Movatterモバイル変換

[0]ホーム
URL:

US20050033048A1 - Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3h-spiroisobenzofuran-1,4'-piperidines - Google Patents

Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3h-spiroisobenzofuran-1,4'-piperidinesDownload PDF

Info

Publication number
US20050033048A1
US20050033048A1US10/415,457US41545703AUS2005033048A1US 20050033048 A1US20050033048 A1US 20050033048A1US 41545703 AUS41545703 AUS 41545703AUS 2005033048 A1US2005033048 A1US 2005033048A1
Authority
US
United States
Prior art keywords
alkyl
halo
halogen
alkoxy
independently selected
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/415,457
Inventor
Rajagopal Bakthavatchalam
Charles Blum
Harry Brielmann
James Darrow
Stephane De Lombaert
Alan Hutchison
Jennifer Tran
Xiaozhang Zheng
Richard Elliott
Marlys Hammond
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pfizer Corp SRL
Neurogen Corp
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by IndividualfiledCriticalIndividual
Priority to US10/415,457priorityCriticalpatent/US20050033048A1/en
Assigned to NEUROGEN CORPORATIONreassignmentNEUROGEN CORPORATIONASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS).Assignors: TRAN, JENNIFER, DARROW, JAMES WILLIAM, HUTCHISON, ALAN, BAKTHAVATCHALAM, RAJAGOPAL, BLUM, CHARLES A., BRIELMANN, HARRY L., DE LOMBAERT, STEPHANE, ZHENG, XIAOZHANG
Assigned to PFIZER INC.reassignmentPFIZER INC.ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS).Assignors: HAMMOND, MARLYS, ELLIOTT, RICHARD LOUIS
Publication of US20050033048A1publicationCriticalpatent/US20050033048A1/en
Abandonedlegal-statusCriticalCurrent

Links

Classifications

Definitions

Landscapes

Abstract

Substituted spiro[isobenzofuran-1,4′-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4′-piperidines capable of modulating NPY5 receptor activity are provided. Such compounds may be used to modulate ligand binding to NPY5 receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of disorders (e.g., eating disorders such as obesity or bulimia, psychiatric disorders, diabetes and cardiovascular disorders such as hypertension) in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and method for treating such disorders are provided, as are methods for using such compounds for detecting NPY5 receptors.

Description

Claims (58)

