公开(公告)号：US4672067A

公开(公告)日：1987-06-09

申请号：US625648

申请日：1984-06-28

申请人： Ian H. Coates ,  Keith Mills ,  Colin F. Webb ,  Michael D. Dowle ,  David E. Bays

发明人： Ian H. Coates ,  Keith Mills ,  Colin F. Webb ,  Michael D. Dowle ,  David E. Bays

IPC分类号： C07D209/14 ,  A61K31/40 ,  A61K31/403 ,  A61K31/4035 ,  A61K31/404 ,  A61P9/00 ,  A61P25/04 ,  C07D209/16 ,  C07D209/48 ,  C07D471/04

CPC分类号： C07D209/16

摘要： Compounds are disclosed of formula (I) ##STR1## wherein R.sub.1 represents CHO, COR.sub.8, CO.sub.2 R.sub.8, CONR.sub.9 R.sub.10, CSNR.sub.9 R.sub.10 or SO.sub.2 NR.sub.9 R.sub.10, whereR.sub.8 represents alkyl, cycloalkyl, aryl or aralkyl,R.sub.9 represents hydrogen or alkyl, andR.sub.10 represents hydrogen or alkyl, cycloalkyl, aryl or aralkyl;R.sub.2, R.sub.3, R.sub.4, R.sub.6 and R.sub.7 each independently represents hydrogen or C.sub.1-3 alkyl;R.sub.5 represents hydrogen, or alkyl, cycloalkyl, alkenyl or aralkyl, orR.sub.4 and R.sub.5 together form an aralkylidene group or R.sub.4 and R.sub.5 together with the attached nitrogen atom form a saturated monocyclic 5- to 7-membered ring; andAlk represents C.sub.2-3 alkylene chain optionally substituted by not more than two C.sub.1-3 alkyl groups;and physiologically acceptable salts and solvates thereof. The compounds are potentially useful for the treatment of migraine and may be formulated as pharmaceutical compositions in conventional manner using pharmaceutically acceptable carriers or excipients. The compounds may be prepared by, for example, reaction of an aminoalkyl indole with an acid of formula R.sub.1 OH or an acylating agent corresponding thereto or with an inorganic cyanate or an organic isocyanate or isothiocyanate in order to introduce the desired R.sub.1 group at the 5-position on the indole nucleus.

摘要翻译： 公开了式（I）的化合物其中R 1表示CHO，COR8，CO 2 R 8，CONR 9 R 10，CSNR 9 R 10或SO 2 NR 9 R 10，其中R 8表示烷基，环烷基，芳基或芳烷基，R 9表示氢或烷基，R 10表示氢 或烷基，环烷基，芳基或芳烷基; R2，R3，R4，R6和R7各自独立地表示氢或C1-3烷基; R5表示氢或烷基，环烷基，烯基或芳烷基，或R4和R5一起形成芳烷叉基或R4和R5与连接的氮原子一起形成饱和的单环5-至7-元环; 并且Alk表示任选被不多于两个C 1-3烷基取代的C 2-3亚烷基链; 及其生理上可接受的盐和溶剂合物。 这些化合物潜在地可用于治疗偏头痛，并且可以使用药学上可接受的载体或赋形剂以常规方式配制成药物组合物。 化合物可以通过例如氨基烷基吲哚与式R1OH的酸或对应于其的酰化剂或与无机氰酸酯或有机异氰酸酯或异硫氰酸酯反应制备，以便在5- 在吲哚核上的位置。

公开(公告)号：US4636521A

公开(公告)日：1987-01-13

申请号：US626383

申请日：1984-06-29

申请人： Ian H. Coates ,  Keith Mills ,  Colin F. Webb ,  Michael D. Dowle ,  David E. Bays

发明人： Ian H. Coates ,  Keith Mills ,  Colin F. Webb ,  Michael D. Dowle ,  David E. Bays

IPC分类号： C07D209/14 ,  A61K31/40 ,  A61K31/403 ,  A61K31/4035 ,  A61K31/404 ,  A61P9/00 ,  A61P25/04 ,  C07D209/16 ,  C07D209/48 ,  C07D471/04

