# US 8,785,629 B2 · Phosphonates synthons for the synthesis of phosphonates derivatives showing better bioavailability

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- Number: US 8,785,629 B2
- Document ID: US8785629B2
- Status: Granted
- Kind: B2
- Application number: 13/377,652
- Filed: 2010-06-17
- Published: 2012-06-07
- Granted: 2014-07-22
- Earliest claimed: 2009-06-18
- Assignees: Centre National De La Recherche Scientifique; Universite D'Orleans
- Applicants: Luigi A. Agrofoglio; Vincent Roy; Ugo Pradere
- Inventors: Luigi A. Agrofoglio; Vincent Roy; Ugo Pradere
- Web page: https://patentgrep.com/patent/US8785629B2

## CPC

- C07F 9/4075: {Esters with hydroxyalkyl compounds}
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07F 9/4006: {Esters of acyclic acids which can have further substituents on alkyl}
- C07F 9/4015: {Esters of acyclic unsaturated acids}
- C07F 9/6512: having the nitrogen atoms in positions 1 and 3
- C07F 9/65616: {containing the ring system [IMAGE cpc-sch-C07F-1006.gif] having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs}
- 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

Synthons for the synthesis of phosphonates prodrugs POM and POC, especially for direct Cross Metathesis.

## Claims

### Claim 1

A compound of formula (I)
wherein
R represents
a group of formula (1)
wherein R1 represents H, a straight or branched (C1-C6) alkyl group or a —(CH2)m—R2 group with R2 selected from the group consisting of hydrogen, halogen, OH, N3, NH2, epoxy groups, leaving groups and carbonyl groups and m is an integer from 0 to 5,
represents a double or a triple bond,
p being equal to 0 when is a triple bond and equal to 1 when
is a double bond or,
R=R2 with R2 selected from the group consisting of hydrogen, halogen, OH, N3, NH2, epoxy groups and analogs, leaving groups, leaving groups involved into a transmetalation step catalyzed by Pd(0), and carbonyl groups,
n is an integer from 0 to 5
X and Y independently of each other represent hydrogen, halogen or a straight or branched (C1-C6)alkyl group or an hydroxymethyl group, and
R′ and R″ independently of each other
represent a group selected from the group consisting of
an oxymethylcarbonyl group of formula (2)
wherein
R1 and R′1 are independently of each other hydrogen or (C1-C4)alkyl group and
R′2 is a straight or branched (C1-C6)alkyl group or straight or branched (C1-C6)alkoxy group
with the proviso that when R is cis-propenyl
n=0 and R′2 is methyl, then R1 and R′1 are not simultaneously hydrogen,
a thioethylcarbonyl group of formula (3)
wherein
R3 is a straight or branched (C1-C6) alkyl group
a lipohilic chain selected from the group consisting of hexadecyloxypropyl (HDP)-, octadecyloxyethyl-, oleyloxypropyl-, and oleyloxyethyl-esters with the proviso that when n=0 then R is not the cis-propenyl
or
R′ and R″ form with the phosphate atom to which they are linked a cycloalkyle group of formula (4)
wherein R4, R5, R6, and R7 each independently represent a straight or branched (C1-C6)alkyl or aryl group or R4 and R7 independently represent a straight or branched (C1-C6) alkyl or aryl group or R5 and R6 form together an aromatic ring, said aromatic ring being optionally substituted
with the proviso that
are excluded.

### Claim 2 (depends on 1)

The compound according to claim 1, corresponding to formula
wherein
is a group
with R1 as defined above.

### Claim 3 (depends on 1)

The compound according to claim 1, corresponding to formula
wherein R is equal to R2 as defined above.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein the compound is selected from the group consisting of:

### Claim 5 (depends on 1)

The compound of claim 1, wherein the compound is selected from the group consisting of: