(+/-)-lithium 3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate | 939410-91-0

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (+/-)-lithium 3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate
• 英文别名: Lithium benzomorpholine-2-carboxylate；lithium;3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate
• CAS: 939410-91-0
• 化学式: C₉H₈NO₃*Li
• 分子量: 185.108
• InChiKey: NQRNXYOUUBYWIZ-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -3.39
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  61.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-lithium 3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate 、 (2R,3S)-3-amino-1-((S)-6-ethylchroman-4-ylamino)-4-phenylbutan-2-ol 在 N-((2S,3R)-4-((S)-6-Ethylchroman-4-ylamino)-3-hydroxy-1-phenylbutan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamide 作用下， 生成 N-((2S,3R)-4-((S)-6-Ethylchroman-4-ylamino)-3-hydroxy-1-phenylbutan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamide
  参考文献：
  名称：

  Beta-secretase modulators and methods of use

  摘要：

  本发明涉及一类新的化合物，可用于调节β-分泌酶酶活性和治疗β-分泌酶介导的疾病，包括阿尔茨海默病（AD）和相关疾病。在一种实施例中，该化合物具有通式I，其中A、B、R3、R4、R5、i和j在此定义。本发明还包括包含一种或多种通式I化合物的药物组合物，以及使用这些化合物的方法，包括通过向受体注射通式I化合物或包含它们的组合物来治疗AD和相关疾病。本发明还包括通式II和III的进一步实施例，以及制备本发明化合物的中间体和过程。

  公开号：

  US08163766B2
• 作为产物：
  描述：

  3,4-二氢-2H-苯并[1,4]噁嗪-2-羧酸乙酯 在 lithium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 21.0h， 生成 (+/-)-lithium 3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate
  参考文献：
  名称：

  WO2007/62007

  摘要：

  公开号：

文献信息

• Non-peptide gnrh antagonists
  申请人：Roe Bryan Michael

  公开号：US20050222139A1

  公开（公告）日：2005-10-06

  Compounds according to general formula 1, wherein A 1 -A 3 are selected from A 5 and A 6 where A 5 is either ═CR 13 — or ═N— and A 6 is —NR 14 —, —O— or —S—; A 4 is either a covalent bond or A 5 , provided that when A 4 is a covalent bond one of A 1 -A 3 must be A 6 and the other two must be A 5 and when A 4 is A 5 then all of A 1 -A 3 must be A 5 ; R 1 is selected from H, NHY′ and COY 2 , in which case R 2 is H, or R 1 and R2 may both be methyl or together represent ═O; R 3 , R 4 and R 5 are each independently selected from H and lower alkyl groups; R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are each independently selected from H, lower alkyl groups, NH 2 , halogens (F, CI and Br) O-alkyl, CH 2 NM 2 and CF 3 ; R 13 is selected from H, F, CI Br, NO 2 , NH 2 , OH, Me, Et, OMe, NMe 2 and CF 3 ; R 14 is selected from H, methyl and ethyl; W is selected from ═CH— and ═N—; X is selected from CH 2 , O, S, SO 2 , NH and N lower alkyl; Y 1 is selected from CO-lower alkyl, CO(CH 2 ) b Y 3 , CO(CH 2 ) b COY 3 and CO(CH)NHCOY 3 , where b is 1-3; Y2 is selected from OR 15 , NR 16 R 17 and NH(CH 2 ) C COY 3 , where c is 1-3; Y 3 is selected from OR 15 and NR 16 R 17 ; R 15 is selected from H, lower alkyl and (CH 2 ) a R 16 , where a is 0-4; R 16 and R 17 are each independently selected from H, lower alkyl and (CH 2 ) a R 16 or together are —(CH 2 ) 2 -Z-(CH 2)2 —; R 18 is OH a phenyl group or an aromatic heterocycle selected from pyridyl, pyrimidinyl, pyrazinyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl and thiadiazolyl, each of which may optionally have a lower alkyl group substituent; and Z is selected from O, CH 2 , S, SO 2 , NH and N-lower alkyl, are new. They are useful in the treatment of breast and prostate cancer, endometriosis and benign prostate hyperplasia, in the regulation of fertility, and in in vitro fertilisation.

