KETOLIDE ANTIBIOTICS - PFIZER PROD INC

Title:

KETOLIDE ANTIBIOTICS

Document Type and Number:

WIPO Patent Application WO/2000/044761

Kind Code:

A2

Abstract:

This invention relates to compounds of formula (1) and to pharmaceutically acceptable salts and solvates thereof wherein X?1¿, X?2¿, R?2¿, R?8¿, R?9¿, R?10¿ and R?11¿ are as defined herein. The compounds of formula (1) are antibacterial and antiprotozoal agents that may be used to treat various bacterial and protozoal infections and disorders related to such infections. The invention also relates to pharmaceutical compositions containing the compounds of formula (1) and to methods of treating bacterial and protozoal infections by administering the compounds of formula (1).

Inventors:

KANEKO TAKUSHI (US)
MCMILLEN WILLIAM THOMAS (US)

Application Number:

PCT/IB1999/002051

Publication Date:

August 03, 2000

Filing Date:

December 28, 1999

Export Citation:

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Assignee:

PFIZER PROD INC (US)
KANEKO TAKUSHI (US)
MCMILLEN WILLIAM THOMAS (US)

International Classes:

A61K31/7048; A61P1/00; A61P1/04; A61P9/10; A61P11/00; A61P11/02; A61P13/02; A61P15/00; A61P15/02; A61P15/04; A61P15/14; A61P17/00; A61P27/02; A61P27/16; A61P31/00; A61P31/04; A61P31/06; A61P33/02; C07H17/00; C07H17/08; (IPC1-7): C07H17/00

Domestic Patent References:

WO1999025365A1

1999-05-27

Foreign References:

US5747467A	1998-05-05
EP0949268A1	1999-10-13
EP1026170A1	2000-08-09
EP1004592A1	2000-05-31
EP1016669A1	2000-07-05

Attorney, Agent or Firm:

Spiegel, Allen J. (235 East 42nd Street New York, NY, US)

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Claims:

CLAIMS

1.

A compound of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: X'is O,CR'R5orNR4 ; X² is =O or =NOR¹; R'is H or C,C, o alkyl, wherein 1 to 3 carbons of said alkyl are optionally replaced by a heteroatom selected from O, S andN (R 4) _, and said alkyl is optionally substituted by 1 to 3 substituents independently selected from the group consisting ofC (O) O (C,C, o alkyl), C,C, o alkoxy, C,C, o alkanoyl, halo, nitro, cyano, 410 membered heterocyclyl, C,C, o alkyl,NR4R55, C6C, o aryl,S (O)" (C,C, o alkyl) wherein n is an integer ranging from 0 to 2, andS02NR4Rs; R2 is (CRRS)" (410 membered heterocyclic) or ~ (CR4Rs) n (C6~Cro aryl), wherein n is an integer from 0 to 6, from 1 to 3 R4 or Rs groups of the (CR4R5)n moiety of the foregoing R2 groups are optionally replaced with a halo substituent, and the heterocyclic and aryl moieties of the foregoing R2 groups are optionally substituted with 1 to 4 R 3groups ; each R³ is independently selected from halo, cyano, nitro, trifluoromethoxy, tnftuoromethyt. azido, hydroxy, C,C6 alkoxy, C,C, o alkyl, C2C6 alkenyl, C2C6 alkynyl,C (O) R6, C (O) OR".OC (O) R6,NR6C (O) R',NR6C (O) NR'R',NR6C (O) OR',C (O) NR6R',NR°R', NR60R',SO2NR6R',S (O) j (C,C6 alkyl) wherein j is an integer from 0 to 2, iCR'R2j (C6C, 0 aryl), (CR4R5)t(410 membered heterocyclic), (CR4R5)qC(O)(CR4R5)t(C6C10 aryl), (CR4R5)qC(O)(CR4R5)t(410 membered heterocyclic), (CR4R5)tO(CR4R5)q(C6C10 aryl), (CR4R5)tO(CR4R5)q(410 membered heterocyclic), (CR4R5)qSO2(CR4R5)t(C6C10 aryl), and (CR4R5) qSO2 (CR4Rs\ (410(CR4R5) qSO2 (CR4Rs\ (410 membered heterocyclic), wherein q and t are each independently an integer from 0 to 5,1 or 2 ring carbon atoms of the heterocyclic moieties of the foregoing R'° groups are optionally substituted by an oxo (=O) moiety, and the alkyl, alkenyl, alkynyl, aryl and heterocyclic moieties of the foregoing R'° groups are optionally substituted by 1 to 3 substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido,OR6,C (O) R6,C (O)OR6, OC(O)R6, NR6C(O) R',C (O)NR6R7, NR6R7, NR6OR7, C1 Ce alkyl, C2Ce alkenyl, C2C6 alkynyl, (CR'R' (C,Clo aryl), and (CR 4R5N (410 membered heterocyclic), wherein t is an integer from 0 to 5; each R4 and Rs is independently selected from H and CiCe alkyl; each R6 and R7 is independently selected from H, CiCe alkyl, (CR4R5)t(C6C10 aryl), and (CRRS) t (410 membered heterocyclic), wherein t is an integer from 0 to 5,1 or 2 ring carbon atoms of the heterocyclic group are optionally substituted by an oxo (=O) moiety, and the alkyl, aryl and heterocyclic moieties of the foregoing R6 and R7 groups are optionally substituted by 1 to 3 substituents independently selected from halo, cyano, nitro,NR4R5, trifluoromethyl, trifluoromethoxy, C1C6 atkyl, C2C6 alkenyl, C2C6 alkynyl, hydroxy, and CiCe alkoxy ; Ra is H,C (O) (CiCe alkyl), benzyl, benzyloxycarbonyl or (CiCe alkyl) 3silyl; R9 is CiCe alkyl; R'° is H or CiCio atkyt; and R"is selected from chloro, bromo, iodo, fluoro, and cyano; with the proviso that where X² is =O then the R"is cyano or from 1 to 3 R4 or Rs groups of the (CR4R5)n moiety of the R2 groups recited above are either CrCs alkyl or replaced with a halo substituent.

