Phosphonic acid, [[3-(6-amino-9H-purin-9-yl)-4-hydroxybutoxy]methyl]- | 612054-70-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: Phosphonic acid, [[3-(6-amino-9H-purin-9-yl)-4-hydroxybutoxy]methyl]-
• 英文别名: [3-(6-aminopurin-9-yl)-4-hydroxybutoxy]methylphosphonic acid
• CAS: 612054-70-3
• 化学式: C₁₀H₁₆N₅O₅P
• 分子量: 317.24
• InChiKey: WCFJWHDBXBUIBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  157
• 氢给体数：
  4
• 氢受体数：
  9

文献信息

• Nucleosides preparation thereof and use as inhibitors of rna viral polymerases
  申请人：Babu S Yarlagadda

  公开号：US20050033051A1

  公开（公告）日：2005-02-10

  Compounds represented by the formula (I) R is H, OH, alkyl, O-alkyl, CH 2 —O-alkyl, (CH 2 )nOH, (CH 2 )nNH 2 , (CH 2 )nCONH 2 , (CH 2 )nOOOH; R 1 is H, OH, alkyl, O-alkyl, CH 2 —O-alkyl, C 6 H 11 , CH 2 OH; R 2 is H, alkyl, OH, CH 2 OH, CH 2 —O-alkyl, CH(OH)-alkyl, CH(OH)CH 2 OH, CH 2 -halogen; R 3 and R 4 independently is H, OH, alkyl; Z is OR 5 , OR 6 , or aminoacids and esters thereof R 5 and R 6 independently is H, alkyl, aryl, pivaloyloxymethyl, C(R 7 ) 2 OC(O) X (R 8 )a formula (II), R 7 independently is —H, C 1 -C 12 alkyl, C 5 -C 12 aryl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 7 -C 12 alkenylaryl, C 7 -C 12 alkynylaryl, or C 6 -C 12 alkaryl, any of which is unsubstituted or is substituted with 1 or 2 halo, cyano, azido, nitro, or —OR 9 ; R 9 is C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or C 5 -C 12 aryl; provided that at least one R 8 is not H; and a is 1 when X is CH 2 , or direct bond, or 1 or 2 when X is N with the proviso that when a is 2 and X is N, (a) two N-linked R groups can be taken together to form a carbocyclic or oxygen containing heterocycle, (b) one N-linked R 8 additionally can be —OR 9 or (c) both N-linked R 8 groups can be —H; R 10 is H or C 1 -C 8 alkyl; R 11 is selected from H, alkyl, alkenyl, alkynyl, aryl, acyloxyalkyl, and pivaloyloxyalkyl n is 1-5 m is 0 to 5 X is S, N(R 8 ) or direct bond Y is O, S, N (R 8 ), and CHR 1 B is selected from the group consisting of adenine, guanine, cytosine, uracil, thymine, modified purines and pyrimidines such as inosin-9-yl, 2-amino-purin-9-yl, 2amino-6-chloro-purin-9-yl, 2-6-diamino-purin-9-yl, 3-carboxamido-1, 2, 4-triazol-1-yl, 3-deaza-adenin-9-yl, 3-deaza-guanin-9-yl, 3-deaza-inosin-9-yl, 3-deaza-2-amino-purin-9-yl, 3-deaza-2-amino-6-chloro-purin-9-yl, 3-deaza-2, 6-diamino-purin-9-yl, 7-deaza-adenin-9-yl, 7-deaza-guanin-9-yl, 7-deaza-inosin-9-yl, 7-deaza-2-amino-purin-9-yl, 7-deaza-2-amino-6-chloro-purin-9-yl, 7-deaza-2-6-diamino-purin-9-yl, 7-deaza-8-aza-adenin-9-yl, 7-deaza-8-aza-guanin-9-yl, 7-deaza-8-aza-inosnin-9-yl, 7-deaza-8-aza-2-amino-purin-9-yl, 7-deaza-8-aza-2-amino-6-chloro-purin-9-yl, 7-deaza-8-aza-2-6-diamino-purin-9-yl, -8-aza-adenin-9-yl,-8-aza-guanin-9-yl, -8-aza-inosnin-9-yl, -8-aza-2-amino-purin-9-yl, -8-aza-2-amino-6-chloro-purin-9-yl, -8-aza-2-6-diamino-purin-9-yl, 5-aza-thymin-1-yl, 5-aza-cytosin-1-yl, 5-aza-uracil-1-yl, 6-aza-thymin-1-yl, 6-aza-cytosin-1-yl, 6-aza-uracil-1-yl, 2-thiouracil-1-yl, 4-thiouracil-1-yl, 2 thiocytosine-1-yl, uracil-5-yl, 2-thiouracil-5-yl, 4-thiouracil-5-yl, substituted pyridine derivatives such as 6-azauracil, and azacyzosine. In general, attachment may be at different positions in the ring at nitrogen or carbon. These B ring systems may be substituted with halo, alkyl, substituted alkyl (F, Cl, Br, I, OH), NH 2 , N 3 , aryl, substituted aryl (F, Cl, Br, I, OH, NH 2 ), aralkyl; and pharmaceutically acceptable salts thereof and prodrugs thereof are provided.

