公开(公告)号：WO2013026942A1

公开(公告)日：2013-02-28

申请号：PCT/EP2012/066627

申请日：2012-08-27

Applicant: The Provost, Fellows, Foundation Scholars, and the other Members of Board, of the College of the Holy and Undivided Trinity of Queen Elizabeth, near Dublin ,  WALSH, John Jarlath ,  SHAH, Richard ,  MCCORMACK, Emmet Martin ,  HUDSON, Gillian Joy ,  WHITE, Martina ,  STACK, Gary Daniel ,  MORAN, Brian William ,  COOGAN, Adrian ,  BREEN, Elaine Carmel

Inventor： WALSH, John Jarlath ,  SHAH, Richard ,  MCCORMACK, Emmet Martin ,  HUDSON, Gillian Joy ,  WHITE, Martina ,  STACK, Gary Daniel ,  MORAN, Brian William ,  COOGAN, Adrian ,  BREEN, Elaine Carmel

IPC: A61K31/122 ,  A61K31/55 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07 ,  C07C49/755 ,  C07C225/22 ,  C07C237/04 ,  C07C251/44 ,  C07C251/60 ,  C07C311/20 ,  C07D313/08 ,  C07D493/18 ,  C07F7/18 ,  C07F9/145 ,  C07K5/02 ,  A61P35/00

CPC classification number: C07C43/23 ,  C07C41/26 ,  C07C45/455 ,  C07C49/255 ,  C07C49/753 ,  C07C49/755 ,  C07C69/734 ,  C07C217/74 ,  C07C217/84 ,  C07C225/22 ,  C07C237/22 ,  C07C251/44 ,  C07C251/60 ,  C07C255/47 ,  C07C259/06 ,  C07C259/08 ,  C07C271/24 ,  C07C309/65 ,  C07C309/66 ,  C07C2602/12 ,  C07D311/16 ,  C07D311/18 ,  C07D313/08 ,  C07D493/18 ,  C07F7/1804 ,  C07F9/094 ,  C07F9/65522 ,  C07F9/65527 ,  C07K5/0202

Abstract: The invention provides combretastatin A-4 like compounds that are modified to have enhanced tubulin binding activity and in some embodiments the ability to promote accumulation in the vasculature undergoing angiogenesis (homing activity). The compounds are based on the combretastatin A-4 skeletal structure having a tubulin-binding pharmacophore comprising two fused rings (A and B rings) in which the B ring is substituted with (a) an aromatic ring structure (C ring) and (b) a second substituent/functional group that comes off the B ring. The aromatic ring structure is typically a six membered ring phenolic or aniline structure, or may also be a fused ring structure such as a substituted or unsubstituted naphthalene. The second substituent on the B ring may for example be a substituent which has been found to provide enhanced tubulin binding activity (for example a carbonyl group), or may be a substituent that facilitates functionalisation of the B ring (for example an hydroxyl or amine group), or it may be a binding agent for a target that is preferentially expressed on vasculature undergoing angiogenesis, and not expressed on quiescent vasculature.

Abstract translation: 本发明提供了修饰为具有增强的微管蛋白结合活性的科曲他汀A-4类化合物，并且在一些实施方案中是促进经历血管生成（归巢活性）的脉管系统中的积累的能力。 该化合物基于具有微管蛋白结合药效团的考布他汀A-4骨架结构，其包含两个稠环（A和B环），其中B环被（a）芳环结构（C环）和（b ）脱离B环的第二取代基/官能团。 芳环结构通常是六元环酚或苯胺结构，或者也可以是稠环结构，例如取代或未取代的萘。 B环上的第二取代基可以是例如已经发现提供增强的微管蛋白结合活性的取代基（例如羰基），或者可以是促进B环官能化的取代基（例如羟基或胺 或者它可以是优先在经历血管生成的脉管系统上表达并且不在静止脉管系统上表达的靶标的结合剂。

