Pyrroloimidazole derivatives and their use as medicaments

• US 6,699,883 B1
• Filed: 04/04/2002
• Issued: 03/02/2004
• Est. Priority Date: 10/07/1999
• Status: Expired due to Fees

• Current Assignee: Morphochem AG (Deinove SA)
• Original Assignee: Morphochem AG (Deinove SA)
• Inventors: Beck, Barbara, Doemling, Alexander
• Primary Examiner(s): DENTZ, BERNARD I
• Application Number:
  US10/089,917
• Time in Patent Office: 698 Days
• Field of Search: 548/312.1, 514/397, 514/323, 546/201
• US Class Current: 514/323
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The present invention relates to 3-pyrroloimidazole derivatives of the general formula (I)

wherein the imidazole radical is an optionally substituted imidazole ring, X, Y, A and B are, each independently of the others, carbon or nitrogen atoms, the radicals Z denote, each independently of the others, a hydrogen atom, a halogen atom, a pseudohalogen, an optionally substituted alkyl, alkenyl, alkynyl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloaralkyl, cycloaralkenyl, cycloaralkynyl, aryl or alkoxy radical or an optionally substituted ring, to which one or two further, optionally substituted rings may be fused, and/or at least two of the radicals Z may be part of an optionally substituted ring, to which one or two further, optionally substituted rings may be fused, and to pharmaceutical compositions comprising at least one of the above-mentioned compounds, optionally in combination with carriers and/or adjuvants and/or excipients customary per se.

Claims

1. A compound of the formula (II)

wherein

R1 is a hydrogen, an optionally substituted aryl or heteroaryl radical;

R2 is a halogen atom, pseudohalogen, an optionally substituted alkyl, alkenyl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloaralkyl, cycloaralkenyl, cycloaralkynyl, aryl or alkoxy radical or a non-aromatic or aromatic or partially aromatic heterocyclic ring;

At least two of the radicals Z taken together are part of an optionally substituted carbocyclic ring, to which one or two further, optionally substituted rings may be fused;

other occurrences of radicals Z in formula (II) denote, each independently of the others, a hydrogen atom, a halogen atom, a pseudohalogen, an optionally substituted alkyl, alkenyl, alkynyl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloaralkyl, cycloaralkenyl, cycloaralkynyl, aryl or alkoxy radical and/or an optionally substituted ring, to which one or two further, optionally substituted, rings may be fused.

2. A compound according to claim 1, which has the following formula:

wherein

at least two of the radicals Z taken together are part of an optionally substituted carbocyclic ring, to which one or two further, optionally substituted rings may be fused;

the other occurrence of radical Z can denote, a hydrogen, a halogen, a pseudohalogen, an optionally substituted alkyl, alkenyl, alkynyl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloaralkyl, cycloaralkenyl, cycloaralkynyl, aryl or alkoxy radical or an optionally substituted ring, to which one or two further, optionally substituted, rings may be fused.

3. A compound according to claim 2, wherein the radicals Z on adjacent carbon atoms of the pyrrole ring are part of an optionally substituted phenyl ring.

4. A compound according to one of the preceding claims, wherein R1 is an optionally substituted phenyl ring.

5. A compound according to any one of claims 1-3, wherein R2 is a cycloalkyl, to which an aryl or heteroaryl is fused.

6. Pharmaceutical composition comprising at least one 3-pyrroloimidazole derivative according to any one of claims 1-3, optionally in combination with carriers and/or adjuvants and/or excipients customary per se.

7. Pharmaceutical composition according to claim 6, which is formulated as a patch, ointment, paste, gel, cream, soluble powder, lotion, emulsion, spray, powder, suspension, suppository or injection solution.

8. Pharmaceutical composition according to claim 6, comprising at least one conjugate comprising a tumour-specific antibody and one or more compounds according to one of the preceding claims.

9. Pharmaceutical composition according to claim 6, wherein the active ingredients and, where applicable, the conjugates with tumour-specific antibodies are packed in liposomes.

10. A method of treatment or prevention of a tumour or cancer disease, the method comprising administering to a patient a 3-pyrroloimidazole derivative according to one of claims 1-3 or pharmaceutical composition thereof.

11. The method according to claim 10, characterized in that the tumour or cancer diseases are benign and malignant tumours that are solid or cystic in nature, adenomas, cystadenomas, papilloimas, adenocarcinonmas, adenocarcinonmas of the cirrhotic typo, basal cell carcinomas, sarcomas, fibrosarcomas, liposarcomas, lymphosarcomas, rhabdomyosarcomas, myxosarcomas, chondrosarcomas, reticulum cell sarcomas, Hodgkin'"'"'s disease, embryonal tumours, neuroblastomas, nephtoblastomas, teratomas, adamantinomas, retroblastomas, haemangiomas, chordomas, odontomas, craniophacyngomas, hamartomas, lymphoangiomas, exostoses, neurofibrantosis, melanomas, lymphomas, hepatoblastomas, mammary carcinomas, cervical carcinomas, choriocarcinomas, adenoacanthomas, androblastomas, leiomyomas, arrhenoblastomas, Sertoli'"'"'s cell tumours, theca and granulosa cell tumours, germinomas and seminomas, ovarian and vulvar carcinomas, urinary bladder and prostate carcinomas, tumours caused by schistosomiasis, astrocytomas, ependymogliomas, glioblastomas, medulloblastoma, oligodendrogliomas, spongioblastomas, meningeomas, tumours of Schwann'"'"'s sheath cells, pinealomas, haemangioblastomas, osteoclastomas, Ewing'"'"'s tumours, multiple myelomas, mycosis fungoides, Burkitt'"'"'s tumours, leukaemias, acute and chronic lymphatic leukaemias, acute and chronic granulocytic leukaemias, acute and chronic monocytic leukaemias, stem cell leukaemias, basaliomas, fibromas, myomas, and metastases of any form of tumour that are accessible by surgical intervention in the form of a local injection.

12. A method for treatment or prevention of an infection by micro-organisms, the method comprising the administration of a 3-pyrroloimidazole derivative of any one of claims 1-3 or pharmaceutical composition thereof having antibiotic activity against micro-organisms.

13. A method of treatment or prevention according to claim 10, characterized in that the 3-pyrroloimidazole derivatives or pharmaceutical compositions are administered to the patient locally or systemically.

14. Pharmaceutical composition according to claim 7, comprising at least one conjugate comprising a tumour-specific antibody and one or more compounds according to one of the preceding claims.

15. Pharmaceutical composition according to claim 7, wherein the active ingredients and, where applicable, the conjugates with tumour-specific antibodies are packed in liposomes.

16. Pharmaceutical composition according to claim 8, wherein the active ingredients and, where applicable, the conjugates with tumor-specific antibodies are packed in liposomes.

17. Pharmaceutical composition according to claim 14, wherein the active ingredients and, where applicable, the conjugates with tumour-specific antibodies are packed in liposomes.