公开(公告)号：DK1140888T3

公开(公告)日：2003-08-25

申请号：DK99965226

申请日：1999-12-10

Applicant: VERTEX PHARMA SAN DIEGO LLC

Inventor： MAKINGS LEWIS ,  ZLOKARNIK GREGOR

IPC: G01N37/00 ,  A61K45/00 ,  A61P43/00 ,  C07D219/06 ,  C07D265/38 ,  C07D311/16 ,  C07D311/82 ,  C07D493/10 ,  C12Q1/26

Abstract: The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods. The optical probe of the invention is a compound having the generic structure Y-L-Q, wherein Y is selected from the group consisting of Q as herein defined, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (-OCR 2 H) p -, wherein for each p, all R 2 are separately selected from the group consisting of a hydrogen atom, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and p is a positive integer no greater than twelve; and Q is a chemical moiety that gives rise to optical properties in its hydroxy or hydroxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, R 2 is hydrogen, and Q is the ether form of a phenoxide fluorophore.

公开(公告)号：AT517106T

公开(公告)日：2011-08-15

申请号：AT07751501

申请日：2007-02-22

Applicant: VERTEX PHARMA

Inventor： MAKINGS LEWIS ,  GARCIA-GUZMAN BLANCO MIGUEL ,  HURLEY DENNIS ,  DRUTU IOANA ,  RAFFAI GABRIEL ,  BERGERON DANIELE ,  NAKATANI AKIKO ,  TERMIN ANDREAS ,  SILINA ALINA

IPC: C07D471/10 ,  A61K31/438 ,  A61K31/46 ,  A61K31/4747 ,  A61P25/00 ,  C07D519/00

Abstract: The present invention relates to modulators of muscarinic receptors of formula (I). The present invention also provides impositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases.

公开(公告)号：ES2199605T3

公开(公告)日：2004-02-16

申请号：ES99965226

申请日：1999-12-10

Applicant: VERTEX PHARMA SAN DIEGO LLC

Inventor： MAKINGS LEWIS ,  ZLOKARNIK GREGOR

IPC: G01N37/00 ,  A61K45/00 ,  A61P43/00 ,  C07D219/06 ,  C07D265/38 ,  C07D311/16 ,  C07D311/82 ,  C07D493/10 ,  C12Q1/26

Abstract: The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods. The optical probe of the invention is a compound having the generic structure Y-L-Q, wherein Y is selected from the group consisting of Q as herein defined, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (-OCR 2 H) p -, wherein for each p, all R 2 are separately selected from the group consisting of a hydrogen atom, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and p is a positive integer no greater than twelve; and Q is a chemical moiety that gives rise to optical properties in its hydroxy or hydroxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, R 2 is hydrogen, and Q is the ether form of a phenoxide fluorophore.

公开(公告)号：AT440825T

公开(公告)日：2009-09-15

申请号：AT04754303

申请日：2004-06-04

Applicant: VERTEX PHARMA

Inventor： MAKINGS LEWIS ,  SINGH ASHVANI ,  MILLER MARK ,  HADIDA RUAH SARAH ,  GROOTENHUIS PETER ,  HAMILTON MATTHEW ,  HAZELWOOD ANNA ,  HUANG LIMING

IPC: C07D239/90 ,  C07D239/36 ,  C07D239/42 ,  C07D239/94 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/10 ,  C07D487/04 ,  C07D491/10 ,  C07D513/04

Abstract: The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator ("CFTR"), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

公开(公告)号：PT1140888E

公开(公告)日：2003-09-30

申请号：PT99965226

申请日：1999-12-10

Applicant: VERTEX PHARMA SAN DIEGO LLC

Inventor： ZLOKARNIK GREGOR ,  MAKINGS LEWIS

IPC: G01N37/00 ,  A61K45/00 ,  A61P43/00 ,  C07D219/06 ,  C07D265/38 ,  C07D311/16 ,  C07D311/82 ,  C07D493/10 ,  C12Q1/26

Abstract: The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods. The optical probe of the invention is a compound having the generic structure Y-L-Q, wherein Y is selected from the group consisting of Q as herein defined, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (-OCR 2 H) p -, wherein for each p, all R 2 are separately selected from the group consisting of a hydrogen atom, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and p is a positive integer no greater than twelve; and Q is a chemical moiety that gives rise to optical properties in its hydroxy or hydroxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, R 2 is hydrogen, and Q is the ether form of a phenoxide fluorophore.

