ZA200701634B - Guanidine derivatives and therapeutic uses thereof - Google Patents

Guanidine derivatives and therapeutic uses thereof Download PDF

Info

Publication number: ZA200701634B
Authority: ZA; South Africa
Prior art keywords: radical; aminopropyl; mass; alkyl radical; methyl
Prior art date: 2004-07-26

Application number

ZA200701634A

Other languages

English (en)

Inventor

Roche Didier

Roux Bruno

Berard Isabelle

Original Assignee

Merck Patent Gmbh

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2004-07-26

Filing date

2007-02-23

Publication date

2008-07-30

2007-02-23 Application filed by Merck Patent Gmbh filed Critical Merck Patent Gmbh

2008-07-30 Publication of ZA200701634B publication Critical patent/ZA200701634B/en

Links

230000001225 therapeutic effect Effects 0.000 title description 5
150000002357 guanidines Chemical class 0.000 title description 4
229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 289
150000003839 salts Chemical class 0.000 claims description 215
-1 alkyl radical Chemical class 0.000 claims description 124
150000001875 compounds Chemical class 0.000 claims description 96
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
235000013350 formula milk Nutrition 0.000 claims description 59
150000003254 radicals Chemical class 0.000 claims description 56
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 55
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 39
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 37
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 31
QUUYRYYUKNNNNS-UHFFFAOYSA-N piperidine-1-carboximidamide Chemical compound NC(=N)N1CCCCC1 QUUYRYYUKNNNNS-UHFFFAOYSA-N 0.000 claims description 31
238000000034 method Methods 0.000 claims description 30
239000011347 resin Substances 0.000 claims description 30
229920005989 resin Polymers 0.000 claims description 30
229910052739 hydrogen Inorganic materials 0.000 claims description 24
125000003118 aryl group Chemical group 0.000 claims description 23
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 22
239000002253 acid Substances 0.000 claims description 22
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 22
125000000623 heterocyclic group Chemical group 0.000 claims description 20
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 20
239000001257 hydrogen Substances 0.000 claims description 18
230000003287 optical effect Effects 0.000 claims description 18
238000002360 preparation method Methods 0.000 claims description 18
150000007513 acids Chemical class 0.000 claims description 17
229910052757 nitrogen Inorganic materials 0.000 claims description 16
230000008569 process Effects 0.000 claims description 15
150000001412 amines Chemical class 0.000 claims description 13
125000000217 alkyl group Chemical group 0.000 claims description 12
125000000753 cycloalkyl group Chemical group 0.000 claims description 10
125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 9
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
150000002431 hydrogen Chemical class 0.000 claims description 7
238000011282 treatment Methods 0.000 claims description 7
230000009471 action Effects 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 5
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208000032928 Dyslipidaemia Diseases 0.000 claims description 4
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229910052799 carbon Inorganic materials 0.000 claims description 3
206010012601 diabetes mellitus Diseases 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
SMDHUXBEGKSBEJ-UHFFFAOYSA-N 2-(3-aminopropyl)-1-(3-methylbutyl)-3-(4-pentoxyphenyl)guanidine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.CCCCCOC1=CC=C(N=C(NCCCN)NCCC(C)C)C=C1 SMDHUXBEGKSBEJ-UHFFFAOYSA-N 0.000 claims description 2
239000000010 aprotic solvent Substances 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
238000010438 heat treatment Methods 0.000 claims description 2
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 2
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 2
LZYVIQJEDPUTJD-UHFFFAOYSA-N 2-(3-amino-2,2-dimethylpropyl)-1-(3-methylbutyl)-3-(4-phenylmethoxyphenyl)guanidine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C1=CC(NC(NCC(C)(C)CN)=NCCC(C)C)=CC=C1OCC1=CC=CC=C1 LZYVIQJEDPUTJD-UHFFFAOYSA-N 0.000 claims 1
QRJZGVVKGFIGLI-UHFFFAOYSA-N 2-phenylguanidine Chemical compound NC(=N)NC1=CC=CC=C1 QRJZGVVKGFIGLI-UHFFFAOYSA-N 0.000 claims 1
SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims 1
125000003342 alkenyl group Chemical group 0.000 claims 1
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ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 claims 1
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
229960004198 guanidine Drugs 0.000 description 20
239000000203 mixture Substances 0.000 description 17
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 15
239000000243 solution Substances 0.000 description 15
239000000725 suspension Substances 0.000 description 13
125000001424 substituent group Chemical group 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 11
102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 9
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
239000002609 medium Substances 0.000 description 8
208000024172 Cardiovascular disease Diseases 0.000 description 7
125000002947 alkylene group Chemical group 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
125000005842 heteroatom Chemical group 0.000 description 6
125000002950 monocyclic group Chemical group 0.000 description 6
229910052717 sulfur Inorganic materials 0.000 description 6
XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
108010007622 LDL Lipoproteins Proteins 0.000 description 5
102000007330 LDL Lipoproteins Human genes 0.000 description 5
