WO1993004047A1 - Derives de quinazoline utilises comme inhibiteurs de transcriptase inverse d'hiv - Google Patents
Derives de quinazoline utilises comme inhibiteurs de transcriptase inverse d'hiv Download PDFInfo
- Publication number
- WO1993004047A1 WO1993004047A1 PCT/US1992/006576 US9206576W WO9304047A1 WO 1993004047 A1 WO1993004047 A1 WO 1993004047A1 US 9206576 W US9206576 W US 9206576W WO 9304047 A1 WO9304047 A1 WO 9304047A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- chloro
- alkyl
- dihydro
- mmol
- substituted
- Prior art date
Links
- OQYGWLUOHRMDJO-UHFFFAOYSA-N CCN(C(COCC)(C1CC1)c(cc(C)cc1)c1N1)C1=O Chemical compound CCN(C(COCC)(C1CC1)c(cc(C)cc1)c1N1)C1=O OQYGWLUOHRMDJO-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
- C07D239/82—Oxygen atoms with an aryl radical attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Definitions
- a retrovirus designated human immunodeficiency virus is the etiological agent of the complex disease that includes progressive destruction of the immune system (acquired immune deficiency syndrome; AIDS) and degeneration of the central and peripheral nervous system.
- This virus was previously known as LAV, HTLV-III, or ARV.
- a common feature of retrovirus replication is reverse transcription of the RNA genome by a virally encoded reverse trairscriptase to generate DNA copies of HIV sequences, a required step in viral replication. It is known that some compounds are reverse transcriptase inhibitors and are effective agents in the treatment of AIDS and similar diseases, e.g., azidothymidine or AZT.
- Compounds of formula I or II, as herein defined, are disclosed. These compounds are useful in the inhibition of HIV reverse transcriptase, the prevention of infection by HIV, the treatment of infection by HIV and in the treatment of AIDS and/or ARC, either as compounds, pharmaceutically acceptable salts (when appropriate), pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators,
- This invention is concerned with compounds of formula I or II, combinations thereof, or
- X is O, S, or NR, and R is CN, H, NH 2 , OH,
- O, N or S in place of benzo in formula I; is H; C 1-8 alkyl; C 2-4 alkenyl; C 2-5 alkynyl; C 3-4 cycloalkyl; hydroxy; C 1-4 alkoxy; C 1-3 alkyl substituted one or more times with halo, carboxy, C 3-4 cycloalkyl, CN, hydroxy, methylsulfinyl, methanesulfonyl, C 1-4 alkoxy, C 2-4 alkenyl C 1-4 alkoxy, C 2-4 alkynl-C 1-4 alkoxy, aryloxy, C 1-4 alkylcarbonyl, or nitro; or aryl unsubstituted or substituted with (G) n furanyl; thienyl; benzofuranyl; R 1 and R 3 may be joined to form a fused heterocycle of 5 or 6 members containing up to one additional heteroatom selected from O, S or NR, provided that the heteroatoms are not directly linked
- R 3 is H; C 1-8 alkyl unsubstituted or substituted with one or more of A, wherein A is halo, hydroxy, amino, C 3-8 cycloalkyl, C 1-4 alkoxy, di-(C 1-4 alkyl)amino, C 1-4 alkylamino, or carbamoyl; C 2-8 alkenyl unsubstituted or substituted with one or more of A; C 2-8 alkynyl unsubstituted or substituted with one or more of A; C 3-8 cycloalkyl; aryl C 1-4 alkyl wherein aryl is optionally substituted with up to three substituents selected from methyl, halo, CN, or methoxy; heterocycle of 5 or 6 members containing up to 3 heteroatoms
- R 4 is H; C 1-8 alkyl unsubstituted or substituted with one or more of A; C 2-8 alkenyl
- alkylamino or di-C 1-4 alkylamino carbamoyl; methylcarbamoyl; dimethylcarbamoyl; formyl; hydroxy; alpha-amino C 1-4 alkanoyl; or meta-cyanobenzyl;
- the compounds of formula I or II are further limited to those wherein X is NR and R is CN, H, NH 2 , OH, C 1-3 alkoxy or C 1-3 alkyl.
