IPC분류정보
국가/구분 |
United States(US) Patent
등록
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국제특허분류(IPC7판) |
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출원번호 |
US-0389712
(1995-02-15)
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발명자
/ 주소 |
- Kunz, Lawrence L.
- Klein, Richard A.
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출원인 / 주소 |
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대리인 / 주소 |
Schwegman, Lundberg, Woessner & Kluth, P.A.
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인용정보 |
피인용 횟수 :
111 인용 특허 :
122 |
초록
▼
Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a ce
Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a cell surface of the vascular smooth muscle cell, coupled to a therapeutic agent dosage form that inhibits a cellular activity of the muscle cell. Methods are also provided for the direct and/or targeted delivery of therapeutic agents to vascular smooth muscle cells that cause a dilation and fixation of the vascular lumen by inhibiting smooth muscle cell contraction, thereby constituting a biological stent.
대표청구항
▼
Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a ce
Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a cell surface of the vascular smooth muscle cell, coupled to a therapeutic agent dosage form that inhibits a cellular activity of the muscle cell. Methods are also provided for the direct and/or targeted delivery of therapeutic agents to vascular smooth muscle cells that cause a dilation and fixation of the vascular lumen by inhibiting smooth muscle cell contraction, thereby constituting a biological stent. olycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, aralkyl, OR6(wherein R6represents hydrogen, lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, or aralkyl), or NR7R8(wherein R7represents hydrogen, substituted or unsubstituted lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted aralkyl, or substituted or unsubstituted heteroarylalkyl; and R8represents substituted or unsubstituted lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted aralkyl, or substituted or unsubstituted heteroarylalkyl; or R7and R8are combined to represent a substituted or unsubstituted heterocyclic group containing at least one nitrogen atom)); or R1and R2are combined to represent a saturated carbon ring together with a carbon atom adjacent thereto; R3represents hydrogen, phenyl, or halogen; R4represents substituted or unsubstituted lower alkoxy; A represents O; B represents O; D represents --CONH--, --CH2CH2--, --CH=CH--, --CH(C6H5)CH2--, --C(C6H5)=CH-- or --COCH2--; and R5represents substituted or unsubstituted pyridyl, or a pharmaceutically acceptable salt thereof. 2. An oxygen-containing heterocyclic compound according to claim 1, wherein R1and R2are combined to represent a saturated carbon ring together with a carbon atom adjacent thereto, or a pharmaceutically acceptable salt thereof. 3. An oxygen-containing heterocyclic compound according to claim 1 or 2, wherein R5is unsubstituted pyridyl, or a pharmaceutically acceptable salt thereof. 4. An oxygen-containing heterocyclic compound according to claim 1 or 2, wherein R5is substituted pyridyl, or a pharmaceutically acceptable salt thereof, wherein the substituent is 1-3 substituents independently selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, lower alkonoyl, lower alkoxycarbonyl, carboxyl, aminocarbonyl, trifluoromethyl, amino cyano, nitro and halogen. 5. An oxygen-containing heterocyclic compound represented by Formula (I): wherein R1represents hydrogen, substituted or unsubstituted lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, lower alkenyl, C4-10 cycloalkenyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, aralkyl, cyano, or --(CH2)n--E1--COG1(wherein n is an integer of 0 to 4; E1represents a bond, O, or NH; and G1represents hydrogen, substituted or unsubstituted lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, aralkyl, OR6(wherein R6represents hydrogen, lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, or aralkyl), or NR7R8(wherein R7represents hydrogen, substituted or unsubstituted lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted aralkyl, or substituted or unsubstituted heteroarylalkyl; and R8represents substituted or unsubstituted lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group , substituted or unsubstituted aralkyl, or substituted or unsubstituted heteroarylalkyl; or R7and R8are combined to represent a substituted or unsubstituted heterocyclic group containing at least one nitrogen atom)); R2represents hydrogen, substituted or unsubstituted lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, lower alkenyl, C4-10 cycloalkenyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, aralkyl, cyano, or --(CH2)q--E4--COG4(wherein q is an integer of 0 to 4; E4represents a bond, O, or NH; and G4represents hydrogen, substituted or unsubstituted lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, aralkyl, OR6(wherein R6represents hydrogen, lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, or aralkyl), or NR7R8(wherein R7represents hydrogen, substituted or unsubstituted lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted aralkyl, or substituted or unsubstituted heteroarylalkyl; and R8represents substituted or unsubstituted lower alkyl, C3-10 cycloalkyl, C4-12 polycycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted aralkyl, or substituted or unsubstituted heteroarylalkyl; or R7and R8are combined to represent a substituted or unsubstituted heterocyclic group containing at least one nitrogen atom)); or R1and R2are combined to represent a saturated carbon ring together with a carbon atom adjacent thereto; R3represents hydrogen, phenyl, or halogen; R4represents substituted or unsubstituted lower alkoxy; A represents O; B represents --C(R12)(R13)-- (wherein R12and R13independently represent hydrogen, substituted or unsubstituted lower alkyl, hydroxy, substituted or unsubstituted lower alkoxy, lower alkanoyloxy, substituted or unsubstituted lower alkanoyl, substituted or unsubstituted cycloalkylcarbonyl, lower alkoxycarbonyl, C3-10 cycloaklyl, C4-12 polycycloalkyl, lower alkenyl, C4-10 cycloalkenyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted aralkyl, halogen, cyano, or --(CH2)p--E3--CO--G3(wherein E3,G3and p have the same meanings as E1,G1and n, respectively); or R13and R2are combined to form a single bond, or a saturated carbon ring together with two carbon atoms adjacent thereto); D represents --CONH--, --CH2CH2--, --CH=CH--, --CH(C6H5)CH2--, --C(C6H5)=CH-- or --COCH2--; and R5represents substituted or unsubstituted pyridyl, or a pharmaceutically acceptable salt thereof. 6. An oxygen-containing heterocyclic compound according to claim 5, wherein R1is --CONR7R8,and R13and R2are combined to form a single bond, or a pharmaceutically acceptable salt thereof. 7. An oxygen-containing heterocyclic compound according to claim 5 or 6, wherein R5is unsubstituted pyridyl, or a pharmaceutically acceptable salt thereof. 8. An oxygen-containing heterocyclic compound according to claim 5 or 6, wherein R5is substituted pyridyl, or a pharmaceutically acceptable salt thereof, wherein the substituent is 1-3 substituents independently selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, lower alkonoyl, lower alkoxycarbonyl, carboxyl, aminocarbonyl, trifluoromethyl, amino cyano, nitro and halogen.
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