  化合物按照通式1进行选择，其中A1-A3选择自A5和A6，其中A5为═CR13—或═N—，A6为—NR14—，—O—或—S—；A4为共价键或A5，若A4为共价键，则A1-A3中必须有一个为A6，其余两个必须为A5，若A4为A5，则A1-A3全部必须为A5；R1选择自H、NHY′和COY2，此时R2为H，或者R1和R2都可以为甲基，或者一起代表═O；R3、R4和R5各自独立选择自H和较低的烷基基团；R6、R7、R8、R9、R10、R11和R12各自独立选择自H、较低的烷基基团、NH2、卤素（F、CI和Br）、O-烷基、 NM2和CF3；R13选择自H、F、CI、Br、NO2、NH2、OH、Me、Et、OMe、NMe2和 ；R14选择自H、甲基和乙基；W选择自═CH—和═N—；X选择自CH2、O、S、SO2、NH和较低的烷基；Y1选择自CO-较低的烷基、CO( )bY3、CO( )bCOY3和CO(CH)NHCOY3，其中b为1-3；Y2选择自OR15、NR16R17和NH( )CCOY3，其中c为1-3；Y3选择自OR15和NR16R17；R15选择自H、较低的烷基和( )aR16，其中a为0-4；R16和R17各自独立选择自H、较低的烷基和( )aR16，或者一起为—( )2-Z-( )2—；R18为OH、苯基或选择自吡啶基、嘧啶基、吡嗪基、呋喃基、噻吩基、吡咯基、咪唑基、吡唑基、噁唑基、异噁唑基、噻唑基、异噻唑基、三唑基、噁二唑基和噻二唑基的芳香杂环，每个都可以选择具有较低的烷基基团取代基；Z选择自O、 、S、SO2、NH和N-较低的烷基。它们在乳腺和前列腺癌、子宫内膜异位症和良性前列腺增生的治疗、生育调节以及体外受精方面有用。
• Non-peptide GnRH antagonists
  申请人：Roe Michael Bryan

  公开号：US20080255109A1

  公开（公告）日：2008-10-16

  Compounds according to general formula 1, wherein A 1 -A 3 are selected from A 5 and A 6 where A 5 is either ═CR 13 — or ═N— and A 6 is —NR 14 —, —O— or —S—; A 4 is either a covalent bond or A 5 , provided that when A 4 is a covalent bond one of A 1 -A 3 must be A 6 and the other two must be A 5 and when A 4 is A 5 then all of A 1 -A 3 must be A 5 ; R 1 is selected from H, NHY′ and COY 2 , in which case R 2 is H, or R 1 and R 2 may both be methyl or together represent ═O; R 3 , R 4 and R 5 are each independently selected from H and lower alkyl groups; R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are each independently selected from H, lower alkyl groups, NH 2 , halogens (F, Cl and Br) O-alkyl, CH 2 NM 2 and CF 3 ; R 13 is selected from H, F, Cl, Br, NO 2 , NH 2 , OH, Me, Et, OMe, NMe 2 and CF 3 ; R 14 is selected from H, methyl and ethyl; W is selected from ═CH— and ═N—; X is selected from CH 2 , O, S, SO 2 , NH and N-lower alkyl; Y 1 is selected from CO-lower alkyl, CO(CH 2 ) b Y 3 , CO(CH 2 ) b COY 3 and CO(CH 2 ) b NHCOY 3 , where b is 1-3; Y 2 is selected from OR 15 , NR 16 R 17 and NH(CH 2 ) c COY3, where c is 1-3; Y 3 is selected from OR 15 and NR 16 R 17 ; R 15 is selected from H, lower alkyl and (CH 2 ) a R 16 , where a is 0-4; R 16 and R 17 are each independently selected from H, lower alkyl and (CH 2 ) a R 16 or together are —(CH 2 ) 2 -Z-(CH 2 ) 2 —; R 18 is OH, a phenyl group or an aromatic heterocycle selected from pyridyl, pyrimidinyl, pyrazinyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl and thiadiazolyl, each of which may optionally have a lower alkyl group substituent; and Z is selected from O, CH 2 , S, SO 2 , NH and N-lower alkyl, are new. They are useful in the treatment of breast and prostate cancer, endometriosis and benign prostate hyperplasia, in the regulation of fertility, and in in vitro fertilisation.