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
239000011149 active material Substances 0.000 description 5
239000002585 base Substances 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
230000037396 body weight Effects 0.000 description 5
230000000694 effects Effects 0.000 description 5
108010010234 HDL Lipoproteins Proteins 0.000 description 4
102000015779 HDL Lipoproteins Human genes 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
125000004450 alkenylene group Chemical group 0.000 description 4
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
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239000000843 powder Substances 0.000 description 4
239000000047 product Substances 0.000 description 4
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239000002904 solvent Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
150000003626 triacylglycerols Chemical class 0.000 description 4
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
150000005840 aryl radicals Chemical class 0.000 description 3
XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
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201000010099 disease Diseases 0.000 description 3
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125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 3
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125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
210000002381 plasma Anatomy 0.000 description 3
238000003756 stirring Methods 0.000 description 3
229960001367 tartaric acid Drugs 0.000 description 3
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IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 description 2
LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
UZEKTDVGUQCDBI-UHFFFAOYSA-N 2-propan-2-ylguanidine Chemical compound CC(C)NC(N)=N UZEKTDVGUQCDBI-UHFFFAOYSA-N 0.000 description 2
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XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Polymers CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
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AWHSNDFWWUDPSX-UHFFFAOYSA-N n'-(3-aminopropyl)-n-(3-phenylmethoxyphenyl)pyrrolidine-1-carboximidamide Chemical compound C1CCCN1C(NCCCN)=NC(C=1)=CC=CC=1OCC1=CC=CC=C1 AWHSNDFWWUDPSX-UHFFFAOYSA-N 0.000 description 1
XXLJXEWJJQZBMJ-UHFFFAOYSA-N n'-(3-aminopropyl)-n-(4-decoxyphenyl)-4-methylpiperidine-1-carboximidamide Chemical compound C1=CC(OCCCCCCCCCC)=CC=C1N=C(NCCCN)N1CCC(C)CC1 XXLJXEWJJQZBMJ-UHFFFAOYSA-N 0.000 description 1
WRNLIGKTCIHWMB-UHFFFAOYSA-N n'-(3-aminopropyl)-n-[4-(2-cyclohexylethoxy)phenyl]-3-methylpiperidine-1-carboximidamide Chemical compound C1C(C)CCCN1C(NCCCN)=NC(C=C1)=CC=C1OCCC1CCCCC1 WRNLIGKTCIHWMB-UHFFFAOYSA-N 0.000 description 1
BJELHSHBVKQBBL-UHFFFAOYSA-N n'-(3-aminopropyl)-n-[4-[(2-cyanophenyl)methoxy]phenyl]-3-methylpiperidine-1-carboximidamide Chemical compound C1C(C)CCCN1C(NCCCN)=NC(C=C1)=CC=C1OCC1=CC=CC=C1C#N BJELHSHBVKQBBL-UHFFFAOYSA-N 0.000 description 1
PGZZZPIDJCWPGV-UHFFFAOYSA-N n'-(3-aminopropyl)-n-[4-[(4-tert-butylphenyl)methoxy]phenyl]-3-methylpiperidine-1-carboximidamide Chemical compound C1C(C)CCCN1C(NCCCN)=NC(C=C1)=CC=C1OCC1=CC=C(C(C)(C)C)C=C1 PGZZZPIDJCWPGV-UHFFFAOYSA-N 0.000 description 1
DCNVJAMKPSQMJT-UHFFFAOYSA-N n'-(3-aminopropyl)-n-[4-[(4-tert-butylphenyl)methoxy]phenyl]-4-methylpiperidine-1-carboximidamide Chemical compound C1CC(C)CCN1C(NCCCN)=NC(C=C1)=CC=C1OCC1=CC=C(C(C)(C)C)C=C1 DCNVJAMKPSQMJT-UHFFFAOYSA-N 0.000 description 1
GKTNLYAAZKKMTQ-UHFFFAOYSA-N n-[bis(dimethylamino)phosphinimyl]-n-methylmethanamine Chemical compound CN(C)P(=N)(N(C)C)N(C)C GKTNLYAAZKKMTQ-UHFFFAOYSA-N 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
150000005054 naphthyridines Chemical class 0.000 description 1
PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 1
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000003921 oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
230000007170 pathology Effects 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229960003742 phenol Drugs 0.000 description 1
229960003531 phenolsulfonphthalein Drugs 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
239000010773 plant oil Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000000207 pro-atherogenic effect Effects 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
PIGIRWPZTWLVLB-UHFFFAOYSA-N pyrrolidine-1-carboximidamide Chemical compound NC(=N)N1CCCC1 PIGIRWPZTWLVLB-UHFFFAOYSA-N 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
229960000948 quinine Drugs 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
230000004044 response Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
230000000276 sedentary effect Effects 0.000 description 1
XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000004208 shellac Substances 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
230000000391 smoking effect Effects 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
125000005504 styryl group Chemical group 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
150000004897 thiazines Chemical class 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
150000003585 thioureas Chemical class 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
238000012546 transfer Methods 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
235000013337 tricalcium citrate Nutrition 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/18—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Diabetes (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Obesity (AREA)
Hematology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Endocrinology (AREA)
Emergency Medicine (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pyrrole Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

