公开(公告)号：US07915450B2

公开(公告)日：2011-03-29

申请号：US12638336

申请日：2009-12-15

申请人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

发明人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

IPC分类号： C07C211/63 ,  C07C233/02 ,  C12N15/88 ,  A61K31/225 ,  A61K31/16 ,  A61K31/14

CPC分类号： A61K47/48046 ,  A61K9/16 ,  A61K31/14 ,  A61K38/28 ,  A61K38/40 ,  A61K47/543 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C229/26 ,  C07D209/48 ,  C07D241/12 ,  C12N15/88 ,  Y10S435/81

摘要： Disclosed are cationic lipid compounds and compositions of lipid aggregates for delivery of macromolecules and other compounds into cells. The compounds can be used alone or in combination with other compounds lo prepare liposomes and other lipid aggregates suitable for iransfcclion or delivery of compounds to target cells, cither in vitro or in vivo. The compounds are preferably polycationic and preferably form highly stable complexes with various anionic macromolecules. particularly polyanions such as nucleic acids. These compounds have the properly, when dispersed in water, of forming lipid aggregates which associate strongly, via their cationic portion, with polyanions. Also disclosed are intermediates for preparing the compound and compositions of the invention and methods of using the compounds to introduce other compounds into cells.

摘要翻译： 公开了阳离子脂质化合物和用于将大分子和其它化合物递送到细胞中的脂质聚集体的组合物。 化合物可以单独使用或与其它化合物组合使用，以制备适合于将体外或体内化合物转运至靶细胞的脂质体和其他脂质聚集体。 该化合物优选是阳离子型的，优选与各种阴离子大分子形成高度稳定的络合物。 特别是聚阴离子如核酸。 当分散在水中时，这些化合物可以适当地形成通过其阳离子部分与聚阴离子强烈缔合的脂质聚集体。 还公开了制备本发明化合物和组合物的中间体以及使用该化合物将其它化合物引入细胞的方法。

公开(公告)号：US07470817B2

公开(公告)日：2008-12-30

申请号：US11617625

申请日：2006-12-28

申请人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

发明人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

IPC分类号： C07C233/00 ,  C07C235/00 ,  C07C237/00 ,  C07C239/00 ,  C07C277/00 ,  C07C211/00 ,  A61K31/13 ,  A61K9/127 ,  A61K9/50 ,  C12N15/86

CPC分类号： A61K47/48046 ,  A61K9/16 ,  A61K31/14 ,  A61K38/28 ,  A61K38/40 ,  A61K47/543 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C229/26 ,  C07D209/48 ,  C07D241/12 ,  C12N15/88 ,  Y10S435/81

摘要： Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)I, or {(CH2)i-Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1-L′-X2-Z or -Z; R1-R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.

公开(公告)号：US20050164391A1

公开(公告)日：2005-07-28

申请号：US11040687

申请日：2005-01-21

申请人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

发明人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

IPC分类号： C12N15/09 ,  A61K9/127 ,  A61K31/14 ,  A61K47/16 ,  A61K47/18 ,  A61K47/22 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C215/18 ,  C07C217/08 ,  C07C229/26 ,  C07C237/10 ,  C07C279/08 ,  C07D211/26 ,  C07D213/38 ,  C07D241/12 ,  C07D273/08 ,  C07D291/02 ,  C12N5/10 ,  C12N15/85 ,  C07C275/14 ,  C07D241/02 ,  C07K14/47

CPC分类号： A61K47/48046 ,  A61K9/16 ,  A61K31/14 ,  A61K38/28 ,  A61K38/40 ,  A61K47/543 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C229/26 ,  C07D209/48 ,  C07D241/12 ,  C12N15/88 ,  Y10S435/81

摘要： Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i-Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1-L′-X2-Z or -Z; R1-R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.

