(Hetero) Bicyclymethanesulfonylamino-substituted hydroxamic acid derivatives
OwnerGordon Bruton, Andrew Faller +3inventors
InventorsGordon Bruton, Andrew Faller, Barry Sidney Orlek, Kishore Kalidas Rana, Graham Walker
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Abstract
Compounds of formula (I) wherein R is hydrogen, alkyl alkenyl, alkynyl, aryl, heteroaryl or heterocyclyl; and R1 is bicyclyl or heterobicyclyl; are useful in the treatment and prophylaxis of conditions mediated by s-CD23 or TNF.
Claims11
A compound of formula (I)—
- 88
- wherein
- R is hydrogen, alkyl alkenyl alkynyl, aryl, heteroaryl or heterocyclyl;
- and
- R1 is bicyclyl or heterobicyclyl;
- but excluding:
- N-hydroxy-2-[(camphorsulfonyl)amino]-3-[4-methoxyphenylsulfonyl)amino]-proponamide,
- N-hydroxy-2-[(camphorsulfouyl)amino]-3-[4-camphorsulfonyl)amino]-proponamide;
- N-hydroxy-2-[(camphorsulfonyl)amino]-3-[1-napthalenylsulfonyl)amino]-proponamide;
- N-hydroxy-2-[(camphorsulfonyl)amino]-3-[2,4-difluorophenylsulfonyl)amino]-proponamide;
- N-hydroxy-2-[(camphorsulfouyl)amino]-3-[2,4,6-trimethylphenylsulfonyl)amino]-proponamide;
- N-hydroxy-2-[(caalphorsulfonyl)amino]-3-[4t-butylphenylsulfonyl)amino]-proponamide;
- N-hydroxy-2-[(camphorsulfonyl)amino]-3-[2,5-dichlorophenylsulfonyl)amino]-proponamide;
- N-hydroxy-2-[(camphorsulfonyl)amino]-3-[4-chlorophenylsulfonyl)amino]-proponamide.
A compound selected from the group consisting of
- (R)-N-Hydroxy-4-Methyl-2-(naphthalen-2-ylmethanesulfonylamino)-pentanoic acidamide
- (R)-N-Hydroxy-2-(naphthalen-2-ylmethanesulfonylamino)-2-phenyl-acetamide
- (R)-N-Hydroxy-2-(napthalen-2-ylmethanesulfonylamino)-4-phenyl-butyramide
- (R)-2-(Benzo[b]thiophen-5-ylmethanesulfonylamino)-N-hydroxy-2-phenylacetamide
- (R)-2-Phenyl-2-[(R)-(1,2,3,4-tetrahydronaphthalen-2-yl)methanesulfonylamino]-N-hydroxyacetamide
- (R)-2-(Indan-2-ylmethanesulfonylamino)-2-phenyl-N-hydroxyacetamide
- (R)-2-(Benzo[b]thiophen-5-ylmethanesulfonylamino)-N-hydroxy-3-(1H-indol-3-yl)propionamide
- (R)-2-(Benzo[b]thiophen-5-ylmethanesulfonylamino)-N-hydroxy-4-phenyl-butyramide
- (R)-2-(Benzo[b]thiophen-6-ylmethanesulfonylamino)-N-hydroxy-2-phenylacetamide
- (R)-2-(Benzo[b]thiophen-5-ylmethanesulfonylamino)-N-hydroxy-2-(4-hydroxyphenyl)acetamide
- (R)-2-(Benzo[b]thiophen-5-ylmethanesulfonylamino)-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-N-hydroxy propionamide
- (R)-3-Benzo[b]thiophen-3-yl-2-(benzo[b]thiophene-5-ylmethanesulfonylamino)-N-hydroxy-propionamide
- (R)-24-Benzo[b]thiophen-5-ylmethanesulfonylamino)-2-4-fluorophenyl)-N-hydroxy-acetamide
- (R)-2-(Benzo[b]thiophen-5-ylmethanesulfonylamino)-2-(4-isopropylphenyl)-N-hydroxy-acetamide
- (R)-2-(Benzo[b]thiophen-5-ylmethanesulfonylamino)-2-(4-trifluoromethoxyphenyl)-N-hydroxy-acetamide
- (R)-2-(Benzo[b]thiophen-5-ylmethanesulfonylamino)-N-hydroxy-2-(4-trifluoromethane-sulfonyloxyphenyl)-acetamide
- (R)-2-(Benzo[b]thiophen-5-ylmethanesulfonylamino)-N-hydroxy-3-(phenylmethanesulfonylamino)-propionamide
Use of a compound according to any preceding claim for the production of a medicament for the treatment or prophylaxis of disorders in which the overproduction of s-CD23 is implicated.
A compound of formula (II):
- 92
- wherein R and R1 are as defined hereinabove, and X is a protecting group.
A process for preparing a compound of formula (VIa):
- 93
- wherein R1 is defined hereinabove,
- comprising converting a compound of formula (VIII):
- R1—CH2-Z (VIII)
- wherein R1 is as defined herein above and Z is halogen, alkylsulfonbate or aryl sulfonate,into a compound of formula (IX).
- 94
- under phase transfer conditions in which the ratio of tetra-n-butylammonium cations to compound of formula (VIII) is greater than 1:1, and converting compound (IX) to compound (VIa) using a chlorinating agent such as phosphorous pentachloride or triphosgene.
The process according to claim 14 wherein the ratio of tetra-n-butylammonium cations to compound of formula (VIII) is about 2:
- 1.
Dependencies are inferred from the claim text.