ZA200701634A 2004-07-26 2007-02-23 Guanidine derivatives and therapeutic uses thereof ZA200701634B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
FR0408237A FR2873368B1 (fr)	2004-07-26	2004-07-26	Derives de guanidine et leurs utilisations en therapeutique

Publications (1)

Publication Number	Publication Date
ZA200701634B true ZA200701634B (en)	2008-07-30

Family

ID=34946751

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200701634A ZA200701634B (en)	2004-07-26	2007-02-23	Guanidine derivatives and therapeutic uses thereof

Country Status (14)

Country	Link
US (1)	US7582656B2 (ru)
EP (1)	EP1771428A1 (ru)
JP (1)	JP2008507571A (ru)
KR (1)	KR20070043804A (ru)
CN (1)	CN1989120A (ru)
AR (1)	AR050180A1 (ru)
AU (1)	AU2005266661A1 (ru)
BR (1)	BRPI0513744A (ru)
CA (1)	CA2574947A1 (ru)
FR (1)	FR2873368B1 (ru)
MX (1)	MX2007000856A (ru)
RU (1)	RU2007106935A (ru)
WO (1)	WO2006010422A1 (ru)
ZA (1)	ZA200701634B (ru)

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BRPI0715160A2 (pt)	2006-08-08	2013-06-11	Sanofi Aventis	imidazolidina-2,4-dionas substituÍdas por arilamimoaril-alquil-, processo para preparÁ-las, medicamentos compeendendo estes compostos, e seu uso
DE102007005045B4 (de)	2007-01-26	2008-12-18	Sanofi-Aventis	Phenothiazin Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
EP2025674A1 (de)	2007-08-15	2009-02-18	sanofi-aventis	Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
DE102007054497B3 (de)	2007-11-13	2009-07-23	Sanofi-Aventis Deutschland Gmbh	Neue kristalline Diphenylazetidinonhydrate und Verfahren zu deren Herstellung
WO2010003624A2 (en)	2008-07-09	2010-01-14	Sanofi-Aventis	Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof
WO2010068601A1 (en)	2008-12-08	2010-06-17	Sanofi-Aventis	A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof
DK2470552T3 (en)	2009-08-26	2014-02-17	Sanofi Sa	NOVEL, CRYSTALLINE, heteroaromatic FLUORGLYCOSIDHYDRATER, MEDICINES COVERING THESE COMPOUNDS AND THEIR USE
US8933024B2 (en)	2010-06-18	2015-01-13	Sanofi	Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases
WO2012120056A1 (de)	2011-03-08	2012-09-13	Sanofi	Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
US8809325B2 (en)	2011-03-08	2014-08-19	Sanofi	Benzyl-oxathiazine derivatives substituted with adamantane and noradamantane, medicaments containing said compounds and use thereof
EP2683704B1 (de)	2011-03-08	2014-12-17	Sanofi	Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
WO2012120050A1 (de)	2011-03-08	2012-09-13	Sanofi	Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung
US8710050B2 (en)	2011-03-08	2014-04-29	Sanofi	Di and tri- substituted oxathiazine derivatives, method for the production, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
EP2683703B1 (de)	2011-03-08	2015-05-27	Sanofi	Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung
WO2012120058A1 (de)	2011-03-08	2012-09-13	Sanofi	Mit benzyl- oder heteromethylengruppen substituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
WO2012120054A1 (de)	2011-03-08	2012-09-13	Sanofi	Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
EP2766349B1 (de)	2011-03-08	2016-06-01	Sanofi	Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung
EP2567959B1 (en)	2011-09-12	2014-04-16	Sanofi	6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
US9388126B2 (en)	2012-07-19	2016-07-12	Drexel University	Sigma receptor ligands and methods of modulating cellular protein homeostasis using same
WO2015002150A1 (ja)	2013-07-03	2015-01-08	株式会社新日本科学	新規化合物，有機カチオントランスポーター３の検出剤及び活性阻害剤
WO2019089902A1 (en)	2017-11-01	2019-05-09	Drexel University	Compounds, compositions, and methods for treating diseases
AU2019318209B2 (en)	2018-08-10	2025-09-25	Diapin Therapeutics, Llc	Tri-peptides and treatment of metabolic, cardiovascular and inflammatory disorders

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DE19610932A1 (de) *	1996-03-20	1997-09-25	Bayer Ag	2-Aryl-substituierte Pyridine
ITRM20020625A1 (it) *	2002-12-17	2004-06-18	Sigma Tau Ind Farmaceuti	Derivati di guanidine variamente sostituite, loro uso come medicamenti ad attivita' antidiabetica e/o antiobesita'.
JP4806628B2 (ja) *	2003-05-05	2011-11-02	プロビオドルグエージー	グルタミニルシクラーゼ阻害剤

2004
- 2004-07-26 FR FR0408237A patent/FR2873368B1/fr not_active Expired - Fee Related
2005
- 2005-06-28 US US11/572,663 patent/US7582656B2/en not_active Expired - Fee Related
- 2005-06-28 RU RU2007106935/04A patent/RU2007106935A/ru unknown
- 2005-06-28 CA CA002574947A patent/CA2574947A1/en not_active Abandoned
- 2005-06-28 KR KR1020077001872A patent/KR20070043804A/ko not_active Withdrawn
- 2005-06-28 CN CNA2005800250453A patent/CN1989120A/zh active Pending
- 2005-06-28 AU AU2005266661A patent/AU2005266661A1/en not_active Abandoned
- 2005-06-28 WO PCT/EP2005/006929 patent/WO2006010422A1/en not_active Ceased
- 2005-06-28 MX MX2007000856A patent/MX2007000856A/es not_active Application Discontinuation
- 2005-06-28 BR BRPI0513744-6A patent/BRPI0513744A/pt not_active Application Discontinuation
- 2005-06-28 JP JP2007522936A patent/JP2008507571A/ja active Pending
- 2005-06-28 EP EP05759228A patent/EP1771428A1/en not_active Withdrawn
- 2005-07-22 AR ARP050103034A patent/AR050180A1/es unknown
2007
- 2007-02-23 ZA ZA200701634A patent/ZA200701634B/en unknown

Also Published As

Publication number	Publication date
CN1989120A (zh)	2007-06-27
AU2005266661A1 (en)	2006-02-02
US7582656B2 (en)	2009-09-01
US20080004315A1 (en)	2008-01-03
KR20070043804A (ko)	2007-04-25
MX2007000856A (es)	2007-03-12
AR050180A1 (es)	2006-10-04
WO2006010422A1 (en)	2006-02-02
FR2873368A1 (fr)	2006-01-27
RU2007106935A (ru)	2008-09-10
JP2008507571A (ja)	2008-03-13
FR2873368B1 (fr)	2008-01-04
CA2574947A1 (en)	2006-02-02
EP1771428A1 (en)	2007-04-11
BRPI0513744A (pt)	2008-05-13

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