3,4-Dihydro-N-(phenylmethyl)-2H-1-benzopyran-2-methanamine | 155427-73-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 3,4-Dihydro-N-(phenylmethyl)-2H-1-benzopyran-2-methanamine
• 英文别名: (+/-)-3,4-dihydro-N-(phenylmethyl)-2H-1-benzopyran-2-methanamine；Benzyl-chroman-2-ylmethyl-amine; oxalic acid；N-benzyl-1-(3,4-dihydro-2H-chromen-2-yl)methanamine
• CAS: 155427-73-9
• 化学式: C₁₇H₁₉NO
• 分子量: 253.344
• InChiKey: YGSXNPFZXQFLSH-UHFFFAOYSA-N

物化性质

• 熔点：
  231.5-232.5 °C
• 沸点：
  389.2±11.0 °C(Predicted)
• 密度：
  1.080±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  苄基三甲基氢氧化铵 、 3,4-Dihydro-N-(phenylmethyl)-2H-1-benzopyran-2-methanamine 以 丙烯腈 为溶剂， 以21 g (28.6%)的产率得到(+/-)-3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl](phenylmethyl)amino]propanenitrile
  参考文献：
  名称：

  [(benzodioxan, benzofuran or benzopyran) alkylamino] alkyl substituted

  摘要：

  本发明涉及具有以下结构的血管收缩性[(苯并二氧杂环戊烷、苯并呋喃或苯并吡喃)烷基氨基]烷基取代胍啶，其化学式为##STR1##其药学上可接受的酸盐，以及其立体化异构体形式，其中X为O、CH.sub.2或直接键；R.sup.1为氢或C.sub.1-6烷基；R.sup.2为氢、C.sub.1-6烷基、C.sub.3-6烯基或C.sub.3-6炔基；R.sup.3为氢或C.sub.1-6烷基；或R.sup.2和R.sup.3可以结合形成式为--(CH.sub.2).sub.m--的二价基团，其中m为4或5；或R.sup.1和R.sup.2结合在一起可以形成式为--CH.dbd.CH--或式为--(CH.sub.2).sub.n--的二价基团，其中n为2、3或4；或R.sup.3可以表示键，当R.sup.1和R.sup.2结合在一起形成式为--CH.dbd.CH--CH.dbd.、--CH.dbd.CH--N.dbd.或--CH.dbd.N--CH.dbd.的二价基团时；R.sup.4为氢或C.sub.1-6烷基；Alk.sup.1为二价C.sub.1-3烷二基基团；A为式的二价基团：##STR2##其中每个R.sup.5为氢或C.sub.1-4烷基；每个R.sup.6为氢或C.sub.1-4烷基；Alk.sup.2为C.sub.2-15烷二基或C.sub.5-7环烷二基；每个p为0、1或2；但[2-[(2,3-二氢-1,4-苯并二氧杂环戊烷-2-基)甲基]氨基]乙基胍啶被排除。作为血管收缩剂有用的药物。包含所述胍啶衍生物作为活性成分的组合物，制备所述胍啶衍生物的方法和新颖的N-氰基胍啶，中间体；以及作为药物的用途。

  公开号：

  US05541180A1
• 作为产物：
  描述：

  氯化苄 、 2-aminomethylchroman hydrochloride 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以31%的产率得到3,4-Dihydro-N-(phenylmethyl)-2H-1-benzopyran-2-methanamine
  参考文献：
  名称：

  New Generation Dopaminergic Agents. 1. Discovery of a Novel Scaffold Which Embraces the D₂ Agonist Pharmacophore. Structure−Activity Relationships of a Series of 2-(Aminomethyl)chromans