- X is O, S, or NR, and R is CN, NH 2 , OH, C 1-3 alkoxy, H or C 1-3 alkyl; G, when present, is 1-4 substituents independently selected from C 1-4 alkyl; halo; amino; nitro; cyano; carboxy; carbamoyl C 1-4 alkyl; wherein R 5 is CH 3 , H or NH 2 ; sulfamoyl; C 1-3 alkylsulfonamido; methanesulfonyl; CF 3 ; hydroxy; or C 1-4 alkoxy; n is 0-4;
- R 1 is C 1-8 alkyl; C 2-4 alkenyl; C 2-5 alkynyl;
- C 3-4 cycloalkyl C 1-3 alkyl substituted one or more times with halo, carboxy, C 3-4 cycloalkyl, CN, hydroxy, methylsulfinyl, methanesulfonyl, C 1-4 alkoxy, C 2-4 alkynyl- C 1-4 alkoxy, or nitro; or aryl unsubstituted or substituted with (G) n ;
- R 1 and R 3 may be joined by a carba bridge to form a ring of 5 to 6 members;
- R 2 is C 1-8 alkyl; C 2-8 alkenyl; C 3-4 cycloalkyl;
- heterocycle of 5 or 6 members containing up to 3 heteroatoms selected from O, S, or NR;
- R 3 is H; C 1-8 alkyl unsubstituted or substituted with one or more of A, wherein A is halo, hydroxy, amino, C 3-8 cycloalkyl, C 1-3 alkoxy, di-(C 1-4 alkyl)amino, C 1-4 alkylamino, or carbamoyl; C 2-8 alkenyl unsubstituted or substituted with one or more of A; C 2-8 alkynyl unsubstituted or substituted with one or more of A; C 3-8 cycloalkyl; aryl C 1-4 alkyl wherein aryl is optionally substituted with up to three substituents selected from methyl, halo, CN, or methoxy; R 4 is H; C 1-8 alkyl unsubstituted or substituted with one or more of A; C 2-8 alkenyl unsubstituted or substituted with one or more of A; C 2-8 alkynyl unsubstituted or substituted
- methylcarbamoyl dimethylcarbamoyl; formyl; hydroxy; alpha-amino C 1-4 alkanoyl; or meta-cyanobenzyl; with the proviso that when R 1 is C 1-2 alkyl, then R 2 is not C 1-2 alkyl;
- a third embodiment encompasses compounds of Formula IV having a more limited scope in R 2 :
- X is O, S, or NR, and R is CN, NH 2 , OH, C 1-3 alkoxy, H or C 1-3 alkyl;
- G when present, is 1-4 substituents independently selected from C 1-4 alkyl; halo; amino; nitro; cyano; carboxy; carbamoyl C 1-4 alkyl; wherein R 5 is CH 3 , H or NH 2 ; sulfamoyl; C 1-3 alkylsulfonamido; methanesulfonyl; CF 3 ; hydroxy; or C 1-4 alkoxy; n is 0-4;
- R 1 is C 1-8 alkyl; C 2-4 alkenyl; C 2-5 alkynyl;
- C 3-4 cycloalkyl C 1-3 alkyl substituted one or more times with halo, carboxy, C 3-4 cycloalkyl, CN, hydroxy, methylsulfinyl, methanesulfonyl, C 1-4 alkoxy, C 2-4 alkynyl- C 1-4 alkoxy, or nitro; or aryl unsubstituted or substituted with (G) n ;
- R 1 and R 3 may be joined by a carba bridge to form a ring of 5 to 6 members;
- R 2 is C 1-8 alkyl; C 2-8 alkenyl; C 3-4 cycloalkyl;
- R 3 is H; C 1-8 alkyl unsubstituted or substituted with one or more of A, wherein A is halo, hydroxy, amino, C 3-8 cycloalkyl, C 1-3 alkoxy, di-(C 1-4 alkyl)amino, C 1-4 alkylamino, or carbamoyl; C 2-8 alkenyl unsubstituted or substituted with one or more of A; C 2-8 alkynyl unsubstituted or substituted with one or more of A; C 3 -8 cycloalkyl; aryl C 1-4 alkyl wherein aryl is optionally substituted with up to three substituents selected from methyl, halo, CN, or methoxy; R 4 is H; C 1-8 alkyl unsubstituted or substituted with one or more of A; C 2-8 alkenyl unsubstituted or substituted with one or more of A; C 2-8 alkynyl unsubstituted or substitute