Figure US20050033048A1-20050210-C00077
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
X is oxygen or H2;
A, D, V, W, Y and Z are independently N or CR1;
B is N or CR2;
E is N or CR3;
R1is independently selected at each occurrence from:
(i) hydrogen, halogen, hydroxy, amino, nitro, cyano, —C(═O)NH2and —COOH; and
(ii) L-RA-Q-G, wherein:
L is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —NRB—, —C(═O)NHRB—, —NHRBC(═O)—, —NRBS(O)n— or —S(O)nNRB—;
n is independently chosen at each occurrence from 0, 1 or 2;
RAis (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkenyl, (C3-C8)cycloalkylnyl or (C3-C8) heterocycloalkyl, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C6)alkyl and halo(C1-C6)alkyl;
Q is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —CHRB—, —NRB—, —C(═O)NHRB—, —NHRBC(═O)—, —NRBS(O)n— or —S(O)nNRB;
RBis independently selected at each occurrence from hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8)alkyl and (C1-C8)alkyl(C3-C8)cycloalkyl; and
G is: hydrogen; or
(C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C8)cycloalkyl(C1-C8)alkyl, or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C8)alkyl, halo(C1-C8)alkyl, (C1-C8)alkoxy, —NH(C1-C8)alkyl, —N((C1-C8)alkyl)2, —NHC(═O)(C1-C8)alkyl, —N(C1-C8)alkylC(═O)(alkyl), —NHS(O)s(C1-C8)alkyl, —S(O)s(C1-C8)alkyl, —S(O)sNH(C1-C8)alkyl and —S(O)sN((C1-C8)alkyl)2, wherein s is 0, 1 or 2;
R2and R3are independently selected at each occurrence from:
(i) hydrogen, halogen, hydroxy, amino, nitro, cyano, —C(═O)NH2and —COOH; and
(ii) T-RC-U-M, wherein:
T is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —NRD—, —C(═O)NHRD—, —NHRDC(═O)—, —NRDS(O)n— or —S(O)nNRD—;
n is independently chosen at each occurrence from 0, 1 or 2;
RCis (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C6)alkyl and halo(C1-C6)alkyl;
U is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —CHRD—, —NRD—, —C(═O)NHRD—, —NHRDC(═O)—, —NRDS(O)n— or —S(O)nNRD—;
RDis independently selected at each occurrence from hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8)alkyl and (C1-C8)alkyl(C3-C8)cycloalkyl; and
M is: hydrogen; or
(C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8) alkynyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C8)alkyl, halo(C1-C8)alkyl, (C1-C8)alkoxy, —NH(C1-C8)alkyl, —N((C1-C8)alkyl)2, —NHC(═O)(C1-C8)alkyl, —N(C1-C8)alkyl C(═O) (alkyl), —NHS(O)s(C1-C8)alkyl, —S(O)s(C1-C8)alkyl, —S(O)sNH(C1-C8)alkyl and —S(O)sN((C1-C8)alkyl)2, wherein s is 0, 1 or 2.
16. A compound according toclaim 6, wherein:
R1is independently selected at each occurrence from hydrogen, hydroxy, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy and halo(C1-C6)alkoxy;
R2is selected from hydrogen, hydroxy, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy and halo(C1-C6)alkoxy; and
R3is selected from hydroxy, halogen, cyano, and (C1-C6)alkyl, (C5-C7)cycloalkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkylaminocarbonyl, (C1-C6) carbamate, (C1-C6)alkylsulfonyl, oxadiazolyl, oxazolyl, isoxazolyl, thiazolyl, thiophenyl, triazolyl, pyrimidinyl, pyridinyl, pyrazinyl, phenyl, benzyl, phenoxy, benzyloxy and benzoyl, wherein each is optionally substituted with from 1 to 3 substituents independently selected from hydroxy, halogen, (C1-C6)alkyl, halo(C1-C6) alkyl, (C1-C6)alkoxy and halo(C1-C6)alkoxy.
17. A compound according toclaim 6, wherein:
R1is independently selected at each occurrence from hydrogen, hydroxy, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy and halo(C1-C6)alkoxy;
R2is selected from hydroxy, halogen, cyano, and (C1-C6)alkyl, (C5-C7)cycloalkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6) alkanoyloxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkylaminocarbonyl, (C1-C6) carbamate, (C1-C6)alkylsulfonyl, oxadiazolyl, oxazolyl, isoxazolyl, thiazolyl, thiophenyl, triazolyl, pyrimidinyl, pyridinyl, pyrazinyl, phenyl, benzyl, phenoxy, benzyloxy and benzoyl, wherein each is optionally substituted with from 1 to 3 substituents independently selected from hydroxy, halogen, (C1-C6)alkyl, halo(C1-C6) alkyl, (C1-C6)alkoxy and halo(C1-C6)alkoxy; and
R3is selected from hydrogen, hydroxy, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy and halo(C1-C6)alkoxy.
18. A compound according toclaim 1, wherein:
V, W, Y and Z are all CR1, and R1is independently selected at each occurrence from hydrogen, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl and (C1-C6)alkoxy;
A and D are CR1, wherein R1is independently selected at each occurrence from hydrogen, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl and (C1-C6)alkoxy; and
B and E are CR2and CR3, respectively, wherein R2and R3are independently selected from:
(i) hydrogen, halogen and cyano; and
(ii) (C1-C6)alkyl, (C3-C7)cycloalkyl, halo(C1-C6)alkyl, (C1-C6) alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6) alkylaminocarbonyl, (C1-C6)alkylsulfonyl, oxadiazolyl, oxazolyl, isoxazolyl, thiazolyl, thiophenyl, triazolyl, pyrimidinyl, pyridinyl, pyrazinyl, phenyl, benzyl, phenoxy, benzyloxy and benzoyl, wherein each is optionally substituted with 1 to 3 substituents selected from halogen and (C1-C6)alkyl.
19. A compound according toclaim 1, wherein the compound is selected from:
1′-(6-trifluoromethyl-3-H-imidazo[4,5-b]pyridine-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(7-chloro-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-n-propylsulfonyl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-cyano-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-acetyl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-carboxy-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one, methyl ester;
1′-(5′pyrazin-2-yl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5′pyridin-3-yl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-trifluoromethoxy-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-methyl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-benzoyl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-methoxy-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-chloro-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
6-bromo-7-chloro-2-(spiro[isobenzofuran-1,4′-piperidin]-3-one-3H-imidazo[4,5-b]pyridine;
1′-(5-fluoro-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-methyl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-methylsulfonyl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-oxazol-2-yl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5,6-difluoro-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-phenyl-1H-imidazo[4,5-b]pyrazin-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-trifluoromethyl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5,7-dichloro-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5,6-dimethoxy-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-trifluoromethylsulfonyl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-(3,5-dimethyl-isoxazol-4-yl)-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
1′-(5-ethoxy-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one;
5-chloro-2-(spiro[isobenzofuran-1,4′-piperidin]-3-one-3H-imidazo[4,5-b]pyridine; and
1′-(6-iodo-1H-quinazolin-4-on-2-yl)spiro[isobenzofuran-1,4′piperidin]-3-one.
Figure US20050033048A1-20050210-C00078
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
V, W, Y and Z are independently N or CR1;
R1is independently selected at each occurrence from:
(i) hydrogen, halogen, hydroxy, amino, nitro, cyano, —C(═O)NH2and —COOH; and
(ii) L-RA-Q-G, wherein:
L is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —NRB—, —C(═O)NHRB—, —NHRBC(═O)—, —NRBS(O)n— or —S(O)nNRB—; n is 0, 1 or 2;
RAis (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8) alkynyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkenyl, (C3-C8)cycloalkylnyl or (C3-C8)heterocycloalkyl, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C6)alkyl and halo(C1-C6)alkyl,
