Patent GB-1314051-A (GB)
Title: Polypeptides and their derivatives
IPC: A61P3/00
Filed: 1970-05-22
Abstract: 1314051 Polypeptides SANDOZ Ltd 22 May 1970 [3 June 1969 20 June 1969 (4) 23 June 1969 (3) 26 June 1969 30 June 1969 9 Sept 1969] 24779/70 Heading C2C Novel compounds I: S - CH 2  - CHX - CO - ser - asn - leu - ser - thr - cys - val - leu - gly - lys - leu - ser - gln - glu - leu - hislys - leu - gln - thr - tyr - pro - arg - thr - asnthr-gly-ser-gly-thr-Y wherein X is H, NH 2 , RCONH or R<SP>1</SP>OCONH; R is alkyl or optionally substituted aryl or aralkyl; R<SP>1</SP> is alkyl, alkenyl or optionally substituted aryl or aralkyl; and Y is -pro-NH 2  or -pro-val-NH 2 ; wherein the terminal peptide unit -S-CH 2 -CHX-CO- has the L-configuration where X is NH 2 , RCONH or R<SP>1</SP>OCONH; and wherein ser may be exchanged for thr or ala; asn for asp, gln or glu; thr for ser or ala; lys for lys(BOC), orn; asn or asp; glu for glu(OtBn), gln, asn or asp; leu for tyr; tyr for phe and arg for orn or lys, provided that when sequence is asin I, and Y is -pro-NH 2 , X is other than NH 2 , are prepared by normal methods of peptide synthesis. Intermediates isolated are Z- or H-thr-pro- NH 2 .HCl; Z-ser-gly-(OEt or NHNH 2 ); Z- or H - ser - gly - thr - pro - NH 2 ; Z - asn - thr - gly- OEt; Z - thr - asn - thr - gly - OEt; BOC- arg(NO 2 ) -thr - asn - thr - gly - (OEt or NHNH 2 ); (BOC or H) - arg - thr - asn - thr - gly - ser - glythr - pro - NH 2 ; (Z- or H-) thr - tyr - pro - (OH or OMe); Z-leu-gln-OMe; H-gln-OMe.HCl; Z- lys(BOC) - leu - gln - OMe: Z - his - lys(BOC)- leu - gln - (OMe or NHNH 2 ); Z - his - lys(BOC)- leu - gln - thr - tyr - pro - OH; Z - gln - thr - tyrpro - OH; Z - lys(BOC) - tyr(OMe); Z - hislys(BOC) - tyr - NHNH 2 ; Z - his - lys(BOC)- tyr - gln - thr - tyr - pro - OH; (Z or H) - hislys(BOC) - leu - gln - thr - tyr - pro - arg - thrasn - thr - gly - ser - gly - thr - pro - NH 2 ; H- his - lys(BOC) - tyr - gln - thr - tyr - pro - argthr - asn - thr - gly - ser - gly - thr - pro - NH 2 ; (H or Z) - glu(OtBn) - leu - OMe; (Z or H) - glnglu(OtBu) - leu - OMe; Z - lys(BOC) - leu - ser- OMe; trityl - gly - lys(BOC) - leu - ser - NHNH 2 ; trityl - gly - lys(BOC) - leu - ser - gln - glu(OtBn)- leu - (NHNH 2  or OMe); H - gly - lys(BOC) - leuser - gln - glu(OtBn) - leu - his - lys(BOC) - leugln - thr - tyr - pro - arg - thr - asn - thr - gly-   ser - gly - thr - pro - NH 2 ; (H or Z) - gln - leu- OMe; (H or Z) - glu - gln - leu - OMe; tritylgly - lys(BOC) - leu - ser - gin - gln - leu- NHNH 2 ; H - gly - lys(BOC) - leu - ser - glngln - leu - his - lys(BOC) - leu - gln - thr - tyrpro - arg - thr - asn - thr - gly - ser - gly - thrpro - NH 2 ; H - gly - lys(BOC) - leu - ser - glnglu(OtBu) - leu - his - lys(BOC) - tyr - glu - thrtyr - pro - arg - thr - asn - thr - gly - ser - gly - thrpro - NH 2 ; H - gly - lys(BOC) - leu - ser - glngln - leu - his - lys(BOC) - tyr - gin - thr - tyrpro - arg - thr - asn - thr - gly - ser - gly - thrpro - NH 2 ; (H or Z) - cys(Bz) - val - leu - OMe; (H or Z) - thr - cys(Bz) - val - leu - OMe; H - thrcys(Bz) - val - leu - OH; (BOC or H) - asn - leuser - OMe; (BOC or H) - ser - asn - leu - ser- OMe; BOC - cys(Bz) - ser - asn - leu - ser- (NHNH 2  or OMe); BOC - cys - ser - asn - leuser - thr - cys - val - leu - OH; BOC - cys(Bz)- ser - asnleu - ser - thr - cys(Bz) - val - leu - OH; BOC - cys - ser - asn - leu-ser-thr-cys-val-leu- OH; pivaloyl - cys - ser - asn - leu - ser - thr - cysval-leu-OH; pivalic acid p-nitrophenyl ester; ethoxycarbonyl - cys - ser - arn - leu - ser - thr - cys - val-leu-OH; carbonic acid p-nitrophenyl ethyl ester; benzylmercaptopropionyl-ser-asn-leu-ser- # NHNH 2 ; and S-CH 2 CH 2 CO-ser - asn - leuser-thr-cys-val-leu-NHNH 2 . Pharmaceutical compositions comprise a compound I together with a suitable carrier and/or diluent and lower the calcium content in the blood.