公开(公告)号：WO2006069246A3

公开(公告)日：2008-09-25

申请号：PCT/US2005046618

申请日：2005-12-21

Applicant: AMBRX INC ,  MIAO ZHENWEI ,  LIU JUNJIE ,  NORMAN THEA ,  DRIVER RUSSELL

Inventor： MIAO ZHENWEI ,  LIU JUNJIE ,  NORMAN THEA ,  DRIVER RUSSELL

IPC: C07C22/00 ,  A61K38/00 ,  C07C227/00 ,  C07K2/00

CPC classification number: C07C225/10 ,  A61K31/198 ,  A61K38/17 ,  A61K47/08 ,  A61K47/10 ,  A61K47/34 ,  C07C229/36 ,  C07C237/32 ,  C07C251/28 ,  C07C251/54 ,  C07C251/60 ,  C07C251/86 ,  C07C323/63 ,  C07C2601/08 ,  C07D209/38 ,  C07D209/46 ,  C07D307/83 ,  C07D307/88 ,  C07D307/89 ,  C07D317/22 ,  C07D317/26 ,  C07D317/28 ,  C07D317/30 ,  C07D333/72 ,  C07K14/61 ,  C12P21/02 ,  G01N33/5008 ,  G01N33/68 ,  G01N33/6848 ,  G01N2500/00 ,  Y02P20/55

Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

Abstract translation: 本文公开了包含至少一种非天然氨基酸的非天然氨基酸和多肽，以及制备这种非天然氨基酸和多肽的方法。 非天然氨基酸本身或作为多肽的一部分可以包括广泛范围的可能的官能团，但是通常具有至少一个肟，羰基，二羰基和/或羟胺基团。 本文还公开了在翻译后进一步修饰的非天然氨基酸多肽，用于实现这种修饰的方法，以及纯化这些多肽的方法。 通常，修饰的非天然氨基酸多肽包括至少一个肟，羰基，二羰基和/或羟胺基团。 进一步披露的是使用这种非天然氨基酸多肽和修饰的非天然氨基酸多肽的方法，包括治疗，诊断和其他生物技术用途。

公开(公告)号：WO2007090434A1

公开(公告)日：2007-08-16

申请号：PCT/EP2006/004256

申请日：2006-05-06

Applicant: BAYER CROPSCIENCE AKTIENGESELLSCHAFT ,  ESCHER, Iris ,  MÜLLER, Michael ,  JESCHKE, Peter ,  BECK, Michael ,  GAERTZEN, Oliver ,  MALSAM, Olga ,  LÖSEL, Peter ,  EBBINGHAUS-KINTSCHER, Ulrich ,  ARNOLD, Christian ,  HAACK, Karl-Josef

Inventor： ESCHER, Iris ,  MÜLLER, Michael ,  JESCHKE, Peter ,  BECK, Michael ,  GAERTZEN, Oliver ,  MALSAM, Olga ,  LÖSEL, Peter ,  EBBINGHAUS-KINTSCHER, Ulrich ,  ARNOLD, Christian ,  HAACK, Karl-Josef

IPC: C07C251/52 ,  C07C251/54 ,  C07C251/58 ,  C07C271/28 ,  C07C323/18 ,  C07C251/60 ,  C07D213/64 ,  C07D213/61 ,  C07D241/12 ,  C07D277/24 ,  C07D307/79 ,  A01N35/10 ,  A01N37/22 ,  A01N47/20 ,  A01N43/40

CPC classification number: A01N43/88 ,  A01N35/10 ,  A01N37/22 ,  A01N43/12 ,  A01N43/30 ,  A01N43/40 ,  A01N43/54 ,  A01N43/713 ,  A01N43/78 ,  A01N47/20 ,  C07C251/52 ,  C07C251/54 ,  C07C251/58 ,  C07C251/60 ,  C07C271/28 ,  C07C2601/02 ,  C07C2601/14 ,  C07D213/61 ,  C07D213/64 ,  C07D241/12 ,  C07D277/24 ,  C07D307/79

Abstract: Su Die Erfindung betrifft Verbindungen der Formel (I), worin A 1 , A 2 , R 1 , R 2 , R 3 , R 4 , R 5 und X die in der Beschreibung angebenene Bedeutung haben, Verfahren und Zwischenverbindungen zu deren Herstellung sowie ihre Verwendung zur Bekämpfung von Schädlingen.

Abstract translation: 苏本发明涉及式（I）的化合物，其中A ^{1 ，A 2 ，R 1 ，R 2 ，R 3 ，R 4 ，R 5 和X已经benene意义在说明书中，方法和中间体及其制备方法和它们的用途 用于防治害虫。}

公开(公告)号：WO2006131482A1

公开(公告)日：2006-12-14

申请号：PCT/EP2006/062790

申请日：2006-05-31

Applicant: SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A. ,  PISANO, Claudio ,  BATTISTUZZZI, Gianfranco ,  DI MARZO, Maria ,  GIANNINI, Giuseppe ,  MARZI, Mauro ,  VESCI, Loredana ,  ZUNINO, Franco ,  PEZZI, Riccardo

