# US 5,707,979 A · Phosphinic acid derivatives, their preparation and their use

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- Number: US 5,707,979 A
- Document ID: US5707979A
- Status: Granted
- Kind: A
- Application number: 08/495,977
- Filed: 1995-06-28
- Granted: 1998-01-13
- Earliest claimed: 1994-06-30
- Assignees: Hoechst Aktiengesellschaft
- Inventors: Anuschirwan Peyman; Wilhelm Stahl; Karl-Heinz Budt; Dieter Ruppert; Henning Schussler; Konrad Wagner
- Web page: https://patentgrep.com/patent/US5707979A

## CPC

- C07F 9/6584: having one phosphorus atom as ring hetero atom
- A61P 31/12: Antivirals
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compounds of the formula I, ##STR1## in which the symbols or substituents A, B, D, D*, E and E* have the meanings given in the specification, inhibit aspartyl proteases and are suitable for controlling viral diseases.

## Claims

### Claim 1

A compound of the formula I ##STR9## in which A is a radical of the formula IIa, ##STR10## in which Y is oxygen;
R.sup.1 is oxygen;
R.sup.2 is
hydrogen,
(C.sub.1 -C.sub.6)-alkyl,
(C.sub.7 -C.sub.13)-arylalkyl,
(C.sub.6 -C.sub.12)-aryl,
all of which are unsubstituted or substituted by hydroxyl,
(C.sub.1 -C.sub.10)-alkyl, (C.sub.1 -C.sub.3)-alkoxy, F, Cl or Br;
an equivalent of a physiologically tolerated salt, or
a residue of a phosphinic acid prodrug;
B is a radical of the formula IIIa ##STR11## where L is oxygen; D and D* are, independently of each other,
R.sup.6 {(C.sub.1 -C.sub.6)-alkyl},
where the alkyl is saturated or unsaturated, branched or unbranched,
where R.sup.6 is
(C.sub.6 -C.sub.12)-aryl, unsubstituted or substituted by R.sup.7 ; or
(C.sub.3 -C.sub.12)-cycloalkyl, unsubstituted or substituted by R.sup.7 ;
where R.sup.7 is, independently of each other,
--R.sup.8
where R.sup.8 is
hydrogen, or
(C.sub.1 -C.sub.6)-alkyl, unsubstituted or substituted by hydroxyl;
E and E* are benzyl.

### Claim 2 (depends on 1)

A compound of the formula I as claimed in claim 1, in which A is a radical of the formula IIa, R.sup.2 is
hydrogen,
(C.sub.1 -C.sub.4)-alkyl,
an equivalent of a physiologically tolerated salt, or
a residue of a phosphinic acid prodrug;
D and D* are, independently of each other, R.sup.6 --CH.sub.2 --, where R.sup.6 is (C.sub.6 -C.sub.12)-aryl which is unsubstituted or substituted once by R.sup.7,
where R.sup.7 is
--R.sup.8,
--F, --Cl or --Br, where
R.sup.8 is
hydrogen,
(C.sub.1 -C.sub.6)-alkyl which is unsubstituted or substituted by hydroxyl or Br, and
E and E* are benzyl.

### Claim 3 (depends on 1)

A compound of the formula 1 as claimed in claim 1, in which
R.sup.2 is
hydrogen,
(C.sub.1 -C.sub.4)-alkyl, or
an equivalent of a physiologically tolerated salt,
and D is benzyl which is substituted by R.sup.8, where
R.sup.8 is hydrogen,
(C.sub.1 -C.sub.3)-alkyl, unsubstituted or substituted by hydroxyl or Br.

### Claim 4 (depends on 1)

A process for preparing a compound of the formula I as claimed in claim 1, which comprises reacting a compound of the formula IV ##STR12## in which A, E and E* are as defined in claim 1, with an activated carbonic acid derivative or an oxalic acid derivative to form a cyclic urea or a cyclic oxalic acid diamide of the formula V ##STR13## in which A, E, E* and B are defined in claim 1 and said compound of the formula V is subsequently alkylated to form a compound of the formula I, or which comprises alkylating the compound of the formula IV to form an intermediate compound and subsequently cyclizing the intermediate compound to form a compound of the formula I.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising an effective quantity of at least one compound of the formula I as claimed in claim 1.

### Claim 6 (depends on 5)

A process for preparing a pharmaceutical composition as claimed in claim 5, which comprises bringing an effective quantity of a compound of the formula I into a suitable form for administration together with customary pharmaceutical auxiliary substances.

### Claim 7 (depends on 1)

A process for treating a disease responsive to aspartyl protease inhibition caused by a virus which process comprises administering an effective amount of a compound of the formula I as claimed in claim 1.

### Claim 8 (depends on 7)

A process for treating a disease as claimed in claim 7, wherein said disease is caused by HIV.