US4021542A
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Derivatives of hydrazino-monosaccharides and aldohexoses which are useful as intermediates for preparing compounds or as compounds which lower the uric acid
Assignee: Takeda GmbH
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Filing: 1974-11-26
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Granted: 1977-05-03
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Expires: 1994-11-26
Abstract
Abstract Substituted hydrazino- and pyrazolo-aldopentoses and aldohexoses, which are useful as intermediates for preparing compounds, as compounds which lower the uric acid level in the blood, and as bactericides, are provided. The substituted hydrazino compounds also enter into chemical reactions which are not possible with their unsubstituted counterparts.
Inventors
- 👤 Richard Schmidt
- 👤 Kurt Klemm
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-31 20:46
CPC Classifications
C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H15/00; C07H15/20; C07H15/203; C07H17/00; C07H17/04; C07H17/08; C07H19/048; C07H19/056
Claims Analysis
Total Claims: 40
Claim 1
Independent Claim
332 words
A compound of the formula ##STR12## wherein s is a positive whole number of at most 2; D is =C(X)--, =C(NH 2 )-- or =N--; E is =C(Y)-- or =N--; F is =C(X)-- or =N--; the residue ##STR13## being aromatic; W is --H, --OH or --NH 2 ; X is --H, alkyl, phenyl or, together with Y, --N=CH--N=C(W)--; Y is --H, carbethoxy, cyano, carbamoyl, formylcarbamoyl, benzoylcarbamoyl or, together with one X, --C(W)=N--=N--; each of n, m and p is a positive whole number of at most 2, the sum of n+m+p is at least 4, and at least one of n, m and p is 1; each of R' 2 , r' 3 , r' 4 , r' 5 and R' 6 is, independently, --H or a member selected from the group consisting of alkyl, ethylenically-unsaturated hydrocarbyl, aryl, aralkyl, and cycloalkyl having from 3 to 6 ring carbon atoms with the proviso that at least one of R' 2 , R' 3 , R' 4 , R' 5 and R' 6 , which is present in the compound, has a meaning other than --H or two respective radicals R' 2 , R' 3 , R' 4 , R' 5 or R' 6 together denote alkylidene or benzylidene, each alkyl, including the alkyl of each aralkyl, each ethylenically-unsaturated hydrocarbyl and each alkylidene having up to seven carbon atoms; each aryl and the aryl of each aralkyl being substituted or unsubstituted phenyl, substituted or unsubstituted α-naphthyl or substituted or unsubstituted β-naphthyl, any substituent of a substituted phenyl, a substituted α-naphthyl or a substituted β-naphthyl being a member selected from the group consisting of alkyl having up to seven carbon atoms, halo, nitro, trifluoromethyl, alkoxy having up to seven carbon atoms, hydroxy, sulfo, sulfino, alkylsulfone having up to seven carbon atoms, alkoxycarbonyl having up to seven carbon atoms, alkylamino having up to seven carbon atoms, dialkylamino having up to seven carbon atoms and carbamoyl; or, when s denotes 2, an open-ring-form tautomer of such compound.
Claim 2
Dependent Claim
332 words
A compound of the formula ##STR12## wherein s is a positive whole number of at most 2; D is =C(X)--, =C(NH 2 )-- or =N--; E is =C(Y)-- or =N--; F is =C(X)-- or =N--; the residue ##STR13## being aromatic; W is --H, --OH or --NH 2 ; X is --H, alkyl, phenyl or, together with Y, --N=CH--N=C(W)--; Y is --H, carbethoxy, cyano, carbamoyl, formylcarbamoyl, benzoylcarbamoyl or, together with one X, --C(W)=N--=N--; each of n, m and p is a positive whole number of at most 2, the sum of n+m+p is at least 4, and at least one of n, m and p is 1; each of R' 2 , r' 3 , r' 4 , r' 5 and R' 6 is, independently, --H or a member selected from the group consisting of alkyl, ethylenically-unsaturated hydrocarbyl, aryl, aralkyl, and cycloalkyl having from 3 to 6 ring carbon atoms with the proviso that at least one of R' 2 , R' 3 , R' 4 , R' 5 and R' 6 , which is present in the compound, has a meaning other than --H or two respective radicals R' 2 , R' 3 , R' 4 , R' 5 or R' 6 together denote alkylidene or benzylidene, each alkyl, including the alkyl of each aralkyl, each ethylenically-unsaturated hydrocarbyl and each alkylidene having up to seven carbon atoms; each aryl and the aryl of each aralkyl being substituted or unsubstituted phenyl, substituted or unsubstituted α-naphthyl or substituted or unsubstituted β-naphthyl, any substituent of a substituted phenyl, a substituted α-naphthyl or a substituted β-naphthyl being a member selected from the group consisting of alkyl having up to seven carbon atoms, halo, nitro, trifluoromethyl, alkoxy having up to seven carbon atoms, hydroxy, sulfo, sulfino, alkylsulfone having up to seven carbon atoms, alkoxycarbonyl having up to seven carbon atoms, alkylamino having up to seven carbon atoms, dialkylamino having up to seven carbon atoms and carbamoyl; or, when s denotes 2, an open-ring-form tautomer of such compound.
