Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

Nippon Kayaku Kabushiki Kaisha

Sanraku-ocean Co., Ltd.

Meiji Seika Kaisha, Ltd.

Other

Mitsubishi Chemical Industries Limited

Banyu Pharmaceutical Co. Ltd

Zaidin Hojin Biseibutsu Kagaku Kenky Kai

Takaaki Aoyagi

Tomio Takeuchi

Hamao Umezawa

Masa Hamada

Masaaki Ishizuka

Tetsushi Saino

Yasuhiko Muraoka

Shunzo Fukatsu

Hiroshi Naganawa

Mitsugu Hachisu

Makoto Tsuda

Rinzo Nishizawa

Taiji Inui

Kenji Kawamura

Shinichi Kondo

Hajime Morishima

Yoshiro Okami

Akira Takamatsu

Tadashi Shirai

Masao Suzuki

Seiji Shibahara

Tomohisa Takita

Hiroshi Tone

Ikuo Matsumoto

Keiji Ogawa

Yasuharu Sekizawa

Tetsuya Someno

Takuzo Yamamoto

Machiko Nagai

Hideo Sugimura

Tsuyoshi Inoue

Kuniaki Tatsuta

Shigeharu Inoue

Yoshiyuki Koyama

Hamao Umezawa, Deceased

Junji Yoshizawa

Tetsuji Miyano

Michinori Koyama

Masaaki Hosoi

Yuji Matsuhashi

Shinichi Ishii

Shingo Uchida

Shinjiro Murata

Takayuki Aoyama

Fumika Yamada

Kohtaro Funaishi

Atsuji Okano

Shizuo Kadoya

Takeo Naito

Masao Shimizu

Yukiko Takahashi

Hajime Morishama

Shigemi Yoshida

Shokichi Ohuchi

Takaaki Nishikiori

Masao Hirayama

Takao Iwaguchi

Mariko Shimamura

The invention relates to novel pyrrolidine derivatives represented by formula (1): ##STR1## wherein: R1 represents (1) a lower alkyl group having 1 to 6 carbon atoms, or (2) a 3- to 15-membered mono- or fused cyclic hydrocarbon group which may contain a hetero atom on the ring, or which may be substituted with a substituent(s); each of n and m represents an integer and the sum of n and m is an integer of 0 to 2; each of X and E represents oxygen, NR' (wherein R' is hydrogen or a lower alkyl group having 1 to 6 carbon atoms), sulfur, phenylene, CH.dbd.CH or CH.sub.2 ; A represents an amino acid residue or an imino acid residue, which functional group may be optionally protected, or a glycine residue which may be substituted at the amino moiety thereof; and, Y1 represents a cycloalkyl group having 3 to 8 carbon atoms; or a salt thereof. The pyrrolidine derivatives inhibit a prolyl endopeptidase and are expected to be effective for the treatment of amnesia.

Pyrrolidine derivatives

A novel, biologically active substance, poststatin, has been isolated from a culture medium of microorganism belonging to Streptomyces. The novel substance is a peptide compound having a novel structure, wherein the peptide chains have ketone radicals. Thus substance has a high endopeptidase inhibition activity. It is possible to chemically synthesize poststatin related compound having ketone radicals in the peptide chains. These compounds also have an endopeptidase inhibition activity.

Poststatin and related compounds or salts thereof

The present invention discloses a new .alpha.-keto amide derivative or a salt thereof represented by the formula (1): ##STR1## wherein X represents (1) a peptide residue or amino acid residue in which the functional group may be protected, (2) a hydrogen atom or (3) an amino-protective group, Y represents a peptide residue or amino acid residue in which the functional group may be protected, E represents a substituent on the alkylene (C.sub.n H.sub.2n-1) and is a halogen, lower alkoxy or hydrogen, A represents a carbonyl group or mono- or di-substituted methylene (the substituent being a hydroxy, lower alkoxy, phenylimino or benzylimino), and n represents an integer of 2 to 6. The compound of the present invention is effective in inhibiting prolyl endopeptidase activity and useful as an active ingredient of an enzyme inhibitor.

