Claims
- 1. A compound of the formula: ##STR30## and the stereoisomers, hydrates, and pharmaceutically acceptable salts thereof wherein
- P.sub.2 is C.sub.1-6 alkyl, cyclopentyl, hydroxy C.sub.1-6 alkyl, phenyl, benzyl or 3-tetrahydrofuryl;
- P.sub.3 is selected from the group consisting of hydrogen, --CH.sub.3, --CH(CH.sub.3).sub.2, --CH.sub.2 CH(CH.sub.3).sub.2, --CH(CH.sub.3)(CH.sub.2 CH.sub.3), --CH.sub.2 SH, --CH.sub.2 CH.sub.2 SCH.sub.3, --CH.sub.2 OH, --CH(CH.sub.3)OH, --CH.sub.2 (CH.sub.2).sub.3 NH.sub.2, --CH.sub.2 (CH.sub.2).sub.2 NHC(.dbd.NH)NH.sub.2, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CO.sub.2 H, --CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 CONH.sub.2, benzyl, ##STR31## R.sub.1 is hydrogen, C.sub.1-15 alkyl, hydroxy C.sub.1-15 alkyl, CH([(CH.sub.2).sub.d -O--CH.sub.2 ].sub.f -R.sub.7).sub.2, CH.sub.2 Si(CH.sub.3).sub.2 (R.sub.8), PDL, --(C.sub.1-6 alkylene)--OR.sub.4, CH(Y)(Z), ##STR32## wherein PDL is --(CH.sub.2).sub.a -2-, 3- or 4-pyridyl; Y is hydroxy C.sub.1-15 alkyl, C.sub.1-6 alkyl or (CH.sub.2).sub.e -C.sub.6 H.sub.4 -(V).sub.e' ; Z is (CH.sub.2).sub.d -O--CHO, C.sub.1-6 alkylene-O-(CH.sub.2).sub.d -(O--CH.sub.2 --CH.sub.2).sub.e -O--C.sub.1-6 alkyl, CHO, CO.sub.2 R.sub.4, CONHR.sub.4, (CH.sub.2).sub.d -O--(CH.sub.2).sub.d' -R.sub.5, (CH.sub.2).sub.e -OR.sub.4 or ##STR33## wherein V is OR.sub.4 or hydroxy C.sub.1-6 alkylene; provided that d'=2 when R.sub.5 is piperazinyl, substituted piperazinyl, piperidyl or morpholinyl;
- R.sub.2 is as defined for R.sub.1 with the proviso that R.sub.2 is other than hydrogen when R.sub.1 is hydrogen, or R.sub.1 and R.sub.2 taken together with the nitrogen atom to which they are attached are selected from the group consisting of; ##STR34## R.sub.4 is hydrogen, C.sub.1-6 alkyl, phenyl or benzyl; R.sub.5 is piperazinyl, substituted piperazinyl, piperidyl, morpholinyl, pyridyl, pyrazinyl, pyrimidinyl or phenyl, wherein substituted piperazinyl is piperazinyl substituted on one nitrogen atom thereof with CHO, C(O)NHR.sub.4, C.sub.1-4 alkyl or CO.sub.2 R.sub.4 ;
- R.sub.7 is pyrimidyl, pyridyl, pyrazinyl or phenyl;
- R.sub.8 is C.sub.1-6 alkylene, hydroxy C.sub.1-6 alkyl or C.sub.1-6 alkyl;
- a is zero, 1, 2 or 3;
- b is zero or 1;
- d and d' are each independently 1 or 2;
- e and e' are each independently zero, 1 or 2;
- f is zero or one; and
- x is 1, 2, 3, or 4.
- 2. A compound according to claim 1 wherein X is 1.
- 3. A compound according to claim 2 wherein P.sub.2 is --CH(CH.sub.3).sub.2.
- 4. A compound according to claim 3 wherein R.sub.1 is hydrogen and R.sub.2 is benzyl.
- 5. A compound according to claim 3 wherein R.sub.1 is hydrogen and R.sub.2 is 2-(3-methyl-1-phenylmethoxy)butyl.
- 6. A compound according to claim 4 wherein P.sub.3 is hydrogen.
- 7. A compound according to claim 4 wherein P.sub.3 is CH.sub.2 CO.sub.2 H.
- 8. A compound according to claim 4 wherein P.sub.3 is CH.sub.2 CONH.sub.2.
- 9. A compound according to claim 4 wherein P.sub.3 is CH.sub.2 CH.sub.2 CO.sub.2 H.
- 10. A compound according to claim 4 wherein P.sub.3 is CH.sub.2 CH.sub.2 CONH.sub.2.
- 11. A compound according to claim 4 wherein P.sub.3 is benzyl.
- 12. A compound according to claim 4 wherein P.sub.3 is ##STR35##
- 13. A compound according to claim 4 wherein P.sub.3 is --CH.sub.2 (CH.sub.2).sub.3 NH.sub.2.
- 14. A compound according to claim 4 wherein the carbon atom in the macrocyclic ring to which P.sub.3 is attached, is in the D configuration.
- 15. A compound according to claim 1 wherein the compound is [9(S),12(S)]-.alpha.,.alpha.-Difluoro-9-(1-methylethyl)-.beta.,4,7,10-tetraoxo-N-(phenylmethyl)-2-oxa-5,8,11,-triazabicyclo[12.2.2]octadeca-14,16,17-triene-12-propanamide.
- 16. A compound according to claim 1 wherein the compound is [9(S),12(S)]-.alpha.,.alpha.-Difluoro-9-(1-methylethyl)-.beta.,4,7,10-tetraoxo-N-[2-methyl-1-[(phenylmethoxy)-methyl]propyl]-2-oxa-5,8,11,-triazabicyclo[12.2.2]octadeca-14,16,17-triene-12-propanamide.
Parent Case Info
This application is a continuation of application Ser. No. 08/192,080, filed Feb. 4, 1994, now abandoned, and had an effective international filing date of Nov. 28, 1994, as application PCT/US94/13711, which designated the U.S. and entered the U.S. national phase on Sep. 9, 1996 under 35 USC 371.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US94/13711 |
11/28/1994 |
|
|
9/9/1996 |
9/9/1996 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO95/21186 |
8/10/1995 |
|
|
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GBX |
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WOX |
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WOX |
9209624 |
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WOX |
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Entry |
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Continuations (1)
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Number |
Date |
Country |
Parent |
192080 |
Feb 1994 |
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