| 摘要 |
<p>1,153,445. D-Ser<SP>1</SP>-Nle<SP>4</SP>-#<SP>1-25</SP>ACTH. SANDOZ Ltd. 4 May, 1966 [24 Aug., 1965], No. 19725/66. Heading C2C. The pentacosapeptide D-Ser-Tyr-Ser-Nle- Glu(OH) - His - Phe - Arg - Try - Gly - Lys- Pro - Val - Gly - Lys - Lys - Arg - Arg - Pro- Val - Lys - Val - Tyr - Pro - Val - (NH 2 ) (also called D-Ser<SP>1</SP>-Nle<SP>4</SP>-pentacosapeptide), its salts and heavy metal complexes is prepared by removing the protecting groups from the compound N - R<SP>1</SP> - D - Ser - Tyr - Ser - Nle - γ- O - R<SP>11</SP> - Glu - Im - R<SP>111</SP> - His - Phe - Arg- (R<SP>1111</SP>) - Try - Gly - # - N - R - Lys - Pro - Val- Gly - # - N - R - Lys - # - N - R - Lys - Arg- (R<SP>1111</SP>) - Arg - (R<SP>1111</SP>) - Pro - Val - # - N - R - Lys- Val-Tyr-Pro-Val-NH 2 , in which R is carbo-t-butoxy or carbo-(-amyloxy, tosyl, phthalyl, formyl, trifluoroacetyl; R<SP>1</SP> is trityl, carbo-t-butoxy, carbo - t - amyloxy, carbobenzoxy, trifluoroacetyl, acetyl, chloroacetyl or formyl; R<SP>11</SP> is t-butoxy, methoxy, ethoxy, t-amyloxy, benzyloxy or amido; R<SP>111</SP> is trityl, carbo-t-butoxy, carbo-t-amyloxy, carbo benzoxy or benzyl; and R<SP>1111</SP> is nitro tosyl, p-nitrocarbobenzoxy, or 2 - (isopropoxycarbonyl) - 3,4,5,6 - tetrachlorobenzoyl or R<SP>1111</SP> signifies that the guanidino group is protonated, in one or more stages in an acid medium and optionally forming the acid addition or metal salt thereof. The following compounds are prepared as starting materials or intermediates by standard methods: CBO-Arg(NO 2 ) - Arg(NO 2 ) - ProOH, H - Arg(NO 2 )Arg(NO 2 ) - ProOH, 3HBr; CBO - Val - Gly - Lys(CTB) - Lys(CTB) - Arg (NO 2 ) - Arg(NO 2 ) - Pro - OH, CBO - Val - Gly- Lys(CTB) - Lys(CTB) - Arg(NO 2 ) - Arg(NO 2 )- Pro - Val - Lys(CTB) - Val - Tyr - Pro - Val- NH 2 and H - Val - Gly - Lys(CTB) - Lys (OTB) - Arg - Arg - Pro - Val - Lys (CTB)- Val - Tyr - Pro - Val - NH 2 , 3 - TosOHTrit- Glu(OtBu) - (Trit) His - Phe - Arg - Try - Gly- Lys (CTB) - Pro - Val - Gly - Lys (CTB)- Lys (CTB) - Arg - Arg - Pro - Val - Lys (CTB)- Val - Tyr - Pro - Val - NH 2 - 3 - Tos - OH, and H - Glu (OtBu) - (Trit) His - Phe - Arg - Try- Gly - Lys (CTB) - Pro - Val - Gly - Lys (CTB)- Lys (CTB) Arg - Arg - Pro - Val - Gly - Lys- (CTB) - Val - Tyr - Pro - ValNH 2 ; CBO - Tyr- Ser - Nle - OMe and H - Tyr - Ser - Nle - OMe, HCl; CTB - D - Ser - OMe, CTB - D - Ser- NHNH 2 , CTB - D - Ser - Tyr - Ser - Nle - OMe and CTB - D - Ser - Tyr - Ser - Nle - NHNH 2 and CTB-D-Ser-Tyr-Ser-Nle-N 3 . Pharmaceutical compositions comprise DSerl-Nle<SP>4</SP>-pentacosapeptide and an acceptable carrier therefor. The compositions which show a high adrenocorticotropic effect are in a form suitable for parenteral administration without antigenic effects.</p> |
