JP2011517697A

JP2011517697A - 置換テトラサイクリン化合物

置換テトラサイクリン化合物 Download PDF

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Publication number: JP2011517697A
Authority: JP; Japan
Prior art keywords: alkyl; aryl; alkenyl; alkynyl; hydroxyl
Prior art date: 2008-04-14
Legal status : Pending

Application number

JP2011505019A

Other languages

English (en)

Japanese (ja)

Other versions

JP2011517697A5 (enExample

Inventor

ジョエルベルニアク

トッドバウサー

Original Assignee

パラテックファーマシューティカルズインコーポレイテッド

Priority date

2008-04-14

Filing date

2009-04-14

Publication date

2011-06-16

2009-04-14 Application filed by パラテックファーマシューティカルズインコーポレイテッド filed Critical パラテックファーマシューティカルズインコーポレイテッド

2011-06-16 Publication of JP2011517697A publication Critical patent/JP2011517697A/ja

2013-05-23 Publication of JP2011517697A5 publication Critical patent/JP2011517697A5/ja

Status Pending legal-status Critical Current

Links

-1 tetracycline compounds Chemical class 0.000 title claims abstract description 301
239000004098 Tetracycline Substances 0.000 title claims abstract description 151
235000019364 tetracycline Nutrition 0.000 title claims abstract description 150
229960002180 tetracycline Drugs 0.000 title claims abstract description 145
229930101283 tetracycline Natural products 0.000 title claims abstract description 145
238000000034 method Methods 0.000 claims abstract description 71
208000015181 infectious disease Diseases 0.000 claims abstract description 42
230000000813 microbial effect Effects 0.000 claims abstract description 33
125000003118 aryl group Chemical group 0.000 claims description 180
125000000217 alkyl group Chemical group 0.000 claims description 168
125000000623 heterocyclic group Chemical group 0.000 claims description 156
229910052739 hydrogen Inorganic materials 0.000 claims description 153
239000001257 hydrogen Substances 0.000 claims description 152
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 147
125000000304 alkynyl group Chemical group 0.000 claims description 145
125000003342 alkenyl group Chemical group 0.000 claims description 143
125000003545 alkoxy group Chemical group 0.000 claims description 130
229910052736 halogen Inorganic materials 0.000 claims description 129
150000002367 halogens Chemical class 0.000 claims description 129
125000002252 acyl group Chemical group 0.000 claims description 124
150000002431 hydrogen Chemical class 0.000 claims description 124
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 121
125000004093 cyano group Chemical group *C#N 0.000 claims description 120
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 120
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 120
150000003568 thioethers Chemical class 0.000 claims description 120
150000003839 salts Chemical class 0.000 claims description 47
229910052757 nitrogen Inorganic materials 0.000 claims description 36
150000002148 esters Chemical class 0.000 claims description 33
125000001931 aliphatic group Chemical group 0.000 claims description 29
239000000651 prodrug Chemical group 0.000 claims description 27
229940002612 prodrug Drugs 0.000 claims description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
229910052760 oxygen Inorganic materials 0.000 claims description 22
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
208000035143 Bacterial infection Diseases 0.000 claims description 17
208000022362 bacterial infectious disease Diseases 0.000 claims description 17
239000003814 drug Substances 0.000 claims description 17
229910052717 sulfur Inorganic materials 0.000 claims description 16
229910052799 carbon Inorganic materials 0.000 claims description 14
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
239000003937 drug carrier Substances 0.000 claims description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
239000008194 pharmaceutical composition Substances 0.000 claims description 9
229910052727 yttrium Inorganic materials 0.000 claims description 7
229940072172 tetracycline antibiotic Drugs 0.000 claims description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
241000588724 Escherichia coli Species 0.000 claims description 4
241000282414 Homo sapiens Species 0.000 claims description 4
244000005700 microbiome Species 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
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 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 2
125000000168 pyrrolyl group Chemical group 0.000 claims description 2
241000193998 Streptococcus pneumoniae Species 0.000 claims 1
125000002541 furyl group Chemical group 0.000 claims 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
125000004193 piperazinyl group Chemical group 0.000 claims 1
125000003386 piperidinyl group Chemical group 0.000 claims 1
125000004076 pyridyl group Chemical group 0.000 claims 1
150000001875 compounds Chemical class 0.000 description 117
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 81
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
239000000243 solution Substances 0.000 description 53