公开(公告)号：US20050124069A1

公开(公告)日：2005-06-09

申请号：US11040562

申请日：2005-01-21

申请人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

发明人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

IPC分类号： C12N15/09 ,  A61K9/127 ,  A61K31/14 ,  A61K47/16 ,  A61K47/18 ,  A61K47/22 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C215/18 ,  C07C217/08 ,  C07C229/26 ,  C07C237/10 ,  C07C279/08 ,  C07D211/26 ,  C07D213/38 ,  C07D241/12 ,  C07D273/08 ,  C07D291/02 ,  C12N5/10 ,  C12N15/88 ,  C07D43/02

CPC分类号： A61K47/48046 ,  A61K9/16 ,  A61K31/14 ,  A61K38/28 ,  A61K38/40 ,  A61K47/543 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C229/26 ,  C07D209/48 ,  C07D241/12 ,  C12N15/88 ,  Y10S435/81

摘要： Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i—Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1-L′-X2-Z or -Z; R1-R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.

公开(公告)号：US08785200B2

公开(公告)日：2014-07-22

申请号：US13420091

申请日：2012-03-14

申请人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

发明人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

IPC分类号： C12N15/88

CPC分类号： A61K47/48046 ,  A61K9/16 ,  A61K31/14 ,  A61K38/28 ,  A61K38/40 ,  A61K47/543 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C229/26 ,  C07D209/48 ,  C07D241/12 ,  C12N15/88 ,  Y10S435/81

摘要： Disclosed are cationic lipid compounds and compositions of lipid aggregates for delivery of macromolecules and other compounds into cells. The compounds can be used alone or in combination with other compounds to prepare liposomes and other lipid aggregates suitable for transfection or delivery of compounds to target cells, either in vitro or in vivo. The compounds are preferably polycationic and preferably form highly stable complexes with various anionic macromolecules, particularly polyanions such as nucleic acids. These compounds have the property, when dispersed in water, of forming lipid aggregates which associate strongly, via their cationic portion, with polyanions. Also disclosed are intermediates for preparing the compound and compositions of the invention and methods of using the compounds to introduce other compounds into cells.

摘要翻译： 公开了阳离子脂质化合物和用于将大分子和其它化合物递送到细胞中的脂质聚集体的组合物。 化合物可以单独使用或与其他化合物组合使用以制备适合于在体外或体内转染或递送化合物到靶细胞的脂质体和其他脂质聚集体。 该化合物优选是阳离子型的，优选与各种阴离子大分子，特别是聚阴离子如核酸形成高度稳定的络合物。 这些化合物在分散于水中时具有形成通过其阳离子部分强力缔合聚阴离子的脂质聚集体的性质。 还公开了制备本发明化合物和组合物的中间体以及使用该化合物将其它化合物引入细胞的方法。

公开(公告)号：US20120238747A1

公开(公告)日：2012-09-20

申请号：US13420091

申请日：2012-03-14

申请人： Yongliang CHU ,  Malek Masoud ,  Gulilat Gebeyehu

发明人： Yongliang CHU ,  Malek Masoud ,  Gulilat Gebeyehu

IPC分类号： C07C211/63 ,  C07D273/08 ,  C07C215/18 ,  C07C237/10 ,  C07J1/00

CPC分类号： A61K47/48046 ,  A61K9/16 ,  A61K31/14 ,  A61K38/28 ,  A61K38/40 ,  A61K47/543 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C229/26 ,  C07D209/48 ,  C07D241/12 ,  C12N15/88 ,  Y10S435/81

摘要： Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i-Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1-L′-X2—Z or —Z; R1-R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; U is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.

公开(公告)号：US08158827B2

公开(公告)日：2012-04-17

申请号：US12353371

申请日：2009-01-14

申请人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

发明人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

IPC分类号： C07C211/62 ,  C07C211/63 ,  C07C211/64 ,  A61K31/13 ,  A61K9/127 ,  A61K9/50 ,  C12N15/88

CPC分类号： A61K47/48046 ,  A61K9/16 ,  A61K31/14 ,  A61K38/28 ,  A61K38/40 ,  A61K47/543 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C229/26 ,  C07D209/48 ,  C07D241/12 ,  C12N15/88 ,  Y10S435/81