CPC分类号： C07D209/16

摘要： Compounds are disclosed of general formula (I) ##STR1## wherein R.sub.1 represents an alkyl, cycloalkyl, aryl or aralkyl group;R.sub.2, R.sub.3, R.sub.4, R.sub.6 and R.sub.7, which may be the same or different, each represents a hydrogen atom or a C.sub.1-3 alkyl group;R.sub.5 represents a hydrogen atom or an alkyl, cycloalkyl, alkenyl or an aralkyl group; or R.sub.4 and R.sub.5 together form an aralkylidene group or R.sub.4 and R.sub.5 together with the nitrogen atom to which they are attached form a saturated monocyclic 5- to 7-membered ring; Alk represents an alkylene chain containing two or three carbon atoms which may be unsubstituted or substituted by not more than two C.sub.1-3 alkyl groups; and physiologically acceptable salts, solvates and bioprecursors thereof. The compounds are described as potentially useful for the treatment of migraine and may be formulated as pharmaceutical compositions in conventional manner using one or more pharmaceutically acceptable carriers or excipients. Various processes for the preparation of the compounds are disclosed including, for example, a process involving reaction of an aminoalkyl indole with a sulphonylating agent in order to introduce the --SO.sub.2 -- group at the 5-position on the indole nucleus.

摘要翻译： 公开了通式（I）的化合物其中R 1表示烷基，环烷基，芳基或芳烷基; R 2，R 3，R 4，R 6和R 7可以相同或不同，各自表示氢原子或C 1-3烷基; R5表示氢原子或烷基，环烷基，烯基或芳烷基; 或R 4和R 5一起形成亚烷基或R 4和R 5与它们所连接的氮原子一起形成饱和的单环5-至7-元环; Alk表示含有两个或三个碳原子的亚烷基链，其可以是未取代的或被不多于两个C 1-3烷基取代; 和其生理上可接受的盐，溶剂化物和生物前体。 这些化合物被描述为潜在地可用于治疗偏头痛，并且可以使用一种或多种药学上可接受的载体或赋形剂以常规方式配制成药物组合物。 公开了制备化合物的各种方法，包括例如涉及氨基烷基吲哚与磺酰化剂反应的方法，以便在吲哚核上的5-位引入-SO 2 - 基团。

公开(公告)号：US4650810A

公开(公告)日：1987-03-17

申请号：US461233

申请日：1983-01-26

申请人： David E. Bays ,  Colin F. Webb ,  Michael D. Dowle

发明人： David E. Bays ,  Colin F. Webb ,  Michael D. Dowle

IPC分类号： C07D209/14 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61P9/00 ,  A61P25/04 ,  C07D209/16 ,  C07D209/18 ,  C07D209/48 ,  C07D401/06 ,  C07D403/06

CPC分类号： C07D209/48 ,  C07C243/00 ,  C07C251/72 ,  C07C255/00 ,  C07D209/16 ,  C07D209/18

摘要： Compounds are disclosed of general formula (I): ##STR1## wherein R.sub.1, R.sub.3, R.sub.4, R.sub.6 and R.sub.7, which may be the same or different, each represents a hydrogen atom or an alkyl group;R.sub.2 represents a hydrogen atom or an alkyl, aryl, aralkyl, cycloalkyl or alkenyl group;or R.sub.1 and R.sub.2, together with the nitrogen atom to which they are attached, form a saturated monocyclic 5 to 7-membered ring which may optionally contain a further hetero function;R.sub.5 represents a hydrogen atom or an alkyl or alkenyl group;or R.sub.4 and R.sub.5 together form an aralkylidene group;Alk represents an alkylene chain containing two or three carbon atoms which may be unsubstituted or substituted by not more than two C.sub.1-3 alkyl groups; andX represents an oxygen or sulphur atom; and physiologically acceptable salts, solvates and bioprecursors thereof. The compounds are described as potentially useful for the treatment of migraine and may be formulated as pharmaceutical compositions in conventional manner using one or more pharmaceutically acceptable carriers or excipients. Various processes for the preparation of the compounds are disclosed including, for example, a process involving reacting an indole having an appropriate nitrile group at the 5-position, with a suitable oxygen- or sulphur-containing compound in order to introduce the required amide or thioamide group at the 5-position on the indole nucleus.