Claim 3
Dependent Claim
105 words
A member selected from the group consisting of a compound according to claim 1 and a counterpart thereof wherein two respective radicals R' 2 , R' 3 , R' 4 , R' 5 or R' 6 together denote ring-substituted benzylidene, any ring substituent of which is a ring substituent selected from the group consisting of alkyl having up to 7 carbon atoms, halo, nitro, trifluoromethyl, alkoxy having up to 7 carbon atoms, hydroxy, sulfo, sulfino, alkylsulfone having up to 7 carbon atoms, alkoxycarbonyl having up to 7 carbon atoms, alkylamino having up to 7 carbon atoms, dialkylamino having up to 7 carbon atoms and carbamoyl.
Claim 4
Dependent Claim
163 words
A compound according to claim 2 of the formula: ##STR14## wherein each of n, m and p is a positive whole number of at most 2, the sum of n+ m+ p is at least 4, and at least one of n, m and p is 1; each of R' 2 , R' 3 , R' 4 , R' 5 and R' 6 is, independently, --H or a member selected from the group consisting of alkyl, ethylenically-unsaturated hydrocarbyl, aryl, aralkyl and cycloalkyl having from 3 to 6 ring carbon atoms, with the proviso that at least one of R' 2 , R' 3 , R' 4 ,R' 5 and R' 6 which is present in the compound has a meaning other than --H, or, two respective radicals R' 2 , R' 3 , R' 4 , R' 5 or R' 6 together denote alkylidene or ring-substituted or unsubstituted benzylidene, each alkyl, each ethylenically-unsaturated hydrocarbyl and each alkylidene having up to seven carbon atoms.
Claim 5
Dependent Claim
24 words
A compound according to claim 3 wherein each alkyl and each ethylenically-unsaturated hydrocarbyl has up to three carbon atoms, and each alkylidene is isopropylidene.
Claim 6
Dependent Claim
6 words
A hydrazino-aldopentose according to claim 3.
Claim 7
Dependent Claim
163 words
A hydrazino D-ribose according to claim 5 in open- or closed-ring form and wherein m is 2; each of n and p is 1; R' 2 has one of the meanings of R' 5 , R' 4 has one of the meanings of R' 5 , R' 5 is --H or a member selected from the group consisting of alkyl, alkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, ring-substituted or unsubstituted benzhydryl, ring-substituted or unsubstituted trityl, ring-substituted or unsubstituted benzyl, ring-substituted or unsubstituted α-naphthylmethyl and ring-substituted or unsubstituted β-naphthylmethyl; any substituent being alkyl having up to seven carbon atoms, halo, nitro, trifluoromethyl, alkoxy having up to seven carbon atoms, hydroxy, sulfo, sulfino, alkylsulfone having up to seven carbon atoms, alkoxycarbonyl having up to seven carbon atoms, alkylamino having up to seven carbon atoms, dialkylamino having up to seven carbon atoms or carbamoyl, or, two respective radicals R' 2 , R' 4 or R' 5 together denote alkylidene or ring-substituted or unsubstituted benzylidene.
