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US6117911A Expired / Lapsed US ⏱️ 0.0 years remaining

Compounds and therapies for the prevention of vascular and non-vascular pathologies

Assignee: Poniard Pharmaceuticals Inc
•
Filing: 1998-04-09
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Granted: 2000-09-12
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Expires: 2018-04-09
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Abstract

Abstract The invention provides a method of treating a mammal having, or at risk of, an indication associated with a TGF-beta deficiency comprising administering one or more agents that is effective to elevate the level of TGF-beta. The invention also provides novel compounds that elevate TGF-beta levels, as well as pharmaceutical compositions comprising compounds that elevate TGF-beta levels, and methods for detecting diseases associated with endothelial cell activation.

Inventors

  • 👤 David J. Grainger
  • 👤 James C. Metcalfe
  • 👤 Sudhakar Kasina

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 01:50
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/275; A61K31/33; A61K31/38; A61K31/381; C; C07; C07D; C07D333/00; C07D333/02; C07D333/04; C07D333/26; C07D333/38; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/74; G01N2333/00; G01N2333/435; G01N2333/475; G01N2333/495; G01N2333/705; G01N2333/71; G01N2800/00; G01N2800/10; G01N2800/108; G01N2800/32; G01N2800/323

Claims Analysis

Total Claims: 28
Claim 1
Independent Claim 481 words
A therapeutic method for preventing or treating a condition or symptom associated with Marfan's syndrome, fibrosis, or senile dementia, comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR20## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 04 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 04 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is 0, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )-, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H (C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim 481 words
A therapeutic method for preventing or treating a condition or symptom associated with Marfan's syndrome, fibrosis, or senile dementia, comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR20## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 04 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 04 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is 0, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )-, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H (C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim 477 words
A therapeutic method for preventing or treating a condition or symptom associated with Parkinson's disease comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR21## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H (C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof.
Claim 4
Dependent Claim 477 words
A therapeutic method for preventing or treating a condition or symptom associated with Parkinson's disease comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR21## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H (C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof.
Claim 5
Dependent Claim 498 words
A therapeutic method for preventing or treating a condition or symptom associated with Alzheimer's disease comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR22## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 21 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 13 --C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 --C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o , together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided the compound of formula VI is not toremifene, tamoxifen, monophenoltamoxifen, 4-hydroxytoremifene, clomifene, 4-hydroxytamoxifen, 3-hydroxytamoxifen, N-desmethyltamoxifen, cyanotamoxifen, N-desmethyltoremifene, monophenoltoremifene, or deaminotoremifene.
Claim 6
Dependent Claim 498 words
A therapeutic method for preventing or treating a condition or symptom associated with Alzheimer's disease comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR22## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 21 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 13 --C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 --C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o , together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided the compound of formula VI is not toremifene, tamoxifen, monophenoltamoxifen, 4-hydroxytoremifene, clomifene, 4-hydroxytamoxifen, 3-hydroxytamoxifen, N-desmethyltamoxifen, cyanotamoxifen, N-desmethyltoremifene, monophenoltoremifene, or deaminotoremifene.
Claim 7
Dependent Claim 488 words
A therapeutic method for preventing or treating a condition or symptom associated with an autoimmune disease comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR23## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 1 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 04 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R,), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided that the compound is not toremifene, tamoxifen, 4-hydroxytamoxifen, 3-hydroxytamoxifen, 4-hydroxytoremifene or N-desmethyltoremifene.
Claim 8
Dependent Claim 488 words
A therapeutic method for preventing or treating a condition or symptom associated with an autoimmune disease comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR23## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 1 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 04 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R,), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided that the compound is not toremifene, tamoxifen, 4-hydroxytamoxifen, 3-hydroxytamoxifen, 4-hydroxytoremifene or N-desmethyltoremifene.
Claim 9
Dependent Claim 12 words
The method of claim 4 wherein the autoimmune disease is lupus erythematosus.
Claim 10
Dependent Claim 12 words
The method of claim 4 wherein the autoimmune disease is rheumatoid arthritis.
Claim 11
Dependent Claim 12 words
The method of claim 4 wherein the autoimmune disease is multiple sclerosis.
Claim 12
Dependent Claim 624 words
A therapeutic method for lowering serum cholesterol comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR24## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R,), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided the compound of formula VI is not tamoxifen; and provided R 9 is not halo when Z is a covalent bond; R 6 is a phenyl radical or a phenyl radical substituted only at the 4-position with a group --O(CH 2 ) 2 R k ; R 7 is a phenyl radical or a phenyl radical substituted with one halogen or (C 1 -C 6 )alkyl; and R 8 is a phenyl radical or a phenyl radical substituted only at the 4-position with a group --O(CH 2 ) 2 R k ; and -- is a single bond; and provided that R 9 is not ethyl when Z is a covalent bond; R 6 is a phenyl radical substituted only at the 4-position with a group --O(CH 2 ) 2 R k ; R k is methylamino, ethylamino, dimethylamino or diethylamino; R 7 is unsubstituted phenyl; and R 8 is 3-hydroxyphenyl; and -- is a single bond.
Claim 13
Dependent Claim 624 words
