5-biphenvl-4-yl-3-oxo-pentanoic acid tert-butyl ester | 811456-29-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-biphenvl-4-yl-3-oxo-pentanoic acid tert-butyl ester
• 英文别名: 5-biphenyl-4-yl-3-oxo-pentanoic acid tert-butyl ester；tert-butyl 5-biphenyl-4-yl-3-oxopentanoate；tert-butyl 3-oxo-5-(4-phenylphenyl)pentanoate
• CAS: 811456-29-8
• 化学式: C₂₁H₂₄O₃
• 分子量: 324.42
• InChiKey: YVDPLXBFEIEOKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-biphenvl-4-yl-3-oxo-pentanoic acid tert-butyl ester 生成 5-(Biphenyl-4-yl)-3-oxopentanoic acid
  参考文献：
  名称：

  The identification of β-hydroxy carboxylic acids as selective MMP-12 inhibitors

  摘要：

  A new class of selective MMP-12 inhibitors have been identified via high throughput screening. Crystallization with MMP-12 confirmed the mode of binding and allowed initial optimization to be carried out using classical structure based design.

  DOI：

  10.1016/j.bmcl.2009.07.155
• 作为产物：
  描述：

  4-溴甲基联苯 在 sodium hydride 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.04h， 以38%的产率得到5-biphenvl-4-yl-3-oxo-pentanoic acid tert-butyl ester
  参考文献：
  名称：

  [EN] MATRIX METALLOPROTEINASE INHIBITORS
  [FR] INHIBITEURS DE METALLOPROTEINASES MATRICIELLES

  摘要：

  式(I)的化合物：其中：A代表键，C1-6烷基或CH=CH-C1-4烷基；B代表键，O，S，SO，SO2，CO，CR7R8，CO2R14，CONR14R15，N(COR14)(COR15)，N(SO2R14)(COR15)或NR14R15；D代表键，或C1-6烷基；E代表取代芳基或取代或未取代的杂环芳基；Q代表可选择取代的5-或6-成员芳基或杂环芳基环；X代表O，S，SO，SO2，CO，CNR5，CNOR5，CNNR5R6，NR11或CR7R8；Y代表CR5OR11，CR5SR11，NOR5，CR5NR6R11，SO，SO2，CO，CNR5，CNOR5或CS；R1和R1'各自独立地代表H，C1-6烷基或C1-4烷基芳基；R2代表CO2R12，CH2OR12或CONR12R13，CONR12OR13，NR12COR13，SR12，PO(OH)2，PONHR12或SONHR12；R3代表H，C1-6烷基或C1-4烷基芳基；R4代表可选择取代的芳基或杂环芳基；Z代表键，CH2，O，S，SO，SO2，NR5，OCR5R6，CR9R10O或Z，R4和Q共同形成可选择取代的融合三环基团；R5和R6各自独立地代表H，C1-6烷基或C1-4烷基芳基；R7和R8各自独立地代表H，卤素，C1-6烷基或C1-4烷基芳基；R9和R10各自独立地代表H，可选择由卤素，氰基，OR11或NR6R11取代的C1-6烷基，可选择由卤素，氰基，OR11或NR6R11取代的C1-4烷基芳基，OR11或，与它们连接的N一起，R9和R10形成杂环基团：R11代表H，C1-6烷基，C1-4烷基芳基或COR5；R12和R13各自独立地代表H，C1-3烷基，C1-3烷基芳基或C1-3烷基杂环芳基或，与它们连接的官能团一起，R12和R13形成杂环基团：R14和R15各自独立地代表H，C1-6烷基，C1-4烷基芳基或C1-4烷基杂环芳基或与它们连接的官能团一起，R14和R15形成杂环或融合杂环基团：以及其生理功能衍生物，其制备方法，含有它们的制药配方以及它们作为基质金属蛋白酶酶（MMPs）抑制剂的用途。

  公开号：

  WO2005026120A1

文献信息

• [EN] MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] COMPOSES PRESENTANT UNE EFFICACITE THERAPEUTIQUE
  申请人：GLAXO GROUP LTD

