CA2996213C - Guanidine substituted imidazo[4,5-c] ring compounds - Google Patents
Guanidine substituted imidazo[4,5-c] ring compounds Download PDFInfo
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- CA2996213C CA2996213C CA2996213A CA2996213A CA2996213C CA 2996213 C CA2996213 C CA 2996213C CA 2996213 A CA2996213 A CA 2996213A CA 2996213 A CA2996213 A CA 2996213A CA 2996213 C CA2996213 C CA 2996213C
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 233
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 title abstract description 51
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 title description 25
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 title description 25
- 241001465754 Metazoa Species 0.000 claims abstract description 78
- -1 6,7,8,9- tetrahydroimidazo[4,5-c]naphthyridine compounds Chemical class 0.000 claims abstract description 50
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 36
- 201000010099 disease Diseases 0.000 claims abstract description 33
- 230000003612 virological effect Effects 0.000 claims abstract description 17
- 230000001613 neoplastic effect Effects 0.000 claims abstract description 13
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims description 226
- 125000000217 alkyl group Chemical group 0.000 claims description 114
- 229910052739 hydrogen Inorganic materials 0.000 claims description 81
- 239000001257 hydrogen Substances 0.000 claims description 80
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 62
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 51
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- 125000004432 carbon atom Chemical group C* 0.000 claims description 44
- 125000002947 alkylene group Chemical group 0.000 claims description 37
- 125000005532 aryl alkyleneoxy group Chemical group 0.000 claims description 37
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 34
- 229910052736 halogen Inorganic materials 0.000 claims description 34
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 33
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 31
- 125000001188 haloalkyl group Chemical group 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
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- 125000004104 aryloxy group Chemical group 0.000 claims description 26
- 125000003282 alkyl amino group Chemical group 0.000 claims description 24
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 24
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 23
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 17
- 150000002825 nitriles Chemical class 0.000 claims description 17
- 125000000304 alkynyl group Chemical group 0.000 claims description 16
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- 125000004122 cyclic group Chemical group 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 125000005466 alkylenyl group Chemical group 0.000 claims description 5
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 45
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- ITIRVXDSMXFTPW-UHFFFAOYSA-N 1H-imidazo[4,5-c]quinoline Chemical class C1=CC=CC2=C(NC=N3)C3=CN=C21 ITIRVXDSMXFTPW-UHFFFAOYSA-N 0.000 abstract 1
- QNLFZRVIACOXAG-UHFFFAOYSA-N 3h-imidazo[4,5-c][1,8]naphthyridine Chemical class N1=CC=CC2=C(NC=N3)C3=CN=C21 QNLFZRVIACOXAG-UHFFFAOYSA-N 0.000 abstract 1
- CZTQJCYFLGFVLG-UHFFFAOYSA-N 6,7,8,9-tetrahydro-3h-imidazo[4,5-c]quinoline Chemical class C1CCCC2=C1N=CC1=C2NC=N1 CZTQJCYFLGFVLG-UHFFFAOYSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 52
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 46
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- 229960004198 guanidine Drugs 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
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- 229910052681 coesite Inorganic materials 0.000 description 17
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- 239000003480 eluent Substances 0.000 description 17
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 17
- 229910052682 stishovite Inorganic materials 0.000 description 17
- 229910052905 tridymite Inorganic materials 0.000 description 17
