化学信息来源/SIRCh/化学专利检索/马库什结构
外观
马库什化学专利权利要求的示例
新闻组: misc.int-property,sci[检查拼写].chem 来自: [email protected] (Gregory Aharonian) 主题: PATNEWS: 一个庞大、分层、化学马库什群体 日期: Thu, 2 Mar 1995 06:45:27 GMT
The following patent recently caught my eye for a variety of reasons
(看看它庞大的多页 OG 条目)。
First it is one of those rare, verrrrrry lengthy first independent claim
专利。其次,这个冗长的第一个权利要求是马库什群体,导致了数以兆计(确切地说是 2.94777 兆)的组合,我假设审查员和申请人对其中每一个都进行了量子化学 GAUSSIAN 评估 :-)
But most interestingly, this is one of the few clean hierarchical Markush
群体,我所见过的最庞大群体。通常,化学马库什群体声明类似“它由 A B 和 C 制成,其中 A 是任何苯衍生物……”,这是一个两级层次结构。然而,这份专利是一个三级和四级层次结构,“它由 A B C 制成,其中 A 是 R1,而 R1 是苯或 R121”。它以其分层风格展现出简约的优雅。
This style can be used quite effectively to create havoc in the software
专利领域,如果你使用类似的层次结构来声明某种对象模式和所有可从所声明的对象类别结构推导出的应用程序(我仍然认为至少有一家公司正在尝试这样做 :-)
Anyways, add it to your patent claim style list.
格雷戈里·阿哈罗尼安 互联网专利新闻服务(订阅信息,请发送“help”到 [email protected]) (专利检索服务信息,请发送“prior”到 [email protected]) (WWW 专利搜索,请尝试 http://sunsite.unc.edu/patents/intropat.html )
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5387671 六肽和七肽过敏毒素受体配体 艾伯维公司
1. An anaphylotoxin activity modulating compound of the formula: A-B-D-E-G-J-L-M-Q
或其药学上可接受的盐,其中基团 A 到 Q 具有以下值
A is R.sub.1 -R.sub.2 -R.sub.3 ; B is selected from the group consisting of R.sub.4 -R.sub.5 -R.sub.6, R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ; D is selected from the group consisting of R.sub.7 -R.sub.8 -R.sub.9, R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ; E is selected from the group consisting of R.sub.10 -R.sub.11 -R.sub.12, R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ; G is selected from the group consisting of R.sub.13 -R.sub.14 -R.sub.15, R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ; J is selected from the group consisting of R.sub.16 -R.sub.17 -R.sub.18, R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ; L is selected from the group consisting of R.sub.19 -R.sub.20 -R.sub.21, R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ; M is a valence bond, or is selected from the group consisting of R.sub.22 -R.sub.23 -R.sub.24, R.sub.31, R.sub.32, R.sub.35, and R.sub.37 ; Q is R.sub.25 -R.sub.26 -R.sub.27 ; or B and D, taken together, optionally represent a group selected from the group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40, R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ; D and E, taken together, optionally represent a group selected from the group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40, R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ; E and G, taken together, optionally represent a group selected from the group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40, R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ; G and J, taken together, optionally represent a group selected from the group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40, R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ; J and L, taken together, optionally represent a group selected from the group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40, R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ; L and M, taken together, optionally represent a group selected from the group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40, R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ; and one or more of the groups R.sub.5 -R.sub.6 -R.sub.7, R.sub.8 -R.sub.9 -R.sub.10, R.sub.11 -R.sub.12 -R.sub.13, R.sub.14 -R.sub.15 -R.sub.16, R.sub.17 -R.sub.18 -R.sub.19, R.sub.20 -R.sub.21 -R.sub.22, and R.sub.23 -R.sub.24 -R.sub.25, independently may optionally represent R.sub.36 ;
其中