Claim 8
Dependent Claim
9 words
The compound according to claim 6 which is 1-hydrazino-5-O-trityl-D-ribose.
Claim 9
Dependent Claim
9 words
The compound according to claim 6 which is 1-hydrazino-2,3-O-isopropylidene-5-trityl-D-ribose.
Claim 10
Dependent Claim
9 words
The compound according to claim 6 which is 1-hydrazino-2,3-O-isopropylidene-D-ribose.
Claim 11
Dependent Claim
9 words
The compound according to claim 6 which is 1-hydrazino-2,3,5-tri-O-benzyl-D-ribose.
Claim 12
Dependent Claim
163 words
A hydrazino D-arabinose according to claim 5 in open- or closed-ring form and wherein m is 2; each of n and p is 1; R' 2 has one of the meanings of R' 5 , R' 4 has one of the meanings of R' 5 , R' 5 is --H or a member selected from the group consisting of alkyl, alkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, ring-substituted or unsubstituted benzhydryl, ring-substituted or unsubstituted trityl, ring-substituted or unsubstituted benzyl, ring-substituted or unsubstituted α-naphthylmethyl and ring-substituted or unsubstituted β-naphthylmethyl; any substituent being alkyl having up to seven carbon atoms, halo, nitro, trifluoromethyl, alkoxy having up to seven carbon atoms, hydroxy, sulfo, sulfino, alkylsulfone having up to seven carbon atoms, alkoxycarbonyl having up to seven carbon atoms, alkylamino having up to seven carbon atoms, dialkylamino having up to seven carbon atoms or carbamoyl, or, two respective radicals R' 2 , R' 4 or R' 5 together denote alkylidene or ring-substituted or unsubstituted benzylidene.
Claim 13
Dependent Claim
9 words
The compound according to claim 11 which is 1-hydrazino-2,3,5-tri-O-benzyl-D-arabinose.
Claim 14
Dependent Claim
6 words
A hydrazino-aldohexose according to claim 3.
Claim 15
Dependent Claim
176 words
A hydrazino-D-glucose according to claim 13 in open- or closed-ring form and wherein each of m and n is 2; p is 1; R' 2 has one of the meanings of R' 5 , R' 3 has one of the meanings of R' 5 , R' 4 has one of the meanings of R' 5 , R' 5 is --H or a member selected from the group consisting of alkyl, alkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, ring-substituted or unsubstituted benzhydryl, ring-substituted or unsubstituted trityl, ring-substituted or unsubstituted benzyl, ring-substituted or unsubstituted α-naphthylmethyl and ring-substituted or unsubstituted β-naphthylmethyl; any substituent being alkyl having up to seven carbon atoms, halo, nitro, trifluoromethyl, alkoxy having up to seven carbon atoms, hydroxy, sulfo, sulfino, alkylsulfone having up to seven carbon atoms, alkoxycarbonyl having up to seven carbon atoms, alkylamino having up to seven carbon atoms, dialkylamino having up to seven carbon atoms or carbamoyl, or, two respective radicals R' 2 , R' 3 , R' 4 and R' 5 together denote alkylidene or ring-substituted or unsubstituted benzylidene.
Claim 16
Dependent Claim
9 words
The compound according to claim 14 which is 1-hydrazino-2,3,4,6-tetra-O-benzyl-D-glucose.
Claim 17
Dependent Claim
43 words
A compound according to claim 3 wherein the member is one which is readily split off, or two respective radicals R' 2 , R' 3 , R' 4 , R' 5 or R' 6 together form a radical which is readily split off.
Claim 18
Dependent Claim
27 words
A compound according to claim 16 wherein said member is a ring-substituted or unsubstituted benzhydryl, trityl or benzyl group, or the alternative meaning, is benzylidene or isopropylidene.
Claim 19
Dependent Claim
22 words
A hydrazino-D-glucose according to claim 3 wherein at least one of R' 2 and R' 5 has a meaning other than --H.
Claim 20
Dependent Claim
22 words
A hydrazino-D-arabinose according to claim 3 wherein at least one of R' 2 and R' 5 has a meaning other than --H.
