公开(公告)号：US4013682A

公开(公告)日：1977-03-22

申请号：US689301

申请日：1976-05-24

Applicant: Harm Jan Panneman

Inventor： Harm Jan Panneman

IPC: C07D317/70 ,  C07D317/44

CPC classification number: C07D317/70

Abstract: The invention relates to novel biologically active compounds of the formula I: ##STR1## in which B is a N-hydroxy-amidino group of the general formula: ##STR2## A represents a methylene-, ethylene- or propylene group, optionally substituted with lower alkyl groupsr stands for the number: 0, 1, 2, 3 or 4R.sub.1 is hydroxy, alkyl, alkylthio or alkoxy, halogen (F, Cl, Br or I), trifluoromethyl, nitro, amino or alkylenedioxy (1-4 C),C.sub.n H.sub.2n is an alkylene group with 0-4 carbon atomsR.sub.2 stands for hydrogen, alkyl, aryl or aralkyl,R.sub.3, r.sub.4, r.sub.5 represent hydrogen, alkyl, aralkyl or acyl, andR.sub.6 stands for hydrogen, alkyl, or phenyl or benzyl optionally substituted with methyl groupsAnd pharmaceutically acceptable acid addition salts thereof. The compounds possess anti-hypertensive and vasodilatory activities.

公开(公告)号：US4101675A

公开(公告)日：1978-07-18

申请号：US653318

申请日：1976-01-29

Applicant: Harm Jan Panneman

Inventor： Harm Jan Panneman

IPC: A61K31/155 ,  C07C281/16 ,  C07C129/08

CPC classification number: A61K31/155 ,  C07C281/16

Abstract: The invention relates to compounds of the general formula: ##STR1## in which one double bond is present between the carbon atom of the quanidine moiety and one of the adjacent nitrogen atoms andR.sub.0 stands for hydrogen, halogen, hydroxy, alkoxy or alkyl (1 to 6 C),R.sub.1, r.sub.2 for halogen, hydroxy, alkyl (1 to 4 C) or alkoxy (1 to 4 C),R.sub.3, r.sub.3 ', r.sub.3 " for hydrogen or alkyl (1 to 4 C), on the understanding that one of the substituents R.sub.3, R.sub.3 ' or R.sub.3 " is absent because of the presence of the double bond,R.sub.4 for hydrogen, alkyl (1-4 C), hydroxy, alkoxy (1-4 C) or amino optionally substituted with one or two alkyl (1 to 4 C) groups,R.sub.5, r.sub.6 for hydrogen, alkyl (1-6 C), acyl or R.sub.5 + R.sub.6 together represent an alkylidene, cyclic alkylidene or aralkylidene group, as well as the acid addition salts thereof,Provided that, if R.sub.4 stands for methyl and R.sub.0, R.sub.3, R.sub.3 ", R.sub.5 and R.sub.6 for hydrogen, R.sub.1 and R.sub.2 may not represent methyl simultaneously, having a strong and long-acting anti-hypertensive activity.

Abstract translation: 本发明涉及以下通式的化合物：其中一个双键存在于喹啉部分的碳原子和一个相邻的氮原子之间，R 0代表氢，卤素，羟基，烷氧基或烷基（ 1至6 C），R 1，R 2为卤素，羟基，烷基（1至4 C）或烷氧基（1至4 C），R 3，R 3'，R 3“为氢或烷基（1至4 C） 由于存在双键，取代基R 3，R 3'或R 3“中的一个不存在，其中R 4表示氢，烷基（1-4C），羟基，烷氧基（1-4C）或任选的氨基 被一个或两个烷基（1至4个C）基团取代，R5，R6代表氢，烷基（1-6C），酰基或R5 + R6一起代表亚烷基，环状亚烷基或亚烷基，以及酸加成 其盐，如果R4代表甲基，R 4，R 3，R 3“，R 5和R 6为氢，R 1和R 2可以不同时表示甲基，具有强而长效的抗高血压活性。

公开(公告)号：US3978126A

公开(公告)日：1976-08-31

申请号：US488648

申请日：1974-07-15

Applicant: Harm Jan Panneman

Inventor： Harm Jan Panneman

IPC: C07C67/00 ,  C07C239/00 ,  C07C251/32 ,  C07C257/14 ,  C07C313/00 ,  C07C323/47 ,  C07D317/70 ,  C07F9/165 ,  C07C123/00