Inventor： PISANO, Claudio ,  BATTISTUZZZI, Gianfranco ,  DI MARZO, Maria ,  GIANNINI, Giuseppe ,  MARZI, Mauro ,  VESCI, Loredana ,  ZUNINO, Franco ,  PEZZI, Riccardo

IPC: C07C251/48 ,  C07C251/80 ,  C07D209/08 ,  A61P35/00 ,  A61K31/165 ,  A61K31/195 ,  A61K31/405

CPC classification number: C07C251/52 ,  C07C251/36 ,  C07C251/40 ,  C07C251/48 ,  C07C251/60 ,  C07C251/86 ,  C07C313/28 ,  C07C381/00 ,  C07D209/08 ,  C07D295/088

Abstract: Cinnamic and phenylpropiolic acid derivatives of Formula (I) having antitumour and chemosensitizing activity are described. Also described are pharmaceutical compositions containing the above-mentioned compounds, for the treatment of tumours.

Abstract translation: 描述了具有抗肿瘤和化学敏化活性的式（I）的肉桂酸和苯基丙酸衍生物。 还描述了含有上述化合物的药物组合物，用于治疗肿瘤。

公开(公告)号：WO2006069246A2

公开(公告)日：2006-06-29

申请号：PCT/US2005/046618

申请日：2005-12-21

Applicant: AMBRX, INC. ,  MIAO, Zhenwei ,  LIU, Junjie ,  NORMAN, Thea ,  DRIVER, Russell

Inventor： MIAO, Zhenwei ,  LIU, Junjie ,  NORMAN, Thea ,  DRIVER, Russell

IPC: C07K1/02

CPC classification number: C07C225/10 ,  A61K31/198 ,  A61K38/17 ,  A61K47/08 ,  A61K47/10 ,  A61K47/34 ,  A61K47/60 ,  C07C229/36 ,  C07C237/32 ,  C07C251/28 ,  C07C251/54 ,  C07C251/60 ,  C07C251/86 ,  C07C323/63 ,  C07C2601/08 ,  C07D209/38 ,  C07D209/46 ,  C07D307/83 ,  C07D307/88 ,  C07D307/89 ,  C07D317/22 ,  C07D317/26 ,  C07D317/28 ,  C07D317/30 ,  C07D333/72 ,  C07K14/61 ,  C12P21/02 ,  G01N33/5008 ,  G01N33/68 ,  G01N33/6848 ,  G01N2500/00 ,  Y02A50/473 ,  Y02P20/55

Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

Abstract translation: 本文公开了包含至少一种非天然氨基酸的非天然氨基酸和多肽，以及制备这种非天然氨基酸和多肽的方法。 非天然氨基酸本身或作为多肽的一部分可以包括广泛范围的可能的官能团，但是通常具有至少一个肟，羰基，二羰基和/或羟胺基团。 本文还公开了在翻译后进一步修饰的非天然氨基酸多肽，用于实现这种修饰的方法，以及纯化这些多肽的方法。 通常，修饰的非天然氨基酸多肽包括至少一个肟，羰基，二羰基和/或羟胺基团。 进一步披露的是使用这种非天然氨基酸多肽和修饰的非天然氨基酸多肽的方法，包括治疗，诊断和其他生物技术用途。

公开(公告)号：WO2002090314A1

公开(公告)日：2002-11-14

申请号：PCT/US2002/014057

申请日：2002-05-03

Applicant: GALILEO LABORATORIES, INC. ,  WANG, Bing ,  MILLER, Guy ,  FLAIM, Stephen, F. ,  DEL BALZO, Ughetta ,  ZHANG, Wei ,  JANAGANI, Satyanarayana ,  SONG, Jingao

Inventor： WANG, Bing ,  MILLER, Guy ,  FLAIM, Stephen, F. ,  DEL BALZO, Ughetta ,  ZHANG, Wei ,  JANAGANI, Satyanarayana ,  SONG, Jingao

IPC: C07C69/66

CPC classification number: C07D213/30 ,  A61K31/12 ,  A61K31/16 ,  A61K31/215 ,  A61K31/223 ,  A61K38/00 ,  C07C249/12 ,  C07C319/20 ,  C07C323/60 ,  C07D207/16 ,  C07D207/22 ,  C07D207/24 ,  C07D211/62 ,  C07D211/74 ,  C07D211/78 ,  C07D217/04 ,  C07D233/42 ,  C07D233/64 ,  C07D233/84 ,  C07D235/28 ,  C07D239/78 ,  C07D249/14 ,  C07D271/113 ,  C07D277/16 ,  C07D277/74 ,  C07D279/12 ,  C07D285/125 ,  C07D285/135 ,  C07D295/13 ,  C07D295/15 ,  C07D295/185 ,  C07D339/08 ,  C07D345/00 ,  C07D405/12 ,  C07D473/38 ,  C07K5/0215 ,  C07K5/0819 ,  C07C323/57 ,  C07C251/60

