EP0365849A2
Expired / Lapsed
EP
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Novel 2'-halomethylidene, 2'-ethenylidene and 2'-ethynyl adenosine derivatives
Assignee: Aventis Pharmaceuticals Inc
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Filing: 1989-09-26
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Granted: —
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Expires: 2009-09-26
Abstract
Abstract This invention relates to certain novel 2′-halomethylidene, 2′-ethenylidene and 2′-ethynyl adenosine derivatives, and pharmaceutical compositions thereof, which are useful in inhibiting AdoMet-dependent transmethylation and in the treatment of patients afflicted with neoplastic or viral disease states.
Inventors
- 👤 James R. Mccarthy
- 👤 David M. Stemerick
- 👤 Nellikunja J. Prakash
- 👤 Michael L. Edwards
- 👤 Esa T. Jarvi
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-05 09:47
CPC Classifications
C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/16; A; A61; A61P; A61P31/00; A61P31/12; C07H19/052; C07H19/056
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
136 words
A process for the preparation of a compound of the general formula wherein E is V is oxy, methylene, or thio, X₁ and X₂ are each halogen, Y₁ is nitrogen, a CH group, a CCl group, a CBr group or a CNH₂ group, Y₂ and Y₃ are each independently nitrogen or a CH group, Q is NH₂, NHOH, NHCH₃, or hydrogen, and Z is hydrogen, halogen, or NH₂; comprising the steps of (a) reacting a 6-chloro-2′keto-adenosine derivative, bearing appropriate blocking groups, with a dihalomethylidene phosphorus ylide to yield a 6-chloro-2′-dihalomethylidene-adenosine derivative, bearing appropriate blocking groups, (b) deblocking the 6-chloro-2′-dihalomethylidene-adenosine derivative by reacting with acid, (c) substituting the 6-chloro moiety of the deblocked 6-chloro-2′-dihalomethylidene-adenosine derivative with a desired moiety as represented by the term "Q", and optionally (d) converting the obtained compound to its pharmaceutically acceptable salt.
Claim 2
Dependent Claim
136 words
A process for the preparation of a compound of the general formula wherein E is V is oxy, methylene, or thio, X₁ and X₂ are each halogen, Y₁ is nitrogen, a CH group, a CCl group, a CBr group or a CNH₂ group, Y₂ and Y₃ are each independently nitrogen or a CH group, Q is NH₂, NHOH, NHCH₃, or hydrogen, and Z is hydrogen, halogen, or NH₂; comprising the steps of (a) reacting a 6-chloro-2′keto-adenosine derivative, bearing appropriate blocking groups, with a dihalomethylidene phosphorus ylide to yield a 6-chloro-2′-dihalomethylidene-adenosine derivative, bearing appropriate blocking groups, (b) deblocking the 6-chloro-2′-dihalomethylidene-adenosine derivative by reacting with acid, (c) substituting the 6-chloro moiety of the deblocked 6-chloro-2′-dihalomethylidene-adenosine derivative with a desired moiety as represented by the term "Q", and optionally (d) converting the obtained compound to its pharmaceutically acceptable salt.
Claim 3
Dependent Claim
96 words
A process for the preparation at a compound of the general formula according to claim 1 wherein E is and one of X₁ and X₂ is hydrogen and the other halogen comprising the steps of (a) reacting a 2′-phenylsulfonyl-halomethylidene adenosine derivative, bearing appropriate blocking groups, with tributyl-tin hydride in the presence of 2,2′-azobis-isobutylnitrile to form the corresponding 2′-tributyl-tin-halomethylidene derivative, (b) reacting the 2′-tributyl-tin-halomethylidene derivative thus formed with hexamethyldisilazane in the presence of a catalytic amount of ammonia in formamide, (c) removing the blocking groups, and optionally (d) converting the obtained compound to its pharmaceutically acceptable salt.
Claim 4
Dependent Claim
94 words
A process for the preparation of a compound of the general formula according to claim 1 wherein E is C = C = CHR; and R is hydrogen or C₁-C₄ alkyl, comprising the steps of (a) reducing a 6-chloro-2′-ethynyl-2′-hydroxy-adenosine derivative, bearing appropriate blocking groups, to yield the 6-chloro-2′-ethenylidene-adenosine derivative, bearing appropriate blocking groups, (b) deblocking the 6-chloro-2′-ethenylidene-adenosine derivative by reacting with acid, (c) substituting the 6-chloro moiety of the deblocked 6-chloro-2′-ethenylidene-adenosine derivative with the desired moiety as represented by the term "Q", and optionally (d) converting the obtained compound to its pharmaceutically acceptable salt.
