Fujirebio Kabushiki Kaisha

Seikagaku Kogyo Kabushiki Kaisha

Fujirebio Inc.

Akihiko Hosoda

Hajime Matsumoto

Yasuo Sekine

Nobuo Kobayashi

Tsuneo Koji

Akihiro Sekine

Noriaki Kashiwaba

Yoshikazu Isowa

Masashi Nishikawa

Takashi Fujita

Nobuhiko Hirakawa

Tomofumi Nishimura

Masahiro Shibata

Hiroshi Ikawa

Tetsuaki Yamaura

Masakatsu Matsumoto

Masato Nishimura

Masaharu Dozen

Naoko Tanabe

Tetsuaki Yamura

The present invention is to provide manufacturing intermediates which can be led to useful &#x3b1;-ketoamide compounds having protease-inhibiting activity extremely economically and stereoselectively, and to provide epoxycarboxamide compounds, azide compounds and amino alcohol compounds represented by the following formulae: 

Epoxycarboxamide compound, azide compound, and amino alcohol compound, and process for preparing &#x3b1;-keto amide compound using them

Epoxycarboxamide compound, azide compound, and amino alcohol compound, and process for preparing alpha-keto amide compound using them

A cyclic amide derivative of formula (I): ##STR1## wherein R.sup.1 represents a substituted alkyl group, a substituted alkenyl group, a substituted amino group, a substituted alkoxyl group, a substituted alkylthio group, a substituted carbamoyl group, a substituted sulfonamide group or a substituted amide group; the ring A represents a saturated cyclic alkyl group with 5 to 7 carbon atoms or a hetero-atom-containing saturated heterocyclic group with 3 to 6 carbon atoms; R.sup.2 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group; R.sup.3 represents a hydrogen atom, a group represented by the general formula R.sup.4 O-- or a group represented by the general formula R.sup.5 (R.sup.6)N-- wherein R.sup.4 represents hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group; R.sup.5 and R.sup.6 may be the same or different and each represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group. The cyclic amide derivative of formula (I) have a strong and selective inhibitory action of a cathepsin K and a clinical efficacy when administered orally.

Cyclic amide derivatives

A method of producing an aminobutene derivative of formula (I) by allowing a butenol derivative of formula (II) to react with an amide derivative of formula (III) is disclosed. The aminobutene derivative of formula (I) can be deprotected to produce an aminobutene derivative of formula (I-1) or an aminobutene derivative of formula (I-2): ##STR1## The aminobutene derivative of formula (I-A) can also be deprotected to produce the aminobutene derivative of formula (I-B). Any or all of the above aminobutene derivatives are useful as intermediates for producing anti-ulcer drugs, and anti-ulcer drugs having an inhibitory effect on gastric acid secretion based on the antagonism against histamine H.sub.2 receptor.

Methods of producing aminobutene derivatives

A phenoxypropyl derivative represented by the following formula ##STR1## wherein A represents a formyl group, a protected formyl group, a hydroxymethyl group, a protected hydroxymethyl group, or a halomethyl group, and Z represents a halogen atom, an amino group, a phthalimide group or a group of the formula ##STR2## in which n is 0, 1 or 2.

Phenoxypropyl derivatives

The compounds of the formulas (VI) and (VII) are useful intermediates in producing pyridyloxy derivatives of the formula (I), such as, for instance, N-{4-[4-(piperidinomethyl)pyridyl-2-oxy]-2-butenyl}-2-(furfurylt hio)acetamide, which are useful as anti-peptic ulcer agents. The compounds of formula (VI) have the formula ##STR1## wherein A represents a formyl group, a protected formyl group, a hydroxymethyl group or a protected hydroxymethyl group. The compounds of formula (VIII) have the formula ##STR2## wherein G represents a formyl group, a protected formyl group, a hydroxymethyl group, a hydroxymethyl group in which the hydroxyl group is protected, or a halogenomethyl group, Y represents --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, and n is 0, 1 or 2.

Intermediates for pyridyloxy compounds having utility as anti-peptic

A compound represented by the following formula or a salt thereof ##STR1## wherein each of R.sub.1 and R.sub.2 represents a lower alkyl group, or R.sub.1 and R.sub.2, together with the nitrogen atom to which they are bonded, may form a substituted or unsubstituted, saturated or partially unsaturated 4- to 8-membered heterocyclic group which may contain a hetero atom selected from N, O and S, Y represents a group of the formula --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, and n is 0, 1 or 2. This compound is useful as anti-peptic ulcer agent.

4-aminomethyl-pyridyl-2-oxy derivatives having anti-ulcer activity

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Shiki, Japan

Akihiko Hosoda