2.	A compound of the formula r N R, z R, s R13 RUZ HN H3C 3 ? N, o ° e I N'o OC3 OH N (CH3) 2 °"'CH H3c t , s HsC, s 2 .,.,,,,, , O s 'z' CH3 F CH3 2 or a pharmaceutically acceptable saft or sotvate thereof, wherein R'2, R'3, R'4 and R'5 are each independently selected from H, halo, methyl and ethyl.

3.	A compound according to claim 2 wherein Rr4 and R15 are both H and R12 and R'3 are each independently selected from H and methyl.

4.	A compound according to claim 2 wherein R, R, R and R are each H.

5.	A compound of the formula or a pharmaceutically acceptable saft or solvate thereof, wherein R, R3, R'4 and R'5 are each independently selected from H, halo, methyl and ethyl with the proviso that at least one of R'2, R'3, R'4 and R'5 is not H.

6.	A compound according to claim 5 wherein R and R 5 are both H, R'2 is methyl, and R"is selected from H and methyl.

7.

A pharmaceutical composition for the treatment of a disorder selected from a bacterial infection, a protozoal infection, and a disorder related to a bacterial infection or protozoal infection in a mammal, fish, or bird which comprises a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable canier.

8.

A method of treating a disorder selected from a bacterial infection, a protozoal infection, and a disorder related to a bacterial infection or protozoal infection in a mammal, fish, or bird which comprises administering to said mammal, fish or bird a therapeutically effective amount of a compound of claim 1.

9.	A method of preparing a compound according to claim 1 wherein R"is a halo group which comprises treating a compound of the formula wherein R8, R9, R'°, X¹, X2 and R are as defined in claim 1, with a halogenating agent.

Description:

INTERNATIONALSEARCHREPORTternaheeai AppUcatio No PCT/IB99/02051 C.(Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT CategoryCitationofdocument,withindication,whereappropriate,o ftherelevantpassagesRelevanttoclaimNo. EEP1026170A(HOECHSTMARIONROUSSEL1,7,8 INC)9August2000(2000-08-09) examples2,4 claims1,4,6 EEP1004592A(HOECHSTMARIONROUSSEL1,7,8 INC)31May2000(2000-05-31) examples2,4 claim1 EEP1016669A(HOECHSTMARIONROUSSEL1,7,8 INC)5July2000(2000-07-05) example2 claim1 2 INTERNATIONALSEARCHREPORT Internahonai AppilcatlonNo lnFormatlononpatentfamilymembers PCT/IB99/02051 PatentdocumentPublicationPatentfamily Publication citedinsearchreportdatemember(s)date US5747467A05-05-1998FR2742757A 27-06-1997 EP0799833A 08-10-1997 JP9176182A 08-07-1997 EP0949268A13-10-1999FR2777282A 15-10-1999 CN1235162A 17-11-1999 HU9900958A 29-11-1999 JP11310591A 09-11-1999 US6121432A 19-09-2000 WO9925365A27-05-1999FR2771008A 21-05-1999 AU1242599A 07-06-1999 EP1030673A 30-08-2000 NO20002435A 07-07-2000 EP1026170A09-08-2000FR2789392A 11-08-2000 EP1004592A31-05-2000FR2786188A 26-05-2000 AU5952299A 25-05-2000 CN1263101A 16-08-2000 JP2000159790A 13-06-2000 NO995745A 25-05-2000 PL336736A 05-06-2000 EP1016669A05-07-2000FR2785612A 12-05-2000 AU1052600A 29-05-2000 WO0027857A 18-05-2000 JP2000143689A 26-05-2000

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