摘要翻译： 公开了通式（I）的化合物：其中R 1，R 3，R 4，R 6和R 7可以相同或不同，各自表示氢原子或烷基; R 2表示氢原子或烷基，芳基，芳烷基，环烷基或烯基; 或R 1和R 2与它们所连接的氮原子一起形成饱和的单环5至7元环，其可任选地含有另外的杂官能; R5表示氢原子或烷基或烯基; 或R4和R5一起形成亚烷基; Alk表示含有两个或三个碳原子的亚烷基链，其可以是未取代的或被不多于两个C 1-3烷基取代; X表示氧或硫原子; 和其生理上可接受的盐，溶剂化物和生物前体。 这些化合物被描述为潜在地可用于治疗偏头痛，并且可以使用一种或多种药学上可接受的载体或赋形剂以常规方式配制成药物组合物。 公开了用于制备化合物的各种方法，包括例如涉及将5-位上具有适当腈基的吲哚与合适的含氧或含硫化合物反应以引入所需酰胺或 硫代酰胺基团在吲哚核上的5位。

公开(公告)号：US4876267A

公开(公告)日：1989-10-24

申请号：US66498

申请日：1987-06-26

申请人： Darko Butina ,  Michael D. Dowle ,  David E. Bays ,  Colin F. Webb

发明人： Darko Butina ,  Michael D. Dowle ,  David E. Bays ,  Colin F. Webb

IPC分类号： A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61P25/04 ,  A61P25/06 ,  C07D209/16

CPC分类号： C07D209/16

摘要： Indole derivatives are disclosed of the formula (I): ##STR1## wherein R.sub.1 represents H, or C.sub.1-6 alkyl or C.sub.3-6 Alkenyl;R.sub.2 represents a H, C.sub.1-3 alkyl, C.sub.3-6 alkenyl or C.sub.5-7 cycloalkyl, or a phenyl or phen(C.sub.1-4)alkyl group in which the phenyl ring is optionally substituted by halogen or C.sub.1-3 alkyl, C.sub.1-3 alkoxy or hydroxyl, or by a group NR.sup.a R.sup.b, or CONR.sup.a R.sup.b, wherein R.sup.a and R.sup.b each independently represents H or C.sub.1-3 alkyl;R.sub.3 and R.sub.4, each independently represents H or C.sub.1-3 alkyl or 2-propenyl;and physiologically acceptable salts and solvates (e.g. hydrates) thereof.The compounds have potent and selective vasoconstrictor activity and are indicated as useful for the treatment of migraine. The compounds may be formulated as pharmaceutical compositions with pharmaceutically acceptable carriers or excipients for administration by any suitable means. Various methods for the preparation of the compounds are disclosed.

摘要翻译： 公开了式（I）的吲哚衍生物：其中R 1表示H或C 1-6烷基或C 3-6烯基的（I） R 2表示H，C 1-3烷基，C 3-6烯基或C 5-7环烷​​基，或苯基或苯基（C 1-4）烷基，其中苯环任选被卤素或C 1-3烷基取代，C1- 3烷氧基或羟基，或NRaRb或CONRaRb基团，其中Ra和Rb各自独立地表示H或C1-3烷基; R 3和R 4各自独立地表示H或C 1-3烷基或2-丙烯基; 和其生理上可接受的盐和溶剂合物（例如水合物）。 这些化合物具有有效和选择性的血管收缩剂活性，并被用于治疗偏头痛。 这些化合物可以配制成具有药学上可接受的载体或赋形剂的药物组合物，用于通过任何合适的方式给药。 公开了制备化合物的各种方法。