  化合物的公式(I)表示为：R为H、OH、烷基、O-烷基、CH2-O-烷基、(CH2)nOH、(CH2)nNH2、(CH2)nCONH2、(CH2)nOOOH；R1为H、OH、烷基、O-烷基、CH2-O-烷基、C6H11、CH2OH；R2为H、烷基、OH、CH2OH、CH2-O-烷基、CH(OH)-烷基、CH(OH)CH2OH、CH2-卤素；R3和R4独立地为H、OH、烷基；Z为OR5、OR6或氨基酸及其酯，其中R5和R6独立地为H、烷基、芳基、pivaloyloxymethyl、C(R7)2OC(O)X (R8)的公式(II)，其中R7独立地为-H、C1-C12烷基、C5-C12芳基、C2-C12烯基、C2-C12炔基、C7-C12烯基芳基、C7-C12炔基芳基或C6-C12烷基，其中任何一个未取代或被1或2个卤素、氰基、叠氮基、硝基或—OR9取代；R9为C1-C12烷基、C2-C12烯基、C2-C12炔基或C5-C12芳基；但至少有一个R8不为H；当X为CH2时，a为1，或直接键，或当X为N时，a为1或2，但须说明当a为2且X为N时，(a)两个N-连接的R基可结合形成含碳或含氧的杂环，(b)一个N-连接的R8还可以是—OR9，或(c)两个N-连接的R8基都可以是—H；R10为H或C1-C8烷基；R11为选自H、烷基、烯基、炔基、芳基、酰氧烷基和pivaloyloxyalkyl的群；n为1-5；m为0-5；X为S、N(R8)或直接键；Y为O、S、N(R8)和CHR1B为腺嘌呤、鸟嘌呤、胞嘧啶、尿嘧啶、胸腺嘧啶、修饰嘌呤和嘧啶如肌苷-9-基、2-氨基嘌呤-9-基、2-氨基-6-氯嘌呤-9-基、2-6-二氨基嘌呤-9-基、3-羧酰胺基-1,2,4-三唑-1-基、3-去氮腺嘌呤-9-基、3-去氮鸟嘌呤-9-基、3-去氮肌苷-9-基、3-去氮-2-氨基嘌呤-9-基、3-去氮-2-氨基-6-氯嘌呤-9-基、3-去氮-2,6-二氨基嘌呤-9-基、7-去氮腺嘌呤-9-基、7-去氮鸟嘌呤-9-基、7-去氮肌苷-9-基、7-去氮-2-氨基嘌呤-9-基、7-去氮-2-氨基-6-氯嘌呤-9-基、7-去氮-2,6-二氨基嘌呤-9-基、7-去氮-8-氮杂腺嘌呤-9-基、7-去氮-8-氮杂鸟嘌呤-9-基、7-去氮-8-氮杂肌苷-9-基、7-去氮-8-氮杂-2-氨基嘌呤-9-基、7-去氮-8-氮杂-2-氨基-6-氯嘌呤-9-基、7-去氮-8-氮杂-2,6-二氨基嘌呤-9-基、-8-氮杂腺嘌呤-9-基、-8-氮杂鸟嘌呤-9-基、-8-氮杂肌苷-9-基、-8-氮杂-2-氨基嘌呤-9-基、-8-氮杂-2-氨基-6-氯嘌呤-9-基、-8-氮杂-2,6-二氨基嘌呤-9-基、5-氮杂胸腺嘧啶-1-基、5-氮杂胞嘧啶-1-基、5-氮杂尿嘧啶-1-基、6-氮杂胸腺嘧啶-1-基、6-氮杂胞嘧啶-1-基、6-氮杂尿嘧啶-1-基、2-硫代尿嘧啶-1-基、4-硫代尿嘧啶-1-基、2-硫代胞嘧啶-1-基、尿嘧啶-5-基、2-硫代尿嘧啶-5-基、4-硫代尿嘧啶-5-基、取代的吡啶衍生物如6-氮杂尿嘧啶和氮杂嘧啶。一般来说，连接可以在环中的氮或碳上的不同位置。提供这些B环系统可以被卤素、烷基、取代烷基(F、Cl、Br、I、OH)、NH2、N3、芳基、取代芳基(F、Cl、Br、I、OH、NH2)、芳基烷基取代物；以及其药学上可接受的盐和前药。
• Nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases
  申请人：BIOCRYST PHARMACEUTICALS, INC.