Q is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —CHRB—, —NRB—, —C(═O)NHRB—, —NHRBC(═O)—, —NRBS(O)n— or —S(O)nNRB—;
RBis independently selected at each occurrence from hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8)alkyl and (C1-C8)alkyl(C3-C8)cycloalkyl; and
G is: hydrogen; or
(C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C8)cycloalkyl(C1-C8)alkyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C8)alkyl, halo(C1-C8)alkyl, (C1-C8)alkoxy, —NH(C1-C8)alkyl, —N((C1-C8)alkyl)2, —NHC(═O)(C1-C8)alkyl, —N(C1-C8)alkylC(═O)(alkyl), —NHS(O)s(C1-C8)alkyl, —S(O)s(C1-C8)alkyl, —S(O)sNH(C1-C8)alkyl and —S(O)sN((C1-C8)alkyl)2, wherein s is 0, 1 or 2;
J is a bond or (C1-C6)alkyl; and
RGis (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl or a 3-to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from:
(i) hydrogen, halogen, hydroxy, amino, nitro, cyano, —C(═O)NH2and —COOH; and
(ii) T-RC-U-M, wherein:
 T is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —NRD—, —C(═O)NHRD—, —NHRDC(═O)—, —NRDS(O)n— or —S(O)nNRD—;
 n is independently chosen at each occurrence from 0, 1 or 2;
 RCis (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C6)alkyl and halo(C1-C6)alkyl;
 U is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —CHRD—, —NRD—, —C(═O)NHRD—, —NHRDC(═O)—, —NRDS(O)n— or —S(O)nNRD—;
 RDis independently selected at each occurrence from hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8) alkyl and (C1-C8)alkyl(C3-C8)cycloalkyl; and
 M is: hydrogen; or
 (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C8)cycloalkyl(C1-C8)alkyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 9 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C8)alkyl, (C3-C8)cycloalkyl, halo(C1-C8)alkyl, (C1-C8)alkoxy, —NH(C1-C8)alkyl, —N((C1-C8)alkyl)2, —NHC(═O)(C1-C8)alkyl, —N(C1-C8)alkylC(═O)(alkyl), —NHS(O)s(C1-C8)alkyl, —S(O)s(C1-C8)alkyl, —S(O)sNH(C1-C8)alkyl and —S(O)sN((C1-C8)alkyl)2, wherein s is 0, 1 or 2.
21. A compound according toclaim 20, wherein RGis:
(i) (C1-C6)alkyl, (C2-C6)alkenyl or (C2-C6)alkynyl, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano and nitro; or
(ii) a 3- to 10-membered carbocyclic or heterocyclic group, optionally substituted with from 1 to 5 substituents independently selected from:
(a) hydroxy, halogen, amino, cyano and nitro; and
(b) (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C5-C7)cycloalkyl(C1-C6)alkyl, (C1-C6)alkylsulfonyl, (C5-C7)cycloalkanesulfonyl, (C5-C7)cycloalkane(C1-C6)alkanesulfonyl, (C1-C6)alkoxy, (C5-C7)cycloalkoxy, (C5-C7)cycloalkyl(C1-C6)alkoxy, mono-N- and di-N,N-(C1-C6)alkylamino, mono-N- and di-N,N-(C5-C7)cycloalkylamino, N-(C1-C6)alkyl-N-(C5-C7)cycloalkylamino, mono-N- and di-N,N-(C5-C7)cycloalkyl(C1-C6)alkylamino, N-(C1-C6)alkyl-N-(C3-C7)cycloalkyl(C1-C6)alkylamino, N-(C5-C7)cycloalkyl-N-(C5-C7)cycloalkyl(C1-C6)alkylamino and 3- to 10-membered carbocyclic and heterocyclic groups, wherein each is optionally independently substituted with from 1 to 9 secondary substituents selected from hydroxy, halogen, amino, cyano and nitro.
22. A compound according toclaim 20, wherein:
J is a bond; and
RGis:
Figure US20050033048A1-20050210-C00079
R2is independently selected at each occurrence from:
(i) hydrogen, halogen, hydroxy, amino, nitro, cyano, —C(═O)NH2and —COOH; and
(ii) T-RC-U-M, wherein:
T is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —NRD—, —C(═O)NHRD—, —NRDC(═O)—, —NRDS(O)n— or —S(O)nNRD—;
n is 0, 1 or 2;
RCis (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C6)alkyl and halo(C1-C6)alkyl;
U is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —CHRD—, —NRD—, —C(═O)NHRD—, —NHRDC(═O)—, —NRDS(O)n— or —S(O)nNRD—;
RDis independently selected at each occurrence from hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8)alkyl and (C1-C8)alkyl(C3-C8)cycloalkyl; and
M is: hydrogen; or
(C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8) alkynyl, (C3-C8)cycloalkyl(C1-C8)alkyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C8)alkyl, halo(C1-C8)alkyl, (C1-C8)alkoxy, —NH(C1-C8)alkyl, —N((C1-C8)alkyl)2, —NHC(═O)(C1-C8)alkyl, —N(C1-C8)alkylC(═O)(alkyl), —NHS(O)s(C1-C8)alkyl, —S(O)s(C1-C8)alkyl, —S(O)sNH(C1-C8)alkyl and —S(O)sN((C1-C8)alkyl)2, wherein s is 0, 1 or 2.
27. A compound according toclaim 20, wherein:
V, W, Y and Z are all CR1, and R1is independently selected at each occurrence from hydrogen, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl and (C1-C6)alkoxy;
D and F are both CR2, wherein R2is independently selected at each occurrence from hydrogen, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl and (C1-C6)alkoxy; and
A, B and E are all CR2, wherein R2is independently selected from:
(i) hydrogen, halogen and cyano; and
(ii) (C1-C6)alkyl, (C3-C7)cycloalkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkylaminocarbonyl, (C1-C6)alkylsulfonyl, oxadiazolyl, oxazolyl, isoxazolyl, thiazolyl, thiophenyl, triazolyl, pyrimidinyl, pyridinyl, pyrazinyl, phenyl and benzoyl, wherein each is optionally substituted with 1 to 3 substituents selected from halogen and (C1-C6)alkyl.
Figure US20050033048A1-20050210-C00080
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
V, W, Y and Z are independently N or CR1;
R1is independently selected at each occurrence from:
(i) hydrogen, halogen, hydroxy, amino, nitro, cyano, —C(═O)NH2and —COOH; and
(ii) L-RA-Q-G, wherein:
L is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —NRB—, —C(═O)NHRB—, —NHRBC(═O)—, —NRBS(O)n— or —S(O)nNRB—; n is 0, 1 or 2;
RAis (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)(C3-C8) cycloalkyl, (C3-C8)cycloalkenyl, (C3-C8)cycloalkynyl or (C3-C8)heterocycloalkyl, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C6)alkyl and halo(C1-C6)alkyl;
Q is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —CHRB—, —NRB—, —C(═O)NHRB—, —NHRBC(═O)—, —NRBS(O)n— or —S(O)nNRB—;
RBis independently selected at each occurrence from hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8)alkyl and (C1-C8)alkyl(C3-C8)cycloalkyl; and
G is: hydrogen; or
(C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C8)cycloalkyl(C1-C8)alkyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C8)alkyl, halo(C1-C8)alkyl, (C1-C8)alkoxy, —NH(C1-C8)alkyl, —N((C1-C8)alkyl)2, —NHC(═O)(C1-C8)alkyl, —N(C1-C8) alkylC(═O)(alkyl), —NHS(O)s(C1-C8)alkyl, —S(O)s(C1-C8)alkyl, —S(O)sNH(C1-C8)alkyl and —S(O)sN((C1-C8)alkyl)2, wherein s is 0, 1 or 2;
J is a bond or (C1-C6)alkyl; and
RGis (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from:
(i) hydrogen, halogen, hydroxy, amino, nitro, cyano, —C(═O)NH2and —COOH; and
(ii) T-RC-U-M, wherein:
T is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —NRD—, —C(═O)NHRD—, —NHRDC(═O)—, —NRDS(O)n— or —S(O)nNRD—; n is independently chosen at each occurrence from 0, 1 or 2;
RCis (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C6)alkyl and halo(C1-C6)alkyl;
U is a bond, —O—, —C(═O)—, —OC(═O))—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —CHRD—, —NRD—, —C(═O)NHRD—, —NHRDC(═O)—, —NRDS(O)n— or —S(O)nNRD—;
RDis independently selected at each occurrence from hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8)alkyl and (C1-C8) alkyl(C3-C8)cycloalkyl; and
M is: hydrogen; or
(C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C8) cycloalkyl(C1-C8)alkyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 9 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C8)alkyl, (C3-C8)cycloalkyl, halo(C1-C8)alkyl, (C1-C8)alkoxy, —NH(C1-C8)alkyl, —N((C1-C8)alkyl)2, —NHC(═O)(C1-C8)alkyl, —N(C1-C8)alkylC(═O)(alkyl), —NHS(O)s(C1-C8)alkyl, —S(O)s(C1-C8)alkyl, —S(O)sNH(C1-C8)alkyl and —S(O)sN((C1-C8)alkyl)2, wherein s is 0, 1 or 2; with the proviso that if RG, M or both are aromatic, then J is (C1-C6)alkyl.
US10/415,4572000-12-122001-12-11Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3h-spiroisobenzofuran-1,4'-piperidinesAbandonedUS20050033048A1 (en)