公开(公告)号：DE69907962D1

公开(公告)日：2003-06-18

申请号：DE69907962

申请日：1999-12-10

Applicant: VERTEX PHARMA SAN DIEGO LLC

Inventor： MAKINGS LEWIS ,  ZLOKARNIK GREGOR

IPC: G01N37/00 ,  A61K45/00 ,  A61P43/00 ,  C07D219/06 ,  C07D265/38 ,  C07D311/16 ,  C07D311/82 ,  C07D493/10 ,  C12Q1/26

Abstract: The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods. The optical probe of the invention is a compound having the generic structure Y-L-Q, wherein Y is selected from the group consisting of Q as herein defined, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (-OCR 2 H) p -, wherein for each p, all R 2 are separately selected from the group consisting of a hydrogen atom, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and p is a positive integer no greater than twelve; and Q is a chemical moiety that gives rise to optical properties in its hydroxy or hydroxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, R 2 is hydrogen, and Q is the ether form of a phenoxide fluorophore.

公开(公告)号：DE69907962T2

公开(公告)日：2004-05-19

申请号：DE69907962

申请日：1999-12-10

Applicant: VERTEX PHARMA SAN DIEGO LLC

Inventor： MAKINGS LEWIS ,  ZLOKARNIK GREGOR

IPC: G01N37/00 ,  A61K45/00 ,  A61P43/00 ,  C07D219/06 ,  C07D265/38 ,  C07D311/16 ,  C07D311/82 ,  C07D493/10 ,  C12Q1/26

Abstract: The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods. The optical probe of the invention is a compound having the generic structure Y-L-Q, wherein Y is selected from the group consisting of Q as herein defined, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (-OCR 2 H) p -, wherein for each p, all R 2 are separately selected from the group consisting of a hydrogen atom, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and p is a positive integer no greater than twelve; and Q is a chemical moiety that gives rise to optical properties in its hydroxy or hydroxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, R 2 is hydrogen, and Q is the ether form of a phenoxide fluorophore.

公开(公告)号：AT240310T

公开(公告)日：2003-05-15

申请号：AT99965226

申请日：1999-12-10

Applicant: VERTEX PHARMA SAN DIEGO LLC

Inventor： MAKINGS LEWIS ,  ZLOKARNIK GREGOR

IPC: G01N37/00 ,  A61K45/00 ,  A61P43/00 ,  C07D219/06 ,  C07D265/38 ,  C07D311/16 ,  C07D311/82 ,  C07D493/10 ,  C12Q1/26

Abstract: The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods. The optical probe of the invention is a compound having the generic structure Y-L-Q, wherein Y is selected from the group consisting of Q as herein defined, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (-OCR 2 H) p -, wherein for each p, all R 2 are separately selected from the group consisting of a hydrogen atom, saturated C 1 -C 20 alkyl, unsaturated C 1 -C 20 alkenyl, unsaturated C 1 -C 20 alkynyl, substituted saturated C 1 -C 20 alkyl, substituted unsaturated C 1 -C 20 alkenyl, substituted unsaturated C 1 -C 20 alkynyl, C 1 -C 20 cycloalkyl, C 1 -C 20 cycloalkenyl, substituted saturated C 1 -C 20 cycloalkyl, substituted unsaturated C 1 -C 20 cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and p is a positive integer no greater than twelve; and Q is a chemical moiety that gives rise to optical properties in its hydroxy or hydroxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, R 2 is hydrogen, and Q is the ether form of a phenoxide fluorophore.