公开(公告)号：US4870096A

公开(公告)日：1989-09-26

申请号：US940652

申请日：1986-12-11

申请人： Alexander W. Oxford ,  Ian H. Coates ,  David E. Bays ,  Colin F. Webb

发明人： Alexander W. Oxford ,  Ian H. Coates ,  David E. Bays ,  Colin F. Webb

IPC分类号： A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61P9/00 ,  A61P25/04 ,  C07D209/16

CPC分类号： C07D209/16

摘要： Indoles are disclosed of formula (I): ##STR1## wherein R.sub.1 represents R.sub.5 R.sub.6 NCOCH.sub.2 --, R.sub.5 CONH(CH.sub.2).sub.p --,R.sub.5 R.sub.6 NSO.sub.2 (CH.sub.2).sub.p -- or R.sub.7 SO.sub.2 NH(CH.sub.2).sub.p --, (where R.sub.5 and R.sub.6 each represents a hydrogen atom or a C.sub.1-3 alkyl group, R.sub.7 represents C.sub.1-3 alkyl and p is zero or one),R.sub.2 is hydrogen or C.sub.1-3 alkyl;R.sub.3 and R.sub.4 each represents hydrogen atom, C.sub.1-3 alkyl, or 2-propenyl;m is zero or an integer from 1 to 4; andn is an integer from 2 to 5; and physiologically acceptable salts and solvates (e.g. hydrates) thereof.The compounds have potent and selective vasoconstrictor activity and are indicated as useful for the treatment of migraine. They may be formulated as pharmaceutical compositions with pharmaceutically acceptable carriers of excipients for administration by any convenient route.Various methods for the preparation of the compounds (I) are disclosed.

摘要翻译： 公开了式（I）的吲哚：其中R1表示R5R6NCOCH2-，R5CONH（CH2）p-，R5R6NSO2（CH2）p-或R7SO2NH（CH2）p-，（其中R5和R6各自表示 氢原子或C 1-3烷基，R 7表示C 1-3烷基，p为0或1），R 2为氢或C 1-3烷基; R3和R4各自表示氢原子，C1-3烷基或2-丙烯基; m为0或1至4的整数; n为2〜5的整数。 和其生理上可接受的盐和溶剂合物（例如水合物）。 这些化合物具有有效和选择性的血管收缩剂活性，并被用于治疗偏头痛。 它们可以配制成具有药学上可接受的赋形剂载体的药物组合物，用于通过任何方便的途径给药。 公开了制备化合物（I）的各种方法。

公开(公告)号：US4855314A

公开(公告)日：1989-08-08

申请号：US1469

申请日：1987-01-08

申请人： Alexander W. Oxford ,  Ian H. Coates ,  David E. Bays ,  Colin F. Webb ,  Michael D. Dowle ,  Keith Mills ,  Colin D. Eldred

发明人： Alexander W. Oxford ,  Ian H. Coates ,  David E. Bays ,  Colin F. Webb ,  Michael D. Dowle ,  Keith Mills ,  Colin D. Eldred

IPC分类号： C07D209/14 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/405 ,  A61P9/00 ,  A61P25/04 ,  C07D209/16

CPC分类号： C07D209/16

摘要： Compounds are disclosed of formula (I): ##STR1## wherein R.sub.1 is halogen, a C.sub.1-3 alkoxy, R.sub.6 R.sub.7 NCO(CH.sub.2).sub.p --, R.sub.6 CONH(CH.sub.2).sub.p --, R.sub.6 R.sub.7 NSO.sub.2 (CH.sub.2).sub.p --, or R.sub.8 SO.sub.2 NH(CH.sub.2).sub.p -- (where R.sub.6 and R.sub.7 each represents hydrogen or C.sub.1-3 alkyl, R.sub.8 represents C.sub.1-3 alkyl and p is zero or 1);R.sub.2 represents hydrogen or C.sub.1-3 alkyl; R.sub.3 represents hydrogen or C.sub.1-3 alkyl;R.sub.4 and R.sub.5 each represents hydrogen, C.sub.1-3 alkyl or 2-propenyl;A represents --CO-- or --SO.sub.2 --;n represents an integer from 2 to 5; and m represents zero or an integer from 1 to 4; and physiologically acceptable salts and solvates (e.g. hydrates) thereof.The compounds have potent and selective vasoconstrictor activity and are indicated as useful for the treatment of migraine. The compounds may be formulated as pharmaceutical compositions with physiologically acceptable carriers or excipients for administration by any convenient route. Various methods for the preparation of the compounds (I) are disclosed.

