Takeda Chemical Industries, Inc.

Mitsuhiro Wakimasu

Masahiko Fujino

Takashi Kikuchi

Akira Kawada

Satoshi Endo

Hiroshi Inooka

Chieko Kitada

Seiichi Tanida

Shigehisa Taketomi

Hideo Shirafuji

Kiyohisa Kawai

Toshifumi Watanabe

Tsuneaki Hida

Kazuki Kubo

Eiichiro Ishikawa

Kohei Nishikawa

Masaaki Mori

Keiji Kusumoto

Giichi Goto

Osamu Nishimura

Susumu Iwasa

Setsuo Harada

Akinobu Nagaoka

Akira Ohneda

Yuzo Ichimori

Hayao Ueno

Koichi Yukishige

Mitsuhiko Mano

Kyozo Tsukamoto

Nobuo Nakajima

Hisashi Aoki

Cyclic pentapeptides are disclosed having the following formula (I)-Cyclo(-A -A -A -A -A -)-wherein A , A , A , A and A are amino acid residues. The pentapeptide has amino acid residues in positions 1-2-3 to form a &ggr;-turn, and amino acid residues in positions 3-4-5-1 to form a &bgr;-turn in combination with the &ggr;-turn. D-&agr;-amino acid residues are selected for A , A , and A and L-&agr;-amino acid residues are selected for A and A . Compounds having &ggr;-turns and &bgr;-turns can be synthesized, regardless of the kinds of amino acid residues, and it is possible to synthesize compounds in which desired amino acid residues are introduced into sites of &bgr;-turn and &ggr;-turn based on their importance from the viewpoint of biological activity. The present invention is therefore available for design of compounds having biological activity.

Pentapeptide with specific conformation, its production and use

Method for controlling conformation of cyclopentapeptide

Compounds having antagonistic activity on endothelin receptors can be effectively used for prophylaxis and/or treatment of hypofunction of organs which occurs in their surgery or transplant.

Methods and compositions for the prophylactic and/or therapeutic

Cyclic pentapeptides are disclosed having the following formula (I) --Cyclo(-A.sub.1 -A.sub.2 -A.sub.3 -A.sub.4 -A.sub.5 -)-- wherein A.sub.1, A.sub.2, A.sub.3, A.sub.4 and A.sub.5, are amino acid residues. The pentapeptide has amino acid residues in positions 1-2-3 to form a .gamma.-turn, and amino acid residues in positions 3-4-5-1 to form a .beta.-turn in combination with the .gamma.-turn. D-.alpha.-amino acid residues are selected for A.sub.1, A.sub.3, and A.sub.5 and L-.alpha.-amino acid residues are selected for A.sub.2 and A.sub.4. Compounds having .gamma.-turns and .beta.-turns can be synthesized, regardless of the kinds of amino acid residues, and it is possible to synthesize compounds in which desired amino acid residues are introduced into sites of .beta.-turn and .gamma.-turn based on their importance from the viewpoint of biological activity. The present invention is therefore available for design of compounds having biological activity.

A cyclic hexapeptide represented by the formula:

Cyclic hexapeptides, their production and use

Disclosed are (1) a cyclic hexapeptide represented by formula I or a salt thereof: ##STR1## wherein X and Y each represent .alpha.-amino acid residues, A represents a D-acidic-.alpha.-amino acid residue, B represents a neutral-.alpha.-amino acid residue, C represents an L-.alpha.-amino acid residue and D represents a D-.alpha.-amino acid residue having an aromatic ring group; and (2) a pharmaceutical composition comprising the peptide represented by formula I or a pharmaceutically aceptable salt thereof as an active ingredient.

Cyclic endothelin antagonists

Cyclic hexapeptides having antagonistic activity on endothelin receptors of the formula �I!: ##STR1## wherein X and Y each is an .alpha.-amino acid residue having D-, L-form or DL-form, A is a D-acidic-.alpha.-amino acid residue, B is a neutral-.alpha.-amino acid residue having D- or L-form, C is an L-.alpha.-amino acid residue and E is a D-.alpha.-amino acid residue having an aromatic ring group can be effectively used for prophylaxis and/or treatment of pulmonary circulatory diseases.