摘要： Disclosed are cationic lipid compounds and compositions of lipid aggregates for delivery of macromolecules and other compounds into cells. The compounds can be used alone or in combination with other compounds to prepare liposomes and other lipid aggregates suitable for transfection or delivery of compounds to target cells, either in vitro or in vivo. The compounds are preferably polycationic and preferably form highly stable complexes with various anionic macromolecules, particularly polyanions such as nucleic acids. These compounds have the property, when dispersed in water, of forming lipid aggregates which associate strongly, via their cationic portion, with polyanions. Also disclosed are intermediates for preparing the compound and compositions of the invention and methods of using the compounds to introduce other compounds into cells.

摘要翻译： 公开了阳离子脂质化合物和用于将大分子和其它化合物递送到细胞中的脂质聚集体的组合物。 化合物可以单独使用或与其他化合物组合使用以制备适合于在体外或体内转染或递送化合物到靶细胞的脂质体和其他脂质聚集体。 该化合物优选是阳离子型的，优选与各种阴离子大分子，特别是聚阴离子如核酸形成高度稳定的络合物。 这些化合物在分散于水中时具有形成通过其阳离子部分强力缔合聚阴离子的脂质聚集体的性质。 还公开了制备本发明化合物和组合物的中间体以及使用该化合物将其它化合物引入细胞的方法。

公开(公告)号：US20050260597A1

公开(公告)日：2005-11-24

申请号：US10629522

申请日：2003-07-28

申请人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

发明人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

IPC分类号： C12N15/09 ,  A61K9/127 ,  A61K31/14 ,  A61K47/16 ,  A61K47/18 ,  A61K47/22 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C215/18 ,  C07C217/08 ,  C07C229/26 ,  C07C237/10 ,  C07C279/08 ,  C07D211/26 ,  C07D213/38 ,  C07D241/12 ,  C07D273/08 ,  C07D291/02 ,  C12N5/10 ,  C12Q1/68 ,  C07F9/06 ,  C07F9/28

CPC分类号： A61K47/48046 ,  A61K9/16 ,  A61K31/14 ,  A61K38/28 ,  A61K38/40 ,  A61K47/543 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C229/26 ,  C07D209/48 ,  C07D241/12 ,  C12N15/88 ,  Y10S435/81

摘要： Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i-Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1-L′-X2-Z or -Z; R1-R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.

公开(公告)号：US07323594B2

公开(公告)日：2008-01-29

申请号：US11617614

申请日：2006-12-28

申请人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

发明人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

IPC分类号： C07C233/00 ,  C07C235/00 ,  C07C237/00 ,  C07C239/00 ,  C07C277/00 ,  A61K31/14

CPC分类号： A61K47/48046 ,  A61K9/16 ,  A61K31/14 ,  A61K38/28 ,  A61K38/40 ,  A61K47/543 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C229/26 ,  C07D209/48 ,  C07D241/12 ,  C12N15/88 ,  Y10S435/81

摘要： Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i-Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by -X1-L′-X2-Z or -Z; R1-R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.

公开(公告)号：US07173154B2

公开(公告)日：2007-02-06

申请号：US10629522

申请日：2003-07-28

申请人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

发明人： Yongliang Chu ,  Malek Masoud ,  Gulilat Gebeyehu

IPC分类号： C07C215/14 ,  A61K31/13 ,  C12N15/63 ,  C12N15/86 ,  C12N15/87 ,  C12N15/85 ,  C12N15/88

CPC分类号： A61K47/48046 ,  A61K9/16 ,  A61K31/14 ,  A61K38/28 ,  A61K38/40 ,  A61K47/543 ,  C07C211/21 ,  C07C211/63 ,  C07C211/64 ,  C07C229/26 ,  C07D209/48 ,  C07D241/12 ,  C12N15/88 ,  Y10S435/81

摘要： Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH2)l, or {(CH2)i-Y—(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by —X1-L′-X2-Z or -Z; R1–R6, independently of one another, are selected from the group consisting of H, —(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R1, R3, R4 and/or R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C{NH), C(S) and (CH2)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.