Takeda Chemical Industries, Inc.

Takeda Pharmaceutical Company Limited

Shizue Nakagawa

Tsunehiko Fukuda

Shigehisa Taketomi

Hitoshi Ikeda

Iwao Yamazaki

Masahiro Kawase

Yasutaka Nagisa

Junko Habashita

To provide a pharmaceutical composition for preventing, treating or development-inhibiting simple retinopathy or preproliferative retinopathy, comprising a compound having angiotensin II antagonistic activity, or a salt thereof.

Method for preventing, treating or inhibiting development of simple retinopathy and preproliferative retinopathy

Disclosed is a parathyroid hormone (PTH) (1-34) derivative in which at least the amino acid residue at the 10-position is substituted by an acidic amino acid residue. The derivatives of the present invention showing potent cAMP-producing activity and bone formation activity, and thus are useful as therapeutic agents for bone diseases, etc.

Parathyroid hormone derivatives and their use

Parathyroid hormone (PTH) derivatives represented by the general formula: ##STR1## or a salt thereof, wherein R.sub.1 represents Ser or a D-.alpha.-amino acid residue of 4 or less carbon atoms; R.sub.2 represents a tetrapeptide chain which contains at least one water-soluble .alpha.-amino acid residue; R.sub.3 represents a tripeptide chain which contains at least one water-soluble .alpha.-amino acid residue; and R.sub.4 represents an aromatic amino acid residue or an amide thereof, except that R.sub.1 is Ser when R.sub.2 is His-Leu-Asn-Ser, R.sub.3 is E-F-G wherein E is Arg or His, F is Lys or His, G is Lys, Leu or Gln, are disclosed. The parathyroid hormone derivatives of the present invention are stable and have high biological activity, therefore they are useful as drugs for bone diseases and the like.

Parathyroid hormone derivatives

Disclosed are peptides and salts thereof represented by general formul ##STR1## wherein R.sub.1 represents Ser or Aib; R.sub.2 represents Met or a naturally occurring hydrophobic amino acid; R.sub.3 represents Leu, Ser, Lys or an aromatic amino acid; R.sub.4 represents Gly or a D-.alpha.-amino acid; R.sub.5 represents Lys or Leu; R.sub.6 represents Met or a naturally occurring hydrophobic amino acid; R.sub.7 represents Glu or a basic amino acid; R.sub.8 represents Val or basic amino acid; R.sub.9 represents Trp or 2-(1,3-dithiolane-2-yl)Trp; R.sub.10 represents Arg or His; R.sub.11 represents Lys or His; R.sub.12 represents Lys, Gln or Leu; and R.sub.13 represents Phe or Phe-NH.sub.2 ; except that simultaneously R.sub.1 consists of Ser, R.sub.2 consists of Met, R.sub.3 consists of Leu, R.sub.4 consists of Gly, D-Ala or D-Pro, R.sub.5 consists of Lys, R.sub.6 consists of Met, R.sub.7 consists of Glu, R.sub.8 consists of Val, R.sub.9 consists of Trp, R.sub.10 consists of Arg, R.sub.11 consists of Lys and R.sub.12 consists of Lys. The parathyroid hormone (1-34) analogs are useful in hormone therapy.

Growing community of inventors

Osaka, Japan

Shizue Nakagawa