Abstract: Certain known and novel pyruvate derivatives are particularly active in restoring or preserving metabolic integrity in oxidatively competent cells that have been subjected to oxygen deprivation. These pyruvate-derived compounds include, but are not limited to oximes, amides, pyruvate analogues, modified pyruvate analogues, esters of pyruvate (e.g., polyol-pyruvate esters, pyruvate thioesters, glycerol-pyruvate esters and dihydroxyacetone-pyruvate esters). Such pyruvate derivatives (including single tautomers, single stereoisomers and mixtures of tautomers and/or stereoisomers, and the pharmaceutically acceptable salts thereof) are useful in the manufacture of pharmaceutical compositions for treating a number of conditions characterized by oxidative stress.

Abstract translation: 某些已知和新颖的丙酮酸衍生物在恢复或保持已经遭受氧剥夺的氧化感受态细胞中的代谢完整性方面特别有活性。 这些丙酮酸衍生化合物包括但不限于肟，酰胺，丙酮酸盐类似物，改性丙酮酸盐类似物，丙酮酸酯（例如多元醇 - 丙酮酸酯，丙酮酸硫酯，甘油 - 丙酮酸酯和二羟基丙酮 - 丙酮酸酯）。 这样的丙酮酸衍生物（包括单互变异构体，单立体异构体和互变异构体和/或立体异构体的混合物及其药学上可接受的盐）可用于制备用于治疗以氧化应激为特征的许多病症的药物组合物。

公开(公告)号：WO0136362A3

公开(公告)日：2002-03-14

申请号：PCT/US0028871

申请日：2000-11-02

Applicant: LILLY CO ELI ,  LEPORE SALVATORE DONATO ,  WILEY MICHAEL ROBERT

Inventor： LEPORE SALVATORE DONATO ,  WILEY MICHAEL ROBERT

IPC: C07B61/00 ,  C07C45/51 ,  C07C205/45 ,  C07C251/44 ,  C07C251/48

CPC classification number: C07C251/48 ,  C07B2200/11 ,  C07C45/516 ,  C07C201/12 ,  C07C205/45 ,  C07C251/44 ,  C07C251/60 ,  C07C2601/14 ,  C40B40/00 ,  C07C49/84 ,  C07C49/657 ,  C07C49/80 ,  C07C49/76 ,  C07C249/04

Abstract: This invention provides a method of synthesizing a compound, comprising reacting a compound of formula (I) with a compound of formula (III) to form a compound of formula (IV)

Abstract translation: 本发明提供合成化合物的方法，包括使式（I）化合物与式（III）化合物反应以形成式（IV）化合物，

公开(公告)号：WO1997015552A1

公开(公告)日：1997-05-01

申请号：PCT/EP1996004446

申请日：1996-10-11

Applicant: BASF AKTIENGESELLSCHAFT ,  GROTE, Thomas ,  BAYER, Herbert ,  MÜLLER, Ruth ,  SAUTER, Hubert ,  KIRSTGEN, Reinhard ,  HARRIES, Volker ,  LORENZ, Gisela ,  AMMERMANN, Eberhard ,  STRATHMANN, Siegfried

Inventor： BASF AKTIENGESELLSCHAFT

IPC: C07C251/60

CPC classification number: A01N37/50 ,  C07C251/60

Abstract: Disclosed are phenylacetic acid derivatives of formula (I) in which the substituents and the index have the following meanings: X is NOCH3, CHOCH3, CHCH3; Y is O or NR; R , R independently of one another stand for hydrogen or C1-C4 alkyl; R stands for cyano, nitro, trifluoromethyl, halogen, alkyl or alkoxy; m is 0, 1 or 2 and the R groups can be different if m is 2; R is hydrogen, cyano, C1-C4 alkyl, C1-C4 alkyl halide, C3-C6 cycloalkyl; R , R and R have the meanings indicated in claim 1. Also disclosed are the salts of the claimed derivatives, a process and intermediate products for producing them and agents containing them for use in pest and fungus control.