(a) R.sub.1 is selected from the group consisting of lower alkyl, aryl, arylalkyl, and hydrogen; (b) R.sub.2 is selected from the group consisting of >CR.sub.99 R.sub.100 and oxygen, with the proviso that when R.sub.2 is oxygen, R.sub.1 is aryl, lower alkyl, or arylalkyl; (c) R.sub.3 is selected from the group consisting of >C.dbd.O and >CH.sub.2, with the proviso that when R.sub.3 is >CH.sub.2 then R.sub.2 cannot be oxygen; (d) R.sub.4 is >NR.sub.101 where R.sub.101 is selected from the group consisting of hydrogen, lower alkyl, arylalkyl, and alkenyl; (e) R.sub.5 is selected from the group consisting of >CR.sub.201 R.sub.202, >NR.sub.203 >C.dbd.CR.sub.205 R.sub.206, existing in either the Z- or E-configuration, and substituted cyclopropyl of the formula ##STR28## (f) R.sub.6, R.sub.9, R.sub.12, R.sub.15, and R.sub.18 are independently selected from the group consisting of >C.dbd.O, >CH.sub.2, --CH.sub.2 C(O)--, --NHC(O)--, >C.dbd.S, >SO.sub.2, and >P(O)X where X is selected from hydroxy, alkoxy, amino, alkylamino and dialkylamino; (g) R.sub.7, R.sub.10, R.sub.13, R.sub.16, R.sub.19, and R.sub.22, are independently selected from the group consisting of >CH.sub.2 and >NR.sub.50 where R.sub.50 is selected from the group consisting of hydrogen, lower alkyl, arylalkyl, aryl, hydroxy and alkoxy; (h) R.sub.21, and R.sub.24 are independently selected from the group consisting of >C.dbd.O, --CH.sub.2 C(O)--,--NHC(O)--, >C.dbd.S, >SO.sub.2, and >P(O)X where X is selected from the group consisting of hydroxy, alkoxy, amino, alkylamino and dialkylamino, with the proviso that when R.sub.22 -R.sub.23 -R.sub.24 is present, R.sub.21 is >CH.sub.2 (i) R.sub.8 is selected from the group consisting of >CR.sub.210 R.sub.211, >NR.sub.213, >C.dbd.CR.sub.215 R.sub.216, existing in either the Z- or E-configuration, and substituted cyclopropyl of the formula ##STR29## (j) R.sub.11 is selected from the group consisting of >CR.sub.220 R.sub.221, >NR.sub.223, >C.dbd.CR.sub.225 R.sub.226, existing in either the Z- or E-configuration, and substituted cyclopropyl of the formula ##STR30## (k) R.sub.14 is selected from the group consisting of >CR.sub.230 R.sub.231, >NR.sub.233, >C.dbd.CR.sub.235 R.sub.236, existing in either the Z- or E-configuration, and substituted cyclopropyl of the formula ##STR31## (l) R.sub.17 is selected from the group consisting of >CR.sub.301 R.sub.302, >NR.sub.303, >C.dbd.CR.sub.305 R.sub.306, existing in either the Z- or E-configuration, and substituted cyclopropyl of the formula ##STR32## (m) R.sub.20 is selected from the group consisting of >CR.sub.310 R.sub.311, >C.dbd.CR.sub.315 R.sub.316, existing in either the Z- or E-configuration, and substituted cyclopropyl of the formula ##STR33## (n) R.sub.23 is selected from the group consisting of >CR.sub.320 R.sub.321, >C.dbd.CR.sub.325 R.sub.326, existing in either the Z- or E-configuration, and substituted cyclopropyl of the formula ##STR34## (o) R.sub.25 is selected from the group consisting of >O, and >NR.sub.109 where R.sub.109 is selected from the group consisting of hydrogen, lower alkyl, and arylalkyl; (p) R.sub.26 is selected from the group consisting of hydrogen, lower alkyl, arylalkyl and >NR.sub.110 where R.sub.110 is selected from the group consisting of hydrogen, lower alkyl, or arylalkyl with the provisos that (i) when R.sub.25 is >O then R.sub.26 is lower alkyl, and (ii) when R.sub.26 is hydrogen, lower alkyl, or arylalkyl, then R.sub.27 is absent; (q) R.sub.27 is selected from the group consisting of hydrogen, and aryl; (r) R.sub.31 is ##STR35## where m and n are integers independently selected from 0, 1 and 2; (s) R.sub.32 is ##STR36## where p and q are integers independently selected from 0, 1 and 2; (t) R.sub.33 is ##STR37## where t and v are integers independently selected from 0, 1, 2 and 3; (u) R.sub.34 is ##STR38## where r and s are integers independently selected from 0, 1, 2 and 3; (v) R.sub.35 is ##STR39## where f is an integer of 0 to 2, X is selected from the group consisting of >C.dbd.O and --CH.sub.2 -- and