Claim 21
Dependent Claim
34 words
A hydrazino D-ribose according to claim 3 wherein at least one of R' 2 and R' 5 has a meaning other than --H; or R' 2 and R' 4 , taken together, are isopropylidene.
Claim 22
Dependent Claim
10 words
A compound according to claim 2 wherein s is 1.
Claim 23
Dependent Claim
6 words
A 5-amino-1-β-D-ribofuranosylpyrazole according to claim 21.
Claim 24
Dependent Claim
9 words
The compound according to claim 22 which is 5-amino-4-(N-formylcarbamoyl)-1-(2,3,5-tri-O-benzyl-β-D-ribofuranosyl)pyrazole.
Claim 25
Dependent Claim
9 words
The compound according to claim 22 which is 5-amino-4-(N-formylcarbamoyl)-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)pyrazole.
Claim 26
Dependent Claim
9 words
The compound according to claim 22 which is 5-amino-4-carbamoyl-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)pyrazole.
Claim 27
Dependent Claim
13 words
A compound according to claim 21 wherein X is H, alkyl or phenyl.
Claim 28
Dependent Claim
14 words
A compound according to claim 21 wherein one X, together with Y, is --N=CH--N=C(W)--.
Claim 29
Dependent Claim
98 words
A method for producing a compound according to claim 2, wherein s is 1, or a counterpart thereof, wherein each R' is --H--, which comprises reacting a starting material, which is a compound according to claim 1, wherein s is 2, with a compound which reacts, without cleavage, with the H 2 NNH-- of the starting material to yield a compound having an aromatic ring with 5 ring atoms, two adjacent ring atoms of which are the nitrogen atoms of said H 2 NNH--, and, when the counterpart is desired, splitting off each member subsequently or during reaction.
Claim 30
Dependent Claim
54 words
A method according to claim 28 wherein the aromatic ring is of the formula ##STR15## each of F and E is =C(H)--; D is =C(X)-- or =N--; X is --H, alkyl or phenyl; and the method further comprises condensing an alicyclic hydrocarbon ring or a heterocyclic ring onto the 3,4-position of the aromatic ring.
Claim 31
Dependent Claim
54 words
A method according to claim 28 wherein the aromatic ring is of the formula ##STR16## each of E and D is =C(H); F is =C(Z)-- or =N--; Z is --H, alkyl or phenyl; and the method further comprises condensing an alicyclic hydrocarbon ring or a heterocyclic ring onto the 4,5-position of the aromatic ring.
Claim 32
Dependent Claim
12 words
A method according to claim 28 which comprises splitting off each member.
Claim 33
Dependent Claim
38 words
A method according to claim 28 in which the compound, wherein s is 2, is a hydrazino-ribose, a hydrazino-arabinose or a hydrazino-glucose in which each member is readily split off, and the aromatic ring is a pyrazole ring.
Claim 34
Dependent Claim
14 words
A method according to claim 28 for the synthesis of β-anomers of pyrazole derivatives.
Claim 35
Dependent Claim
14 words
A method according to claim 28 for the synthesis of α-anomers of pyrazole derivatives.
Claim 36
Dependent Claim
19 words
A therapeutically-active and pharmacologically-acceptable compound according to claim 2, wherein s is 1, or a physiologically-acceptable acid-addition salt thereof.
Claim 37
Dependent Claim
41 words
A pharmaceutical composition useful for treating gout which comprises a physiologically-acceptable carrier admixed with a sufficient concentration of a compound according to claim 35 to effect uric-acid level reduction in blood of a warm-blooded animal to which the composition is administered.
Claim 38
Dependent Claim
31 words
A method of reducing uric acid level in blood of a mammal which comprises administering to the mammal a non-toxic, but uric-acid-level reducing, amount of a composition according to claim 36.
Claim 39
Dependent Claim
20 words
A compound according to claim 21 wherein said residue comprises a 5-membered ring with 2 or 3 ring nitrogen atoms.
Claim 40
Dependent Claim
10 words
A compound according to claim 38 wherein E is =N--.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-05-02 | 1980-11-01 | 1981-05-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-05-02 | 1984-11-01 | 1985-05-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-05-02 | 1988-11-01 | 1989-05-03 | $7700.00 | Window Closed / Lapsed |