Priority Applications (1)

Application NumberPriority DateFiling DateTitle
US10/415,457US20050033048A1 (en)2000-12-122001-12-11Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3h-spiroisobenzofuran-1,4'-piperidines

Applications Claiming Priority (3)

Application NumberPriority DateFiling DateTitle
US25499000P2000-12-122000-12-12
PCT/US2001/047863WO2002048152A2 (en)2000-12-122001-12-11Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3h-spiroisobenzofuran-1,4'-piperidines
US10/415,457US20050033048A1 (en)2000-12-122001-12-11Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3h-spiroisobenzofuran-1,4'-piperidines

Publications (1)

Publication NumberPublication Date
US20050033048A1true US20050033048A1 (en)2005-02-10

Family

ID=22966369

Family Applications (4)

Application NumberTitlePriority DateFiling Date
US10/013,846Expired - Fee RelatedUS6566367B2 (en)2000-12-122001-12-11Spiro[isobenzofuran-1,4′-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4′-piperidines
US10/415,457AbandonedUS20050033048A1 (en)2000-12-122001-12-11Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3h-spiroisobenzofuran-1,4'-piperidines
US10/410,648Expired - Fee RelatedUS6943199B2 (en)2000-12-122003-04-09Spiro[isobenzofuran-1,4′-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4′-piperidines
US11/183,615AbandonedUS20060040964A1 (en)2000-12-122005-07-18Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4'-piperidines

Family Applications Before (1)

Application NumberTitlePriority DateFiling Date
US10/013,846Expired - Fee RelatedUS6566367B2 (en)2000-12-122001-12-11Spiro[isobenzofuran-1,4′-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4′-piperidines

Family Applications After (2)

Application NumberTitlePriority DateFiling Date
US10/410,648Expired - Fee RelatedUS6943199B2 (en)2000-12-122003-04-09Spiro[isobenzofuran-1,4′-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4′-piperidines
US11/183,615AbandonedUS20060040964A1 (en)2000-12-122005-07-18Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4'-piperidines

Country Status (10)

CountryLink
US (4)US6566367B2 (en)
EP (1)EP1347982B1 (en)
JP (1)JP2004520299A (en)
AT (1)ATE310004T1 (en)
AU (1)AU2002220276A1 (en)
BR (1)BR0116113A (en)
DE (1)DE60115092T2 (en)
ES (1)ES2249384T3 (en)
MX (1)MXPA03004245A (en)
WO (1)WO2002048152A2 (en)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
US20060079505A1 (en)*2004-08-192006-04-13Vertex Pharmaceuticals, IncorporatedModulators of muscarinic receptors
US20060270653A1 (en)*2004-11-292006-11-30Ioana DrutuModulators of muscarinic receptors
US20070043023A1 (en)*2004-08-192007-02-22Makings Lewis RModulators of muscarinic receptors
US20070213315A1 (en)*2006-02-222007-09-13Robert DaviesModulators of muscarinic receptors
US20080015179A1 (en)*2005-12-222008-01-17Makings Lewis RModulators of muscarinic receptors
US20080033002A1 (en)*2006-06-292008-02-07Bandarage Upul KModulators of muscarinic receptors
US20080047479A1 (en)*1997-10-272008-02-28Correct Craft, Inc.Water Sport Towing Apparatus and Method
US20080176843A1 (en)*2006-08-152008-07-24Makings Lewis RModulators of muscarinic receptors
US20090099222A1 (en)*2007-10-032009-04-16Davies Robert JModulators of muscarinic receptors
US20090227614A1 (en)*2006-02-222009-09-10Makings Lewis RModulators of Muscarinic Receptors
US7786107B2 (en)2006-08-182010-08-31Vertex Pharmaceuticals IncorporatedModulators of muscarinic receptors
US11414429B2 (en)2016-06-302022-08-16RikenCompound or pharmaceutically acceptable salt thereof