公开(公告)号：US4252803A

公开(公告)日：1981-02-24

申请号：US83343

申请日：1979-10-10

申请人： Colin F. Webb

发明人： Colin F. Webb

IPC分类号： A61K31/40 ,  A61K31/403 ,  A61K31/4035 ,  A61K31/404 ,  A61K31/405 ,  A61K31/495 ,  A61K31/535 ,  A61P9/00 ,  A61P9/12 ,  A61P25/04 ,  C07D209/10 ,  C07D209/14 ,  C07D209/16 ,  C07D209/48 ,  C07D471/04 ,  C07D209/20 ,  C07D413/06

CPC分类号： C07D209/48 ,  C07D209/10 ,  C07D209/14 ,  C07D209/16

摘要： Compounds are disclosed of general formula (I): ##STR1## wherein R.sub.1 and R.sub.2 each independently represents a hydrogen atom, or an aryl, aralkyl, cycloalkyl, fluoroalkyl or alkyl group, which alkyl group is optionally substituted by an alkenyl group or by a group -OR.sub.7 or by ##STR2## where R.sub.7 and R.sub.8 each independently represents a hydrogen atom, an alkyl, aryl or aralkyl group; or R.sub.1 and R.sub.2 together with the nitrogen atom to which they are attached form a saturated monocyclic 5 to 7 membered ring which may contain a further hetero function (viz--O--, --NH or ##STR3## R.sub.3 and R.sub.4 have the same meanings as R.sub.1 and R.sub.2 and may together form an aralkylidene group;R.sub.5 represents a hydrogen atom or an alkyl or aralkyl group;R.sub.6 represents a hydrogen atom or an aryl or C.sub.1 -C.sub.3 alkyl group;Alk represents an C.sub.1 -C.sub.4 alkylene group optionally substituted at one or more of its carbon atoms by one to three C.sub.1 -C.sub.3 alkyl groups; andX represents an oxygen or sulphur atom,and its physiologically acceptable salts, hydrates and bioprecursors.The indoles (I) may be prepared by combinations of reactions to introduce the desired substituents into suitable intermediates either before or after cyclization to form the indole nucleus. The compounds have selective actions on blood vessels and, in particular exhibit antihypertensive properties. They may be formulated in conventional manner as pharmaceutical compositions.

摘要翻译： 公开了通式（I）的化合物：其中R 1和R 2各自独立地表示氢原子，或芳基，芳烷基，环烷基，氟烷基或烷基，该烷基任选被烯基取代 或者由基团-OR7或通过，其中R 7和R 8各自独立地表示氢原子，烷基，芳基或芳烷基; 或R 1和R 2与它们所连接的氮原子一起形成饱和的单环5至7元环，其可以含有另外的杂官能（viz-O-，-NH或R 3和R 4具有相同的含义 R1和R2可以一起形成亚烷基; R 5表示氢原子或烷基或芳烷基; R 6表示氢原子或芳基或C 1 -C 3烷基; Alk表示任选地被一个取代的C 1 -C 4亚烷基 或更多的碳原子被一至三个C 1 -C 3烷基取代; X代表氧或硫原子，以及其生理上可接受的盐，水合物和生物前体。吲哚（I）可以通过反应的组合制备，以引入 所需的取代基在环化之前或之后形成合适的中间体以形成吲哚核。化合物对血管具有选择性作用，特别是表现出抗高血压性质，它们可以以常规方式配制成p 药物组合物。

