GB1333723A - Hypocalcaemic peptides and process for their manufacture - Google Patents

Hypocalcaemic peptides and process for their manufacture

Info

Publication number
GB1333723A
GB1333723A GB4924870A GB4924870A GB1333723A GB 1333723 A GB1333723 A GB 1333723A GB 4924870 A GB4924870 A GB 4924870A GB 4924870 A GB4924870 A GB 4924870A GB 1333723 A GB1333723 A GB 1333723A
Authority
GB
United Kingdom
Prior art keywords
tbu
thr
leu
gly
gln
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB4924870A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis AG
Original Assignee
Ciba Geigy AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CH1014670A external-priority patent/CH534663A/en
Application filed by Ciba Geigy AG filed Critical Ciba Geigy AG
Publication of GB1333723A publication Critical patent/GB1333723A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/585—Calcitonins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

1333723 Calcitonine-M derivatives CIBAGEIGY AG 16 Oct 1970 [22 Oct 1969 3 July 1970] 49248/70 Heading C2C Compounds (I), their salts, complexes, Nα- acyl and their desamino<SP>1</SP>-derivatives: H-Cys - Gly - Asn - Leu - Ser - Thr - Cys - XLeu - Gly - Thr - Tyr - Thr - Gln - Asp - Phe- Asn - Lys - Phe - His - Thr - Phe - Pro - Gln- Thr - Ala - Ile - Gly - Val - Gly - Ala - ProNH 2 (I) (where X is Met, Val, Nval, Leu, Ile, Nle, Abu and wherein at least one of the amino acids in positions 11, 12, 16, 17, 19, 20, 22 and 24 is replaced by another namely Thr<SP>11</SP> by Lys, Tyr<SP>12</SP> by Leu, Phe<SP>16</SP> by Leu, Asn<SP>17</SP> by His, Phe<SP>19</SP> by Leu, His<SP>20</SP> by Gln, Phe<SP>22</SP> by Tyr and Gln<SP>24</SP> by Arg) are prepared (a) by removing amino and/or carboxylic protecting groups from an appropriately protected dotriacontapeptide or (b) by oxidizing the corresponding linear dotriacontapeptide wherein the mercapto groups in the residues -Cysare free or protected by trityl groups. Starting materials and intermediates prepared are: Z- and H-Tyr(tBu)-ProOH, Z-Thr (tBu) - Tyr (tBu) ProOH, H-Gln-Thr (tBu)- Ala-Ile-Gly-Ome, Z-Thr (tBu)-Tyr (tBu)-Pro- Gln - Thr - (tBu) - Ala - lie - Gly OMe and OH and the unprotected octapeptide acetate salt, Z- and H - Asn - Lys (BOC) Phe - His - Thr (tBu)- Tyr (tBu) Pro - Gln - Thr (tBu) - Ala - Ile- Gly OH, Z - Thr (tBu) Tyr (tBu) - Thr (tBu)- Gln - Asp (OtBu) - Phe - Asn - Lys (BOC) - Phe- His - Thr (tBu) - Tyr (tBu) - Pro - Gln - Thr (tBu) - Ala - lie - Gly OH, Z- and H - Thr (tBu) - Tyr (tBu) - Thr (tBu) - Gln - Asp (OtBu)- Phe - Asn - Lys (BoC) - Phe - His - Thr (tBu)- Tyr (tBu) - Pro - Gln - Thr (tBu) - Ala - Ile - Gly- Val - Gly - Ala - Pro NH 2 and BoC-protected- Tyr<SP>22</SP> - calcitonine M. Z- and H-Asn-Leu-OMe, Z- and H - Asn - Leu OMe, BOC - Cys (Tri)- Gly - Asn - Leu OMe and -NHNH 2 , BOC and H - Met - Leu - Gly OMe, Tri- and H - Cys (Tri) - Met - Leu - Gly - OMe, H - Thr (tBu)- OMe, DPC - Ser (tBu) Thr (tBu) - OMe and -NHNH 2 DPC- and H-Ser (tBu) - Thr (tBu)- Cys (Tri) - Met - Leu - Gly - OMe and the free hexapeptide acid, BOC-Cys (Tri)-Gly-Asn-Leu- Ser (tBu) - Thr (tBu) Cys (Tri) - Met - Leu - Gly OH and the cyclic peptide (by oxidation), Z and HAsp (OtBu) Leu OMe, Z and H-Gln-Asp (OtBu)-Leu OMe, Z and H-Thr (tBu)-Gln-Asp (OtBu) - Leu - OMe, Z and H - Leu - Thr (tBu)- Gln - Asp (OtBu) - Leu - OMe, Z - Thr (tBu)- Leu - Thr (tBu) - Gln - Asp (OtBu) - Leu OMe and -NHNH 2 , Z- and H - Lys (BOC) Leu- His - OMe, Z - Asn - Lys (BOC) Leu - His - OMe and -NHNH 2 , Z- and H-Asn-Lys (BOC) Leu- His - Thr (tBu) - Phe - Pro - Gln - Thr (tBu)-Ala- Ile - Gly OH, Z - Thr (tBu) - Leu - Thr (tBu)-Gln- Asp (OtBu) - Leu - Asn - Lys (BOC) - Leu - His- Thr (tBu) - Phe - Pro - Gln - Thr (tBu) - Ala-Ile- Gly OH. H - Val - Gly - Ala - Pro NH 2 Z- and H - Thr (tBu) - Leu - Thr (tBu) - Gln - Asp (OtBu) Leu - Asn - Lys (BOC) - Leu - His - Thr (tBu) - Phe - Pro - Gln - Thr (tBu) - Ala - Ile-Gly- Val-Gly-Ala-Pro NH 2 and BOC-Leu<SP>12,16,19</SP>-calcitonine - M, Z and H - Arg - Thr (tBu) - Ala- Ile - Gly - OH, Z - Thr (tBu) - Phe - Pro - Arg- Thr (tBu) - Ala - Ile - Gly OH, Z-Asn-Lys (BOC) Phe - His - Thr (tBu) - Phe - Pro - Arg - Thr (tBu)- Ala - Ile - Gly OH, Z - Lys (BOC) - Tyr (tBu)- Thr (tBu) - Gln - Asp (OtBu) - Phe - OMe and -NHNH 2 , Z - Lys (BOC) - Tyr (tBu) - Thr (tBu)- Gln - Asp (OtBu) - Phe - Asn - Lys (BOC) - Phe- His - Thr (tBu) - Phe - Pro - Arg - Thr (tBu)-Ala- Ile - Gly OH, Z and H - Lys (BOC) - Tyr (tBu)- Thr (tBu) - Gln - Asp (OtBu) - Phe - Asn - Lys (BOC) - Phe - His - Thr (tBu) - Phe - Pro - Arg- Thr (tBu) - Ala - Ile - Gly OH and BOC - Lys<SP>11</SP>- Arg<SP>24</SP> - calcitonine - M. Z - Lys (BOC) - Leu-OMe and -NHNH 2 , Z- and H-Lys (BOC)-Leu-Gln- OMe, Z - His - Lys (BOC) - Leu - Gln - OMe, HHis - Lys (BOC) - Leu - Gln - Thr (tBu) - Phe- Pro - Gln - Thr (tBu) - Ala - Ile - Gly OH, Z-Thr (tBu) - Tyr (tBu) - Thr (tBu) - Gln - Asp (OtBu)- Phe - His - Lys (BOC) - Leu - Gln - Thr (tBu)- Phe - Pro - Gln - Thr (tBu) - Ala - lie - Gly OH, Z- and H - Thr (tBu) - Tyr (tBu) - Thr (tBu)- Gln - Asp (OtBu) - Phe - His - Lys (BOC) - Leu- Gln - Thr (tBu) - Phe - Pro - Gln - Thr (tBu)-Ala- Ile - Gly - Val - Gly - Ala - Pro NH 2 and BOCHis<SP>17</SP> - Leu<SP>19</SP> - Gln<SP>20</SP> - calcitonine - M. Z and HLeu - Gly OMe, Z and H - Val - Leu - Gly OMe, TRI- and H-Cys (TRI)-Val-Leu-Gly OMe, DPC- and H-Ser (tBu)-Thr (tBu)-Cys (TRI)-Val- Leu - Gly - OMe, H - Ser (tBu) - Thr (tBu) - Cys (TRI) - Val - Leu - Gly - OH, BOC - Cys (TRI)- Gly - Asn - Leu - Ser (tBu) - Thr (tBu) - Cys (TRI) - Val - Leu - Gly OH, the corresponding cyclic peptide by oxidation and BOG-Val<SP>8</SP>-Tyr<SP>22</SP>- calcitonine - M). BOC - Val<SP>s</SP> - Leu<SP>12,16,19</SP>-calcitonine - M. BOC - desamino<SP>1</SP> - Leu<SP>12,16,19</SP>-calcitonine M. BOC - desamino<SP>1</SP> - Tyr<SP>22</SP>-calcitonine- M. Bmp (TRI) - Gly - Asn - Leu - Ser (tBu)- Thr (tBu) - Cys (TRI) - Val - Leu - Gly OH the corresponding cyclic peptide by oxidation and BOC - desamino<SP>1</SP> - Val<SP>8</SP> - Leu<SP>12,16,19</SP> - calcitonine - M. Z - Asn - Lys (BOC) - Leu- His - Thr (tBu) - Tyr (tBu) - Pro - Gln- Thr (tBu) - Ala - Ile - Gly OH, Z- and HAsn - Lys (BOC) - Leu - His - Thr (tBu) - Tyr (tBu) - Pro - Gln - Thr (tBu) - Ala - Ile - Gly - Val- Gly - Ala - Pro NH 2 , Z- and H - Thr (tBu)-Leu- Thr (tBu) - Gln - Asp (OtBu) - Leu - Asn - Lys (BOC) - Leu - His - Thr (tBu) - Tyr (tBu) - Pro- Gln - Thr (tBu) - Ala - lie - Gly - Val - Gly - Ala- Pro NH 2 and BOC - Leu<SP>12,16,19</SP>-Tyr<SP>22</SP>-calcitonine- M, BOC - Val<SP>s</SP>-Leu<SP>12,16,19</SP>-Tyr<SP>22</SP>-calcitonine-M. BOC - desamino<SP>1</SP>-Val<SP>8</SP>-Leu<SP>12,16,19</SP> - Tyr<SP>22</SP> - calcitonine - M. H - Thr (tBu) - Gln - Asp (OtBu)-Phe- OMe, Z - Leu - Thr (tBu) - Gln - Asp (OtBu)-Phe OMe, Z - Thr (tBu) - Leu - Thr (tBu) - Gln-Asp (OtBu) - Phe - OMe and NHNH 2 , Z- and HAsn - Lys (BOC) - Phe - His - Thr (tBu) - Phe- Pro - Gln - Thr (tBu) - Ala - lie - Gly - Val - Gly- Ala - Pro - NH 2 , H - Thr (tBu) - Leu - Thr (tBu)- Gln - Asp (OtBu) - Phe - Asn - Lys (BOC) - Phe- His - Thr (tBu) - Phe - Pro - Gln - Thr (tBu) - Ala- Ile - Gly - Val - Gly - Ala - Pro NH 2 and BOCLeu<SP>12</SP>-calcitonine - M. Z- and H - Asp (OtBu)- Leu - OMe, Z- and H - Gln - Asp (OtBu) - Leu OMe, Z- and H - Thr (tBu) - Gln - Asp (OtBu)- Leu - OMe, Z - Tyr (tBu) - Thr (tBu) - Gln-Asp (OtBu) - Leu - OMe, Z - Thr (tBu) - Tyr (tBu)- Thr (tBu)- Gln - Asp (OtBu) - Leu - OMe and- -NHNH 2 , Z- and H-Thr (tBu)-Tyr (tBu)-Thr (tBu) - Gln - Asp (OtBu) - Leu - Asn - Lys (BOC)- Phe - His - Thr (tBu) - Phe - Pro - Gln - Thr (tBu)- Ala - lie - Gly - Val - Gly - Ala - Pro NH 2 and BOC - Leu<SP>16</SP>-calcitonine - M. Z- and H-Asn- Lys (BOC) - Leu - His - Thr (tBu) - Phe - Pro- Gln - Thr (tBu) - Ala - Ile - Gly - Val - Gly - Ala- Pro NH 2 , Z- and H-Thr (tBu)-Tyr (tBu)-Thr (tBu) - Gln - Asp (OtBu) - Phe - Asn - Lys (BOC)- Leu - His - Thr (tBu) - Phe - Pro - Gln - Thr (tBu)- Ala - Ile - Gly - Val - Gly - Ala - Pro NH 2 and BOC-Leu<SP>19</SP>-calcitonine-M.
GB4924870A 1970-07-03 1970-09-16 Hypocalcaemic peptides and process for their manufacture Expired GB1333723A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH1014670A CH534663A (en) 1969-10-22 1970-07-03 Process for the preparation of new dotriacontapeptide amides and their derivatives

Publications (1)

Publication Number Publication Date
GB1333723A true GB1333723A (en) 1973-10-17

Family

ID=4359871

Family Applications (1)

Application Number Title Priority Date Filing Date
GB4924870A Expired GB1333723A (en) 1970-07-03 1970-09-16 Hypocalcaemic peptides and process for their manufacture

Country Status (1)

Country Link
GB (1) GB1333723A (en)

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