Sanwa Kagaku Kenkyusho Co., Ltd.

Mitsuhiro Makino

Yuji Hayashi

Motohiro Takeda

Takahito Jomori

Takuji Kakigami

Mitsuru Oka

Masahiro Shirai

Toshiyuki Kouzaki

Masahiro Yoshida

Mitsuaki Takeuchi

Noriyasu Katoh

Toru Murase

Masao Sakairi

Takayo Murase

Takayo Yamamoto

A dipeptidyl peptidase IV inhibitor which is satisfactory in respect of activity, stability and safety and has an excellent action as a pharmaceutical agent. A compound represented by the following general formula or a pharmaceutically acceptable salt thereof: wherein Rand Reach represents hydrogen, an optionally substituted C1-6 alkyl group, or &#x2014;COORwhereupon Rrepresents hydrogen or an optionally substituted C1-6 alkyl group, or R, R, and a carbon atom together represent a 3- to 6-membered cycloalkyl group, Rrepresents hydrogen or an optionally substituted C6-10 aryl group, Rrepresents a hydrogen or a cyano group, D represents &#x2014;CONR-, &#x2014;CO&#x2014; or &#x2014;NRCO&#x2014;, Rrepresents hydrogen or an optionally substituted C1-6 alkyl group, E represents &#x2014;(CH)&#x2014; whereupon m is 1 to 3, &#x2014;CHOCH&#x2014;, or &#x2014;SCH&#x2014;, n is 0 to 3, and A represents an optionally substituted bicyclic heterocyclic group or bicyclic hydrocarbon group.

Compound inhibiting dipeptidyl peptidase IV

A GLP-1 derivative is provided including an amino acid sequence of GLP-1 (7-35) having deletion, substitution and/or addition of one or more amino acids and having Waa-(Xaa)n-Yaa (in which Waa is Arg or Lys, Xaa is Arg or Lys, n is an integer of 0 to 14, and Yaa is Arg, Arg-NH, Lys, Lys-NHor Hse) added to the C-terminus of the peptide having a GLP-1 activity. These derivatives are highly absorbable via a mucous membrane. The GLP-1 derivative can be conferred with resistance to dipeptidyl peptidase IV by substituting amino acid 8 in its GLP-1 amino acid sequence with Ser, or with resistance to trypsin by substituting amino acids 26 and 34 with Gln and Asn, respectively. The absorption efficiency of the GLP-1 derivatives via mucous membranes can be further improved by preparing a composition using a charge-regulated fat emulsion regulated to be negatively charged thereon.

GLP-1 derivative and preparation thereof absorbable via mucous membrane

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Nagoya, Japan

Mitsuhiro Makino