公开(公告)号：US4839377A

公开(公告)日：1989-06-13

申请号：US82132

申请日：1987-08-06

申请人： David E. Bays ,  Colin F. Webb ,  Michael D. Dowle

发明人： David E. Bays ,  Colin F. Webb ,  Michael D. Dowle

IPC分类号： A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61P9/00 ,  A61P25/04 ,  C07D209/14 ,  C07D209/16 ,  C07D209/18 ,  C07D209/48

CPC分类号： C07D209/48 ,  C07D209/14 ,  C07D209/16 ,  C07D209/18

摘要： Compounds are disclosed of general formula (I) ##STR1## wherein R.sub.1 represents a group CHO, COR.sub.8, CO.sub.2 R.sub.8, CONR.sub.9 R.sub.10, CSNR.sub.9 R.sub.10 or SO.sub.2 NR.sub.9 R.sub.10,where R.sub.8 represents an alkyl, cycloalkyl, aryl or aralkyl group,R.sub.9 represents a hydrogen atom or an alkyl group, andR.sub.10 represents a hydrogen atom or an alkyl, cyclo-alkyl, aryl or aralkyl group;R.sub.2, R.sub.3, R.sub.4, R.sub.6 and R.sub.7, which may be the same or different, each represents a hydrogen atom or a C.sub.1-3 alkyl group;R.sub.5 represents a hydrogen atom or an alkyl, cycloalkyl, alkenyl or an aralkyl group orR.sub.4 and R.sub.5 together form an aralkylidene group orR.sub.4 and R.sub.5 together with the nitrogen atom to which they are attached form a saturated monocyclic 5- to 7-membered ring; andAlk represents an alkylene chain containing two or three carbon atoms which may be unsubstituted or substituted by not more than two C.sub.1-3 alkyl groups;with the provisos that when R.sub.4 and R.sub.5 both represent alkyl groups R.sub.1 does not represent the group CHO or COR.sub.8 and that when R.sub.4, R.sub.5, R.sub.6 and R.sub.7 all represent hydrogen R.sub.1 does not represent the group SO.sub.2 NH.sub.2 ;and physiologically acceptable salts, solvates and bioprecursors thereof. The components are described as potentially useful for the treatment of migraine and may be formulated as pharmaceutical compositions in convention manner using one or more pharmaceutically acceptable carriers or excipients. Various processes for the preparation of the compounds are disclosed including, for example, reaction of an aminoalkyl indole with an acid of formula R.sub.1 OH or an acylating agent corresponding thereto or with an inorganic cyanate or an organic isocyanate or isothiocyanate in order to introduce the desired R.sub.1 group at the 5-position on the indole nucleus.

摘要翻译： 公开了通式（I）的化合物其中R 1表示基团CHO，COR 8，CO 2 R 8，CONR 9 R 10，CSNR 9 R 10或SO 2 NR 9 R 10，其中R 8表示烷基，环烷基，芳基或芳烷基，R 9表示氢原子 或烷基，R 10表示氢原子或烷基，环烷基，芳基或芳烷基; R 2，R 3，R 4，R 6和R 7可以相同或不同，各自表示氢原子或C 1-3烷基; R5表示氢原子或烷基，环烷基，烯基或芳烷基或R4和R5一起形成芳烷叉基或R 4和R 5与它们所连接的氮原子一起形成饱和单环5-至7-元环 ; Alk表示可以未被取代或被不多于两个C 1-3烷基取代的含有两个或三个碳原子的亚烷基链; 条件是当R4和R5都表示烷基R1不表示基团CHO或COR8时，当R4，R5，R6和R7均表示氢时，R1不表示SO2NH2基团; 和其生理上可接受的盐，溶剂化物和生物前体。 这些组分被描述为可用于治疗偏头痛，并且可以使用一种或多种药学上可接受的载体或赋形剂以常规方式配制成药物组合物。 公开了制备化合物的各种方法，包括例如氨基烷基吲哚与式R1OH的酸或与其对应的酰化剂或与无机氰酸酯或有机异氰酸酯或异硫氰酸酯反应以引入所需的R 1 组在吲哚核上的5位。