  公开号：WO2004110974A1

  公开（公告）日：2004-12-23

  Compounds of formula (1): Wherein: Q represents an optionally substituted 5- or 6-membered aryl or heteroaryl ring; X represents 0, S, NR5 or CR6 R7; Y represents CHOH, CHSH, NOR8, CNR8 or CNOR8; Z represents a bond, CR10 R11, 0,S,S0,S02, NR10, OCR10R11, CR10R11O or Z, R4 and Q together form an optionally substituted fused tricyclic group; R1, R1’, R3 and R3 each independently represents H, C1-6 alkyl or C1-4 alkylaryl; R2 represents C02 R8, CONR5OR9 or NR5 COR9; R4 represents optionally substituted 5- or 6-membered aryl or heteroaryl; R5 represents H or C1-3 alkyl; R6 and R7 each independently represents H, C1-3 alkyl or halo; R8 represents H or C1-2 alkyl; R9 represents H or C1-3 alkyl; R10 and R11 each independently represents H, C1-6 alkyl or C1-4 alkylaryl; and physiologically functional derivatives thereof, processes for their preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metal loproteinase enzymes (MMPs) are described.

  式（1）的化合物：其中：Q代表可选择地取代的5-或6-成员芳基或杂芳基环；X代表0、S、NR5或CR6R7；Y代表CHOH、CHSH、NOR8、CNR8或CNOR8；Z代表键、CR10R11、O、S、SO、SO2、NR10、OCR10R11、CR10R11O或Z，R4和Q共同形成可选择地取代的融合三环基团；R1、R1’、R3和R3各自独立地代表H、C1-6烷基或C1-4烷基芳基；R2代表C02R8、CONR5OR9或NR5COR9；R4代表可选择地取代的5-或6-成员芳基或杂芳基；R5代表H或C1-3烷基；R6和R7各自独立地代表H、C1-3烷基或卤素；R8代表H或C1-2烷基；R9代表H或C1-3烷基；R10和R11各自独立地代表H、C1-6烷基或C1-4烷基芳基；以及其生理功能衍生物、其制备方法、含有它们的制药配方和它们作为基质金属蛋白酶酶（MMPs）抑制剂的用途。
• [EN] MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] INHIBITEURS DE METALLOPROTEINASES MATRICIELLES
  申请人：GLAXO GROUP LTD

  公开号：WO2005026120A1

  公开（公告）日：2005-03-24

  Compounds of Formula (I): Wherein: A represents bond, C1-6alkyl or CH=CH-C1-4alkyl; B represents bond, O, S, SO, SO2, CO, CR7R8, CO2R14, CONR14R15, N(COR14)(COR15), N(SO2R14)(COR15) or NR14R15; D represents bond, or C1-6alkyl; E represents substituted aryl or substituted or unsubstituted heteroaryl; Q represents an optionally substituted 5- or 6-membered aryl or heteroaryl ring; X represents O, S, SO, SO2, CO, CNR5, CNOR5, CNNR5R6, NR11 or CR7R8; Y represents CR5OR11, CR5SR11, NOR5, CR5NR6R11, SO, SO2, CO, CNR5, CNOR5 or CS; R1 and R1' each independently represents H, C1-6alkyl or C1-4alkylaryl; R2 represents CO2R12, CH2OR12 or CONR12R13, CONR12OR13, NR12COR13, SR12, PO(OH)2, PONHR12 or SONHR12; R3 represents H, C1-6alkyl or C1-4alkylaryl; R4 represents optionally substituted aryl or heteroaryl; Z represents a bond, CH2, O, S, SO, SO2, NR5, OCR5R6, CR9R10O or Z, R4 and Q together form an optionally substituted fused tricyclic group; R5 and R6 each independently represent H, C1-6 alkyl or C1-4 alkylaryl; R7 and R8 each independently represent H, halo, C1-6 alkyl or C1-4 alkylaryl; R9 and R10 each independently represents H, C1-6 alkyl optionally substituted by halo, cyano, OR11 or NR6R11 , C1-4 alkylaryl optionally substituted by halo, cyano, OR11 or NR6R11, OR11 or, together with the N to which they are attached, R9 and R10 form a heterocyclic group: R11 represents H, C1-6 alkyl, C1-4 alkylaryl or COR5; R12 and R13 each independently represent H, C1-3 alkyl, C1-3 alkylaryl or C1-3 alkylheteroaryl or, together with the functionality to which they are attached, R12 and R13 form a heterocyclic group: R14 and R15 each independently represent H, C1-6 alkyl, C1-4 alkylaryl or C1-4 alkylheteroaryl or together with the functionality to which they are attached R14 and R15 form a heterocyclic or fused heterocyclic group: and physiologically functional derivatives thereof, processes for their preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metallproteinase enzymes (MMPs) are described.

