURCKO MARK ,  TRUDEAU MARTIN

IPC: A61K31/4155 ,  A61K31/421 ,  A61K31/422 ,  A61K31/427 ,  A61P31/04 ,  C12Q1/25 ,  G06F19/16 ,  G06F19/18

Abstract: Disclosed herein are compounds comprising the pharmacophore features HBA, HBD, Grpl, and at least two features selected from Grp2, Grp3 or Grp4 in which HBA is a hydrogen bond acceptor, HBD is a hydrogen bond donor, and Grps 1-4 are as described in the specification. The compounds are inhibitors of bacterial DNA gyrase and are useful in treating bacterial infections. The pharmacophore features may be used to identify and design new inhibitors.

公开(公告)号：CY1107854T1

公开(公告)日：2013-06-19

申请号：CY081100042

申请日：2008-01-11

Applicant: VERTEX PHARMA

Inventor： GRILLOT ANNE-LAURE ,  CHARIFSON PAUL ,  STAMOS DEAN ,  LIAO YUSHENG ,  BADIA MICHAEL ,  TRUDEAU MARTIN

IPC: C07D235/30 ,  C07D235/32 ,  A61K31/00 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/4245 ,  A61K31/437 ,  A61K31/4412 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61K45/06 ,  A61P31/00 ,  A61P31/04 ,  A61P43/00 ,  C07D213/00 ,  C07D221/00 ,  C07D235/00 ,  C07D263/58 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D471/04 ,  C07D471/14 ,  C07D491/04 ,  C07D491/056 ,  C07D498/04 ,  C07D521/00 ,  C07F9/6558 ,  C07F9/6561

Abstract: Ηπαρούσαεφεύρεσιςαναφέρεταιειςενώσειςτουτύπου (I): ήφαρμακευτικώςαποδεκτόνπαράγωγονή προφάρμακοναυτών. Αιενώσειςείναιχρήσιμοιωςαναστολείςβακτηριακήςδράσεωςγυράσης (gyrase). Ηπαρούσαεφεύρεσιςαναφέρεταιεπίσηςειςμεθόδουςδιανοσηλείανβακτηριακώνλοιμώξεωνειςθηλαστικά. Ηπαρούσαεφεύρεσιςαναφέρεταιεπίσηςειςμεθόδουςδιαμείωσιντηςβακτηριακήςποσότητοςειςβιολογικόνδείγμα.

公开(公告)号：ES2405316T3

公开(公告)日：2013-05-30

申请号：ES00916479

申请日：2000-03-17

Applicant: VERTEX PHARMA

Inventor： STAMOS DEAN ,  TRUDEAU MARTIN ,  BETHIEL SCOTT ,  BADIA MICHAEL ,  SAUNDERS JEFFREY

IPC: C07C275/42 ,  C07D307/20 ,  A61K31/27 ,  A61K31/275 ,  A61K31/341 ,  A61K31/421 ,  A61K31/422 ,  A61K31/454 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/00 ,  A61P1/18 ,  A61P9/10 ,  A61P11/06 ,  A61P19/02 ,  A61P29/00 ,  A61P31/12 ,  A61P35/00 ,  A61P37/02 ,  A61P43/00 ,  C07C275/40 ,  C07D263/32 ,  C07D413/12 ,  C07D417/12 ,  C07F9/653

Abstract: Un compuesto de fórmula (IA): **Fórmula** en donde: uno de R1 o R2 se selecciona de hidrógeno, etilo o fenilo; y el otro de R1 o R2 se selecciona de -CH2OH, -CH2CN, -CH2CH2CN o -CH2N(CH2CH3)2, o R1 y R2 se toman juntos para formar un anillo 3-tetrahidrofuranilo;R9 se selecciona de (S)-metilo, (S)-etilo o (S)-hidroximetilo; R10 se selecciona de -C≡N o 5-oxazolilo; y R11 se selecciona de halo, -O-alquilo lineal de (C1-C3), u -O-alquenilo o alquinilo lineal de (C2-C3).

公开(公告)号：CA2433197C

公开(公告)日：2009-11-24

申请号：CA2433197

申请日：2001-12-12

Applicant: VERTEX PHARMA

Inventor： GRILLOT ANNE-LAURE ,  TRUDEAU MARTIN ,  BADIA MICHAEL ,  STAMOS DEAN ,  LIAO YUSHENG ,  CHARIFSON PAUL

IPC: C07D235/30 ,  C07D235/32 ,  A61K31/00 ,  A61K31/33 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/4245 ,  A61K31/437 ,  A61K31/4412 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61K45/06 ,  A61P31/00 ,  A61P31/04 ,  A61P43/00 ,  C07D213/00 ,  C07D221/00 ,  C07D235/00 ,  C07D263/58 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D471/04 ,  C07D471/14 ,  C07D491/04 ,  C07D491/056 ,  C07D498/04 ,  C07D521/00 ,  C07F9/6558 ,  C07F9/6561

Abstract: The present invention relates to compounds of the formula (I): or a pharmaceutically acceptable derivative or prodrug thereof. The compounds are useful as inhibitors of bacterial gyrase activity. The present invention als o relates to methods for treating bacterial infections in mammals. The present invention also relates to methods for decreasing bacterial quantity in a biological sample.

公开(公告)号：CA2367017C

公开(公告)日：2009-05-26

申请号：CA2367017

申请日：2000-03-17

Applicant: VERTEX PHARMA

Inventor： STAMOS DEAN ,  BETHIEL SCOTT ,  BADIA MICHAEL ,  TRUDEAU MARTIN ,  SAUNDERS JEFFREY ,  RONKIN STEVEN

IPC: C07D263/32 ,  C07D307/20 ,  A61K31/27 ,  A61K31/275 ,  A61K31/277 ,  A61K31/341 ,  A61K31/421 ,  A61K31/422 ,  A61K31/454 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/00 ,  A61P1/18 ,  A61P9/10 ,  A61P11/06 ,  A61P19/02 ,  A61P29/00 ,  A61P31/12 ,  A61P35/00 ,  A61P37/02 ,  A61P43/00 ,  C07C275/40 ,  C07C275/42 ,  C07D413/12 ,  C07D417/12 ,  C07F9/653

Abstract: The present invention relates to compounds of formula (A) which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.