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- 229960005486 vaccine Drugs 0.000 description 16
- 239000007832 Na2SO4 Substances 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 15
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- 239000000377 silicon dioxide Substances 0.000 description 15
- 235000012239 silicon dioxide Nutrition 0.000 description 15
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 14
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- CALVPZNSFFEPJG-UHFFFAOYSA-N guanidine;dihydrochloride Chemical compound Cl.Cl.NC(N)=N CALVPZNSFFEPJG-UHFFFAOYSA-N 0.000 description 12
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- RBZRMBCLZMEYEH-UHFFFAOYSA-N 1h-pyrazol-1-ium-1-carboximidamide;chloride Chemical compound Cl.NC(=N)N1C=CC=N1 RBZRMBCLZMEYEH-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
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- FQYRLEXKXQRZDH-UHFFFAOYSA-N 4-aminoquinoline Chemical compound C1=CC=C2C(N)=CC=NC2=C1 FQYRLEXKXQRZDH-UHFFFAOYSA-N 0.000 description 8
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Landscapes
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Applications Claiming Priority (3)
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| US201562211894P | 2015-08-31 | 2015-08-31 | |
| US62/211,894 | 2015-08-31 | ||
| PCT/US2016/048830 WO2017040233A1 (en) | 2015-08-31 | 2016-08-26 | GUANIDINE SUBSTITUTED IMIDAZO[4,5-c] RING COMPOUNDS |
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| CA2996213A1 CA2996213A1 (en) | 2017-03-09 |
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| CA3029902A1 (en) | 2016-07-07 | 2018-01-11 | The Board Of Trustees Of The Leland Stanford Junior University | Antibody adjuvant conjugates |
| JP7010286B2 (ja) | 2016-08-26 | 2022-01-26 | スリーエム イノベイティブ プロパティズ カンパニー | グアニジノ基で置換された縮合［１，２］イミダゾ［４，５－ｃ］環状化合物 |
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| SG11202001926QA (en) | 2017-09-06 | 2020-04-29 | BioNTech SE | Substituted imidazoquinolines as agonists of tlr7 |
| CN111566120B (zh) | 2017-12-20 | 2023-09-29 | 捷克共和国有机化学与生物化学研究所 | 活化sting转接蛋白的具有膦酸酯键的3’3’环状二核苷酸 |
| JP7098748B2 (ja) | 2017-12-20 | 2022-07-11 | インスティチュート オブ オーガニック ケミストリー アンド バイオケミストリー エーエスシーアール，ヴイ．ヴイ．アイ． | Ｓｔｉｎｇアダプタータンパク質を活性化するホスホン酸結合を有する２’３’環状ジヌクレオチド |
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| TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
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| US11142750B2 (en) | 2018-04-12 | 2021-10-12 | Precision Biosciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome |
| WO2019211799A1 (en) | 2018-05-03 | 2019-11-07 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide |
| WO2020028097A1 (en) | 2018-08-01 | 2020-02-06 | Gilead Sciences, Inc. | Solid forms of (r)-11-(methoxymethyl)-12-(3-methoxypropoxy)-3,3-dimethyl-8-0x0-2,3,8,13b-tetrahydro-1h-pyrido[2,1-a]pyrrolo[1,2-c] phthalazine-7-c arboxylic acid |
| US11071730B2 (en) | 2018-10-31 | 2021-07-27 | Gilead Sciences, Inc. | Substituted 6-azabenzimidazole compounds |
| US11203591B2 (en) | 2018-10-31 | 2021-12-21 | Gilead Sciences, Inc. | Substituted 6-azabenzimidazole compounds |
| US12318403B2 (en) | 2019-03-07 | 2025-06-03 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2′3′-cyclic dinucleotides and prodrugs thereof |
| WO2020178768A1 (en) | 2019-03-07 | 2020-09-10 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| US20220143061A1 (en) | 2019-03-07 | 2022-05-12 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| JP2022525594A (ja) | 2019-03-15 | 2022-05-18 | ボルト バイオセラピューティクス、インコーポレーテッド | Ｈｅｒ２を標的とする免疫結合体 |
| TW202210480A (zh) | 2019-04-17 | 2022-03-16 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TW202212339A (zh) | 2019-04-17 | 2022-04-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| WO2020237025A1 (en) | 2019-05-23 | 2020-11-26 | Gilead Sciences, Inc. | Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors |
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| WO2017040233A1 (en) | 2017-03-09 |
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