  式(I)的化合物：其中：A代表键，C1-6烷基或CH=CH-C1-4烷基；B代表键，O，S，SO，SO2，CO，CR7R8，CO2R14，CONR14R15，N(COR14)(COR15)，N(SO2R14)(COR15)或NR14R15；D代表键，或C1-6烷基；E代表取代芳基或取代或未取代的杂环芳基；Q代表可选择取代的5-或6-成员芳基或杂环芳基环；X代表O，S，SO，SO2，CO，CNR5，CNOR5，CNNR5R6，NR11或CR7R8；Y代表CR5OR11，CR5SR11，NOR5，CR5NR6R11，SO，SO2，CO，CNR5，CNOR5或CS；R1和R1'各自独立地代表H，C1-6烷基或C1-4烷基芳基；R2代表CO2R12，CH2OR12或CONR12R13，CONR12OR13，NR12COR13，SR12，PO(OH)2，PONHR12或SONHR12；R3代表H，C1-6烷基或C1-4烷基芳基；R4代表可选择取代的芳基或杂环芳基；Z代表键，CH2，O，S，SO，SO2，NR5，OCR5R6，CR9R10O或Z，R4和Q共同形成可选择取代的融合三环基团；R5和R6各自独立地代表H，C1-6烷基或C1-4烷基芳基；R7和R8各自独立地代表H，卤素，C1-6烷基或C1-4烷基芳基；R9和R10各自独立地代表H，可选择由卤素，氰基，OR11或NR6R11取代的C1-6烷基，可选择由卤素，氰基，OR11或NR6R11取代的C1-4烷基芳基，OR11或，与它们连接的N一起，R9和R10形成杂环基团：R11代表H，C1-6烷基，C1-4烷基芳基或COR5；R12和R13各自独立地代表H，C1-3烷基，C1-3烷基芳基或C1-3烷基杂环芳基或，与它们连接的官能团一起，R12和R13形成杂环基团：R14和R15各自独立地代表H，C1-6烷基，C1-4烷基芳基或C1-4烷基杂环芳基或与它们连接的官能团一起，R14和R15形成杂环或融合杂环基团：以及其生理功能衍生物，其制备方法，含有它们的制药配方以及它们作为基质金属蛋白酶酶（MMPs）抑制剂的用途。
• 5-Phenyl-Pentanoic Acid Derivatives as Matrix Metalloproteinase Inhibitors for the Treatment of Asthma and Other Diseases
  申请人：Palle Venkata P.

  公开号：US20080194565A1

  公开（公告）日：2008-08-14

  The present invention relates to C ompounds having the structure of Formula I: wherein n is an integer from 1 to 5; R 1 is optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, alkoxy, aryloxy, alkenyloxy or alkynyloxy; R 2 is alkenyl, allcynyl, aryl, heterocyclyl, heteroaryl, cycloalkyl, NR 4 R 5 , —NHC(═Y)R 4 , —NHC(═Y)NR 5 R x , —NHC(═O)OR 4 , —NHSO 2 R 4 , C(═Y)NR 4 R 5 , C(═O)OR 6 [wherein Y is oxygen or sulphur], OR 5 , —O(C═O)NR 4 R 5 , O-acyl, S(O) m R 4 , —SO 2 N(R 4 ) 2 , cyano, amidino or guanidino [wherein R 4 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclylalkyl or cycloalkylalkyl and m is an integer 0-2; R 5 is hydrogen or R 4 ; R x is R 4 or —SO 2 N(R 4 ) 2 and R 6 is hydrogen, alkyl, cycloalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl or cycloalkylalkyl]; R 3 is hydrogen, fluorine, alkyl, cycloalkylalkyl or aralkyl; A is OH, OR 4 , —OC(═O)NR 4 R 5 , O-acyl, NH 2 , NR 4 R 5 , —NHC(═Y)R 4 , —NHC(═Y)NR 5 R x , —NHC(═O)OR 4 , —NHSO 2 R 4 , and to processes for the synthesis of the same. This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by over-expression and over-activation of an matrix metalloproteinase, using the compounds.