CPC classification number: C07D317/70 ,  C07F9/1651

Abstract: The invention relates to novel biologically active compounds of the formula I: ##SPC1##in which B is a N-hydroxy-amidino group of the general formula: ##EQU1## or ##EQU2## A represents a methylene-, ethylene- or propylene group, optionally substituted with lower alkyl groupsR stands for the number: 0, 1, 2, 3 or 4R.sub.1 is hydroxy, alkyl, alkylthio or alkoxy, halogen (F, Cl, Br or I), trifluoromethyl, nitro, amino or alkylenedioxy (1-4 C),C.sub.n H.sub.2n is an alkylene group with 0-4 carbon atomsR.sub.2 stands for hydrogen, alkyl, aryl or aralkyl,R.sub.3, r.sub.4, r.sub.5 represent hydrogen, alkyl, aralkyl or acyl, andR.sub.6 stands for hydrogen, alkyl, or phenyl or benzyl optionally substituted with methyl groupsAnd pharmaceutically acceptable acid addition salts thereof.

公开(公告)号：US4028380A

公开(公告)日：1977-06-07

申请号：US639495

申请日：1975-12-10

Applicant: Harm Jan Panneman ,  Antonius Hermanus Nicolaas Maria Bruins

Inventor： Harm Jan Panneman ,  Antonius Hermanus Nicolaas Maria Bruins

IPC: C07C281/18 ,  C07D233/50

CPC classification number: C07C281/18 ,  Y10S514/822

Abstract: The invention relates to novel amidino-hydrazone derivatives of the general formula: ##STR1## in which the dotted lines mean one extra bond starting from the (guanidine-)carbon atom to one of the adjacent nitrogen atoms, andA stands for methylene, ethylene, propylene or butylene, which groups may optionally be substituted with alkyl (1-4 C),R stands for hydroxy, alkyl (1-4 C), alkylthio or alkoxy (1-4 C), halogen, trifluoromethyl, nitro, amino, hydroxymethyl, acyloxy or an alkylenedioxy group,n is the number 0, 1, 2, 3 or 4,R.sub.1, r.sub.4 and R.sub.5 represent hydrogen or alkyl (1-4 C), with the proviso that one of them is absent in view of the presence of the double bond,R.sub.2 and R.sub.3 stand for hydrogen, alkyl (1-4 C), aralkyl, aryl, hydroxy or amino, with the proviso thatR.sub.2 + r.sub.3 together may also represent a saturated or unsaturated alkylene group with 2 or 3 carbon atoms, orR.sub.3 + r.sub.4 together with the nitrogen atom may also stand for a heterocyclic five- or six-membered ring,As well as the pharmaceutically acceptable acid addition salts thereof, having valuable, antihypertensive and antithrombosis activities.

Abstract translation: 本发明涉及以下通式的新颖的脒基腙衍生物：其中虚线表示从（胍） - 碳原子到相邻的氮原子之一起始的一个额外的键，A代表亚甲基， 乙烯，丙烯或丁烯，这些基团可以任选被烷基（1-4C）取代，R代表羟基，（1-4C）烷基，烷硫基或烷氧基（1-4C），卤素，三氟甲基，硝基， 氨基，羟甲基，酰氧基或亚烷基二氧基，N为0,1,2,3或4，R1，R4和R5代表氢或烷基（1-4C），条件是其中一个不存在于 双键存在的观点，R2和R3代表氢，烷基（1-4C），芳烷基，芳基，羟基或氨基，条件是R2 + R3一起也可以表示饱和或不饱和的亚烷基与 2或3个碳原子，或R3 + R4与氮原子一起也可以代表杂环五元或六元环， 具有可接受的酸补充剂，具有有价值，有抗药性和抗血栓活性。