238000006243 chemical reaction Methods 0.000 description 36
150000003522 tetracyclines Chemical class 0.000 description 34
MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical class C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 29
239000000203 mixture Substances 0.000 description 29
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 18
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
239000007864 aqueous solution Substances 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 16
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
239000003960 organic solvent Substances 0.000 description 14
229950000614 sancycline Drugs 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
230000015572 biosynthetic process Effects 0.000 description 13
125000004432 carbon atom Chemical group C* 0.000 description 13
238000002953 preparative HPLC Methods 0.000 description 13
239000007787 solid Substances 0.000 description 13
238000003786 synthesis reaction Methods 0.000 description 13
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
229910052786 argon Inorganic materials 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 12
125000001424 substituent group Chemical group 0.000 description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
125000001072 heteroaryl group Chemical group 0.000 description 11
238000003756 stirring Methods 0.000 description 11
238000011282 treatment Methods 0.000 description 11
229910019142 PO4 Inorganic materials 0.000 description 10
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 10
125000003282 alkyl amino group Chemical group 0.000 description 10
125000004448 alkyl carbonyl group Chemical group 0.000 description 10
125000001769 aryl amino group Chemical group 0.000 description 10
239000002585 base Substances 0.000 description 10
125000005842 heteroatom Chemical group 0.000 description 10
150000002430 hydrocarbons Chemical group 0.000 description 10
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 10
239000010452 phosphate Substances 0.000 description 10
239000001632 sodium acetate Substances 0.000 description 10
235000017281 sodium acetate Nutrition 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
125000004442 acylamino group Chemical group 0.000 description 9
125000004453 alkoxycarbonyl group Chemical group 0.000 description 9
125000002877 alkyl aryl group Chemical group 0.000 description 9
125000004658 aryl carbonyl amino group Chemical group 0.000 description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
125000004663 dialkyl amino group Chemical group 0.000 description 9
125000004986 diarylamino group Chemical group 0.000 description 9
239000001301 oxygen Substances 0.000 description 9
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 8
125000004457 alkyl amino carbonyl group Chemical group 0.000 description 8
125000004947 alkyl aryl amino group Chemical group 0.000 description 8
125000003806 alkyl carbonyl amino group Chemical group 0.000 description 8
125000005196 alkyl carbonyloxy group Chemical group 0.000 description 8
125000004644 alkyl sulfinyl group Chemical group 0.000 description 8
125000004691 alkyl thio carbonyl group Chemical group 0.000 description 8
125000005129 aryl carbonyl group Chemical group 0.000 description 8
125000005199 aryl carbonyloxy group Chemical group 0.000 description 8
125000005110 aryl thio group Chemical group 0.000 description 8
125000005200 aryloxy carbonyloxy group Chemical group 0.000 description 8
125000000753 cycloalkyl group Chemical group 0.000 description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
239000012153 distilled water Substances 0.000 description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
229940124597 therapeutic agent Drugs 0.000 description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
MTCQOMXDZUULRV-ADOAZJKMSA-N (4s,4as,5ar,12ar)-4-(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=CC=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O MTCQOMXDZUULRV-ADOAZJKMSA-N 0.000 description 7
238000005160 1H NMR spectroscopy Methods 0.000 description 7
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
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QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical group [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 7
125000004414 alkyl thio group Chemical group 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
150000007942 carboxylates Chemical class 0.000 description 7
238000001704 evaporation Methods 0.000 description 7
235000019253 formic acid Nutrition 0.000 description 7
150000003840 hydrochlorides Chemical class 0.000 description 7
229910052763 palladium Inorganic materials 0.000 description 7
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 7
241000894006 Bacteria Species 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
238000006069 Suzuki reaction reaction Methods 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
125000005907 alkyl ester group Chemical group 0.000 description 6
KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical group [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