  本发明涉及具有以下结构的化合物：其中n是1到5之间的整数；R1是可选择地取代的烷基、烯基、炔基、环烷基、芳基、杂环烷基、杂芳基、芳基烷基、烷氧基、芳氧基、烯基氧基或炔基氧基；R2是烯基、炔基、芳基、杂环烷基、杂芳基、环烷基、NR4R5、—NHC(═Y)R4、—NHC(═Y)NR5Rx、—NHC(═O)OR4、—NHSO2R4、C(═Y)NR4R5、C(═O)OR6[其中Y是氧或硫]、OR5、—O(C═O)NR4R5、O-酰基、S(O)mR4、—SO2N(R4)2、氰基、胺基亚胺基或胍基[其中R4是烷基、烯基、炔基、环烷基、芳基、杂环烷基、杂芳基、芳基烷基、杂芳基烷基、杂环烷基烷基或环烷基烷基，m是0-2的整数；R5是氢或R4；Rx是R4或—SO2N(R4)2，R6是氢、烷基、环烷基、芳基烷基、杂芳基烷基、杂环烷基烷基或环烷基烷基]；R3是氢、氟、烷基、环烷基烷基或芳基烷基；A是OH、OR4、—OC(═O)NR4R5、O-酰基、NH2、NR4R5、—NHC(═Y)R4、—NHC(═Y)NR5Rx、—NHC(═O)OR4、—NHSO2R4等，以及其合成方法。本发明还涉及含有本发明化合物的药理学组合物，以及治疗哮喘、类风湿关节炎、慢性阻塞性肺病、鼻炎、骨关节炎、银屑病性关节炎、牛皮癣、肺纤维化、肺部炎症、急性呼吸窘迫综合征、牙周炎、多发性硬化症、牙龈炎、动脉粥样硬化、新生内膜增生导致再狭窄和缺血性心力衰竭、中风、肾脏疾病、肿瘤转移和其他炎症性疾病的方法，这些疾病特征是矩阵金属蛋白酶的过度表达和过度激活，使用这些化合物。
• Matrix metalloproteinase inhibitors
  申请人：Gaines Simon

  公开号：US20060160875A1

  公开（公告）日：2006-07-20

  Compounds of formula (I): wherein: Q represents an optionally substituted 5- or 6-membered aryl or heteroaryl ring; X represents O, S, NR 5 or CR 6 R 7 ; Y represents CHOH, CHSH, NOR 8 , CNR 8 or CNOR 8 ; Z represents a bond, CR 10 R 11 , O, S, SO, SO 2 , NR 10 , OCR 10 R 11 , CR 10 R 11 O or Z, R 4 and Q together form an optionally substituted fused tricyclic group; R 1 , R 1′ , R 3 and R 3′ each independently represents H, C 1-6 alkyl or C 1-4 alkylaryl; R 2 represents CO 2 R 8 , CONR 5 OR 9 or NR 5 COR 9 ; R 4 represents optionally substituted 5- or 6-membered aryl or heteroaryl; R 5 represents H or C 1-3 alkyl; R 6 and R 7 each independently represents H, C 1-3 alkyl or halo; R 8 represents H or C 1-2 alkyl; R 9 represents H or C 1-3 alkyl; R 10 and R 11 each independently represents H, C 1-6 alkyl or C 1-4 alkylaryl; and physiologically functional derivatives thereof, processes for their preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metalloproteinase enzymes (MMPs) are described.

  式(I)的化合物：其中：Q代表可选取代的5-或6-成员芳基或杂芳基环；X代表O、S、NR5或CR6R7；Y代表CHOH、CHSH、NOR8、CNR8或CNOR8；Z代表键、CR10R11、O、S、SO、SO2、NR10、OCR10R11、CR10R11O或Z，R4和Q共同形成可选取代的融合三环基团；R1、R1'、R3和R3'各自独立地代表H、C1-6烷基或C1-4烷基芳基；R2代表CO2R8、CONR5OR9或NR5COR9；R4代表可选取代的5-或6-成员芳基或杂芳基；R5代表H或C1-3烷基；R6和R7各自独立地代表H、C1-3烷基或卤素；R8代表H或C1-2烷基；R9代表H或C1-3烷基；R10和R11各自独立地代表H、C1-6烷基或C1-4烷基芳基；以及其生理功能衍生物、制备过程、含有它们的制药配方和作为基质金属蛋白酶酶（MMPs）抑制剂的用途。
• MATRIX METALLOPROTEINASE INHIBITORS
  申请人：Gaines Simon

  公开号：US20100029699A1

  公开（公告）日：2010-02-04

  The present invention relates to compounds of Formula (I): pharmaceutically acceptable salts thereof, corresponding preparation processes, pharmaceutical formulations and methods for use as inhibitors of matrix metallproteinase enzymes (MMPs).

  本发明涉及式（I）的化合物：其药学上可接受的盐，相应的制备过程，制药配方以及用作基质金属蛋白酶酶（MMPs）抑制剂的方法。