Families Citing this family (132)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
US6191160B1 (en)1998-11-102001-02-20Merck & Co., Inc.Spiro-indolines as Y5 receptor antagonists
CA2379585C (en)*1999-09-302006-06-20James W. DarrowCertain alkylene diamine-substituted pyrazolo[1,5,-a]-1,5-pyrimidines and pyrazolo[1,5-a]-1,3,5-triazines
NZ517575A (en)*1999-09-302004-04-30Neurogen CorpCertain alkylene diamine-substituted heterocycles
AU2001239731A1 (en)*2000-01-282001-08-07Neurogen CorporationChimeric neuropeptide y receptors
BR0116113A (en)*2000-12-122004-08-03Neurogen Corp Spiro [isobenzofuran-1,4'-piperidin] -3-ones and 3h-spiroisoben-zofuran-1,4'-piperidines
US6900220B2 (en)*2001-01-022005-05-31Syntex (U.S.A.) LlcQuinazolone derivatives as alpha 1A/B adrenergic receptor antagonists
WO2002094825A1 (en)*2001-05-222002-11-28Banyu Pharmaceutical Co., Ltd.Novel spiropiperidine derivative
EP1415986B1 (en)*2001-08-072009-04-08Banyu Pharmaceutical Co., Ltd.Spiro isobenzofuranes as neuropeptide y receptor antagonists
CA2403307A1 (en)*2001-10-232003-04-23Neurogen CorporationSubstituted 2-cyclohexyl-4-phenyl-1h-imidazole derivatives
AUPR975601A0 (en)*2001-12-242002-01-31Fujisawa Pharmaceutical Co., Ltd.Quinazolinone derivatives
US7704995B2 (en)*2002-05-032010-04-27Exelixis, Inc.Protein kinase modulators and methods of use
EP1501514B1 (en)*2002-05-032012-12-19Exelixis, Inc.Protein kinase modulators and methods of use
US7405234B2 (en)*2002-05-172008-07-29Bristol-Myers Squibb CompanyBicyclic modulators of androgen receptor function
JP4496722B2 (en)*2002-06-282010-07-07萬有製薬株式会社 New benzimidazole derivatives
US7105526B2 (en)2002-06-282006-09-12Banyu Pharmaceuticals Co., Ltd.Benzimidazole derivatives
SE0202462D0 (en)*2002-08-142002-08-14Astrazeneca Ab Novel use
EP1398032A1 (en)*2002-09-102004-03-17PheneX Pharmaceuticals AG4-Oxo-quinazolines as LXR nuclear receptor binding compounds
EP1407774A1 (en)*2002-09-102004-04-14LION Bioscience AG2-Amino-4-quinazolinones as LXR nuclear receptor binding compounds
WO2004045518A2 (en)*2002-11-152004-06-03Bristol-Myers Squibb CompanyOpen chain prolyl urea-related modulators of androgen receptor function
US7365079B2 (en)2002-11-292008-04-29Banyu Pharmaceutical Co., Ltd.Azole derivatives
US7772188B2 (en)2003-01-282010-08-10Ironwood Pharmaceuticals, Inc.Methods and compositions for the treatment of gastrointestinal disorders
JP2006519833A (en)2003-03-112006-08-31ファイザー・プロダクツ・インク Pyrazine compounds as transforming growth factor (TGF) inhibitors
JP2009513502A (en)2003-07-022009-04-02エフ．ホフマン−ラ ロシュ アーゲー Arylamine-substituted quinazolinone compounds
CA2551037A1 (en)2003-09-222005-03-31Banyu Pharmaceutical Co., Ltd.Novel piperidine derivative
CA2540190A1 (en)*2003-09-262005-04-07Pfizer Products Inc.Use of npy y5 receptor antagonist for the treatment of circadian rhythm disorders
MXPA06003393A (en)*2003-09-262006-06-08Pfizer Prod IncTreatment of neurological disorders related to rapid eye movement (rem) sleep disturbances with npy y5 receptor antagonists.
US7256208B2 (en)*2003-11-132007-08-14Bristol-Myers Squibb CompanyMonocyclic N-Aryl hydantoin modulators of androgen receptor function
WO2005056036A2 (en)*2003-12-092005-06-23Novo Nordisk A/SRegulation of food preference using glp-1 agonists
US7820702B2 (en)2004-02-042010-10-26Bristol-Myers Squibb CompanySulfonylpyrrolidine modulators of androgen receptor function and method
US20050182105A1 (en)*2004-02-042005-08-18Nirschl Alexandra A.Method of using 3-cyano-4-arylpyridine derivatives as modulators of androgen receptor function
US7625923B2 (en)2004-03-042009-12-01Bristol-Myers Squibb CompanyBicyclic modulators of androgen receptor function
US7388027B2 (en)*2004-03-042008-06-17Bristol-Myers Squibb CompanyBicyclic compounds as modulators of androgen receptor function and method
US7696241B2 (en)*2004-03-042010-04-13Bristol-Myers Squibb CompanyBicyclic compounds as modulators of androgen receptor function and method
EP1734963A4 (en)2004-04-022008-06-18Merck & Co IncMethod of treating men with metabolic and anthropometric disorders
CN1950374A (en)2004-05-252007-04-18辉瑞产品公司Tetraazabenzo[e]azulene derivatives and analogs thereof
WO2006052608A2 (en)2004-11-012006-05-18Amylin Pharmaceuticals, Inc.Treatment of obesity and related disorders
US7534796B2 (en)2005-02-182009-05-19WyethImidazo[4,5-b]pyridine antagonists of gonadotropin releasing hormone receptor
US7582634B2 (en)2005-02-182009-09-01Wyeth7-substituted imidazo[4,5-c]pyridine antagonists of gonadotropin releasing hormone receptor
US7538113B2 (en)2005-02-182009-05-26Wyeth4-substituted imidazo[4,5-c]pyridine antagonists of gonadotropin releasing hormone receptor
DE102005012874A1 (en)2005-03-192006-09-21Sanofi-Aventis Deutschland Gmbh Amide-substituted 8-N-benzimidazoles, process for their preparation and their use as pharmaceuticals
US7737155B2 (en)2005-05-172010-06-15Schering CorporationNitrogen-containing heterocyclic compounds and methods of use thereof
US7531542B2 (en)2005-05-182009-05-12WyethBenzooxazole and benzothiazole antagonists of gonadotropin releasing hormone receptor
US7582636B2 (en)2005-05-262009-09-01WyethPiperazinylimidazopyridine and piperazinyltriazolopyridine antagonists of Gonadotropin Releasing Hormone receptor
RU2417985C2 (en)2005-05-302011-05-10Баниу Фармасьютикал Ко., Лтд.Novel piperidine derivatives
US8071768B2 (en)2005-06-102011-12-06Janssen Pharmaceutica, N.V.Alkylquinoline and alkylquinazoline kinase modulators
US7825244B2 (en)2005-06-102010-11-02Janssen Pharmaceutica NvIntermediates useful in the synthesis of alkylquinoline and alkylquinazoline kinase modulators, and related methods of synthesis
AU2006277253A1 (en)2005-08-102007-02-15Msd K.K.Pyridone compound
BRPI0614649A2 (en)2005-08-112011-04-12Amylin Pharmaceuticals Inc hybrid polypeptides with selectable properties
EP2330124B1 (en)2005-08-112015-02-25Amylin Pharmaceuticals, LLCHybrid polypeptides with selectable properties
EP1921065B1 (en)2005-08-242010-10-20Banyu Pharmaceutical Co., Ltd.Phenylpyridone derivative
CN101253152A (en)*2005-09-022008-08-27安斯泰来制药株式会社Amide derivatives as ROCK inhibitors
AU2006288153A1 (en)2005-09-072007-03-15Msd K.K.Bicyclic aromatic substituted pyridone derivative
KR20080048502A (en)2005-09-292008-06-02머크 앤드 캄파니 인코포레이티드Acylated spiropiperidine derivatives as melanocortin-4 receptor modulators
JP2009512715A (en)2005-10-212009-03-26ノバルティス アクチエンゲゼルシャフト Combination of renin inhibitor and anti-dyslipidemic agent and / or anti-obesity agent
EP1944301A4 (en)2005-10-272012-01-04Msd Kk NEW BENZOXATHINE DERIVATIVE
EP1953165B1 (en)2005-11-102012-02-01Msd K.K.Aza-substituted spiro derivative
EP1847542A1 (en)*2006-04-212007-10-24Laboratorios del Dr. Esteve S.A.Spiro[benzopyran] or spiro[benzofuran] derivatives which inhibit the sigma receptor
FR2903985B1 (en)2006-07-242008-09-05Sanofi Aventis Sa N- (AMINO-HETEROARYL) -1H-INDOLE-2-CARBOXAMIDE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC USE
FR2904316B1 (en)2006-07-312008-09-05Sanofi Aventis Sa N- (AMINO-HETEROARYL) -1H-INDOLE-2-CARBOXAMIDE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC USE.
US8927715B2 (en)*2006-08-252015-01-06Vitae Pharmaceuticals, Inc.Inhibitors of 11β-hydroxysteroid dehydrogenase type 1
WO2008039327A2 (en)2006-09-222008-04-03Merck & Co., Inc.Method of treatment using fatty acid synthesis inhibitors
AU2007301126A1 (en)2006-09-282008-04-03Banyu Pharmaceutical Co., Ltd.Diaryl ketimine derivative
NZ576278A (en)2006-10-192011-12-22Signal Pharm LlcHeteroaryl compounds, compositions thereof, and their use as protein kinase inhibitors
ATE517866T1 (en)*2006-12-222011-08-15Hoffmann La Roche SPIROPIPERIDINE DERIVATIVES
FR2910473B1 (en)*2006-12-262009-02-13Sanofi Aventis Sa N- (AMINO-HETEROARYL) -1H-PYRROLOPYRIDINE-2-CARBOXAMIDE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC USE.
AU2008233662B2 (en)2007-04-022012-08-23Msd K.K.Indoledione derivative
CA2688161C (en)2007-06-042020-10-20Kunwar ShailubhaiAgonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
US8969514B2 (en)2007-06-042015-03-03Synergy Pharmaceuticals, Inc.Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
US20100120694A1 (en)2008-06-042010-05-13Synergy Pharmaceuticals, Inc.Agonists of Guanylate Cyclase Useful for the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders
WO2009070583A1 (en)*2007-11-302009-06-04WyethPyrido[3,2-e]pyrazines, process for preparing the same, and their use as inhibitors of phosphodiesterase 10