公开(公告)号：US4076726A

公开(公告)日：1978-02-28

申请号：US579633

申请日：1975-05-21

Applicant: Harm Jan Panneman ,  Antonius Hermanus Nicolaas Maria Bruins

Inventor： Harm Jan Panneman ,  Antonius Hermanus Nicolaas Maria Bruins

IPC: C07C67/00 ,  C07C281/18 ,  C07C313/00 ,  C07C323/44 ,  C07D233/52 ,  C07D239/18 ,  C07C123/00 ,  C07D317/44

CPC classification number: C07C281/18 ,  C07D233/52

Abstract: The invention relates to novel amidino-hydrazone derivatives of the general formula: ##STR1## in which the dotted lines mean one extra bond starting from the (guanidine-) carbon atom to one of the adjacent nitrogen atoms, andA stands for methylene, ethylene, propylene or butylene, which groups may optionally be substituted with alkyl (1-4 C),R stands for hydroxy, alkyl (1-4 C), alkylthio or alkoxy (1-4 C), halogen, trifluoromethyl, nitro, amino, hydroxymethyl, acyloxy or an alkylenedioxy group,N is the number 0, 1, 2, 3 or 4,R.sub.1, r.sub.4 and R.sub.5 represent hydrogen or alkyl (1-4 C), with the proviso that one of them is absent in view of the presence of the double bond,R.sub.2 and R.sub.3 stand for hydrogen, alkyl (1-4 C), aralkyl, aryl, hydroxy or amino, with the proviso thatR.sub.2 + r.sub.3 together may also represent a saturated or unsaturated alkylene group with 2 or 3 carbon atoms, orR.sub.3 + r.sub.4 together with the nitrogen atom may also stand for a heterocyclic five- or six-membered ring,As well as the pharmaceutically acceptable acid addition salts thereof, having valuable, antihypertensive and antithrombosis activities.

Abstract translation: 本发明涉及以下通式的新颖的脒基腙衍生物：其中虚线表示从（胍） - 碳原子到相邻的氮原子之一起始的一个额外的键，A代表亚甲基， 乙烯，丙烯或丁烯，这些基团可以任选被烷基（1-4C）取代，R代表羟基，（1-4C）烷基，烷硫基或烷氧基（1-4C），卤素，三氟甲基，硝基， 氨基，羟甲基，酰氧基或亚烷基二氧基，N为0,1,2,3或4，R1，R4和R5代表氢或烷基（1-4C），条件是其中一个不存在于 双键存在的观点，R2和R3代表氢，烷基（1-4C），芳烷基，芳基，羟基或氨基，条件是R2 + R3一起也可以表示饱和或不饱和的亚烷基与 2或3个碳原子或R3 + R4与氮原子一起也可以代表杂环五元或六元环，就像P 具有良好的可接受的酸添加剂，具有有价值，抗生素和抗凝血活性。

公开(公告)号：US3972932A

公开(公告)日：1976-08-03

申请号：US517554

申请日：1974-10-24

Applicant: Harm Jan Panneman

Inventor： Harm Jan Panneman

IPC: A61K31/155 ,  A61P9/12 ,  C07C67/00 ,  C07C239/00 ,  C07C281/16 ,  C07C281/18 ,  C07C133/10

CPC classification number: A61K31/155 ,  C07C281/16

Abstract: The invention relates to compounds of the general formula: ##EQU1## in which one double bond is present between the carbon atom of the guanidine moiety and one of the adjacent nitrogen atoms andR.sub.0 stands for hydrogen, halogen, hydroxy, alkoxy or alkyl (1 to 6 C),R.sub.1, r.sub.2 for halogen, hydroxy, alkyl (1 to 4 C) or alkoxy (1 to 4 C),R.sub.3, r.sub.3 ', r.sub.3 " for hydrogen or alkyl (1 to 4 C) on the understanding that one of the substituents R.sub.3, R.sub.3 ' or R.sub.3 " is absent because of the presence of the double bond,R.sub.4 for hydrogen, alkyl (1-4 C), hydroxy, alkoxy (1-4 C) or amino optionally substituted with one or two alkyl (1 to 4 C) groups,R.sub.5, r.sub.6 for hydrogen, alkyl (1-6 C), acyl or R.sub.5 + R.sub.6 together represent an alkylidene, cyclic alklidene or aralkylidene group,As well as the acid addition salts thereof, provided that, if R.sub.4 stands for methyl and R.sub.0, R.sub.3, R.sub.3 ", R.sub.5 and R.sub.6 for hydrogen, R.sub.1 and R.sub.2 may not represent methyl simultaneously, having a strong and long-acting anti-hypertensive activity.

Abstract translation: 本发明涉及以下通式的化合物：其中一个双键存在于胍部分的碳原子和相邻的一个之间的一个双键的通式为R'| N-R 4 N ANGLE R 5 | 氮原子，R 0表示氢，卤素，羟基，烷氧基或烷基（1-6），R 1，R 2为卤素，羟基，烷基（1至4 C）或烷氧基（1至4 C），R 3， ，由于存在双键，取代基R 3，R 3'或R 3“中的一个不存在，R 4表示氢，烷基（1-4），R 3表示氢或烷基（1至4 C） 任选被一个或两个烷基（1至4 C）基团取代的羟基，烷氧基（1-4C）或氨基，R5，R6代表氢，烷基（1-6C），酰基或R5 + R6一起代表 亚烷基，环状亚烷基或亚烷基亚烷，作为其酸加成盐，如果R4代表甲基，R0，R3，R3“，R5和R6表示氢，R1和R2可能不同时表示甲基， 有一个强大的和长的交流 抗高血压活动。