  摘要：

  A series of 2-(aminomethyl)chromans (2-AMCs) was synthesized and evaluated for their affinity and selectivity for both the high-and low-affinity agonist states (D-2(High) and D-2(Low), respectively) of the dopamine (DA) D-2 receptor. The 7-hydroxy-2-(aminomethyl)chroman moiety was observed to be the primary D-2 agonist pharmacophore. The 2-methylchroman moiety was discovered to be an entirely novel scaffold which could be used to access the D-2 agonist pharmacophore. Attaching various simple alkyl and arylalkyl side chains to the 7-hydroxy 2-AMC nucleus had significant effects on selectivity for the D-2(High) receptor vs the 5HT(1A) and alpha(1) receptors. A novel DA partial agonist, (R)-(-)-2-(benzylamino)methyl)chroman-7-ol [R-(-)-35c], was identified as having the highest affinity and best selectivity for the D-2(High) receptor vs the alpha(1) and 5HT(1A) receptors. Several regions of the 2-AMC nucleus were modified and recognized as potential sites to modulate the level of intrinsic activity. The global minimum conformer of the 7-hydroxy-2-AMC moiety was identified as fulfilling the McDermed model D-2 agonist pharmacophoric criteria and was proposed as the D-2 receptor-bound conformation. Structure-activity relationships gained from these studies have aided in the synthesis of D-2 partial agonists of varying intrinsic activity levels. These agents should be of therapeutic value in treating disorders resulting from hypo-and hyperdopaminergic activity, without the side effects associated with complete D-2 agonism or antagonism.

  DOI：

  10.1021/jm9703653

文献信息

• Aminoalkyl substituted (benzodioxan, benzofuran or benzopyran) derivatives
  申请人：Van Emelen Kristof

  公开号：US20050096378A1

  公开（公告）日：2005-05-05

  The present invention concerns compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, wherein -Z 1 -Z 2 - is a bivalent radical; R 1 , R 2 and R 3 are each independently selected from hydrogen, C 1-6 alkyl, hydroxy, halo and the like; or when R 1 and R 2 are on adjacent carbon atoms, R 1 and R 2 taken together may form a bivalent radical of formula; Alk 1 and Alk 2 are optionally substituted C 1-6 alkanediyl; R 6 is hydrogen or phenylmethyl; R 5 is a radical of formula wherein n is 1 or 2; p 1 is 0, and p 2 is 1 or 2; or p 1 is 1 or 2, and p 2 is 0; X is oxygen, sulfur or ═NR 9 ; Y is oxygen or sulfur; R 7 is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, phenyl or phenylmethyl; R 8 is C 1-6 alkyl, C 3-6 cycloalkyl phenyl or phenylmethyl; R 9 is cyano, C 1-6 alkyl, C 3-6 cyclo-alkyl, C 1-6 alkyloxycarbonyl or aminocarbonyl; R 10 is hydrogen or C 1-6 alkyl; and Q is a bivalent radical. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impaired fundic relaxation.

  本发明涉及式(I)的化合物，其立体化学异构体形式，其N-氧化物形式或其药学上可接受的酸加合盐，其中-Z1-Z2-是二价基团；R1，R2和R3分别独立地选择自氢，C1-6烷基，羟基，卤素等；或当R1和R2在相邻碳原子上时，R1和R2结合在一起可以形成式的二价基团；Alk1和Alk2是可选择的取代的C1-6烷二基基团；R6是氢或苯甲基；R5是式其中n为1或2；p1为0，p2为1或2；或p1为1或2，p2为0；X是氧，硫或═NR9；Y是氧或硫；R7是氢，C1-6烷基，C3-6环烷基，苯基或苯甲基；R8是C1-6烷基，C3-6环烷基，苯基或苯甲基；R9是氰基，C1-6烷基，C3-6环烷基，C1-6烷氧基羰基或氨基羰基；R10是氢或C1-6烷基；Q是二价基团。公开了制备所述产品的方法，包括所述产品的配方以及其作为药物的用途，特别是用于治疗与胃底松弛受损相关的疾病。
• [(Benzodioxan, benzofuran or benzopyran) alkylamino] alkyl substituted
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05607949A1