JP2011505366A (en)*2007-11-302011-02-24ワイス・エルエルシー Aryl and heteroaryl fused imidazo [1,5-a] pyrazines as inhibitors of phosphoesterase 10
US8383629B2 (en)*2008-02-272013-02-26Vitae Pharmaceuticals, Inc.Inhibitors of 11β-hydroxysteroid dehydrogenase type 1
JPWO2009110510A1 (en)2008-03-062011-07-14Ｍｓｄ株式会社 Alkylaminopyridine derivatives
CA2717384A1 (en)2008-03-282009-10-01Banyu Pharmaceutical Co., Ltd.Diarylmethylamide derivative having melanin-concentrating hormone receptor antagonism
EP2301936A1 (en)2008-06-192011-03-30Banyu Pharmaceutical Co., Ltd.Spirodiamine-diarylketoxime derivative
ES2624828T3 (en)2008-07-162017-07-17Synergy Pharmaceuticals Inc. Guanylate cyclase agonists useful for the treatment of gastrointestinal disorders, inflammation, cancer and others
AU2009277736A1 (en)2008-07-302010-02-04Banyu Pharmaceutical Co., Ltd.(5-membered)-(5-membered) or (5-membered)-(6-membered) fused ring cycloalkylamine derivative
MX2011004258A (en)2008-10-222011-06-01Merck Sharp & DohmeNovel cyclic benzimidazole derivatives useful anti-diabetic agents.
US8110578B2 (en)2008-10-272012-02-07Signal Pharmaceuticals, LlcPyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway
MX2011004551A (en)2008-10-302011-05-25Merck Sharp & DohmeIsonicotinamide orexin receptor antagonists.
CA2741672A1 (en)2008-10-312010-05-06Merck Sharp & Dohme Corp.Novel cyclic benzimidazole derivatives useful anti-diabetic agents
US20110245209A1 (en)2008-12-162011-10-06Schering CorporationPyridopyrimidine derivatives and methods of use thereof
US20110243940A1 (en)2008-12-162011-10-06Schering CorporationBicyclic pyranone derivatives and methods of use thereof
TW201111383A (en)2009-05-292011-04-01Wyeth LlcSubstituted imidazo[1,5-a]quinoxalines as inhibitors of phosphodiesterase 10
AU2010313585B2 (en)2009-10-262015-11-26Signal Pharmaceuticals, LlcMethods of synthesis and purification of heteroaryl compounds
JP2013520502A (en)2010-02-252013-06-06メルク・シャープ・エンド・ドーム・コーポレイション Novel cyclic benzimidazole derivatives that are useful anti-diabetic drugs
US8680098B2 (en)2010-03-052014-03-25Janssen Pharmaceutica, NvSubstituted aza-bicyclic imidazole derivatives useful as TRPM8 receptor modulators
US20130072519A1 (en)2010-05-212013-03-21Edward Lee Conn2-phenyl benzoylamides
US9616097B2 (en)2010-09-152017-04-11Synergy Pharmaceuticals, Inc.Formulations of guanylate cyclase C agonists and methods of use
ES2652662T3 (en)2011-02-252018-02-05Merck Sharp & Dohme Corp. Novel cyclic azabenzimidazole derivatives useful as antidiabetic agents
EP2680874A2 (en)2011-03-042014-01-08Pfizer IncEdn3-like peptides and uses thereof
AR088352A1 (en)2011-10-192014-05-28Merck Sharp & Dohme ANTAGONISTS OF THE RECEIVER OF 2-PIRIDILOXI-4-NITRILE OREXINE
JP2014530861A (en)2011-10-192014-11-20シグナル ファーマシューティカルズ，エルエルシー Treatment of cancer with a TOR kinase inhibitor
US9403829B2 (en)2011-12-022016-08-02Signal Pharmaceuticals, LlcPharmaceutical compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino [2,3-b]pyrazin-2(1H)-one, a solid form thereof and methods of their use
EP2817029B1 (en)2012-02-242019-07-10Signal Pharmaceuticals, LLCMethods for treating non-small cell lung cancer using tor kinase inhibitor combination therapy
AU2013296470B2 (en)2012-08-022016-03-17Merck Sharp & Dohme Corp.Antidiabetic tricyclic compounds
AU2013203714B2 (en)2012-10-182015-12-03Signal Pharmaceuticals, LlcInhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity
NZ630467A (en)2013-01-162017-02-24Signal Pharm LlcSubstituted pyrrolopyrimidine compounds, compositions thereof, and methods of treatment therewith
CA2898482A1 (en)2013-02-222014-08-28Linda L. BrockunierAntidiabetic bicyclic compounds
US9650375B2 (en)2013-03-142017-05-16Merck Sharp & Dohme Corp.Indole derivatives useful as anti-diabetic agents
WO2014151200A2 (en)2013-03-152014-09-25Synergy Pharmaceuticals Inc.Compositions useful for the treatment of gastrointestinal disorders
EP2970384A1 (en)2013-03-152016-01-20Synergy Pharmaceuticals Inc.Agonists of guanylate cyclase and their uses
KR20160004273A (en)2013-04-172016-01-12시그날 파마소티칼 엘엘씨PHARMACEUTICAL FORMULATIONS, PROCESSES, SOLID FORMS AND METHODS OF USE RELATING TO 1-ETHYL-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-3-YL)PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO[2,3-b]PYRAZIN-2(1H)-ONE
KR102240356B1 (en)2013-04-172021-04-14시그날 파마소티칼 엘엘씨Combination therapy comprising a tor kinase inhibitor and a 5-substituted quinazolinone compound for treating cancer
WO2014172426A1 (en)2013-04-172014-10-23Signal Pharmaceuticals, LlcTreatment of cancer with dihydropyrazino-pyrazines
BR112015026238A8 (en)2013-04-172019-12-24Signal Pharm Llc dihydropyrazino-pyrazine compound, pharmaceutical composition comprising it, use of the compound, methods to inhibit or measure phosphorylation and to inhibit protein kinase activity, as well as a kit
KR102242505B1 (en)2013-04-172021-04-20시그날 파마소티칼 엘엘씨Combination therapy comprising a tor kinase inhibitor and a cytidine analog for treating cancer
UA115805C2 (en)2013-04-172017-12-26Сігнал Фармасьютікалз, ЕлелсіCombination therapy comprising a dihydropyrazino-pyrazine compound and an androgen receptor antagonist for treating prostate cancer
KR20160002792A (en)2013-04-172016-01-08시그날 파마소티칼 엘엘씨Combination therapy comprising a tor kinase inhibitor and n-(3-(5-fluoro-2-(4-(2-methoxyethyoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide for treating cancer
CN109503591B (en)2013-05-292022-03-01西格诺药品有限公司Pharmaceutical compositions of dihydropyrazinopyrazine compounds, solid forms thereof and their use
AU2014274812B2 (en)2013-06-052018-09-27Bausch Health Ireland LimitedUltra-pure agonists of guanylate cyclase C, method of making and using same
WO2015051496A1 (en)2013-10-082015-04-16Merck Sharp & Dohme Corp.Antidiabetic tricyclic compounds
ES2823756T3 (en)2014-04-162021-05-10Signal Pharm Llc Methods for treating cancer using TOR kinase inhibitor combination therapy
US9718824B2 (en)2014-04-162017-08-01Signal Pharmaceuticals, LlcSolid forms comprising 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, and a coformer, compositions and methods of use thereof
WO2015160880A1 (en)2014-04-162015-10-22Signal Pharmaceuticals, LlcSOLID FORMS COMPRISING 1-ETHYL-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-3-YL) PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO(2,3-b)PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF
NZ714742A (en)2014-04-162017-04-28Signal Pharm LlcSolid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use
CA2955009A1 (en)2014-07-142016-01-21Signal Pharmaceuticals, LlcMethods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
NZ629796A (en)2014-07-142015-12-24Signal Pharm LlcAmorphous form of 4-((4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-n-methylbenzamide, compositions thereof and methods of their use
US9708272B2 (en)2014-08-292017-07-18Tes Pharma S.R.L.Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
CN104387367A (en)*2014-11-022015-03-04湖南华腾制药有限公司Method for preparing disubstituted benzimidazole derivative
CN109952292A (en)2016-10-142019-06-28Tes制药有限责任公司 Inhibitors of α-amino-β-carboxyhexadienedioic acid semialdehyde decarboxylase
US11072602B2 (en)2016-12-062021-07-27Merck Sharp & Dohme Corp.Antidiabetic heterocyclic compounds
US10968232B2 (en)2016-12-202021-04-06Merck Sharp & Dohme Corp.Antidiabetic spirochroman compounds
US11628159B2 (en)*2017-01-102023-04-18Eth ZurichCell-protective compounds and their use
CN110996955A (en)2017-06-222020-04-10细胞基因公司 Treatment of hepatocellular carcinoma characterized by hepatitis B virus infection
EP3733206A4 (en)*2017-12-272021-12-01Japanese Foundation For Cancer Research ANTI-CANCER AGENTS
JOP20200338A1 (en)*2018-06-272020-12-24Reborna Biosciences Inc Preventive or treatment agent for spinal muscular atrophy
BR112021009589A2 (en)2018-11-202021-08-17Tes Pharma S.R.L. alpha-amino-beta-carboxymuconic acid semialdehyde decarboxylase inhibitors
WO2020167706A1 (en)2019-02-132020-08-20Merck Sharp & Dohme Corp.5-alkyl pyrrolidine orexin receptor agonists
WO2021026047A1 (en)2019-08-082021-02-11Merck Sharp & Dohme Corp.Heteroaryl pyrrolidine and piperidine orexin receptor agonists
EP3772513A1 (en)*2019-08-092021-02-10C.N.C.C.S. S.c.a.r.l. Collezione Nazionale Dei Composti Chimici e Centro ScreeningShp2 inhibitors
CN116249697A (en)2020-08-182023-06-09默沙东有限责任公司Bicycloheptane pyrrolidine orexin receptor agonists