.alpha.-keto amide derivatives

A novel actinonin derivative and a salt thereof are provided, which are useful as enzyme inhibitors and particularly have strong inhibitory activities against enkephalinase and angiotensin-converting enzymes. This actinonin derivative is represented by general formula (I): ##STR1## wherein R.sup.1 is sulfoxymethyl or carboxyl or a substituted carboxyl group selected from carboxamide, hydroxyaminocarbonyl and alkoxycarbonyl groups; and R.sup.2 is hydroxyl, alkoxy, hydroxyamino or sulfoxyamino group.

Actinonin derivatives and pharmaceutically acceptable salts thereof

Actinonin or a salt thereof is active as an inhibitor of angiogenesis in a mammal and is useful as a therapeutic agent for inhibiting angiogenesis in a mammal having diabetic retinopathy or inflammatory response accompanied by angiogenesis.

Pharmaceutical composition and method for angiogenesis inhibition

Benastatins A and B which are novel and physiologically active substances having the formula ##STR1## wherein R represents --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, exhibit a potent immunomodifier activity, a glutathione transferase inhibition activity and an anti-microorganism activity and are therefore extremely useful for various drugs.

Physiologically active substances, benastatins A and B, and production

New physiologically active substances, named probestin and prostatin, respectively, are produced from a new microorganism, Streptomyces azureus MH663-2F6 strain identified as FERM P-9541 or FERM BP-1963. Probestin and prostatin have an activity inhibitory to aminopeptidase M and also have immunopotentiating properties.

Physiologically active substances, probestin and prostatin and

As new compounds are provided a class of derivatives of actinonin represented by the general formula ##STR1## where R is a hydrogen or a lower alkyl group, which can exhibit the enzyme-inhibitory activities to a limited range of peptidases and show a remarkable enzyme-specificity, and which are effective to treat a cycloheximide-induced experimental amnesia in mice and are expectable to be useful to treat an amnesia in a mammalian animal, including human.

Actinonin derivatives having physiological activities

Known compound, optically active arphamenine A can now be synthesized in an optically active pure form and in a favorable yield by a new process comprising consecutive steps with starting from L-arginine, wherein racemization of intermediate reaction products can be minimized.

Synthesis of arphamenine A

New physiologically active substances, arphamenine A and arphamenine B which are generically termed arphamenine are produced from a new microorganism, BMG361-CF4 strain identified as FERM P-6521 or FERM BP-286 or ATCC No. 39373. Arphamenine is useful as a host defence stimulator having an activity to enhance cell-mediated immunity, and also as an anti-tumor agent.

New physiologically active substance, arphamenine and production thereof

Plipastatin represented by the general formula ##STR1## wherein R.sub.1 is --C.sub.13 H.sub.27 or --C.sub.14 H.sub.29 ; and R.sub.2 is Ala or Val, or salts thereof, which is prepared by culturing a Plipastatin-producing strain belonging to the genus Bacillus to produce and accumulate Plipastatin in a cultured broth and then isolating Plipastatin from the cultured broth. Plipastatin exhibits an enzyme inhibiting activity against phospholipase A.sub.2, C and D and which will be useful as an immunosuppressive agent or as a type I anti-allergic agent.

Plipastatin and method for preparation thereof

New 3-[N-(mercaptoacyl)]amino-4-arylbutanoic acid derivatives are now provided, which exhibit analgesic activity and are effective to enhance the analgesia induced by a known analgesic compound, ]D-ala.sup.2,met.sup.5 ]-enkephalin (DAME).

3-[N-(mercaptoacyl)]amino-4-arylbutanoic acid derivatives and an

A compound of the formula (I) ##STR1## which is identified as an actinonin has now been found to potentiate the immune response in animals bearing Ascites Sarcoma 180 tumor cells.

Pharmaceutical composition and method for immunopotentiation

Growing community of inventors

Fujisawa, Japan

Takaaki Aoyagi