A therapeutic method for lowering serum cholesterol comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR24## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R,), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided the compound of formula VI is not tamoxifen; and provided R 9 is not halo when Z is a covalent bond; R 6 is a phenyl radical or a phenyl radical substituted only at the 4-position with a group --O(CH 2 ) 2 R k ; R 7 is a phenyl radical or a phenyl radical substituted with one halogen or (C 1 -C 6 )alkyl; and R 8 is a phenyl radical or a phenyl radical substituted only at the 4-position with a group --O(CH 2 ) 2 R k ; and -- is a single bond; and provided that R 9 is not ethyl when Z is a covalent bond; R 6 is a phenyl radical substituted only at the 4-position with a group --O(CH 2 ) 2 R k ; R k is methylamino, ethylamino, dimethylamino or diethylamino; R 7 is unsubstituted phenyl; and R 8 is 3-hydroxyphenyl; and -- is a single bond.
Claim 14
Dependent Claim 468 words
A therapeutic method for enhancing or promoting wound healing, comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR25## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is 0, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R,), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl;, R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof.
Claim 15
Dependent Claim 468 words
A therapeutic method for enhancing or promoting wound healing, comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR25## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is 0, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R,), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl;, R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof.
Claim 16
Independent Claim 37 words
The method of any one of claims 1, 2, 3, 4, 8, and 9 wherein Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, or a covalent bond.
Claim 17
Independent Claim 29 words
The method of any one of claims 1, 2, 3, 4, 8, and 9 wherein Z is --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, or --N(R q )--.
Claim 18
Independent Claim 28 words
The method of any one of claims 1, 2, 3, 4, 8, and 9 wherein R 6 is not phenyl or phenyl substituted by 1 or 2 V.
Claim 19
Independent Claim 28 words
The method of any one of claims 1, 2, 3, 4, 8, and 9 wherein R 7 is not phenyl or phenyl substituted by 1 or 2 V.
Claim 20
Independent Claim 28 words
The method of any one of claims 1, 2, 3, 4, 8, and 9 wherein R 8 is not phenyl, or phenyl substituted by 1 or 2 V.
Claim 21
Dependent Claim 556 words
A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR26## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R,), S, or nonperoxide O, wherein R1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided that R 9 is not methyl, ethyl, chloro, or bromo when Z is a covalent bond; and provided that Z is not --CH 2 -- when R 6 is phenyl, substituted only at the 4-position with --O(CH 2 ) 1-3 R k ; wherein R k is pyrrolidino, piperidino, 4-morpholino, dimethylamino, diethylamino, or hexamethyleneimino; and provided that R 9 is not 2-chloroethyl when Z is a covalent bond; and R 6 is phenyl, substituted only at the 4-position with --O(CH 2 ) 2 OH.
Claim 22
Dependent Claim 556 words
A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR26## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R,), S, or nonperoxide O, wherein R1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided that R 9 is not methyl, ethyl, chloro, or bromo when Z is a covalent bond; and provided that Z is not --CH 2 -- when R 6 is phenyl, substituted only at the 4-position with --O(CH 2 ) 1-3 R k ; wherein R k is pyrrolidino, piperidino, 4-morpholino, dimethylamino, diethylamino, or hexamethyleneimino; and provided that R 9 is not 2-chloroethyl when Z is a covalent bond; and R 6 is phenyl, substituted only at the 4-position with --O(CH 2 ) 2 OH.
Claim 23
Dependent Claim 564 words
A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR27## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 )O 4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided that Z is not a covalent bond when R 9 is methyl, ethyl, chloro, or bromo; and provided that Z is not --CH 2 -- when R 6 is phenyl, substituted only at the 4-position with --O(CH 2 ) 1-3 R k ; wherein R k is pyrrolidino, piperidino, 4-morpholino, dimethylamino, diethylamino, or hexamethyleneimino; and provided that R 9 is not halo(C 1 -C 3 )alkyl when Z is a covalent bond; and R 6 is phenyl, substituted only at the 4-position with --O(CH 2 ) 2 OH.
Claim 24
Dependent Claim 564 words
A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR27## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 )O 4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided that Z is not a covalent bond when R 9 is methyl, ethyl, chloro, or bromo; and provided that Z is not --CH 2 -- when R 6 is phenyl, substituted only at the 4-position with --O(CH 2 ) 1-3 R k ; wherein R k is pyrrolidino, piperidino, 4-morpholino, dimethylamino, diethylamino, or hexamethyleneimino; and provided that R 9 is not halo(C 1 -C 3 )alkyl when Z is a covalent bond; and R 6 is phenyl, substituted only at the 4-position with --O(CH 2 ) 2 OH.
Claim 25
Dependent Claim 466 words
A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR28## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, or --N(R q )--; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof.
Claim 26
Dependent Claim 466 words
A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR28## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 ) 0-4 R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, or --N(R q )--; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof.
Claim 27
Dependent Claim 487 words
A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR29## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 )R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided R 6 is not phenyl or phenyl substituted by 1 or 2 V.
Claim 28
Dependent Claim 487 words
A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI: ##STR29## wherein R 6 is (C 1 -C 6 )alkyl, or aryl, optionally substituted by 1, 2, or 3 V; R 7 is phenyl, optionally substituted by 1, 2, or 3 V; or R 7 is (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkylcyclo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkenyl, or (C 1 -C 6 )alkyl(C 3 -C 6 )cycloalkenyl; R 8 is hydrogen or phenyl, optionally substituted by 1, 2, or 3 V; R 9 is hydrogen, halo, aryl, aryl(C 1 -C 3 )alkyl, halo(C 1 -C 12 )alkyl, cyano(C 1 -C 12 )alkyl, or (C 1 -C 12 )alkyl, wherein any aryl may optionally be substituted by 1, 2, or 3, V; or -- is a single bond or is --C(B)(D)--, wherein B and D are each independently hydrogen, (C 1 -C 6 )alkyl, or halo; V is OPO 3 H 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mercapto, (C 1 -C 4 )alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(R n )(R o ), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, --(CH 2 ) 0-4 C(═O)(C 1 -C 6 )alkyl, --UC(═O)(C 1 -C 6 )alkyl, benzyl, --OSO 2 (CH 2 ) 0-4 CH 3 , --U(CH 2 ) 1-4 COOR p , --(CH 2 ) 0-4 COOR p , --U(CH 2 ) 2-4 OR p , --(CH 2 ) 0-4 OR p , --U(CH 2 ) 1-4 C(═O)R k , --(CH 2 ) 0-4 C(═O)R k , --U(CH 2 ) 1-4 R k , --(CH 2 )R k , or --U(CH 2 ) 2-4 OC(═O)R p ; wherein U is O, N(R m ), or S; Z is --(CH 2 ) 1-3 --, --O--, --OCH 2 --, --CH 2 O--, --C(═O)O--, --N(R q )--, C═O, or a covalent bond; R k is amino, optionally substituted with one or two (C 1 -C 6 )alkyl; or an N-heterocyclic ring optionally containing 1 or 2 additional N(R 1 ), S, or nonperoxide O, wherein R 1 is H(C 1 -C 6 )alkyl, phenyl, or benzyl; R n and R o are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; or R n and R o together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring; R p is H or (C 1 -C 6 )alkyl; and R m and R q are independently hydrogen, (C 1 -C 6 )alkyl, phenyl, benzyl, or (C 1 -C 6 )alkanoyl; the compound is MER25; or a pharmaceutically acceptable salt thereof; provided R 6 is not phenyl or phenyl substituted by 1 or 2 V.