R is selected from the group consisting of hydrogen and lower alkyl, with the provisos that (i) when f is 0, X is at C-2 and R is at C-3 or C-4; (ii) when f is 1, X is at C-2 and R is at C-3, C-4 or C-5 and C-3,4 are saturated or unsaturated; (iii) when f is 2, X is at C-2, C-3 or C-4 and R is at C-2, C-3, C-4, C-5 or C-6 when the position is unoccupied by X and C-3,4 or C-4,5 are saturated or unsaturated; and (w) R.sub.36 is ##STR40## where g is an integer of from 0 to 3; (x) R.sub.37 is ##STR41## wherein h is 1 and j is 0 or 1; (y) R.sub.38 is ##STR42## where k is an integer of from zero to two; (ae) R.sub.44 is ##STR43## (af) R.sub.1 and R.sub.2, taken together, optionally represent a group selected from the group consisting of aryl, and hydrogen; (ag) R.sub.1, R.sub.2 and R.sub.3, taken together, optionally represent a group selected from the group consisting of lower alkyl, arylalkyl, alkenyl, hydrogen, and an N-terminal protecting group; (ah) R.sub.6 and R.sub.7 ; R.sub.9 and R.sub.10 ; R.sub.12 and R.sub.13 ; R.sub.15 and R.sub.16 ; R.sub.18 and R.sub.19 ; R.sub.21 and R.sub.22 ; each pair taken together, optionally and independently represent a group selected from the group consisting of --C(O)NH--, >CH.sub.2, --(CH.sub.2).sub.3 --, --CH.dbd.CH--, --CH(OH)--, --C.tbd.C--,--C(.dbd.CH.sub.2)CH.sub.2 --, --CH(OH)CH.sub.2 --, --C(O)O--, --C(O)S--, --CH.sub.2 C(O)O--, --CH.sub.2 C(O)S--, --CH.sub.2 O--, --CH.sub.2 S--, and --NHC(O)--, with the provisos that (i) at least one of said pair, taken together, must be other than --C(O)NH--; and (ii) when R.sub.5 is >NR.sub.203 or >C.dbd.CR.sub.205 R.sub.206, R.sub.6 and R.sub.7, taken together, represent --C(O)NH-- or --C(O)NCH.sub.3 ; (iii) when R.sub.8 is >NR.sub.213 or >C.dbd.CR.sub.215 R.sub.216, R.sub.9 and R.sub.10, taken together, represent --C(O)NH-- or --C(O)NCH.sub.3 --; (iv) when R.sub.11 is >NR.sub.223 or >C.dbd.CR.sub.225 R.sub.226, R.sub.12 and R.sub.13, taken together represent --C(O)NH-- or --C(O)NCH.sub.3 --; (v) when R.sub.14 is >NR.sub.233 or >C.dbd.CR.sub.235 R.sub.236, R.sub.15 and R.sub.16, taken together, represent --C(O)NH-- or --C(O)NCH.sub.3 --; (vi) when R.sub.17 is >NR.sub.303 or >C.dbd.CR.sub.305 R.sub.306, R.sub.18 and R.sub.19, taken together, represent --C(O)NH-- or --C(O)NCH.sub.3 --; (vii) when R.sub.20 is >C.dbd.CR.sub.315 R.sub.316, R.sub.21 and R.sub.22, taken together, represent --C(O)NH-- or --C(O)NCH.sub.3 --; (ai) R.sub.26 and R.sub.27, taken together, optionally represent hydrogen, with the proviso that when R.sub.25 is >O then R.sub.26 and R.sub.27, taken together, represent hydrogen, lower alkyl, or arylalkyl; (aj) R.sub.99, R.sub.202, R.sub.211, R.sub.221, R.sub.231, R.sub.302, R.sub.311, and R.sub.321 are independently selected from the group consisting of hydrogen, arylalkyl with the proviso that for R.sub.302 and R.sub.311, arylalkyl is limited to benzyl when R.sub.19 -R.sub.20 -R.sub.21 or R.sub.22 -R.sub.23 -R.sub.24 respectively represent an L-arginyl residue, and lower alkyl; (ak) R.sub.100 is selected from the group consisting of hydrogen, and lower alkyl; (al) R.sub.201 is selected from the group consisting of hydrogen, lower alkyl, alkenyl, aryl, arylalkyl, (cycloalkyl)alkyl, aminoalkyl, amidoalkyl, hydroxyalkyl, guanidinoalkyl, carboxyalkyl, (carboxyamido)alkyl, (carboxyhydrazino)alkyl, ureidoalkyl, (heterocyclic)alkyl, (thioalkoxy)alkyl, and sulfhydrylalkyl; (am) R.sub.201 and R.sub.202, R.sub.210 and R.sub.211, R.sub.220 and R.sub.221, R.sub.230 and R.sub.231, R.sub.301 and R.sub.302, R.sub.310 and R.sub.311, R.sub.320 and R.sub.321, each pair taken together, independently may optionally represent --(CH.sub.2).sub.z -- where z is an integer of from 2 to 6; (an) R.sub.203 is selected from the group consisting of hydrogen, lower