Composition for prophylaxis or treatment of pulmonary circulatory

Cyclic peptides and their salts have antagonistic activity on endothelin receptors and antagonistic activity on NK2 receptors. The peptides have the formula ##STR1## wherein X and Y each represent .alpha.-amino acid residues, A represents a D-acidic-.alpha.-amino acid residue, B represents a neutral .alpha.-amino acid residue, C represents an L-.alpha.-amino acid residue and D represents a D-.alpha.-amino acid residue having an aromatic ring group; wherein hydroxy, thiol, amino, imino and carboxyl groups can be substituted or unsubstituted. Pharmaceutical compositions containing such peptides are also described.

Cyclic peptides and use thereof

A compound of the formula: ##STR1## wherein each of R.sup.1 and R.sup.2 is hydrogen or aliphatic acyl, A is amino which may be protected, X is an amino acid sequence consisting of 1 to 10 amino acid residues which contain at least one amino acid residue having a water-solubility enhancing group, or a salt thereof has an activity of remarkably improving hematopoietic disorder and is useful as an immuno-stimulating agent or an agent for treating thrombocytopenia.

2-amino-6,7-dihydroxy-4-thiaheptanoic acid derivatives, production and

A compound of the formula: ##STR1## wherein each R.sup.1, R.sup.2 and R.sup.3 is an aliphatic acyl group, X is an amino acid sequence consisting of 1 to 5 amino acid residues which contain at least one acidic amino acid residue, n is an integer of 0 to 4, provided that when n is 0, X has glutamyl-glycyl at its N-terminal and when n is 1 or 2, the acidic amino acid residue is an acidic amino acid residue other than D-glutamyl, or a salt thereof has an activity of remarkably improving anhematopoiesis and is useful as an immuno-stimulating agent having a leukocyte-increasing activity.

TAN-1511, its derivatives, production and use thereof

Disclosed are a peptide represented by formula (I) or a pharmaceutically acceptable salt thereof: ##STR1## wherein M represents a mercaptoacyl group; P, Q, R, S, T, U, V, W, X, Y and Z each represent amino acid residues, wherein an amino acid side chain of Y is either a substituted saturated aliphatic hydrocarbon group having 1 to 15 carbon atoms or an unsubstituted saturated aliphatic hydrocarbon group having 4 to 15 carbon atoms other than (1S)-1-methylpropyl; (2) a method for producing the above-mentioned peptide or the salt thereof, which comprises subjecting a peptide represented by formula (II) or a salt thereof to an oxidation reaction:

Endothelin analogs and uses thereof

A phosphonic acid derivative compound represented by formula [I ] or a pharmaceutically acceptable salt thereof: ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 each represent hydrocarbon groups which may be substituted, except cases in which (1) R.sub.2 is unsubstituted methyl, ( 2 ) R.sub.3 is an unsubstituted hydrocarbon group having 1 to 3 carbon atoms, and (3) R.sub.1 is benzyloxycarbonylaminomethyl, R.sub.2 is isobutyl and R.sub.3 is isobutyl or phenylmethyl, which has endothelin-converting enzyme inhibiting activity and is useful as pharmaceutical drugs such as therapeutic agents for hypertension, cardiac or cerebral circulatory diseases and renal diseases.

Phosphonic acid derivatives and use thereof

Peptide derivatives having vasodilating activity

A peptide derivative of the formula ##STR1## wherein A is hydrogen or a hydrocarbon acyl having 2 to 18 carbon atoms which is substituted by an amino group at the .alpha.-position; B is F-Gly wherein F is a neutral .alpha.-amino acid residue, or NH-(CH.sub.2)nCO wherein n is an integer of 1 to 4; C is a neutral .alpha.-amino acid residue; and E is L-Arg or D-Arg; when A, B and C are hydrogen, Gly-Gly, and Met or Ile, respectively, E is D-Arg, or its pharmacologically acceptable salt has strong hypotensive and natriuretic activity; therefore it is useful as a therapeutic drug for hypertension, a diuretic, and a therapeutic drug for cardiac and cerebral circulatory diseases.

Atrial natriuretic peptide derivative

A peptide derivative of the general formula ##STR1## wherein R.sup.1 is a hydrogen atom, a C.sub.1-18 alkyl group or a substituted or unsubstituted phenyl C.sub.1-3 alkyl group;

Growing community of inventors

Ibaraki, Japan

Mitsuhiro Wakimasu