  公开号：US20040014722A1

  公开（公告）日：2004-01-22

  Compounds represented by the formula: 1 Wherein A is —(CH 2 ) n —R, —CH═CH 2 , —CH 2 —CH═CH 2 , —O—(CH 2 ) n —R, —CH(OH)CH 3 , —CH(OH)—CH 2 OH, —CH 2 —CH(OH)CH 3 , —CH 2 —CH(OH)—CH 2 OH, —CH(OH)—CH(OH)—CH 3 ; R is H, OH, F, N 3 , NH 2 , CO 2 H, SH, alkyl, S-alkyl, O-acyl, CONH 2 , CONH-alkyl; Z and Z′ independently is OR 1 , OR 2 , O—(CH 2 ) n —O-alkyl or aminoacids and esters thereof; R 1 and R 2 independently is H, alkyl, aryl, pivaloyloxymethyl, phthalyl or substituted phthalyl, C(R 3 ) 2 OC(O)X(R 4 )a, 2 R 3 is —H, C 1 -C 12 alkyl, C 5 -C 12 aryl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 7 -C 12 alkenylaryl, C 7 -C 12 alkynylaryl, or C 6 -C 12 alkaryl, any of which is unsubstituted or is substituted with 1 or 2 halo, cyano, azido, nitro, or —OR 5 ; R 4 is —H, C 1 -C 12 alkyl, C 5 -C 12 aryl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 7 -C 12 alkenylaryl, C 7 -C 12 alkynylaryl, or C 6 -C 12 alkaryl, any of which is unsubstituted or is substituted with 1 or 2 halo, cyano, azido, nitro, —N(R 6 ) 2 or —OR 5 ; R 5 is C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or C 5 -C 12 aryl; provided that at least one R 4 is not H; and a is 1 when X is CH 2 , or direct bond, or 1 or 2 when X is N with the proviso that when a is 2 and X is N, (a) two N-linked R groups can be taken together to form a carbocyclic or oxygen containing heterocycle, (b) one N-linked R 4 additionally can be —OR 5 or (c) both N-linked R 4 groups can be —H; R 6 is H or C 1 -C 8 alkyl; R 7 is selected from H, alkyl, alkenyl, alkynyl, aryl, acyloxyalkyl, and pivaloyloxyalkyl; n is 1-3; Y is O, S or NH; W is O or S; B is selected from the group consisting of adenine, guanine, cytosine, uracil, thymine, modified purines, pyrimidines and pyridines are provided.

  由以下式子表示的化合物 1 其中 A 为-(CH 2 ) n -R、-CH═CH 2 ，-CH 2 -CH═CH 2 , -O-(CH 2 ) n -R、-CH(OH)CH 3 、-CH(OH)-CH 2 OH, -CH 2 -CH(OH)-CH 3 ，-CH 2 -CH(OH)-CH 2 OH，-CH(OH)-CH(OH)-CH 3 ; R 是 H、OH、F、N 3 、NH 2 CO 2 H、SH、烷基、S-烷基、O-酰基、CONH 2 、CONH-烷基； Z 和 Z′各自是 OR 1 、OR 2 O-(CH 2 ) n -O-烷基或氨基酸及其酯； R 1 和 R 2 独立地为 H、烷基、芳基、新戊酰氧基甲基、邻苯二甲酸酯或取代邻苯二甲酸酯、C(R 3 ) 2 OC(O)X(R 4 )a, 2 R 3 是-H，C 1 -C 12 烷基、C 5 -C 12 芳基，C 2 -C 12 烯基，C 2 -C 12 炔基，C 7 -C 12 烯芳基，C 7 -C 12 炔芳基，或 C 6 -C 12 烷芳基，其中任何一个未被取代或被 1 或 2 个卤代、氰基、叠氮基、硝基或 -OR 5 ; R 4 是-H、C 1 -C 12 烷基、C 5 -C 12 芳基，C 2 -C 12 烯基，C 2 -C 12 炔基，C 7 -C 12 烯芳基，C 7 -C 12 炔芳基，或 C 6 -C 12 烷芳基，其中任何一个未被取代或被 1 或 2 个卤代、氰基、叠氮基、硝基、-N(R 6 ) 2 或-OR 5 ; R 5 是 C 1 -C 12 烷基、C 2 -C 12 烯基、C 2 -C 12 炔基或 C 5 -C 12 芳基； 条件是至少有一个 R 4 不是 H 时，a 为 1。 2 或直接键，或当 X 为 N 时为 1 或 2，但当 a 为 2 且 X 为 N 时，(a) 两个 N-连接的 R 基团可结合在一起形成碳环或含氧杂环，(b) 一个 N-连接的 R 4 还可以是-OR 5 或 (c) 两个 N-连接的 R 4 基团都可以是-H； R 6 是 H 或 C 1 -C 8 烷基； R 7 选自 H、烷基、烯基、炔基、芳基、酰氧基烷基和新戊酰氧基烷基； n 为 1-3； Y 是 O、S 或 NH； W 是 O 或 S； B 选自腺嘌呤、鸟嘌呤、胞嘧啶、尿嘧啶、胸腺嘧啶、改良嘌呤、嘧啶和吡啶组成的组。