alkyl, alkenyl, arylalkyl, (cycloalkyl)alkyl, aminoalkyl, amidoalkyl, hydroxyalkyl, guanidinoalkyl, carboxyalkyl, (carboxyamido)alkyl, (carboxyhydrazino)alkyl, ureidoalkyl, (heterocyclic)alkyl, (thioalkoxy)alkyl, and sulfhydrylalkyl with the proviso that R.sub.203 may not be a vinyl group nor have a heteroatom directly attached to the nitrogen or separated from it by one methylene unit; (ao) R.sub.205, R.sub.206, R.sub.215, R.sub.216, R.sub.225, R.sub.226, R.sub.235, R.sub.236, R.sub.305, and R.sub.306 are independently selected from the group consisting of hydrogen, lower alkyl, aryl, arylalkyl, wherein arylalkyl is excluded from R.sub.305 and R.sub.306 when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue, (cycloalkyl)alkyl, amidoalkyl, wherein benzoyl amides and their heterocyclic variants are excluded from R.sub.305 and R.sub.306 when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue (carboxyamido)alkyl, wherein aniline amides and their heterocyclic variants are excluded from R.sub.305 and R.sub.306 when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue; ureidoalkyl, and (heterocyclic)alkyl, wherein when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue, then the heterocycle at from R.sub.305 and R.sub.306 can only be separated by one methylene unit from the alpha-carbon; (ap) R.sub.210 selected from the group consisting of lower alkyl, arylalkyl, aminoalkyl, and guanidinoalkyl; (aq) R.sub.213 is selected from the group consisting of lower alkyl, arylalkyl, aminoalkyl, and guanidinoalkyl with the proviso that R.sub.213 may not be a vinyl group nor have a heteroatom directly attached to the nitrogen or separated from it by one methylene unit; (ar) R.sub.220 is selected from the group consisting of hydrogen, lower alkyl, arylalkyl, (cycloalkyl)alkyl, and guanidinoalkyl; (as) R.sub.223 is selected from the group consisting of hydrogen, lower alkyl, arylalkyl, (cycloalkyl)alkyl,and guanidinoalkyl, with the proviso that R.sub.223 may not be a vinyl group nor have a heteroatom directly attached to the nitrogen or separated from it by one methylene unit; (at) R.sub.230 is selected from the group consisting of hydrogen, lower alkyl, arylalkyl, and (cycloalkyl)alkyl; (au) R.sub.233 is selected from the group consisting of hydrogen, lower alkyl, arylalkyl, and (cycloalkyl)alkyl with the proviso that R.sub.233 may not be a vinyl group nor have a heteroatom directly attached to the nitrogen or separated from it by one methylene unit; (av) R.sub.301 is independently selected from the group consisting of hydrogen; lower alkyl; alkenyl; aryl; arylalkyl, wherein arylalkyl is limited to benzyl, when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue; (cycloalkyl)alkyl; aminoalkyl, wherein aryl and arylalkyl amines are excluded when R.sub.19 -R.sub.20 -R.sub.21 represents
an L-arginyl residue; amidoalkyl, wherein benzoyl amides and their heterocyclic variants are excluded when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue; hydroxyalkyl; guanidinoalkyl; carboxyalkyl; (carboxyamido)alkyl, wherein aniline amides of aspartyl residues and heterocyclic variants are excluded when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue; carboxyhydrazino)alkyl; ureidoalkyl; (heterocyclic)alkyl, wherein when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue, then the heterocycle can only be separated by one methylene unit from the alpha-carbon; (thioalkoxy)alkyl, and sulfhydrylalkyl; (aw) R.sub.303 is independently selected from the group consisting of lower alkyl, arylalkyl, wherein arylalkyl is limited to benzyl when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue, and (cycloalkyl)alkyl, with the proviso that R.sub.303 may not be a vinyl group or have a heteroatom directly attached to the nitrogen or separated from it by one methylene unit; (ax) R.sub.304 is independently