  化合物的一般式为1，其中A1-A3从A5和A6中选择，其中A5是═CR13—或═N—，A6是—NR14—，—O—或—S—; A4是共价键或A5，如果A4是共价键，则A1-A3中必须有一个为A6，另外两个必须为A5，如果A4是A5，则A1-A3必须全部为A5; R1从H，NHY'和COY2中选择，此时R2为H，或者R1和R2都可以是甲基或者一起表示为═O; R3，R4和R5各自独立选择自H和较低的烷基基团; R6，R7，R8，R9，R10，R11和R12各自独立选择自H，较低的烷基基团，NH2，卤素（F，Cl和Br），O-烷基， NM2和CF3; R13从H，F，Cl，Br，NO2，NH2，OH，Me，Et，OMe，NMe2和 中选择; R14从H，甲基和乙基中选择; W从═CH—和═N—中选择; X从CH2，O，S，SO2，NH和N-较低的烷基中选择; Y1从CO-较低的烷基，CO( )bY3，CO( )bCOY3和CO( )bNHCOY3中选择，其中b为1-3; Y2从OR15，NR16R17和NH( )cCOY3中选择，其中c为1-3; Y3从OR15和NR16R17中选择; R15从H，较低的烷基和( )aR16中选择，其中a为0-4; R16和R17各自独立选择自H，较低的烷基和( )aR16，或者一起为—( )2-Z-( )2—; R18为OH，苯基或从吡啶基，嘧啶基，吡嗪基，呋喃基，噻吩基，吡咯基，咪唑基，吡唑基，噁唑基，异噁唑基，噻唑基，异噻唑基，三唑基，噁二唑基和噻二唑基中选择的芳香杂环，每个芳香杂环可以选择有较低的烷基基团取代物; Z从O， ，S，SO2，NH和N-较低的烷基中选择。它们在乳腺癌和前列腺癌，子宫内膜异位症和良性前列腺增生的治疗，调节生育能力以及体外受精方面有用。
• Beta-Secretase modulators and methods of use
  申请人：Amgen Inc.

  公开号：US07872009B2

  公开（公告）日：2011-01-18

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A, B, R3, R4, R5, i and j are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, methods of use for these compounds, including treatment of AD and related diseases, by administering the compound(s) of Formula I, or compositions including them, to a subject. The invention also comprises further embodiments of Formulas II and III, intermediates and processes useful for the preparation of compounds of the invention.

  本发明涉及一种新型化合物类别，可用于调节β-秘鲁酶酶活性和治疗β-秘鲁酶介导的疾病，包括阿尔茨海默病（AD）和相关病症。在一种实施例中，该化合物具有一般式I，其中A、B、R3、R4、R5、i和j在此定义。本发明还包括包括一种或多种I式化合物的制药组合物，使用这些化合物的方法，包括通过将I式化合物或包括它们的组合物用于治疗AD和相关疾病来给予受试者。本发明还包括II式和III式的进一步实施例，中间体和制备本发明化合物的有用过程。
• BETA-SECRETASE MODULATORS AND METHODS OF USE
  申请人：Albrecht Brian K.

  公开号：US20110118250A1

  公开（公告）日：2011-05-19

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A, B, R 3 , R 4 , R 5 , i and j are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, methods of use for these compounds, including treatment of AD and related diseases, by administering the compound(s) of Formula I, or compositions including them, to a subject. The invention also comprises further embodiments of Formulas II and III, intermediates and processes useful for the preparation of compounds of the invention.

  本发明涉及一类新型化合物，可用于调节β-分泌酶酶活性和治疗β-分泌酶介导的疾病，包括阿尔茨海默病（AD）和相关疾病。在一种实施例中，所述化合物具有一般式I，其中A、B、R3、R4、R5、i和j在此被定义。本发明还包括包括一种或多种式I化合物的制药组合物，以及使用这些化合物的方法，包括将式I化合物或包含它们的组合物用于治疗AD和相关疾病，通过将式I化合物或包含它们的组合物用于给予受试者的方法。本发明还包括式II和III的进一步实施例，以及用于制备本发明化合物的中间体和方法。
• NON-PEPTIDE GnRH ANTAGONISTS
  申请人：Ferring BV

  公开号：EP1485356A1

  公开（公告）日：2004-12-15