Citations (6)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
US5602024A (en)*1994-12-021997-02-11Synaptic Pharmaceutical CorporationDNA encoding a hypothalamic atypical neuropeptide Y/peptide YY receptor (Y5) and uses thereof
US20010031474A1 (en)*2000-01-282001-10-18Neurogen CorporationChimeric neuropeptide Y receptors
US6372743B1 (en)*1999-09-302002-04-16Neurogen CorporationCertain alkylene diamine-substituted pyrazlo (1,5-a)-1,5-pyrimidines and pyrazolo (1,5-a) 1,3,5-triazines
US6506762B1 (en)*1999-09-302003-01-14Neurogen CorporationCertain alkylene diamine-substituted heterocycles
US6566367B2 (en)*2000-12-122003-05-20Pfizer Inc.Spiro[isobenzofuran-1,4′-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4′-piperidines
US20030144290A1 (en)*2001-10-232003-07-31Neurogen CorporationSubstituted 2-cyclohexyl-4-phenyl-1H-imidazole derivatives

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
JPS55143980A (en)*1979-04-271980-11-10Dai Ichi Seiyaku Co LtdAnti-allergic preparation
AU2223495A (en)*1994-04-151995-11-10Yamanouchi Pharmaceutical Co., Ltd.Spiro compound and medicinal composition thereof
ID29137A (en)*1998-07-272001-08-02Schering Corp HIGH AFINITY LIGANS FOR ORL-1 NOSISEPTIN RECEPTORS
US6191160B1 (en)1998-11-102001-02-20Merck & Co., Inc.Spiro-indolines as Y5 receptor antagonists
TWI279402B (en)1999-08-202007-04-21Banyu Pharma Co LtdSpiro compounds having NPY antagonistic activities and agents containing the same
AU2001264376A1 (en)2000-06-152001-12-24Chaconne Nsi Co., Ltd.Urea derivative useful as an anti-cancer agent and process for preparing same

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
US5602024A (en)*1994-12-021997-02-11Synaptic Pharmaceutical CorporationDNA encoding a hypothalamic atypical neuropeptide Y/peptide YY receptor (Y5) and uses thereof
US6372743B1 (en)*1999-09-302002-04-16Neurogen CorporationCertain alkylene diamine-substituted pyrazlo (1,5-a)-1,5-pyrimidines and pyrazolo (1,5-a) 1,3,5-triazines
US6506762B1 (en)*1999-09-302003-01-14Neurogen CorporationCertain alkylene diamine-substituted heterocycles
US20030069246A1 (en)*1999-09-302003-04-10Neurogen CorporationCertain alkylene diamine-substituted pyrazolo[1,5,-a]-1,5-pyrimidines and pyrazolo [1,5-a]-1,3,5-triazines
US6696445B2 (en)*1999-09-302004-02-24Neurogen CorporationCertain alkylene diamine-substituted heterocycles
US20010031474A1 (en)*2000-01-282001-10-18Neurogen CorporationChimeric neuropeptide Y receptors
US6566367B2 (en)*2000-12-122003-05-20Pfizer Inc.Spiro[isobenzofuran-1,4′-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4′-piperidines
US20040072847A1 (en)*2000-12-122004-04-15Neurogen CorporationSpiro[isobenzofuran-1,4'-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4'-piperidines
US20030144290A1 (en)*2001-10-232003-07-31Neurogen CorporationSubstituted 2-cyclohexyl-4-phenyl-1H-imidazole derivatives