  公开（公告）日：1997-03-04

  The present invention is concerned with vasoconstricive [(benzodioxan, benzofuran or benzopyran)alkylamino]alkyl substituted guanidines having the formula ##STR1## the pharmaceutically acceptable acid addition salts thereof, and the stereochemically isomeric forms thereof, wherein X is O, CH.sub.2 or a direct bond; R.sup.1 is hydrogen or C.sub.1-6 alkyl; R.sup.2 is hydrogen, C.sub.1-6 alkyl, C.sub.3-6 alkenyl or C.sub.3-6 alkynyl; R.sup.3 is hydrogen or C.sub.1-6 alkyl; or R.sup.2 and R.sup.3 may be taken together to form a bivalent radical of formula --(CH.sub.2).sub.m --, wherein m is 4 or 5; or R.sup.1 and R.sup.2 taken together may form a bivalent radical of formula --CH.dbd.CH-- or of formula --(CH.sub.2).sub.n --, wherein n is 2, 3 or 4; or R.sup.3 may represent a bond when R.sup.1 and R.sup.2 taken together form a bivalent radical of formula --CH.dbd.CH--CH.dbd., --CH.dbd.CH--N.dbd., or --CH.dbd.N--CH.dbd.; R.sup.4 is hydrogen or C.sub.1-6 alkyl; Alk.sup.1 is a bivalent C.sub.1-3 alkanediyl radical; A is a bivalent radical of formula: ##STR2## wherein each R.sup.5 is hydrogen or C.sub.1-4 alkyl; wherein each R.sup.6 is hydrogen or C.sub.1-4 alkyl; Alk.sup.2 is C.sub.2-15 alkanediyl or C.sub.5-7 cycloalkanediyl; and each p is 0, 1 or 2; provided that [2-[(2,3-dihydro-1,4-benzodioxin-2-yl)methyl]amino]ethyl guanidine is excluded. Pharmaceuticals which are useful as vasoconstrictors. Compositions comprising said guanidine derivatives as active ingredients, processes for preparing said guanidine derivatives and novel N-cyano guanidine, intermediates; and a use as a medicine are described.

  本发明涉及具有以下公式的血管收缩性[(苯并二氧杂环、苯并呋喃或苯并吡喃)烷基氨基]烷基取代的胍类化合物，其药学上可接受的酸加成盐以及其立体化学异构体形式：##STR1## 其中X是O、CH.sub.2或直接键；R.sup.1是氢或C.sub.1-6烷基；R.sup.2是氢、C.sub.1-6烷基、C.sub.3-6烯基或C.sub.3-6炔基；R.sup.3是氢或C.sub.1-6烷基；或R.sup.2和R.sup.3可以结合成为式--(CH.sub.2).sub.m--的二价基团，其中m为4或5；或R.sup.1和R.sup.2结合可以形成式--CH.dbd.CH--或式--(CH.sub.2).sub.n--的二价基团，其中n为2、3或4；或当R.sup.1和R.sup.2结合形成式--CH.dbd.CH--CH.dbd.、--CH.dbd.CH--N.dbd.或--CH.dbd.N--CH.dbd.的二价基团时，R.sup.3可以表示键；R.sup.4是氢或C.sub.1-6烷基；Alk.sup.1是二价的C.sub.1-3烷二基基团；A是式的二价基团：##STR2## 其中每个R.sup.5是氢或C.sub.1-4烷基；其中每个R.sup.6是氢或C.sub.1-4烷基；Alk.sup.2是C.sub.2-15烷二基或C.sub.5-7环烷二基；每个p为0、1或2；但[2-[(2,3-二氢-1,4-苯并二氧杂环-2-基)甲基]氨基]乙基胍被排除。本发明还涉及作为血管收缩剂有用的药物，包含该胍衍生物作为活性成分的组合物，制备该胍衍生物的方法和新的N-氰基胍、中间体；以及作为药物的用途。
• \x9b(Benzodioxan benzofuran or benzopyran) alkylamino!alkyl substituted
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US05688952A1

