CS195829B1 - Derivatives of urea and method of preparing - Google Patents
Derivatives of urea and method of preparing Download PDFInfo
- Publication number
- CS195829B1 CS195829B1 CS764874A CS764874A CS195829B1 CS 195829 B1 CS195829 B1 CS 195829B1 CS 764874 A CS764874 A CS 764874A CS 764874 A CS764874 A CS 764874A CS 195829 B1 CS195829 B1 CS 195829B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- derivatives
- sugar
- benzoyl
- chloroethylamine
- formula
- Prior art date
Links
- 150000003672 ureas Chemical class 0.000 title claims description 8
- 238000000034 method Methods 0.000 title claims description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- VKPPFDPXZWFDFA-UHFFFAOYSA-N 2-chloroethanamine Chemical compound NCCCl VKPPFDPXZWFDFA-UHFFFAOYSA-N 0.000 claims description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
- -1 aliphatic organic acid Chemical class 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 2
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 229910052788 barium Inorganic materials 0.000 claims description 2
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 4
- 244000309464 bull Species 0.000 description 3
- 230000000340 anti-metabolite Effects 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- RYLTXMGSVFOQKY-UHFFFAOYSA-N 1,3-thiazolidin-5-one Chemical compound O=C1CNCS1 RYLTXMGSVFOQKY-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- TXHIDIHEXDFONW-UHFFFAOYSA-N benzene;propan-2-one Chemical compound CC(C)=O.C1=CC=CC=C1 TXHIDIHEXDFONW-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Description
Předmětem vynálezu jsou nové deriváty močoviny a způsob jejich přípravy.The present invention provides novel urea derivatives and processes for their preparation.
Z derivátů močoviny je například hydroxymočovina užívána jako významné léčivo v chemoterapii rakoviny. V literatuře nejsou dosud popsány její cukerné deriváty, které by podle analogie s jinými nukleosídovými antimetabolity měly mít zvýšenou účinnost, popřípadě nižší toxicitu při klinické aplikaci nežli základní látka, hydroxymočovina. Další deriváty močoviny jsou užívanými meziprodukty ve farmaceutickém průmyslu a v chemii nukleosidových antimetabolitů Ukita T. Hamada A. Yoshida ML: Chem. Pharm. Bull. 12, 454 (1964); Naito T. Hirata M. Kawakami T, Sáno N.: Chem. Pharm. Bull. 9 703 (1961); Naito T., Sáno M.: Chem. Pharm. Bull. 9 709 (1961).Among urea derivatives, for example, hydroxyurea is used as an important drug in cancer chemotherapy. Its sugar derivatives, which by analogy with other nucleoside antimetabolites, should have increased efficacy or lower toxicity in clinical application than the parent substance, hydroxyurea, have not yet been described in the literature. Other urea derivatives are used intermediates in the pharmaceutical industry and in the chemistry of nucleoside antimetabolites Ukita T. Hamada A. Yoshida ML: Chem. Pharm. Bull. 12, 454 (1964); Naito T. Hirata M. Kawakami T, Sano N .: Chem. Pharm. Bull. 9,703 (1961); Naito T., Sano M. Chem. Pharm. Bull. 9, 709 (1961).
Podle vynálezu je možno připravit zcela nové deriváty močoviny obecného vzorce I NHCOR1 kdeAccording to the invention, it is possible to prepare novel urea derivatives of the general formula I NHCOR 1 wherein
R1 je skupinaR 1 is a group
NHOH,NHOH,
NHNH2NHNH2
NHCH2CH2R3,NHCH2CH2R 3 ,
N(CH2CH2R3)2,N (CH 2 CH 2 R 3 ) 2,
R2 je cukerný zbytek, ribosa, 2-deoxyribosa aR 2 is a sugar residue, ribose, 2-deoxyribose and
R3 je hydroxyl nebo chlor.R 3 is hydroxyl or chlorine.