- alkylamino or di-C 1-4 alkylamino carbamoyl; methylcarbamoyl; dimethylcarbamoyl; formyl; hydroxy; alpha-amino C 1-4 alkanoyl; or meta-cyanobenzyl; with the proviso that when R 1 is C 1-2 alkyl, then R 2 is not C 1-2 alkyl;
- X is 0;
- G when present, is C 1-4 alkyl; halo; amino;
- n 0-4;
- R 1 is C 3-4 alkyl; C 3-4 alkenyl; C 2-5 alkynyl;
- R 1 and R 3 may be joined by a carba bridge to form a ring of 5 to 6 members;
- R 2 is C 1-3 alkyl, C 2-3 alkenyl, C 2-3 alkynyl,
- R 3 is H; C 1-4 alkyl unsubstituted or
- R 4 is H; C 1-8 alkyl unsubstituted or
- X is S
- G is 6-chloro
- R 1 is phenyl
- R 2 is ethyl
- R 3 is methyl
- R 4 is H.
- X is S or O
- G is 6-chloro
- R 1 is phenyl
- R 2 is ethynyl
- R 3 is methyl
- R 4 is methyl, including each isomeric form.
- X is S or O
- G is 6-chloro
- R 1 is phenyl
- R 2 is ethynyl
- R 3 is cyclopropyl
- R 4 is H.
- X is S or O
- G is 6-chloro
- R 1 is phenyl
- R 2 is cyclopropyl
- R 3 is ethynyl
- R 4 is H.
- X is O
- G is 6-chloro
- R 1 is propyl
- R 2 is cyclopropyl
- R 3 is cyclopropylmethyl
- R 4 is H.
- X is O, G is 6-chloro, R 1 is phenyl, R 2 is ethynyl, R 3 is ethyl, and R 4 is H.
- X is O, G is 6-chloro, R 1 is phenyl, R 2 is ethynyl, R 3 is
- X is O
- G is 6-chloro
- R 1 is propyl
- R 2 is cyclopropyl
- R 3 is methyl
- R 4 is H.
- compositions include, but are not limited to, the list in the following Tables.
- alkyl is intended to include both branched- and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms; "alkenyl” is intended to cover both branched- and straight chain alkyl groups with at least one carbon-carbon double bond; “alkynyl” is intended to cover both branched- and straight chain alkyl groups with at least one carbon-carbon triple bond.
- Halogen or “halo” as used herein, means fluoro, chloro, bromo and iodo.
- aryl is intended to mean phenyl, naphthyl,
- heterocycle or heterocyclic represents a stable 5- to 7-membered monocyclic or stable 8- to 11-membered bicyclic ring which is either saturated or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected f rom the group consisting of N, O and S, and wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring.
- the heterocyclic ring may be attached at any heteroatom or carbon atom which results in the creation of a stable structure. Examples of such heterocyclic elements include
- piperidinyl piperazinyl, 2-oxopiperazinyl, 2-oxo- piperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl,
- the compounds of the present invention can be synthesized by the following schemes.
- Scheme I is subject to a variety of modifications or adaptations, including Scheme IA.
- Schemes I and Ia are also specifically illustrated in Examples 93-100 among others.
- Scheme II is another method of synthesizing the compounds of this invention, although not preferred
- Scheme III is preferred in the synthesis of 4,4-dialkyl quinazolin-2-ones.
- Scheme III is characterized by the Grignard addition to quinazoline 10.
- R 1 and R 2 lack an aromatic or heterocyclic ring.
- Appropriate protecting groups can be employed as needed.
