# US 2010/0168149 A1 · Camptothecin Analogue Compounds, a Process for Their Preparation and Pharmaceutical Compositions Containing Them

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2010/0168149 A1
- Document ID: US20100168149A1
- Status: Published application
- Kind: A1
- Application number: 11/990,065
- Filed: 2006-08-04
- Published: 2010-07-01
- Earliest claimed: 2005-08-05
- Inventors: Gilbert Lavielle; Patrick Hautefaye; Alain Pierre; John Hickman; Stephane Leonce
- Web page: https://patentgrep.com/patent/US20100168149A1

## CPC

- C07D 471/14: Ortho-condensed systems
- A61P 35/00: Antineoplastic agents
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compound of formula (I): wherein: R1, R2, R3, R4, R5, R80, R90, R81, R91, Alk and G are as defined in the description. Medicinal products containing the same which are useful in the treatment of cancer diseases.

## Claims

### Claim at position 1

1-16. (canceled)

### Claim 17

A compound selected from those of formula (I):
wherein:
Alk represents an alkyl group,
R1, R2, R3, R4 and R5 are independently selected from a hydrogen atom, a halogen atom, an alkyl group, an alkenyl group, an alkynyl group, a polyhaloalkyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, a hydroxy group, a hydroxyalkyl group, an alkoxy group, an alkoxyalkyl group, a nitro group, a cyano group, an acyloxy group, a —C(O)—R group, and the groups —(CH2)p—NRaRb, —O—C(O)—NRaRb and —Z—Ar, wherein:
R represents an alkyl group, an alkoxy group or an amino group optionally substituted on the nitrogen atom by one or two alkyl groups;
p is an integer from 0 to 6;
Ra and Rb independently represent a hydrogen atom, an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an acyl group, an optionally substituted aryl group or an optionally substituted arylalkyl group, or Ra and Rb together with the nitrogen atom carrying them form a pyrrolyl, piperidyl or piperazinyl group, wherein each of these cyclic groups may be optionally substituted;
Z represents a bond, an oxygen atom, a sulphur atom or a group selected from —Z′—S(O)—, —S(O)r—Z′— and —Z′—(CRcRd)q—Z″—;
Ar represents an optionally substituted aryl or an optionally substituted heteroaryl group;
Z′ and Z″, which are the same or different, represent an oxygen atom, a sulphur atom, a group —NRe— or a bond;
Rc, Rd and Re which are the same or different, represent a hydrogen atom or an alkyl group;
q represents an integer from 1 to 6;
and r represents an integer 1 or 2;
or two adjacent groups from R2, R3, R4 and R5 together with the carbon atoms carrying them form a group -T-(CRgRh)t-T′-, wherein T and T′, which are the same or different, represent an oxygen atom, a sulphur atom or a group N—Ri; Rg and Rh, which are the same or different, represent a hydrogen atom or a halogen atom; t is an integer from 1 to 3 inclusive; and Ri represents a hydrogen atom, an alkyl group or a benzyl group,
R80 and R90 independently represent a hydrogen atom, a hydroxy group, an alkyl group or an alkoxy group,
R81 and R91 independently represent a hydrogen atom, an alkyl group, an alkenyl group or an alkynyl group, or, R81 and R91 together form a bond or an oxirane group, or two geminal groups, R80 and R81, and/or R90 and R91 together form an oxo group or a group —O—(CH2)t1—O—, t1 represents an integer from 1 to 3 inclusive,
G represents a group *—XH or *—X—C(X′)-Alk′-G′, wherein:
* represents the point of attachment to the C7 carbon atom;
X and X′, which are the same or different, represent an oxygen atom, a sulphur atom, an amino group or an alkylamino group;
Alk′ represents an alkylene, alkenylene or alkynylene chain;
G′ represents a hydrogen atom or a group NR6R7 wherein:
i) R6 and R7 represent, each independently of the other, a hydrogen atom, an alkyl group, a cycloalkyl group, an optionally substituted aryl group, an optionally substituted arylalkyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted heteroaryl group or an optionally substituted heteroarylalkyl group,
ii) or R6 and R7 together with the nitrogen atom carrying them form a 5- to 8-membered monocyclic heterocycloalkyl group
or a 5- to 11-membered bicyclic heterocycloalkyl group
wherein:
Y represents a nitrogen atom, an oxygen atom or a CH2 group and
R8 represents a hydrogen atom, an alkyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted aryl group, an optionally substituted arylalkyl group, an optionally substituted heterocycloalkyl group, an optionally substituted heterocycloalkylalkyl group, an optionally substituted heteroaryl group or an optionally substituted heteroarylalkyl group,
its enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base,
it being understood that at least one of the substituents R1 to R5 represents a group —Z—Ar,
and it being understood that:
alkyl means a linear or branched chain of from 1 to 6 carbon atoms,
alkenyl means a linear or branched chain of from 2 to 6 carbon atoms containing from 1 to 3 double bonds,
alkynyl means a linear or branched chain of from 2 to 6 carbon atoms containing from 1 to 3 triple bonds,
alkylene means a linear or branched divalent radical containing from 1 to 6 carbon atoms,
alkenylene means a linear or branched divalent radical containing from 2 to 6 carbon atoms and from 1 to 3 double bonds,
alkynylene means a linear or branched divalent radical containing from 2 to 6 carbon atoms and from 1 to 3 triple bonds,
acyl means a linear or branched alkyl-carbonyl radical containing from 1 to 6 carbon atoms,
alkoxy means an alkyl-oxy radical, the alkyl group of which is linear or branched and contains from 1 to 6 carbon atoms,
acyloxy means an acyl-oxy radical, the acyl group of which is a linear or branched alkylcarbonyl radical,
aryloxyalkyl means an aryl-oxy-alkyl group, the alkyl group of which is linear or branched and contains from 1 to 6 carbon atoms,
arylalkyl, cycloalkylalkyl, heteroarylalkyl and heterocycloalkylalkyl mean aryl-alkyl, cycloalkyl-alkyl, heteroaryl-alkyl and heterocycloalkyl-alkyl radicals, the alkyl group of which is a linear or branched chain of from 1 to 6 carbon atoms,
polyhaloalkyl means a linear or branched carbon chain containing from 1 to 3 carbon atoms and from 1 to 7 halogen atoms,
halogen means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom,
aryl means a phenyl, naphthyl, indanyl, indenyl, dihydronaphthyl or tetrahydronaphthyl group,
cycloalkyl means a monocyclic or bicyclic hydrocarbon group containing from 3 to 11 carbon atoms and optionally being unsaturated with 1 or 2 unsaturated bonds,
heteroaryl means a monocyclic or bicyclic group wherein at least one of the rings is aromatic, containing from 5 to 11 ring members and containing from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulphur,
heterocycloalkyl means a mono- or bi-cyclic group which is saturated or unsaturated with 1 or 2 unsaturated bonds, containing from 4 to 11 ring members and containing from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulphur,
the expression “optionally substituted” when referring to aryl or arylalkyl, cycloalkyl or cycloalkylalkyl, heteroaryl or heteroarylalkyl, and heterocycloalkyl or heterocycloalkylalkyl groups means that these respective aryl, cycloalkyl, heteroaryl and heterocycloalkyl groups may be substituted by from 1 to 3 identical or different substituents selected from a halogen atom and the groups alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, hydroxy, mercapto, cyano, nitro, amino optionally substituted by one or two alkyl groups, acyl, formyl, aminocarbonyl optionally substituted on the nitrogen atom by one or two alkyl groups, acylamino optionally substituted on the nitrogen atom by an alkyl group, alkoxycarbonyl, carboxy and sulpho,
the expression “optionally substituted” when referring to the groups pyrrolyl, piperidyl or piperazinyl means that these groups may be substituted by from 1 to 3 identical or different groups selected from alkyl, alkoxy, aryl, arylalkyl, aryloxy and aryloxyalkyl.