  公开（公告）日：1997-11-18

  The present invention is concerned with vasoconstricive \x9b(benzodioxan, benzofuran or benzopyran)alkylamino!alkyl substituted guanidines having the formula ##STR1## the pharmaceutically acceptable acid addition salts thereof, and the stereochemically isomeric forms thereof, wherein X is O, CH.sub.2 or a direct bond; R.sup.1 is hydrogen or C.sub.1-6 alkyl; R.sup.2 is hydrogen, C.sub.1-6 alkyl, C.sub.3-6 alkenyl or C.sub.3-6 alkynyl; R.sup.3 is hydrogen or C.sub.1-6 alkyl; or R.sup.2 and R.sup.3 may be taken together to form a bivalent radical of formula --(CH.sub.2).sub.m --, wherein m is 4 or 5; or R.sup.1 and R.sup.2 taken together may form a bivalent radical of formula --CH.dbd.CH-- or of formula --(CH.sub.2).sub.n --, wherein n is 2, 3 or 4; or R.sup.3 may represent a bond when R.sup.1 and R.sup.2 taken together form a bivalent radical of formula --CH.dbd.CH--CH.dbd., --CH.dbd.CH--N.dbd., or --CH.dbd.N--CH.dbd.; R.sup.4 is hydrogen or C.sub.1-6 alkyl; Alk.sup.1 is a bivalent C.sub.1-3 alkanediyl radical; A is a bivalent radical of formula: ##STR2## wherein each R.sup.5 is hydrogen or C.sub.1-4 alkyl; wherein each R.sup.6 is hydrogen or C.sub.1-4 alkyl; Alk.sup.2 is C.sub.2-15 alkanediyl or C.sub.5-7 cycloalkanediyl; and each p is 0, 1 or 2; provided that \x9b2-\x9b(2,3- dihydro-1,4-benzodioxin-2-yl)methyl!amino!ethyl guanidine is excluded. Pharmaceuticals which are useful as vasoconstrictors. Compositions comprising said guanidine derivatives as active ingredients, processes for preparing said guanidine derivatives and novel N-cyano guanidine, intermediates; and a use as a medicine are described.

  本发明涉及具有以下结构式的血管收缩剂\ x9b（苯并二氧杂环，苯并呋喃或苯并吡喃）烷基氨基烷基取代的胍类化合物：## STR1 ##其药学上可接受的酸加成盐，立体化学异构体形式，其中X为O，CH.sub.2或直接键；R.sup.1为氢或C.sub.1-6烷基；R.sup.2为氢，C.sub.1-6烷基，C.sub.3-6烯基或C.sub.3-6炔基；R.sup.3为氢或C.sub.1-6烷基；或R.sup.2和R.sup.3可以结合成为式--（CH.sub.2）.sub.m--的二价基团，其中m为4或5；或R.sup.1和R.sup.2结合可以形成式--CH.dbd.CH--或式--（CH.sub.2）.sub.n--的二价基团，其中n为2，3或4；或当R.sup.1和R.sup.2结合形成式--CH.dbd.CH--CH.dbd.，--CH.dbd.CH--N.dbd.或--CH.dbd.N--CH.dbd.的二价基团时，R.sup.3可以代表一个键；R.sup.4为氢或C.sub.1-6烷基；Alk.sup.1为二价C.sub.1-3烷基二基基团；A为以下结构式的二价基团：## STR2 ##其中每个R.sup.5为氢或C.sub.1-4烷基；每个R.sup.6为氢或C.sub.1-4烷基；Alk.sup.2为C.sub.2-15烷基二基基团或C.sub.5-7环烷基二基基团；每个p为0，1或2；但排除\x9b2-\x9b（2,3-二氢-1,4-苯并二氧杂环-2-基）甲基！氨基！乙基胍。本发明还描述了作为血管收缩剂有用的药物，包括上述胍衍生物作为活性成分的组合物，制备上述胍衍生物的过程和新的N-氰基胍，以及用作药物的用途。
• \x9b(benzodioxan, benzofuran or benzopyran) alkylamino! alkyl substituted
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US05703115A1

  公开（公告）日：1997-12-30

  The present invention is concerned with vasoconstricive \x9bbenzodioxan, benzofuran or benzopyran)alkylamino!alkyl substituted guanidines having the formula ##STR1## the pharmaceutically acceptable acid addition salts thereof, and the stereochemically isomeric forms thereof, wherein X is O, CH.sub.2 or a direct bond; R.sup.1 is hydrogen or C.sub.1-6 alkyl; R.sup.2 is hydrogen, C.sub.1-6 alkyl, C.sub.3-6 alkenyl or C.sub.3-6 alkynyl; R.sup.3 is hydrogen or C.sub.1-6 alkyl; or R.sup.2 and R.sup.3 may be taken together to form a bivalent radical of formula --(CH.sub.2).sub.m --, wherein m is 4 or 5; or R.sup.1 and R.sup.2 taken together may form a bivalent radical of formula --CH.dbd.CH-- or of formula --(CH.sub.2).sub.n --, wherein n is 2, 3 or 4; or R.sup.3 may represent a bond when R.sup.1 and R.sup.2 taken together form a bivalent radical of formula --CH.dbd.CH--CH.dbd., --CH.dbd.CH--N.dbd., or --CH.dbd.N--CH.dbd.; R.sup.4 is hydrogen or C.sub.1-6 alkyl; Alk.sup.1 is a bivalent C.sub.1-3 alkanediyl radical; A is a bivalent radical of formula: ##STR2## wherein each R.sup.5 is hydrogen or C.sub.1-4 alkyl; wherein each R.sup.6 is hydrogen or C.sub.1-4 alkyl; Alk.sup.2 is C.sub.2-15 alkanediyl or C.sub.5-7 cycloalkanediyl; and each p is 0, 1 or 2; provided that \x9b2-\x9b(2,3-dihydro-1,4-benzodioxin-2-yl)methyl!amino!ethyl guanidine is excluded. Pharmaceuticals which are useful as vasoconstrictors. Compositions comprising said guanidine derivatives as active ingredients, processes for preparing said guanidine derivatives and novel N-cyano guanidine, intermediates; and a use as a medicine are described.

  本发明涉及一种血管收缩剂，其为具有以下式子的\ x9bbenzodioxan，benzofuran或benzopyran）alkylamino！alkyl取代的胍类：##STR1##其中X为O，CH.sub.2或直接键；R.sup.1为氢或C.sub.1-6烷基；R.sup.2为氢，C.sub.1-6烷基，C.sub.3-6烯基或C.sub.3-6炔基；R.sup.3为氢或C.sub.1-6烷基；或R.sup.2和R.sup.3可以结合成为式子--（CH.sub.2）.sub.m--的双价基团，其中m为4或5；或R.sup.1和R.sup.2结合可以形成式子--CH.dbd.CH-或式子--（CH.sub.2）.sub.n--的双价基团，其中n为2、3或4；或当R.sup.1和R.sup.2结合形成式子--CH.dbd.CH--CH.dbd.，--CH.dbd.CH--N.dbd.或--CH.dbd.N--CH.dbd.时，R.sup.3可以代表键；R.sup.4为氢或C.sub.1-6烷基；Alk.sup.1为双价的C.sub.1-3烷二基基团；A为式子的双价基团：##STR2##其中每个R.sup.5为氢或C.sub.1-4烷基；每个R.sup.6为氢或C.sub.1-4烷基；Alk.sup.2为C.sub.2-15烷二基或C.sub.5-7环烷二基；每个p为0、1或2；但排除\x9b2-\x9b（2,3-二氢-1,4-苯并二氧杂环己烷-2-基）甲基！氨基！乙基胍。本发明还涉及作为血管收缩剂有用的药物、包含所述胍衍生物作为活性成分的组合物、制备所述胍衍生物的方法和新的N-氰基胍中间体以及作为药物的用途。
• AMINOALKYL SUBSTITUTED (BENZODIOXAN, BENZOFURAN OR BENZOPYRAN) DERIVATIVES
  申请人：Janssen Pharmaceutica N.V.

  公开号：EP1187829B1

  公开（公告）日：2003-12-10