Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-07-14
1997-12-02
Ivy, C. Warren
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
546155, C07D21504, C07D21520
Patent
active
056938152
DESCRIPTION:
BRIEF SUMMARY
SUMMARY OF THE INVENTION
The invention relates to compounds of the formula ##STR2## wherein Ar is ##STR3## * indicates a mixture of isomers at this carbon ##STR4##
R.sub.10 is H or OH;
X is O or an electron pair;
W is ##STR5##
Q is ##STR6##
n is 0 to 4: ##STR7##
R.sub.1 is ##STR8##
Z is H or Z and Q taken together are --(CH.sub.2).sub.3 -- or --(CH.sub.2).sub.4 --
U is ##STR9##
R.sub.3 is C.sub.1-11 -alkyl or ##STR10## wherein R.sub.20 is H or C.sub.1-10 -alkyl; and Ac is formyl or ##STR11## wherein R.sub.21 is C.sub.1-10 alkyl;
L is ##STR12##
R.sub.2 is ##STR13##
m is 0, 1 or 2;
p is 0, 1, or 2; and
q is 0, 1, or 2;
an epimer or racemate thereof, or a pharmaceutically acceptable salt thereof.
Preferred are compounds of formula I wherein Ar is ##STR14##
Among these the preferred compounds are those wherein Ar is ##STR15##
Also preferred are compounds of formula I wherein Ar is ##STR16##
Preferred among the just above mentioned compounds are those wherein Ar is ##STR17##
Most preferred are compounds wherein Ar is ##STR18##
Also preferred are compounds of formula I wherein W is --SO.sub.2 -- and --CO--. Most preferred are compounds of formula I wherein W is CO.
Also preferred are compounds of formula I wherein Q is ##STR19## Most preferred are compounds of formula I wherein Q is ##STR20##
Also preferred are compounds of formula I wherein R.sub.1 is ##STR21##
Preferred are compounds of formula I wherein U is ##STR22## Most preferred are compounds of formula I wherein U is ##STR23##
Preferred are compounds of formula I wherein --O-L is ##STR24##
Most preferred are compounds of formula I wherein --O-L is ##STR25##
Most preferred are those compounds as described just above wherein R.sub.2 is NH tBu or NHPh.
As used herein, alkyl denotes straight or branched saturated hydrocarbons which contain from 1 to 12 carbon atoms. Representative examples include methyl, butyl, isobutyl, isoamyl, and the like. Alternatively, the number of carbon atoms in a particular alkyl may be specified. For example, C.sub.1 -C.sub.7 alkyl refers to an alkyl which may have one to seven carbon atoms.
Alkoxy denotes --O-alkyl wherein alkyl is as described above.
Ph denotes phenyl. Ms denotes mesyl. Halogen denotes chlorine, fluorine or bromine, and iodine.
As used herein, a bold faced line denotes a bond that comes up above the plane of the page. A dashed line denotes a bond that goes down below the plane of the page. A wavy line denotes either racemic mixture or that the stereochemistry of this bond is not known.
Exemplary compounds of the invention include:
__________________________________________________________________________ ##STR26##
Com
pound
ArW Q U L
__________________________________________________________________________
##STR27##
##STR28##
##STR29##
##STR30##
B
##STR31##
##STR32##
##STR33##
##STR34##
C
##STR35##
##STR36##
##STR37##
##STR38##
D
##STR39##
##STR40##
##STR41##
##STR42##
E
##STR43##
##STR44##
##STR45##
##STR46##
F
##STR47##
##STR48##
##STR49##
##STR50##
G
##STR51##
##STR52##
##STR53##
##STR54##
H
##STR55##
##STR56##
##STR57##
##STR58##
I
##STR59##
##STR60##
##STR61##
##STR62##
J
##STR63##
##STR64##
##STR65##
##STR66##
K
##STR67##
##STR68##
##STR69##
##STR70##
L
##STR71##
##STR72##
##STR73##
##STR74##
M
##STR75##
##STR76##
##STR77##
##STR78##
N
##STR79##
##STR80##
##STR81##
##STR82##
O
##STR83##
##STR84##
##STR85##
##STR86##
P
##STR87##
##STR88##
##STR89##
##STR90##
Q
##STR91##
##STR92##
##STR93##
##STR94##
R
##STR95##
##STR96##
##STR97##
##STR98##
S
##STR99##
##STR100##
##STR101##
##STR102##
T
##STR103##
##STR104##
##STR105##
##STR106##
__________________________________________________________________________
Other compounds of the invention are compounds of the formula U': ##STR107## wherein * denotes all the possible stereoisomers at the particular carbon, and mixtures thereof or pharmaceutically accep
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Repine et al J. Med Chem (1991) 34, 1935-1943.
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Plattner et al., J. Med Chem, 31(12) pp. 2277-2288 (1988).
Bennett Frank
Girijavallabhan Viyyoor M.
Patel Naginbhai M.
Boxer Matthew
Ivy C. Warren
M. Mach D. Margaret
Maitner John J.
Schering Corporation
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