References Cited (Backward Citations)

GB1015787A Cited
US3634517A Cited
US4323707A Cited
US4133814A Cited
US4230862A Cited
US4310523A Cited
US4239778A Cited
US4307111A Cited
US4382143A Cited
US5098903A Cited
US5658951A Cited
US5658927A Cited
US4442119A Cited
US5047431A Cited
US4418068A Cited
US4380635A Cited
US5015666A Cited
US4879315A Cited
EP0095875A2 Cited
US4696949A Cited
US5491173A Cited
US4996225A Cited
EP0260066A1 Cited
US4839155A Cited
US5075321A Cited
US4973755A Cited
US5393785A Cited
US5395842A Cited
EP0377526A2 Cited
US4990538A Cited
US5401730A Cited
US5189212A Cited
US5192525A Cited
US5219548A Cited
US5446070A Cited
US5254594A Cited
US5480888A Cited
US5605700A Cited
US5393763A Cited
US5534527A Cited
EP0584952A1 Cited
US5457117A Cited
GB2273873A Cited
US5733925A Cited
US5770609A Cited
US5480903A Cited
US5451603A Cited
US5280040A Cited
US5482949A Cited
US5847007A Cited
US5445941A Cited
EP0629697A2 Cited
DE4320898A1 Cited
US5510370A Cited
US5418252A Cited
US5482950A Cited
US5391557A Cited
US5441964A Cited
US5461065A Cited
US5457116A Cited
US5411988A Cited
US5480904A Cited
US5436243A Cited
US5446053A Cited
US5521198A Cited
US5447941A Cited
US5451590A Cited
US5451589A Cited
US5686476A Cited
EP0664123A1 Cited
EP0659418A1 Cited
EP0659415A2 Cited
US5461064A Cited
EP0659419A1 Cited
US5462949A Cited
US5462950A Cited
US5389670A Cited
EP0659429A1 Cited
EP0668075A2 Cited
EP0659413A2 Cited
US5441966A Cited
US5652259A Cited
EP0664122A1 Cited
EP0664124A1 Cited
US5552415A Cited
EP0664125A1 Cited
US5439923A Cited
US5492927A Cited
US5439931A Cited
EP0665015A2 Cited
EP0670162A1 Cited
EP0675121A1 Cited
US5455275A Cited
EP0684259B1 Cited
US5466810A Cited
US5441986A Cited
US5496828A Cited
US5434166A Cited
US5491159A Cited
EP0699673B1 Cited

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