Eisai Company, Limited

Takeru Kaneko

Hachiro Sugimoto

Kiyomi Yamatsu

Takahiro Nakazawa

Masuhiro Ikeda

Isao Saito

Takaharu Nakamura

Norio Karibe

Masahiro Yonaga

Masataka Ueno

Kohshi Ueno

Shinro Tachibana

Kunizo Higurashi

Yoshihiro Arakawa

Kimie Takizawa

Satoru Ozaki

Hiroshi Yoshino

Sachiyuki Hamano

Yutaka Tsuchiya

Tadao Shoji

Shin Araki

Kunizou Higurashi

Shizuko Ohya

Takeshi Uzuo

A cyclic amine is defined by the formula: ##STR1## in which A is naphthyl, phenyl, quinolyl or alkyl, X is a group containing carbonyl, n is 2 or 3 and B is alkyl, halogen, phenyl or --YZ, Y being --0--, --CO-- or --NH--, Z being phenyl, naphthyl, pyridyl, alkyl or cycloalkyl. It is useful to treat a mental symptoms associated with a cerebrovascular disease.

Cyclic amine and pharmacological composition

A cyclic amine is defined by the formula: ##STR1## in which A is naphthyl, phenyl, quinolyl or alkyl, X is a group containing carbonyl, n is 2 or 3 and B is alkyl, halogen, phenyl or --YZ, Y being --O--, --CO-- or --NH--, Z being phenyl, naphthyl, pyridyl, alkyl or cycloalkyl. It is useful to treat mental symptoms associated with a cerebrovascular disease.

Piperidine compounds useful to treat cerebrovascular diseases

Cyclic amine derivatives

A novel polypeptide is defined by the below shown formula and is useful as an analgesic. ##STR1## wherein R.sup.1 and R.sup.2 may be the same or different and each represents a hydrogen atom or a lower alkyl or lower alkenyl group, A represents a D-amino acid, Gly or Sar provided that when the D-amino acid is D-Cys, it is bonded with L-Cys or D-Cys in position 5 through a S--S bond to effect intramolecular ring closure, B represents L-Phe or D-Phe in which the benzene ring may be substituted or an .alpha.-N-alkyl derivative thereof, C represents an L-amino acid, D-Cys or an .alpha.-N-alkyl derivative thereof, D and E each represent an L- or D-basic amino acid or an .alpha.-N-alkyl derivative thereof, F represents a group of the formula --OR.sup.3 (in which R.sup.3 is H or a lower alkyl group), a group of the formula: ##STR2## (in which R.sup.4 and R.sup.5 are the same or different and each represents H or a lower alkyl group), a group of the formula: --G--OR.sup.6 (in which G is an L- or D-amino acid or Gly or an .alpha.-N-alkyl derivative thereof and R.sup.6 represents H or a lower alkyl group), a group of the formula: ##STR3## (in which G is as defined above and R.sup.7 and R.sup.8 may be the same or different and each represents H or a lower alkyl group), a group of the formula: --G--L--Arg--OR.sup.9 or --G--D--Arg--OR.sup.9 (in which G is as defined above and R.sup.9 represents H or a lower alkyl group or a group of the formula: ##STR4## (in which G is as defined above and R.sup.10 and R.sup.11 may be the same or different and each represents H or a lower alkyl group), a group of the formula: --G--J--OR.sup.12 in which G is defined as above, J is a neutral amono acid group or an acidic amino acid group and R.sup.12 is hydrogen or a lower alkyl group; or a group of the formula: --G--Arg--M--OR.sup.13 in which M is D-amino acid group and R.sup.13 is hydrogen or a lower alkyl group, provided that all of the amino acids constituting the polypeptide of the above formula do not represent at the same time an L-amino acid of the general formula: ##STR5## (in which R represents a group corresponding to a structural formula of an amino acid deprived of a group of the formula: ##STR6## or pharmacologically acceptable salts of them.

Polypeptide

Treatment methods are disclosed which utilize antiphlogistic/antipyretic/analgesic agents containing as active ingredient theobromine and theophylline derivatives represented by the general formula: ##STR1## wherein one of A and B is --CH.sub.3 and the other of A and B is ##STR2## wherein R is a hydrogen atom or a lower alkyl group, Z is selected from the group consisting of (1) a group of the formula ##STR3## wherein X.sub.1 and X.sub.2 are the same or different and each represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group or a halogen atom; (2) a pyridyl group; or (3) a group of the formula: ##STR4## wherein Y.sub.1 and Y.sub.2 may be the same or different and Y.sub.1 and Y.sub.2 are selected from the group consisting of a hydrogen atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group and a halogen atom, X is a nitrogen atom or a carbon atom, m is 2 or 3, and n is an integer of from 2 to 10, with the provisos that when (i) A is --CH.sub.3, m is 2, and (ii) when A is ##STR5## Z is not pyridyl and X is nitrogen, and acid addition salts thereof.

Antiphlogistic/antipyretic/analgesic agents containing theobromine or

A novel peptide having the primary structure: N-Me-Tyr-Gly-Gly-Phe-Leu-Arg-Arg-D.Ile-Arg-Pro-Lys-D.Leu-Lys-Trp-NH.sub.2 (in which D.Ile and D.Leu represent a D-Ile and a D-Leu residue respectively, other abbreviations of amino acids represent each an L-amino acid residue and Me represents a methyl group), which exhibits a remarkable analgesic effect when administered peripherally. A process for the preparation thereof by a solid phase method is also disclosed.

Analgesic peptide and process for the preparation thereof

Treatment methods are disclosed which utilize antiphlogistic/antipyretic/analgesic agents containing as active ingredient theobromine and theophylline derivatives represented by the general formula: ##STR1## wherein one of A and B is --CH.sub.3 and the other of A and B is ##STR2## wherein R is a hydrogen atom or a lower alkyl group, Z is selected from the group consisting of (1) a group of the formula ##STR3## wherein X.sub.1 and X.sub.2 are the same or different and each represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group or a halogen atom; (2) a pyridyl group; or (3) a group of the formula: ##STR4## wherein Y.sub.1 and Y.sub.2 may be the same or different and Y.sub.1 and Y.sub.2 are selected from the group consisting of a hydrogen atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group and a halogen atom, X is a nitrogen atom or &gt;CH--, m is 2 or 3, and n is an integer of from 2 to 10, with the provisos that when (i) A is --CH.sub.3, m is 2, and (ii) when A is ##STR5## Z is not pyridyl and X is nitrogen, and acid addition salts thereof.

There are disclosed theobromine derivatives wherein theobromine is substituted at the 1 position with substituted piperazino, homopiperazino and piperidino groups, and pharmacologically acceptable acid addition salts thereof. The compounds exhibit vasodilating and psychotropic and analgesic activities.

Theobromine derivatives

Growing community of inventors

Tsukuba, Japan

Takeru Kaneko