Claim 5
Dependent Claim
88 words
A process for the preparation of a compound of the general formula according to claim 1 wherein E is one of A₁ and A₂ is hydrogen, the other -C ≡ CR and R is hydrogen or C₁-C₄ alkyl comprising the steps of (a) reducing a 6-chloro-2′-ethynyl-2′-hydroxy-adenosine derivative, bearing appropriate blocking groups, to yield the 6-chloro-2′-ethynyl-adenosine derivative, (b) substituting the 6-chloro moiety of the deblocked 6-chloro-2′-ethenylidene-adenosine derivative with the desired moiety as represented by the term "Q", and optionally (c) converting the obtained compound to its pharmaceutically acceptable salt.
Claim 6
Dependent Claim
14 words
The process according to clain 2 wherein X₁ is fluoro and X₂ is hydrogen.
Claim 7
Dependent Claim
14 words
The process according to clain 2 wherein X₁ is fluoro and X₂ is hydrogen.
Claim 8
Dependent Claim
14 words
The process according to claim 2 wherein X₁ is hydrogen and X₂ is fluoro.
Claim 9
Dependent Claim
12 words
The process according to claim 3 or 4 wherein R is hydrogen.
Claim 10
Dependent Claim
15 words
The process according to any one of claims 1 to 7 wherein V is oxy.
Claim 11
Dependent Claim
15 words
The process according to any one of claims 1 to 8 wherein Q is NH₂.
Claim 12
Dependent Claim
16 words
The process according to any one of claims 1 to to 9 wherein Z is hydrogen.
Claim 13
Dependent Claim
17 words
The process according to any one of claims 1 to 10 wherein Y₁ is a CH group.
Claim 14
Dependent Claim
15 words
The process according to any one of claims 1 to 11 wherein Y₂ is nitrogen.
Claim 15
Dependent Claim
15 words
The process according to any one of claims 1 to 12 wherein Y₃ is nitrogen.
Claim 16
Dependent Claim
17 words
The process according to any one of claims 1 to 13 wherein Y₂ is a CH group.
Claim 17
Dependent Claim
11 words
The process according to claim 1 wherein the compound is 2′-deoxy-2′-difluoromethylidene-adenosine.
Claim 18
Dependent Claim
11 words
The process according to claim 2 wherein the compound is (Z)-2′-deoxy-2′-fluoromethylidene-adenosine.
Claim 19
Dependent Claim
11 words
The process according to claim 2 wherein the compound is (E)-2′-deoxy-2′-fluoromethylidene-adenosine.
Claim 20
Dependent Claim
11 words
The process according to claim 3 wherein the compound is 2′-deoxy-2′-ethenylidene-adenosine.
Claim 21
Dependent Claim
11 words
The process according to claim 4 wherein the compound is 2′-deoxy-2′(R)-ethynyl-adenosine.
Claim 22
Dependent Claim
11 words
The process according to claim 4 wherein the compound is 2′-deoxy-2′(S)-ethynyl-adenosine.
Claim 23
Dependent Claim
11 words
The process according to claim 1 wherein the compound is 2′-deoxy-2′-difluoromethylidene-aristeromycin.
Claim 24
Dependent Claim
11 words
The process according to claim 1 wherein the compound is 2′-deoxy-2′-difluoromethylidene-3-deazaadenosine.
Claim 25
Dependent Claim
13 words
The process according to claim 2 wherein the compound is (E) or (Z)-2′-deoxy-2′-fluoromethylidene-aristeromycin.
Claim 26
Dependent Claim
13 words
The process according to claim 2 wherein the compound is (E) and (Z)-2′-deoxy-2′-fluoromethylidene-3-deazaadenosine.
Claim 27
Dependent Claim
11 words
The process according to claim 3 wherein the compound is 2′-deoxy-2′-ethenylidene-aristeromycin.
Claim 28
Dependent Claim
11 words
The process according to claim 3 wherein the compound is 2′-deoxy-2′-ethenylidene-3-deazaadenosine.
Claim 29
Dependent Claim
13 words
The process according to claim 3 wherein the compound is 2′-deoxy-2′(R or S)-ethynyl-aristeromycin.
Claim 30
Dependent Claim
13 words
The process according to claim 4, wherein the compound is 2′-deoxy-2′(R or S)-ethynyl-3-deazaadenosine.
References Cited (Backward Citations)
No citation records indexed.
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