Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2002-10-28
2004-11-16
Rao, Deepak (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C544S323000, C544S324000, C544S325000
Reexamination Certificate
active
06818649
ABSTRACT:
This invention is concerned with substituted chromene derivatives of the general formula
in which
R
1
represents alkyl or cycloalkylalkyl,
R
2
and R
3
each independently represent alkyl or cycloalkyl or taken together with the adjacent carbon atom represent a saturated 3- to 6-membered carbocyclic or heterocyclic ring, the alkyl, cycloalkyl, carbocyclic or heterocyclic ring being unsubstituted or substituted, and
R
4
represents hydrogen, halogen, cyano, alkyl, alkylthio, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkynyl, alkoxyalkyl, alkoxyalkynyl, trialkylsilyl, aryl or heteroaryl,
and pharmaceutically acceptable acid addition salts of these compounds.
The above compounds are novel and possess valuable antibiotic properties. They can be used in the control and prevention of infectious diseases. In particular, they exhibit a pronounced antibacterial activity, including against multi-resistant gram-positive strains, such as
Streptococcus pneumoniae
and
Staphylococcus aureus.
These compounds can also be administered in combination with known antibacterially active substances and then exhibit a synergistic effect. Typical combination partners are e.g. sulphonamides, which can be admixed with the compounds of formula I or their salts in various ratios.
Objects of the present invention are compounds of formula I and their pharmaceutically acceptable acid addition salts per se and their use as therapeutically active substances; medicaments based on these substances, optionally in combination with sulphonamides, and their production; the use of these substances as medicaments and for the production of antibacterially-active medicaments; as well as the manufacture of the compounds of formula I and their pharmaceutically acceptable acid addition salts and intermediates for their manufacture.
The groups named above are defined below. In combined residues such as hydroxyalkyl, cycloalkylalkyl etc. the exemplification is to be understood accordingly.
The term “halogen” means fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.
The term “alkyl” denotes a straight or branched chain hydrocarbon group which carries up to and including 6, preferably 4 carbon atoms, if not otherwise specified. Examples are, e.g., methyl, ethyl, n-propyl, isopropyl, isobutyl, sec-butyl, t-butyl. The alkyl group being optionally substituted, e.g., by halogen (e.g. chlorine, bromine, fluorine); cyano; lower alkoxy (e.g. methoxy, n-butoxy); nitro; amino; lower alkoxycarbonylamino (e.g. t-butoxycarbonylamino); lower alkanoylamino (e.g. acetylamino).
The term “alkoxy” and “alkylthio” denote groups wherein the alkyl part is as defined above and which are attached via an oxygen or sulfur atom, respectively, examples of such groups are methoxy, ethoxy, n-propoxy, isopropoxy, isobutoxy, sec-butoxy, t-butoxy; and methylthio, ethylthio, n-propylthio, isopropylthio, isobutylthio, sec-butylthio, t-butylthio.
“Alkenyl” and “alkynyl” are unsaturated straight or branched chain hydrocarbon groups which carry up to and including 6, preferably 4 carbon atoms having at least one double or triple bond, respectively, e.g. vinyl, 2-propenyl, 2,4-butadienyl, isopropenyl; 1-propynyl, 2-propynyl, 1-butynyl, 3-butynyl. These groups may be unsubstituted or substituted. Examples of substituted alkynyl groups are, e.g., 3-hydroxy-1-propynyl, 3-hydroxy-1-butynyl, 3-methoxy-1-propynyl.
“Cycloalkyl” denotes a saturated carbocyclic group which carries 3 to 6 carbon atoms, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. The cycloalkyl group being optionally substituted, e.g., by halogen (e.g. chlorine, bromine, fluorine); cyano; lower alkoxy (e.g. methoxy, n-butoxy); nitro; amino; lower alkoxycarbonylamino (e.g. t-butoxycarbonylamino); lower alkanoylamino (e.g. acetylamino).
“Cycloalkylalkyl” denotes the combination of cycloalkyl and alkyl as defined above, e.g., cyclopropylmethyl, 2-cyclopropylethyl, cyclopentylmethyl.
“Carbocyclic rings” (formed with R
2
and R
3
) are saturated and contain 3 to 6 carbon atoms, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. This carbocyclic group being optionally substituted, e.g., by halogen (e.g., chlorine, bromine, fluorine); cyano; lower alkoxy (e.g. methoxy, n-butoxy); nitro; amino; lower alkoxycarbonylamino (e.g. t-butoxycarbonylamino); lower alkanoylamino (e.g. acetylamino).
Heterocyclic rings (formed with R
2
and R
3
) refer to heterocyclic, saturated 3 to 6 membered rings containing one or two heteroatoms selected from nitrogen, oxygen and sulfur, e.g. aziridinyl, oxiranyl, thiiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuryl, tetrahydrothienyl, piperidyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholinyl, thiomorpholinyl, piperazinyl, dioxolanyl, imidazolidinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, pyrazolidinyl, etc. These rings may be further substituted, e.g. by t-butoxycarbonyl.
“Aryl” denotes phenyl or naphthyl groups which can optionally be substituted e.g. by halogen (e.g. chlorine, bromine, fluorine); cyano; lover alkoxy (e.g. methoxy, n-butoxy); nitro; amino; lower alkoxycarbonylamino (e.g. t-butoxycarbonylamino); lower alkanoylamino (e.g. acetylamino).
“Heteroaryl” denotes 5- or 6-membered heteroaromatic groups which contain one or more rings and which have 5-9 carbon atoms and 1-4 hetero atoms, preferably N, O and/or S. Examples of such rings are for example furyl, pyranyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl and triazinyl. These groups can also be fused preferably to a phenyl ring, e.g. benzopyranyl, benzofuranyl, indolyl and quinolinyl. The “heteroaryl groups” are unsubstituted or substituted by halogen (e.g. chlorine, bromine, fluorine); cyano; lower alkoxy (e.g. methoxy, n-butoxy); nitro; amino; lower alkoxycarbonylamino (e.g. t-butoxycarbonylamino); lower alkanoylamino (e.g. acetylamino).
Preferred compounds of formula I are:
5-(4-Bromo-8-methoxy-2,2-dimethyl-2H-chromen-6-ylmethyl) -pyrimidine-2,4-diamine,
5-[(4-bromo-2′,3′,5′,6′-tetrahydro-8-methoxyspiro[2H-1-benzopyran-2,4′-[4H]pyran]-6-yl) -methyl]-2,4-pyrimidinediamine,
5-(8-ethoxy-2,2,4-trimethyl-2H-chromen-6-ylmethyl) -pyrimidine-2,4-diamine,
5-(4-chloro-8-methoxy-2,2-dimethyl-2H-chromen-6-ylmethyl)-pyrimidine-2,4-diamine,
5-(8-ethoxy-4-ethyl-2,2-dimethyl-2H-chromen-6-ylmethyl)-pyrimidine-2,4-diamine,
5-(8-methoxy-2,2-dimethyl-4-methylsulfanyl-2H-chromen-6-ylmethyl)-pyrimidine-2,4-diamine,
5-(8-ethoxy-2,2-dimethyl-4-propyl-2H-chromen6-ylmethyl) -pyrimidine-2,4-diamine,
5-[8-methoxy-4-(3-methoxy-prop-1-ynyl)-2,2-dimethyl-2H-chromen-6-ylmethyl]-pyrimidine-2,4-diamine,
5-[4-(4-fluoro-phenyl)-8-methoxy-2,2-dimethyl-2H-chromen-6-ylmethyl]-pyrimidine-2,4-diamine,
5-[(4-bromo-8-ethoxyspiro[2H-1-benzopyran-2,1′-cyclobutan]-6-yl)methyl]-2,4-pyrimidinediamine,
5-(4-bromo-8-ethoxy-2,2-dimethyl-2H-chromen-6-ylmethyl)-pyrimidine-2,4-diamine
and their pharmaceutically acceptable acid addition salts.
The compounds of formula I form pharmaceutically acceptable acid addition salts with organic and inorganic acids. Examples of acid addition salts of compounds of formula I are salts with mineral acids, for example hydrohalic acids such as hydrochloric acid, hydrogen bromide and hydrogen iodide, sulphuric acid, nitric acid, phosphoric acid and the like, salts with organic sulphonic acids, for example with alkyl- and arylsulphonic acids such as methanesulphonic acid, p-toluenesulphonic acid, benzenesulphonic acid and the like as well as salts with organic carboxylic acids, for example with acetic acid, tartaric acid, maleic acid, citric acid, benzoic acid, salicyclic acid, ascorbic acid and the like.
The compounds of formula I and their pharmaceutically acceptable acid addition salts can be manufactured by methods known in the art, especially in accordance with the invention by
a) reacting a compound of the general formula
i
Mohr Peter
Pflieger Philippe
Basilea Pharmaceutica AG
Rao Deepak
LandOfFree
Chromenylmethyl pyrimidinediamines as antibacterial agents does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Chromenylmethyl pyrimidinediamines as antibacterial agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Chromenylmethyl pyrimidinediamines as antibacterial agents will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3348025