Dalším význakem vynálezu je příprava těchto nových derivátů močoviny obecného vzorce I, spočívající v tom, že se na cukerný derivát 2,4-thiazolidinonu obecného vzorce IIA further feature of the invention is the preparation of these novel urea derivatives of the formula (I), characterized in that the sugar derivative of the 2,4-thiazolidinone of the formula (II) is
SWITH
Z\ Z+Z \ Z +
ONOIT
Rl (II), kdeR1 (II), where
Ri je cukerný zbytek, jako triacylribofuranosa, dlacyl-2-deoxyribofuranosa, přičemž acyl je benzoyl nebo zbytek alifatické organické kyseliny s 2 až 5 atomy uhlíku, působí aminem, jako hydroxylaminem, hydrazinem, aminoethanolem, diethanolaminem, chlorethylaminem nebo 2,2‘-dlchlorethyl195829R 1 is a sugar moiety such as triacylribofuranose, dlacyl-2-deoxyribofuranose, wherein the acyl is benzoyl or an aliphatic organic acid having 2 to 5 carbon atoms, acts with an amine such as hydroxylamine, hydrazine, aminoethanol, diethanolamine, chlorethylamine or 2,2‘-dlchloroethyl 195829
aminem při teplotě 0 až 60 °C v organickém rozpouštědle, s výhodou v methanolu nebo vodném alkoholu s 1 až 5 atomy uhlíku.amine at 0 to 60 ° C in an organic solvent, preferably methanol or a C 1 to C 5 aqueous alcohol.
Dalším význakem vynálezu způsobu přípravy derivátů močoviny obecného vzorce I, je že se na látku obecného vzorce II působí amoniakem, alkalickým alkoholátem sodným, draselným nebo barnatým, v alkoholu s 1 až 5 atomy uhlíku.Another aspect of the invention for the preparation of urea derivatives of formula I is that the compound of formula II is treated with ammonia, an alkali sodium, potassium or barium alcoholate in a C 1 -C 5 alcohol.
V dalším je vynález blíže objasněn v příkladech provedení, aniž se na tyto výlučně omezuje.In the following, the invention is illustrated in more detail by the examples without being limited thereto.
Příklad 1Example 1
Směs 3- (2,3,5-tri-O-benzoyl-j3-D-ribiofuranosyl)-2,4-thiazolldindionu (281 mg), hydrazin hydrátu (0,1 ml) a methanolu (3 ml) se míchá 5 hod. při teplotě místnosti. Vyloučená krystalická látka se odfiltruje a krystaluje z ethanolu. Získá se 200 mg 4- (2,3,5-triO-benzoyl-/?-D-ribofuranosyl) semikarbazldu o t. t. 166 až 167,5 °C. Z matečných louhů se získá ještě 20 mg téže látky. Celkový výtěžek je 85 %.A mixture of 3- (2,3,5-tri-O-benzoyl-β-D-ribiofuranosyl) -2,4-thiazolldinedione (281 mg), hydrazine hydrate (0.1 ml) and methanol (3 ml) was stirred for 5 hours. hours at room temperature. The precipitated crystalline material is filtered off and crystallized from ethanol. 200 mg of 4- (2,3,5-triO-benzoyl-β-D-ribofuranosyl) semicarbazld are obtained, m.p. 166-167.5 ° C. An additional 20 mg of the same is obtained from the mother liquors. The overall yield is 85%.
Pro C27H25N3O8 (519,5) vypočteno:For C27H25N3O8 (519.5) calculated:
62,42 % C, 4,85% H, 8,09% N, nalezeno:% C, 62.42;% H, 4.85;% N, 8.09.