### Claim 18 (depends on 17)

The compound of claim 17, wherein Alk represents an ethyl group.

### Claim 19 (depends on 17)

The compound of claim 17, wherein R80 and R81 together form an oxo group, or wherein R90 and R91 together form an oxo group, or wherein R80 and R81 and also R90 and R91 form two oxo groups.

### Claim 20 (depends on 17)

The compound of claim 17, wherein R5 represents a hydrogen atom.

### Claim 21 (depends on 17)

The compound of claim 17, wherein R3 and R4 together form a methylenedioxy or ethylenedioxy group.

### Claim 22 (depends on 17)

The compound of claim 17, wherein R2 represents a hydrogen atom.

### Claim 23 (depends on 17)

The compound of claim 17, wherein R1 represents an optionally substituted aryl group or an optionally substituted arylalkyl group.

### Claim 24 (depends on 17)

The compound of claim 17, wherein G represents a hydroxy group.

### Claim 25 (depends on 17)

The compound of claim 17, wherein G represents *—X—C(X′)-Alk′-G′ wherein G′ represents a hydrogen atom.

### Claim 26 (depends on 17)

The compound of claim 17, wherein G represents a group *—X—C(X′)-Alk′-NR6R7 wherein R6 and R7 form together with the nitrogen atom carrying them a 5- to 8-membered monocyclic heterocycloalkyl group
wherein Y represents a nitrogen atom, an oxygen atom or a group CH2 and R8 represents a hydrogen atom or an alkyl group.

### Claim 27 (depends on 17)

The compound of claim 17, wherein Alk′ represents an alkylene group.

### Claim 28 (depends on 17)

The compound of claim 17, wherein X and X′, which are the same or different, represent an oxygen atom or a sulphur atom.

### Claim 29 (depends on 17)

The compound of claim 17, which is 7-ethyl-7-hydroxy-2,3-methylenedioxy-13-(4-methylphenyl)-9,12-dihydro-7H-cyclopenta[6,7]indolizino[1,2-b]quinoline-8,10-dione, its enantiomers, and addition salts thereof with a pharmaceutically acceptable acid or base.

### Claim 30 (depends on 17)

A pharmaceutical composition comprising as active ingredient at least one compound of claim 17, alone or in combination with one or more inert, non-toxic, pharmaceutically acceptable excipients or carriers.

### Claim 31 (depends on 17)

A method of treating a living animal body, including a human, afflicted with a cancer disease, comprising the step of administering to the living animal body, including a human, an amount of a compound of claim 17 which is effective for treatment of the disease.