Abstract translation: 式（I），其中取代基和指数具有以下含义的苯乙酸衍生物：X是NOCH 3，CHOCH 3，CHCH 3; Y是O，NR; [R <1>，R独立地是氢，C1-C4烷基; [R <2>氰基，硝基，三氟甲基，卤素，烷基和烷氧基; m是0，1或2，其中基团可以是与R <2>中，当m是2不同; [R <3>是氢，氰基，C1-C4烷基，C1-C4卤代烷基，C3-C6环烷基; [R <4>，R <5>和R <6>具有用于制备这些化合物和含有它们用于控制动物害虫和有害真菌的组合物如权利要求1中所示的含义，和它们的盐，一个方法和中间体。

公开(公告)号：WO1994008968A1

公开(公告)日：1994-04-28

申请号：PCT/GB1993001990

申请日：1993-09-22

Applicant: ZENECA LIMITED ,  DE FRAINE, Paul, John ,  PILKINGTON, Brian, Leslie

Inventor： ZENECA LIMITED

IPC: C07D217/14

CPC classification number: C07D239/26 ,  A01N43/40 ,  A01N43/42 ,  A01N43/54 ,  C07C251/60 ,  C07C2601/08 ,  C07C2601/14 ,  C07D213/64 ,  C07D217/14 ,  C07D239/90 ,  C07D401/04 ,  C07D487/04 ,  C07D495/04

Abstract: A fungicidal compound having formula (I), wherein either: A is hydrogen, halogen, hydroxy, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 alkylcarbonyl, C1-4 alkoxycarbonyl, phenoxy, nitro or cyano; and one of R and R is optionally substituted isoquinoline while the other is hydrogen, C1-4 alkyl, C1-4 haloalkyl, halogen or cyano; or A is hydrogen, R is methyl and R is 4-t &cir& _e &cir& _r &cir& _t &cir& _-butylpyrid-2-yl, 4t &cir& _e &cir& _r &cir& _t &cir& _-butylpyrimidin-2-yl, 5-methyl-6-i &cir& _s &cir& _o &cir& _-propoxypyrimidin-4-yl or 4-(C1-4 chlorofluoroalkyl)pyrid-2-yl.

Abstract translation: 具有式（I）的杀真菌化合物，其中：A是氢，卤素，羟基，C 1-4烷基，C 1-4烷氧基，C 1-4卤代烷基，C 1-4卤代烷氧基，C 1-4烷基羰基，C 1-4烷氧基羰基， 苯氧基，硝基或氰基; R 1和R 2之一是任选取代的异喹啉，而另一个是氢，C 1-4烷基，C 1-4卤代烷基，卤素或氰基; 或A为氢，R 2为甲基，R 1为4-叔丁基 - 吡啶-2-基，4'，“ - ” - “和” ，5-甲基-6-氨基嘧啶-4-基或4-（C1-4氯氟代烷基）吡啶-2-基。

公开(公告)号：WO1992019585A1

公开(公告)日：1992-11-12

申请号：PCT/JP1992000570

申请日：1992-04-30

Applicant: ASAHI KASEI KOGYO KABUSHIKI KAISHA ,  KOUJI, Hiroyuki ,  ANDO, Satoshi

Inventor： ASAHI KASEI KOGYO KABUSHIKI KAISHA

IPC: C07C217/14

CPC classification number: C07D295/088 ,  C07C217/18 ,  C07C217/30 ,  C07C217/34 ,  C07C217/42 ,  C07C219/06 ,  C07C251/48 ,  C07C251/60 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07D317/50 ,  C07D317/54 ,  C07F9/12 ,  C07F9/65517 ,  C07F9/65586

Abstract: A triphenylalkene derivative represented by general formula (1), a pharmaceutically acceptable acid addition salt thereof, and a pharmaceutical composition thereof having a tumor inhibitory action and an osteoporosis curing activity. In general formula (1) R1 represents a group selected among those represented by formulae (2), (3) and (4); R6 and R7 represent each hydrogen, alkyl or cycloalkyl, or R6 and R7 together form a heterocyclic group with the adjacent nitrogen atom, provided that R6 and R7 should not be hydrogen atoms at the same time; R8 represents hydrogen or alkylcarbonyl; R2 represents alkyl or cycloalkyl; R3 represents phenyl or 3,4-methylenedioxyphenyl, provided that when R3 represents phenyl, the case where R1 represents a group of formula (4) is excluded; R4 represents hydrogen, hydroxyl, R9C(O)O-, R10OCH2O-, -OPO(OH)2 or CH=NOR11; R9 represents alkyl; R10 represents alkyl or alkylcarbonyl; R5 represents hydrogen or CH=NOR11; and R11 represents hydrogen, alkyl or substituted alkyl.