公开(公告)号：US07560454B2

公开(公告)日：2009-07-14

申请号：US11370861

申请日：2006-03-09

申请人： Doreen Mary Ashworth ,  Gary Robert William Pitt ,  Peter Hudson ,  Christopher Martyn Yea ,  Richard Jeremy Franklin

发明人： Doreen Mary Ashworth ,  Gary Robert William Pitt ,  Peter Hudson ,  Christopher Martyn Yea ,  Richard Jeremy Franklin

IPC分类号： A61P13/00 ,  A61K31/55 ,  C07D403/12 ,  C07D495/04 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04

CPC分类号： C07D403/12 ,  C07D413/12 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04

摘要： This invention provides novel compounds according to general formula (1) wherein A is a bicyclic or tricyclic azepine derivative, V1 and V2 are both H, OMe or F, or one of V1 and V2 is Br, Cl, F, OH, OMe, OBn, OPh, O-acyl, N3, NH2, NHBn or NH-acyl and the other is H, or V1 and V2 together are ═O, —O(CH2)pO— or —S(CH2)pS—; W1 is either O or S; X1 and X2 are both H, or together are ═O or ═S; Y is OR5 or NR6R7; R1, R2, R3 and R4 are independently selected from H, lower alkyl, lower alkyloxy, F, Cl and Br; R5 is selected from H and lower alkyl; R6 and R7 are independently selected from H and lower alkyl, or together are —(CH2)n—; n=3, 4, 5, 6; and p is 2 or 3. The compounds are agonists at the vasopressin V2 receptor and are useful as antidiuretics and procoagulants. The invention further comprises pharmaceutical compositions incorporating these vasopressin agonists, which compositions are particularly useful in the treatment of central diabetes insipidus, nocturnal enuresis and nocturia.

摘要翻译： 本发明提供根据通式（1）的新化合物，其中A为双环或三环吖庚因衍生物，V1和V2均为H，OMe或F，或V1和V2中的一个为Br，Cl，F，OH，OMe， OBn，OPh，O-酰基，N3，NH2，NHBn或NH-酰基，另一个为H，或V 1和V 2一起为-O，-O（CH 2）p O-或-S（CH 2）p -S-; W1是O或S; X1和X2均为H，或一起为-O或-S; Y为OR5或NR6R7; R 1，R 2，R 3和R 4独立地选自H，低级烷基，低级烷氧基，F，Cl和Br; R5选自H和低级烷基; R6和R7独立地选自H和低级烷基，或一起是 - （CH 2）n - ; n = 3,4,5,6; p是2或3.化合物是加压素V2受体的激动剂，可用作抗利尿剂和促凝剂。 本发明还包括掺入这些加压素激动剂的药物组合物，该组合物特别可用于治疗中枢性尿崩症，夜间遗尿和夜尿症。

公开(公告)号：US20080261951A1

公开(公告)日：2008-10-23

申请号：US12213651

申请日：2008-06-23

申请人： Doreen Mary Ashworth ,  Gary Robert William Pitt ,  Peter Hudson ,  Christopher Martyn Yea ,  Richard Jeremy Franklin

发明人： Doreen Mary Ashworth ,  Gary Robert William Pitt ,  Peter Hudson ,  Christopher Martyn Yea ,  Richard Jeremy Franklin

IPC分类号： C07D403/12 ,  C07D495/04 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04 ,  A61K31/55 ,  A61K31/551 ,  A61K31/553 ,  A61P13/00

CPC分类号： C07D403/12 ,  C07D413/12 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04

摘要： This invention provides novel compounds according to general formula (1) wherein A is a bicyclic or tricyclic azepine derivative, V1 and V2 are both H, OMe or F, or one of V1 and V2 is Br, Cl, F, OH, OMe, OBn, OPh, O-acyl, N3, NH2, NHBn or NH-acyl and the other is H, or V1 and V2 together are ═O, —O(CH2)pO— or —S(CH2)S—; W1 is either O or S; X1 and X2 are both H, or together are ═O or ═S; Y is OR5 or NR6R7; R1, R2, R3 and R4 are independently selected from H, lower alkyl, lower alkyloxy, F, Cl and Br; R5 is selected from H and lower alkyl; R6 and R7 are independently selected from H and lower alkyl, or together are —(CH2)n—; n=3, 4, 5, 6; and p is 2 or 3. The compounds are agonists at the vasopressin V2 receptor and are useful as antidiuretics and procoagulants. The invention further comprises pharmaceutical compositions incorporating these vasopressin agonists, which compositions are particularly useful in the treatment of central diabetes insipidus, nocturnal enuresis and nocturia.