62,68 % C, 4,88% H, 7,89% N. Příklad 2H, 4.88; N, 7.89. Example 2
3-(2,3,5-Tri-0-benzoyl-/3-D-ribofuranosyl)-2,4-thiazolidindion (112 mg) se za míchání rozpustí v 0,3 M roztoku NH3 v methanolu a roztok se nechá 8 hodin stát při teplotě místnosti, potom se ve vakuu odpaří, odparek se kodestiluje s toluenem (2 ml) a chromatografuje na sloupci silikagelu (25 g, 30 až 60 μ] v soustavě benzen — aceton (3:1). Po krystalizací z ethanolu se získá 60 mg látky 2‘,3‘,5‘-trl-O-benzoyl-/?-D-rlbofuranosylmočoviny tající při 188,5 až 190,5 °C. Z matečných louhů se získá ještě 20 mg téže látky. Celkový výtěžek je 73 %.3- (2,3,5-Tri-O-benzoyl- [3-D-ribofuranosyl) -2,4-thiazolidinedione (112 mg) was dissolved in a 0.3 M solution of NH 3 in methanol with stirring and the solution was allowed to stand for 8 hours. After standing for 1 hour at room temperature, the mixture is concentrated by evaporation in a vacuum, the residue is codistilled with toluene (2 ml) and chromatographed on a silica gel column (25 g, 30 to 60 μ) in benzene-acetone (3: 1). 60 mg of 2 ', 3', 5'-trl-O-benzoyl-R-D-1-furanosylurea melting at 188.5 to 190.5 ° C are obtained, yielding 20 mg of the same substance from the mother liquors. yield 73%.
Pro C27H24N2O8 vypočteno:For C27H24N2O8 calculated:
64,28 % C, 4,80% H, 5,55% N, nalezeno:% C, 64.28;% H, 4.80;% N, 5.55.
64,39 % C, 4,90% H, 5,57% N. Příklad 3H, 4.90; N, 5.57. Example 3
K míchané směsi 3-(2,3,5-tri-0-benzoyl-|S'-ribofuranosyl)-2,4-thlazolldindionu (112 mg) a methanolu (1,4 ml) se během 2 hodin přikapává 1 M roztok hydroxylamlnu v methanolu (0,6 ml) se 3 ekvivalenty vody. Vzniklý roztok se nechá ještě 3 hodiny při teplotě místnosti a potom se ve vakuu odpaří. Odparek se destiluje s toluenem, extrahuje vodou a krystaluje z ethanolu. Získá se 50 mg (35%) N- (2,3,5-tri-O-benzóyl-/3-D-ribofuranosylj-Nf-hydroxymočoviny o t. t. 164 až 166 stupňů Celsia.To a stirred mixture of 3- (2,3,5-tri-O-benzoyl-5'-ribofuranosyl) -2,4-thlazolldindione (112 mg) and methanol (1.4 mL) was added dropwise a 1M solution over 2 hours hydroxylamine in methanol (0.6 mL) with 3 equivalents of water. The solution was left at room temperature for 3 hours and then evaporated in vacuo. The residue is distilled with toluene, extracted with water and crystallized from ethanol. 50 mg (35%) of N- (2,3,5-tri-O-benzoyl- [beta] -D-ribofuranosyl] -NH-hydroxyurea, m.p. 164-166 DEG C., are obtained.
Pro C27H24N2O9 (520,5) vypočteno:For C27H24N2O9 (520.5) calculated:
62,30 % C, 4,65% H, 5,38% N, πλΊο'τοτία·% C, 62.30;% H, 4.65;% N, 5.38.
62,32 % C, 4,77 % H, 5,39% N.% C, 62.32;% H, 4.77;% N, 5.39.
Claims (3)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS764874A CS195829B1 (en) | 1974-11-11 | 1974-11-11 | Derivatives of urea and method of preparing |
| DD18538375A DD121508A1 (en) | 1974-11-11 | 1975-04-11 | |
| HUCE001047 HU170389B (en) | 1974-11-11 | 1975-05-20 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS764874A CS195829B1 (en) | 1974-11-11 | 1974-11-11 | Derivatives of urea and method of preparing |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS195829B1 true CS195829B1 (en) | 1980-02-29 |
Family
ID=5426001
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS764874A CS195829B1 (en) | 1974-11-11 | 1974-11-11 | Derivatives of urea and method of preparing |
Country Status (3)
| Country | Link |
|---|---|
| CS (1) | CS195829B1 (en) |
| DD (1) | DD121508A1 (en) |
| HU (1) | HU170389B (en) |
-
1974
- 1974-11-11 CS CS764874A patent/CS195829B1/en unknown
-
1975
- 1975-04-11 DD DD18538375A patent/DD121508A1/xx unknown
- 1975-05-20 HU HUCE001047 patent/HU170389B/hu unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HU170389B (en) | 1977-06-28 |
| DD121508A1 (en) | 1976-08-05 |
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