selected from the group consisting of hydrogen; lower alkyl; alkenyl; aryl, arylalkyl, wherein arylalkyl is excluded when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue; (cycloalkyl)alkyl; aminoalkyl, wherein aryl and arylalkyl amines are excluded when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue; amidoalkyl, wherein benzoyl amides and their heterocyclic variants are excluded when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue; hydroxyalkyl; guanidinoalkyl; carboxyalkyl; (carboxyamido)alkyl, wherein aniline amides and heterocyclic variants are excluded when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl residue; (carboxyhydrazino)alkyl; ureidoalkyl; (heterocyclic)alkyl, wherein (heterocyclic)alkyl is excluded when R 19-R.sub.20 -R.sub.21 represents an L-arginyl residue; (thioalkoxy)alkyl; and sulfhydrylalkyl; (ay) R.sub.307 and R.sub.317 are independently selected from hydrogen; lower alkyl; aryl and arylalkyl, wherein arylalkyl is excluded for R.sub.307 and R.sub.317 when R.sub.19 -R.sub.20 -R.sub.21 and R.sub.22 -R.sub.23 -R.sub.24 respectively represent an L-arginyl residue; (az) R.sub.310 is independently selected from the group consisting of hydrogen; lower alkyl; alkenyl; aryl; arylalkyl, wherein arylalkyl is limited to benzyl when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl residue; (cycloalkyl)alkyl; aminoalkyl, aryl and arylalkyl amines are excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl residue; amidoalkyl, wherein benzoyl amides and their heterocyclic variants are excluded, when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl residue; hydroxyalkyl; guanidinoalkyl; (carboxyamido)alkyl, wherein aniline amides of aspartyl residues and heterocyclic variants are excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl residue; (carboxyhydrazino)alkyl; ureidoalkyl; (heterocyclic)alkyl, wherein when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl residue, then the heterocycle can only be separated by one methylene unit from the alpha-carbon; and sulfhydrylalkyl; (ba) R.sub.312 is independently selected from the group consisting of hydrogen; lower alkyl; alkenyl; aryl; arylalkyl, wherein arylalkyl is excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl residue; (cycloalkyl)alkyl; aminoalkyl, wherein aryl and arylalkyl amines are excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl residue; amidoalkyl, wherein benzoyl amides and their heterocyclic variants are excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl residue; hydroxyalkyl; guanidinoalkyl; carboxyalkyl; (carboxyamido)alkyl, wherein aniline amides and heterocyclic variants are excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl residue; (carboxyhydrazino)alkyl; ureidoalkyl; (heterocyclic)alkyl, wherein (heterocyclic)alkyl is excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl residue; (thioalkoxy)alkyl; and sulfhydrylalkyl; (bb) R.sub.315 and R.sub.316 are independently selected from the group consisting of hydrogen, lower alkyl, arylalkyl, wherein arylalkyl is excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl residue, and (cycloalkyl)alkyl; (bc) R.sub.310 it is selected from the group consisting of hydrogen, lower alkyl, arylalkyl, alkenyl, (cycloalkyl)alkyl, aminoalkyl, and guanidinoalkyl; (bd) R.sub.325 and R.sub.326 are independently selected from the group consisting of hydrogen, lower alkyl, aryl, arylalkyl, and (cycloalkyl)alkyl;
以上所有内容均需符合以下条件
(i) when more than one sulfhydrylalkyl is present in the compound, the compound exists in the oxidized disulfide form producing a cyclic molecule, or the two sulfhydryl moieties are connected by a C.sub.2 to C.sub.8 alkylene chain and (ii) when the compound contains a free amino group and carboxyl group, they can be cyclized to give the corresponding lactam.