Cited By (27)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
US20080047479A1 (en)*1997-10-272008-02-28Correct Craft, Inc.Water Sport Towing Apparatus and Method
US7786141B2 (en)2004-08-192010-08-31Vertex Pharmaceuticals IncorporatedDihydrospiroindene modulators of muscarinic receptors
US8497295B2 (en)2004-08-192013-07-30Vertex Pharmaceuticals IncorporatedSpiroindoline modulators of muscarinic receptors
US8367691B2 (en)2004-08-192013-02-05Vertex Pharmaceutical IncorporatedModulators of muscarinic receptors
US20100311720A1 (en)*2004-08-192010-12-09Vertex Pharmaceuticals IncorporatedSpiroindoline Modulators of Muscarinic Receptors
US8258148B2 (en)2004-08-192012-09-04Vertex Pharmaceutical IncorporatedSpiroindoline modulators of muscarinic receptors
US20100311746A1 (en)*2004-08-192010-12-09Vertex Pharmaceuticals IncorporatedModulators of muscarinic receptors
US7879834B2 (en)2004-08-192011-02-01Vertex Pharmaceuticals IncorporatedSpiroindoline modulators of muscarinic receptors
US20060079505A1 (en)*2004-08-192006-04-13Vertex Pharmaceuticals, IncorporatedModulators of muscarinic receptors
US20070043023A1 (en)*2004-08-192007-02-22Makings Lewis RModulators of muscarinic receptors
US20060270653A1 (en)*2004-11-292006-11-30Ioana DrutuModulators of muscarinic receptors
US7863449B2 (en)2004-11-292011-01-04Vertex Pharmaceuticals IncorporatedModulators of muscarinic receptors
US7858635B2 (en)2005-12-222010-12-28Vertex Pharmaceuticals IncorporatedSpiro compounds as modulators of muscarinic receptors
US20080015179A1 (en)*2005-12-222008-01-17Makings Lewis RModulators of muscarinic receptors
US8003660B2 (en)2006-02-222011-08-23Vertex Pharmaceuticals IncorporatedModulators of muscarinic receptors
US8304423B2 (en)2006-02-222012-11-06Vertex Pharmaceutical IncorporatedModulators of muscarinic receptors
US20090227614A1 (en)*2006-02-222009-09-10Makings Lewis RModulators of Muscarinic Receptors
US8263605B2 (en)2006-02-222012-09-11Vertex Pharmaceutical IncorporatedModulators of muscarinic receptors
US20070213315A1 (en)*2006-02-222007-09-13Robert DaviesModulators of muscarinic receptors
US7858790B2 (en)2006-06-292010-12-28Vertex Pharmaceuticals IncorporatedModulators of muscarinic receptors
US20080033002A1 (en)*2006-06-292008-02-07Bandarage Upul KModulators of muscarinic receptors
US7696201B2 (en)2006-08-152010-04-13Vertex Pharmaceuticals IncorporatedModulators of muscarinic receptors
US20080176843A1 (en)*2006-08-152008-07-24Makings Lewis RModulators of muscarinic receptors
US7786107B2 (en)2006-08-182010-08-31Vertex Pharmaceuticals IncorporatedModulators of muscarinic receptors
US7973162B2 (en)2007-10-032011-07-05Vertex Pharmaceuticals IncorporatedModulators of muscarinic receptors
US20090099222A1 (en)*2007-10-032009-04-16Davies Robert JModulators of muscarinic receptors
US11414429B2 (en)2016-06-302022-08-16RikenCompound or pharmaceutically acceptable salt thereof

Also Published As

Publication numberPublication date
EP1347982A2 (en)2003-10-01
ES2249384T3 (en)2006-04-01
US6566367B2 (en)2003-05-20
DE60115092T2 (en)2006-03-30
US20030036652A1 (en)2003-02-20
BR0116113A (en)2004-08-03
AU2002220276A1 (en)2002-06-24
DE60115092D1 (en)2005-12-22
WO2002048152A2 (en)2002-06-20
ATE310004T1 (en)2005-12-15
WO2002048152A3 (en)2003-05-08
US20060040964A1 (en)2006-02-23
MXPA03004245A (en)2003-09-22
EP1347982B1 (en)2005-11-16
US6943199B2 (en)2005-09-13
US20040072847A1 (en)2004-04-15
JP2004520299A (en)2004-07-08

Similar Documents

PublicationPublication DateTitle
US6943199B2 (en)Spiro[isobenzofuran-1,4′-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4′-piperidines
US6372743B1 (en)Certain alkylene diamine-substituted pyrazlo (1,5-a)-1,5-pyrimidines and pyrazolo (1,5-a) 1,3,5-triazines
US6476038B1 (en)Amino substituted pyrazolo[1,5,-a]-1,5-pyrimidines and pyrazolo[1,5-a]-1,3,5-triazines
EP1224187B1 (en)Certain alkylene diamine-substituted heterocycles
US20080247964A1 (en)Substituted azaspiro derivatives
US20100317679A1 (en)Substituted aryl-fused spirocyclic amines
CA3229686A1 (en)2-amino-5,5-dimethylhexanoic acid derivatives as sortilin modulators for use in the treatment of disease of the central nervous system
US7034034B2 (en)Substituted 2-cyclohexyl-4-phenyl-1H-imidazole derivatives
EP1695977A2 (en)Spiro [isobenzofuran-1,4'piperidin]-3-ones and 3H-spiroisobenzofuran-1, 4'-piperidines

Legal Events

DateCodeTitleDescription
ASAssignment

Owner name:PFIZER INC., NEW YORK

Free format text:ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:ELLIOTT, RICHARD LOUIS;HAMMOND, MARLYS;REEL/FRAME:014647/0119;SIGNING DATES FROM 20030604 TO 20030605

Owner name:NEUROGEN CORPORATION, CONNECTICUT

Free format text:ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BAKTHAVATCHALAM, RAJAGOPAL;BLUM, CHARLES A.;BRIELMANN, HARRY L.;AND OTHERS;REEL/FRAME:014647/0108;SIGNING DATES FROM 20030515 TO 20030709

STCBInformation on status: application discontinuation

Free format text:ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION
[8]ページ先頭
©2009-2025 Movatter.jp