125000000392 cycloalkenyl group Chemical group 0.000 description 6
125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 6
201000010099 disease Diseases 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
239000000126 substance Substances 0.000 description 6
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 6
125000004434 sulfur atom Chemical group 0.000 description 6
229940040944 tetracyclines Drugs 0.000 description 6
238000002560 therapeutic procedure Methods 0.000 description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
206010017533 Fungal infection Diseases 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
239000012981 Hank's balanced salt solution Substances 0.000 description 5
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
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208000031888 Mycoses Diseases 0.000 description 5
239000004100 Oxytetracycline Substances 0.000 description 5
208000030852 Parasitic disease Diseases 0.000 description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
208000036142 Viral infection Diseases 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 5
125000004429 atom Chemical group 0.000 description 5
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
238000005859 coupling reaction Methods 0.000 description 5
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 5
229960004023 minocycline Drugs 0.000 description 5
125000004433 nitrogen atom Chemical group N* 0.000 description 5
229960000625 oxytetracycline Drugs 0.000 description 5
235000019366 oxytetracycline Nutrition 0.000 description 5
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 5
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 5
ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 5
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical group [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 5
239000011593 sulfur Substances 0.000 description 5
IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 5
230000001225 therapeutic effect Effects 0.000 description 5
230000000699 topical effect Effects 0.000 description 5
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
239000000969 carrier Substances 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 4
230000008878 coupling Effects 0.000 description 4
238000010168 coupling process Methods 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
239000008101 lactose Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
125000004430 oxygen atom Chemical group O* 0.000 description 4
IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
230000009385 viral infection Effects 0.000 description 4
241000283690 Bos taurus Species 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
0 CN(C)C(C(CC(Cc(*(C1=O)c(c(C2=CC=C*(C=O)C=C2)c2)O)*2N(C)C)C1=C1O)[C@]11O)C(O)=C(CC(N)=O)C1=O Chemical compound CN(C)C(C(CC(Cc(*(C1=O)c(c(C2=CC=C*(C=O)C=C2)c2)O)*2N(C)C)C1=C1O)[C@]11O)C(O)=C(CC(N)=O)C1=O 0.000 description 3
239000004099 Chlortetracycline Substances 0.000 description 3
FMTDIUIBLCQGJB-UHFFFAOYSA-N Demethylchlortetracyclin Natural products C1C2C(O)C3=C(Cl)C=CC(O)=C3C(=O)C2=C(O)C2(O)C1C(N(C)C)C(O)=C(C(N)=O)C2=O FMTDIUIBLCQGJB-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 3
125000002723 alicyclic group Chemical group 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
230000000844 anti-bacterial effect Effects 0.000 description 3
230000003115 biocidal effect Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000011575 calcium Substances 0.000 description 3
150000001768 cations Chemical class 0.000 description 3
229960004475 chlortetracycline Drugs 0.000 description 3
CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 3
235000019365 chlortetracycline Nutrition 0.000 description 3
229960002398 demeclocycline Drugs 0.000 description 3
238000011161 development Methods 0.000 description 3
235000014113 dietary fatty acids Nutrition 0.000 description 3
239000000539 dimer Substances 0.000 description 3
239000000194 fatty acid Substances 0.000 description 3
229930195729 fatty acid Natural products 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
239000012458 free base Substances 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
229940042016 methacycline Drugs 0.000 description 3
239000002674 ointment Substances 0.000 description 3
150000002923 oximes Chemical class 0.000 description 3
125000004437 phosphorous atom Chemical group 0.000 description 3
229910052698 phosphorus Chemical group 0.000 description 3
125000003367 polycyclic group Chemical group 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
239000000047 product Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
238000005932 reductive alkylation reaction Methods 0.000 description 3
239000007921 spray Substances 0.000 description 3
239000003826 tablet Substances 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
238000012360 testing method Methods 0.000 description 3
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
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