公开(公告)号：US3868357A

公开(公告)日：1975-02-25

申请号：US22106072

申请日：1972-01-26

Applicant: NAT RES DEV

Inventor： SMYTH DEREK GEORGE ,  KO ARTHUR SAI CHUN

IPC: A61K38/00 ,  C07K14/62 ,  C07K14/625 ,  C07C103/52 ,  A61K17/02 ,  C07G7/00

CPC classification number: C07K14/62 ,  A61K38/00 ,  C07K14/625

Abstract: Insulin derivatives which are water soluble, readily isolated, immunologically acceptable and which retain hypoglycaemic activity are those in which at least one of the A1, B1 and B29 aminoacid amino groups is converted into a blocked amino group having a substituent capable of forming an anion, e.g., by substitution with dicarboxylic acid radicals.

Abstract translation: 水溶性，易分离，免疫学可接受且保持低血糖活性的胰岛素衍生物是其中A1，B1和B29氨基酸氨基中的至少一个转化为具有能够形成阴离子的取代基的封闭氨基的那些， 例如，用二羧酸基取代。

公开(公告)号：US3864325A

公开(公告)日：1975-02-04

申请号：US30636972

申请日：1972-11-13

Applicant: NAT RES DEV

Inventor： SMYTH DEREK GEORGE

IPC: A61K38/00 ,  C07K14/62 ,  C07C103/52 ,  A61K17/02 ,  C07G7/00

CPC classification number: C07K14/62 ,  A61K38/00

Abstract: Insulin derivatives which have an improved profile of hypoglycaemic activity, or which are intermediates for the production of such derivatives, are those in which at least one of the A1(glycine, B1(phenylalanine) and B29 (lysine) amino acid units is blocked by a carbamyl group or a substituted carbamyl group R1R2NCO- wherein R1 and R2 can be hydrogen, alkyl, aryl or other radicals. Masking of the initial activity is achieved by blocking tryosine hydroxyl groups with substituents which are releasable in vivo. N, N'', N''''- tricarbamyl and -triethylcarbamyl insulin, and Osubstituted derivatives thereof are typical compounds of the invention.

Abstract translation: 具有改善的降血糖活性概况或作为制备这种衍生物的中间体的胰岛素衍生物是其中A1（甘氨酸，B1（苯丙氨酸）和B29（赖氨酸）氨基酸单元）中的至少一种被 氨基甲酰基或取代的氨基甲酰基R 1 R 2 NCO-，其中R 1和R 2可以是氢，烷基，芳基或其它基团。

公开(公告)号：US3868356A

公开(公告)日：1975-02-25

申请号：US22105972

申请日：1972-01-26

Applicant: NAT RES DEV

Inventor： SMYTH DEREK GEORGE

IPC: A61K38/00 ,  C07K14/62 ,  C07K14/625 ,  C07C103/52 ,  A61K17/04 ,  C07G7/00

CPC classification number: C07K14/625 ,  A61K38/00 ,  C07K14/62

Abstract: Insulin derivatives which are water soluble, readily isolated, immunologically acceptable and which retain hypolgycaemic activity are those in which at least one of the A1, B1 and B29 aminoacid amino groups is converted into a blocked amino group having a substituent capable of forming an anion e.g. by substitution with dicarboxylic acid radicals. An additional refinement comprises blocking tyrosine hydroxyl groups with substituents which are releasable in vivo thereby achieving latent activity which is revealed progressively in order to provide prolonged action.

Abstract translation: 水溶性，易分离，免疫学可接受并且保留低胆固醇活性的胰岛素衍生物是其中A1，B1和B29氨基酸氨基中的至少一个转化为具有能够形成阴离子的取代基的封闭氨基的那些。 通过二羧酸基取代。 另外的改进包括用具有在体内可释放的取代基封闭酪氨酸羟基，从而实现逐渐显露以提供延长作用的潜在活性。