# US 2010/0168104 A1 · Hiv inhibiting 5-amido substituted pyrimidines

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- Number: US 2010/0168104 A1
- Document ID: US20100168104A1
- Status: Published application
- Kind: A1
- Application number: 12/294,692
- Filed: 2007-03-30
- Published: 2010-07-01
- Earliest claimed: 2006-03-30
- Assignees: Janssen R&D Ireland
- Inventors: Jerôme Emile Georges Guillemont; Mikaël Paugam; Bruno François Marie Delest
- Web page: https://patentgrep.com/patent/US20100168104A1

## CPC

- C07D 417/12: linked by a chain containing hetero atoms as chain links
- A61P 31/18: for HIV
- C07D 239/48: Two nitrogen atoms
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention concerns pyrimidine derivatives of formula having HIV (Human Immunodeficiency Virus) replication inhibiting properties, the preparation thereof and pharmaceutical compositions comprising these compounds.

## Claims

### Claim 1

A compound of formula
or a stereochemically isomeric form thereof, or a pharmaceutically acceptable addition salt thereof, or a pharmaceutically acceptable hydrate or solvate thereof, or a N-oxide thereof, wherein
each R1 independently is hydrogen; aryl; formyl; C1-6alkylcarbonyl; C1-6alkyl; C1-6alkyloxycarbonyl;
R2, R3, R7 and R8 independently are hydrogen; hydroxy; halo; C3-7cycloalkyl; C1-6alkyloxy; carboxyl; C1-6alkyloxycarbonyl; cyano; nitro; amino; mono- or di(C1-6alkyl)amino; polyhaloC1-6alkyl; polyhaloC1-6alkyloxy; —C(═O)R10; C1-6alkyl optionally substituted with halo, cyano, or —C(═O)R10; C2-6alkenyl optionally substituted with halo, cyano or —C(═O)R10; C2-6alkynyl optionally substituted with halo, cyano, or —C(═O)R10;
R4 and R9 independently are hydroxy; halo; C3-7cycloalkyl; C1-6alkyloxy; carboxyl;
C1-6alkyloxycarbonyl; formyl; cyano; nitro; amino; mono- or di(C1-6alkyl)amino; polyhaloC1-6alkyl; polyhaloC1-6alkyloxy; —C(═O)R10; —S(═O)rR10; —NH—S(═O)rR10; —NHC(═O)H; —C(═O)NHNH2; —NHC(═O)R10; Het; -Y-Het; C1-12alkyl optionally substituted with halo, cyano, amino, mono- or di(C1-6alkyl)amino, —C(═O)—R10, Het or with C1-6alkyloxy; C2-12alkenyl optionally substituted with halo, cyano, amino, mono- or di(C1-6alkyl)amino, —C(═O)—R10, Het or with C1-6alkyloxy; C2-12alkynyl optionally substituted with halo, cyano, amino, mono- or di(C1-6alkyl)amino, —C(═O)—R10, Het, or with C1-6alkyloxy;
R5 is C3-7cycloalkyl; C1-6alkyloxy; aryl; Het; C1-6alkyl substituted with a radical selected from hydroxy, C1-6alkyloxy, cyano, amino, mono- and di-C1-6alkylamino, C1-6alkylcarbonylamino, aryl, Het, dioxolanyl optionally substituted with one or two C1-6alkyl radicals, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, piperazinyl optionally substituted with C1-6alkyl or C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, arylC1-6alkyloxycarbonyl, and C3-7cycloalkyl; or R5 is C1-6alkyl substituted with two C1-6alkyloxy radicals;
R6 is hydrogen or C1-6alkyl; or
R5 and R6 taken together with the nitrogen atom to which they are attached form pyrrolidinyl; piperidinyl; morpholinyl; piperazinyl; piperazinyl optionally substituted with C1-6alkyl or C1-6alkylcarbonyl;
each R10 independently is C1-6alkyl, amino, mono- or di(C1-6alkyl)amino, or
polyhalo-C1-6alkyl;
X is —NR1—, —O—, —C(═O)—, —CH2—, —CHOH—, —S—, —S(═O)r—;
each Y independently is —NR1—, —O—, —C(═O)—, —S—, —S(═O)r—;
each r independently is 1 or 2;
each Het independently is pyridyl, thienyl, furanyl, oxazolyl, thiazolyl, thiadiazolyl, oxadiazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyrazolyl, quinolinyl, benzothienyl, benzofuranyl, benzoxazolyl, benzothiazolyl; which each may optionally be substituted with one or two substituents each independently selected from C1-6alkyl, halo, hydroxy, cyano, C1-6alkyloxy, C2-12alkenyl substituted with halo, hydroxy or with cyano;
each aryl independently is phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, hydroxyC1-6alkyl, aminoC1-6alkyl, mono and di(C1-6alkyl)-amino-C1-6alkyl, C1-6alkylcarbonyl, C3-7cycloalkyl, C1-6alkyloxy, phenylC1-6alkyloxy, C1-6alkyloxycarbonyl, aminosulfonyl, C1-6alkylthio, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, phenyl, Het, and -Y-Het.

### Claim 2 (depends on 1)

A compound according to claim 1 wherein the compound is of formula
wherein X, R1, R4, R5, R6, R7, R8 and R9 are as defined in claim 1.

### Claim 3 (depends on 1)

A compound according to claim 1 wherein R1 is hydrogen.

### Claim 4 (depends on 1)

A compound according to claim 1 wherein R2, R3, R7 and R8 independently are hydrogen; hydroxy; halo; C1-6alkyl; C1-6alkyloxy; cyano; amino; mono- or di(C1-6alkyl)amino; polyhaloC1-6alkyl.

### Claim 5 (depends on 1)

A compound according to claim 1 wherein R4 and R9 independently are cyano; C1-6alkyl substituted with cyano; C2-6alkenyl substituted with cyano.

### Claim 6 (depends on 1)

A compound according to claim 1 wherein R5 is C3-7cycloalkyl; C1-6alkyloxy; aryl; Het; C1-6alkyl substituted with a radical selected from hydroxy, C1-6alkyloxy, cyano, di-C1-6alkylamino, C1-6alkylcarbonylamino, aryl, Het, dioxolanyl substituted with two C1-6alkyl radicals, tetrahydrofuranyl, pyrrolidinyl, C1-6alkyloxycarbonyl, and C3-7cycloalkyl;
R6 is hydrogen or C1-6alkyl; or
R5 and R6 taken together with the nitrogen atom to which they are substituted form morpholinyl; piperazinyl substituted with C1-6alkyl;

### Claim 7 (depends on 1)

A compound according to claim 1 wherein R5 is C3-7cycloalkyl; C1-6alkyloxy; C1-6alkyl substituted with a radical selected from hydroxy, C1-6alkyloxy, cyano, C1-6alkylcarbonylamino, aryl, Het, C1-6alkyloxycarbonyl;
R6 is hydrogen;

### Claim 8 (depends on 1)

A compound according to claim 1 wherein each Het independently is pyridyl, thienyl, thiazolyl, furanyl, each of which may be optionally substituted with a radical selected from C1-6alkyl.

### Claim 9 (depends on 1)

A compound according to claim 1 wherein each aryl independently may be phenyl optionally substituted with C1-6alkyl. amino, mono- or diC1-6alkyl-amino, C1-6alkyloxy, aminosulfonyl, Het, the latter more in particular being thiadiazolyl

### Claim 10 (depends on 1)

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredient a therapeutically effective amount of a compound as claimed in claim 1.