Armour Pharmaceutical Company

Other

Armour and Company

John Lawrence Hughes

Robert Chung-Huan Liu

Jay K Seyler

Takashi Enkoji

James Winslow Bastian

Carroll M Smith

Robert Chung-Huang Liu

A new peptide which has calcitonin-like biological activity which has a shorter amino acid chain and which is chemically more stable than natural calcitonins. Also resin peptides are disclosed which may be converted to peptides having biological activity and processes for producing said resin peptides and said peptides having biological activity.

Synthesis of biologically active peptides

A new peptide is disclosed which has biological activity of the same type as known calcitonins and which has a shorter amino acid chain than natural calcitonins. Also resin peptides are disclosed which may be converted to peptides having such biological activity; and processes for producing said resin peptides and said calcitonin peptides.

Synthesis of peptides

The synthesis of a disulfide cyclic peptide by preparing an intermediate peptide containing two cysteine moieties, each of which is protected by an n-alkylthio group, or when one of such moieties is in an amino terminal position, this one moiety may be protected by a cysteine group while the other is protected by an n-alkylthio group, and placing such intermediate peptide in a solution substantially free of oxygen and preferably at a pH of from 5 to 10 until rearrangement has taken place, to yield a cyclic disulfide peptide. The disclosure also embraces said intermediate peptides as new compounds and the processes by which they are prepared.

Cyclization of peptides

Novel aromatic guanidine compounds having the formula: ##STR1## wherein: R.sub.1 is hydroxyl, methyl or hydroxymethyl and R.sub.2 is hydrogen or methyl, are found to have biological activity. The guanidine compounds and their salts are shown to be active as vasoconstrictor agents and create useful pharmaceutical preparations when deployed with a pharmaceutically acceptable carrier for administration to a host, e.g., man, requiring vasoconstrictive therapy.

Pharmaceutical, compositions containing substituted 4'-hydroxyphenyl

Resin peptides useful in the preparation of salmon calcitonin are disclosed along with processes for preparing the same. The invention also embraces peptides from which the resin moiety has been cleaved and which are useful in the synthesis of salmon calcitonin together with processes for preparing the cleaved peptides. In general, the processes involve the solid phase synthesis procedures.

Resin peptides

Novel aromatic guanidine compounds having the formula: ##STR1## wherein: R.sub.1 is hydroxyl, methyl or hydroxymethyl and R.sub.2 is hydrogen or methyl, are found to have biological activity. The guanidine compounds and their salts are shown to be activate as vasoconstrictor agents and create useful pharmaceutical preparations when deployed with a pharmaceutically acceptable carrier for administration to a host, e.g., man, requiring vasoconstrictive therapy.

Substituted 4-hydroxyphenyl guanidines

The synthesis of a disulfide cyclic peptide by preparing an intermediate peptide containing an amino terminal cystine residue and a cysteine residue located in a position within the amino acid sequence, to give a desired peptide, and placing such intermediate peptide in a solution substantially free of oxygen at a pH of from about 5 to 10 until rearrangement takes place to yield a cyclic disulfide peptide and to displace a molecule of cysteine from the amino terminal cysteine residue. The disclosure also embraces said intermediate peptides as new compounds and the processes by which they are prepared.

Substituted 4'-hydroxyphenyl guanidines and methods of using the same

A pharmaceutical preparation consisting of a pharmaceutical grade carrier and a therapeutically active amount of an aromatic guanidine compound having the formula: ##STR1## or a non-toxic acid addition salt thereof are found to have biologically useful activity. These guanidine preparations and salts are shown to be active as vasoconstrictor agents and obtain useful biological results when deployed with a pharmaceutically acceptable carrier for administration to a host, e.g., man, requiring vasoconstrictive therapy.

Pharmaceutical preparations containing 5'-(8'-hydroxyquinolyl)guanidine

Tetrahydroisoquinoline compounds represented by the formula: ##SPC1## In which

Tetrahydroisoquinoline compounds

Pharmaceutical preparations and methods of using the same to treat a host having a condition requiring vasoconstrictive therapy. The preparations comprise a pharmaceutically acceptable carrier and a guanidine compound, or non-toxic acid addition salt thereof, having the structural notation: ##SPC1## Wherein: R.sub.1 is hydrogen or alkyl having 1-4 carbon atoms; R.sub.2 is hydrogen, hydroxy, chloro, fluoro or bromo; and R.sub.3 is hydrogen or the same as R.sub.2 when R.sub.2 is chloro, bromo or fluoro.

Pharmaceutical guanidine preparations and methods of using same

Compounds having the structure: ##SPC1## In which R.sub.1 and R.sub.2 are alkoxy groups of one to four carbon atoms, R.sub.3 and R.sub.4 each is hydrogen or an alkoxy group of one to four carbon atoms, and R.sub.5 and R.sub.6 each is an alkyl group of one to four carbon atoms or an arylalkyl group such as benzyl or R.sub.5 taken with R.sub.6 and N are pyrrolidinyl, piperidino, or morpholino groups and the pharmaceutically acceptable salts thereof and processes for preparing these compounds. These compounds are useful as vasodilators.

1-(.alpha.-Aminomethylbenzyl)isoquinoline compounds

A novel aromatic guanidine compound having the formula: ##SPC1## Is found to have biological activity. This guanidine compound and its salts are shown to be active as vasoconstrictor agents and create useful pharmaceutical preparations when deployed with a pharmaceutically acceptable carrier for administration to a host, e.g., man, requiring vasoconstrictive therapy.

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Kankakee, IL, United States of America

John Lawrence Hughes