摘要翻译： 本发明提供了根据通式（1）的新化合物，其中A是双环或三环吖庚因衍生物，V 1和V 2均为H，OMe或F，或 V 1和V 2之一是Br，Cl，F，OH，OMe，OBn，OPh，O-酰基，N 3， NH 2，NHBn或NH-酰基，另一个是H，或V 1和V 2一起是-O，-O（CH O-或-S（CH 2 CH 2）S - ; O 1或O 2是O或S; X 1和X 2均为H或一起为-O或-S; Y是OR 5或NR 6 R 7; R 1，R 2，R 3和R 4独立地选自H，低级烷基，低级烷氧基 ，F，Cl和Br; R 5选自H和低级烷基; R 6和R 7独立地选自H和低级烷基，或者一起是 - （CH 2）n - ; n = 3,4,5,6; p是2或3.化合物是加压素V2受体的激动剂，可用作抗利尿剂和促凝剂。 本发明还包括掺入这些加压素激动剂的药物组合物，该组合物特别可用于治疗中枢性尿崩症，夜间遗尿和夜尿症。

公开(公告)号：US07074781B2

公开(公告)日：2006-07-11

申请号：US10130749

申请日：2001-01-04

申请人： Doreen Mary Ashworth ,  Gary Robert William Pitt ,  Peter Hudson ,  Christopher Martyn Yea ,  Richard Jeremy Franklin

发明人： Doreen Mary Ashworth ,  Gary Robert William Pitt ,  Peter Hudson ,  Christopher Martyn Yea ,  Richard Jeremy Franklin

IPC分类号： A61P13/00 ,  A61K31/55 ,  C07D403/12 ,  C07D471/04 ,  C07D495/04

CPC分类号： C07D403/12 ,  C07D413/12 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04

摘要： This invention provides novel compounds according to general formula (1) wherein A is a bicyclic or tricyclic azepine derivative, V1 and V2 are both H, OMe or F, or one of V1 and V2 is Br, Cl, F, OH, OMe, OBn, OPh, O-acyl, N3, NH2, NHBn or NH-acyl and the other is H, or V1 and V2 together are ═O, —O(CH2)pO— or —S(CH2)pS—; W1 is either O or S; X1 and X2 are both H, or together are ═O or ═S; Y is OR5 or NR6R7; R1, R2, R3 and R4 are independently selected from H, lower alkyl, lower alkyloxy, F, Cl and Br; R5 is selected from H and lower alkyl; R6 and R7 are independently selected from H and lower alkyl, or together are —(CH2)n—; n=3, 4, 5, 6; and p is 2 or 3. The compounds are agonists at the vasopressin V2 receptor and are useful as antidiuretics and procoagulants. The invention further comprises pharmaceutical compositions incorporating these vasopressin agonists, which compositions are particularly useful in the treatment of central diabetes insipidus, nocturnal enuresis and nocturia.

摘要翻译： 本发明提供了根据通式（1）的新化合物，其中A是双环或三环吖庚因衍生物，V 1和V 2均为H，OMe或F，或 V 1和V 2之一是Br，Cl，F，OH，OMe，OBn，OPh，O-酰基，N 3， NH 2，NHBn或NH-酰基，另一个是H，或V 1和V 2一起是-O，-O（CH O - 或-S（CH 2）n -S-; -S-（CH 2）n - O 1或O 2是O或S; X 1和X 2均为H或一起为-O或-S; Y是OR 5或NR 6 R 7; R 1，R 2，R 3和R 4独立地选自H，低级烷基，低级烷氧基 ，F，Cl和Br; R 5选自H和低级烷基; R 6和R 7独立地选自H和低级烷基，或者一起是 - （CH 2）n - ; n = 3,4,5,6; 并且p是2或3.化合物是加压素V2受体的激动剂，并且可用作抗利尿剂和促凝剂。 本发明还包括掺入这些加压素激动剂的药物组合物，该组合物特别可用于治疗中枢性尿崩症，夜间遗尿和夜尿症。

公开(公告)号：US06664249B1

公开(公告)日：2003-12-16

申请号：US10111007

申请日：2002-06-10

申请人： Doreen Mary Ashworth ,  Gary Robert William Pitt ,  Peter Hudson ,  Christopher Martyn Yea ,  Richard Jeremy Franklin

发明人： Doreen Mary Ashworth ,  Gary Robert William Pitt ,  Peter Hudson ,  Christopher Martyn Yea ,  Richard Jeremy Franklin

IPC分类号： A01N4300

CPC分类号： C07D223/16 ,  C07D495/04

摘要： Compounds according to general formula (1), and pharmaceutically acceptable salts thereof, wherein V is a covalent bond or NH, X is selected from CH2, O and N-alkyl, Z is either S or —CH═CH—, R1 and R2 are independently selected from H, F, Cl, Br and alkyl, R3 is selected from OH, O-alkyl and NR4R5, R4 and R5 are each independently H or alkyl, or together are —(CH2)q—, p is 0, 1, 2, 3 or 4, and q is 4 or 5, are new. They are agonists at the asopressin V2 receptor and are useful as antidiuretics and pro-coagulants.

摘要翻译： 根据通式（1）的化合物及其药学上可接受的盐，其中V是共价键或NH，X选自CH 2，O和N-烷基，Z是S或-CH = CH-，R 1 且R 2独立地选自H，F，Cl，Br和烷基，R 3选自OH，O-烷基和NR 4 R 5，R 4和R 5 各自独立地为H或烷基，或一起为 - （CH 2）q - ，p为0,1,2,3或4，q为4或5，为新的。 它们是加压素V2受体的激动剂，可用作抗利尿剂和促凝血剂。