| 摘要 |
<p>1,273,873. Octadecapeptides. SHIONOGI & CO. Ltd. 6 March, 1970 [6 March, 1969; 28 May, 1969], No. 10953/70. Heading C2C. Compounds (I): and their non-toxic acid addition salts and complexes with heavy metals, polyamino acids and mixtures thereof, where X is Glu or Gln and Y is ArgOH or ArgNH 2 and derivatives of (I) where the free amino and free carboxylic groups are protected and Y is ArgOH, ArgOHydrocarbyl, ArgNH 2 or ArgNHNH 2 are prepared by linking the amino acids in the indicated order by the step by step elongation method or peptide unit condensation method, especially by reacting a decapeptide R 1 -#-Ala-Tyr-Ser-Met-R 2 - Glu-His-Phe-Arg-Trp-GlyOH with an octapeptide N<SP>#</SP>-R 3 -Lys-Pro-Val-Gly-N<SP>#</SP>-R 3 -Lys-N<SP>#</SP>-R 3 - Lys-Arg-Y where R 1 , R 2 and R 3 are protecting groups, the decapeptide being optionally prepared from the tripeptide H-(NO 2 )Arg-Trp-Gly- OMe through the tetrapeptide-HPhe-(NO 2 )Arg- Trp-GlyOMe, the pentapeptide, H-His-Phe- (NO) 2 Arg-Trp-GlyOH, the hexapeptide HGlu- (OtBu)-His-Phe-Arg-Trp-GlyOH, and finally removing the protecting groups from the octadecapeptide formed. The following starting materials and intermediates are prepared: BOC-#-AlaOH; BOC-#-Ala- TyrOMe; BOC-#-Ala-Tyr-NHNH 2 ; BOC-#-Ala- Tyr - Ser - MetOMe- BOC - # - Ala - Tyr - Ser- Met-NHNH 2 ; H-(NO 2 )-Arg-Trp-GlyOMe and its formate; BOC-Phe-(NO 2 )-Arg-Trp-GlyOMe; H-Phe-(NO 2 )Arg-Trp-OlyOMe formate; N<SP>α</SP>,N<SP>Im</SP>- di - Z - His - Phe - (NO 2 )Arg - Trp - GlyOMe; H-His-Phe-Arg-Trp-GlyOH, HOAc; Z-Glu(Ot- Bu)-His-Phe-Arg-Trp-Gly, HOAc; H-Glu- (OtBu)-His-Phe-Arg-Trp-Gly, HOAc; and BOC - # - Ala - Tyr - Ser - Met - Glu(OtBu) - His- Phe-Arg-Trp-GlyOH. Pharmaceutical compositions comprise compounds (I) and a carrier in a form suitable for oral or parenteral administration. The medicaments are used to treat articular rheumatism.</p> |