- Preparation of 14, wherein R 4 is not H, is conveniently achieved by reaction of 13 with R 4 -Br.
- Organosilane processes are also illustrated by Examples 58-71.
- Scheme V is spetifically illustrated by Examples 72, 74-78.
- the compounds of the present inventions are useful in the inhibition of HIV reverse transcriptase
- HIV human immunodeficiency virus
- Treating AIDS or preventing or treating infection by HIV is defined as including, but not limited to, treating a wide range of states of HIV infection: AIDS, ARC (AIDS related complex), both symptomatic and asymptomatic, and actual or potential exposure to HIV.
- AIDS AIDS
- ARC AIDS related complex
- compounds of this invention are useful in treating infection by HIV after suspected past exposure to HIV by e.g., blood transfusion, exchange of body fluids, bites, accidental needle stick, or exposure to patient blood during surgery.
- the compounds of the present invention may be administered orally,
- parenterally including subcutaneous injections, intravenous, intramuscular, intrasternal injection or infusion techniques), by inhalation spray, or rectally, in dosage unit formulations containing conventional non-toxic pharmaceutically-acceptable carriers,
- the treatment involves
- a pharmaceutical composition comprising a pharmaceutical carrier and a therapeutically-effective amount of a compound of the present invention.
- compositions may be in the form of orally-administrable suspensions or
- sterile injectable preparations for example, as sterile injectable aqueous or
- compositions When administered orally as a suspension, these compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may contain microcrystalline cellulose
- compositions for imparting bulk, alginic acid or sodium alginate as a suspending agent, methylcellulose as a viscosity enhancer, and sweeteners/flavoring agents known in the art.
- these compositions may contain microcrystalline cellulose, dicalcium phosphate, starch, magnesium stearate and lactose and/or other excipients, binders, extenders,
- compositions When administered by nasal aerosol or inhalation, these compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable
- injectable solutions or suspensions may be formulated according to known art, using suitable non-toxic, parenterally-acceptable diluents or
- solvents such as mannitol, 1,3-butanediol, water, Ringer's solution or isotonic sodium chloride solution, or suitable dispersing or wetting and suspending agents, such as sterile, bland, fixed oils, including synthetic mono- or diglycerides, and fatty acids, including oleic acid.
- compositions When rectally administered in the form of suppositories, these compositions may be prepared by mixing the drug with a suitable non-irritating agent.
- excipient such as cocoa butter, synthetic glyceride esters or polyethylene glycols, which are solid at ordinary temperatures, but liquidify and/or dissolve in the rectal cavity to release the drug.
- the compounds of this invention can be administered orally to humans in a dosage range of 1 to 100 mg/kg body weight in divided doses.
- One preferred dosage range is 1 to 10 mg/kg body weight orally in divided doses.
- Another preferred dosage range is 1 to 20 mg/kg body weight orally in divided doses. It will be understood, however, that the specific dose level and frequency of dosage for any particular patient may be varied and will depend upon a variety of factors including the activity of the specific compound
- the present invention is also directed to combinations of the HIV reverse transcriptase inhibitor compounds with one or more agents useful in the
- the compounds of this invention may be effectively administered, whether at periods of pre-exposure and/or post-exposure, in combination with effective amounts of the AIDS
- antivirals such as those in the following table.
- Ganciclovir peripheral CMV retinitis d4T Bristol-Myers AIDS, ARC
- HIV Ribavirin Costa Mesa, CA
- LAS ARC Alpha Interferon Burroughs Wellcome Kaposi's sarcoma
- HIV Ribavirin Costa Mesa, CA
- LAS ARC Alpha Interferon Burroughs Wellcome Kaposi's sarcoma
- Tumor Necrosis Genentech ARC in combina- Factor; TNF (S. San Francisco, tion w/gamma
- the resulting mixture was stirred 1.5 hr under N 2 during which the yellow color discharged.
- the mixture was decanted under N 2 into a mixture of 50 mL of 10% aqueous citric acid and 50 mL ethyl acetate.
- 6-chloro-3-isopropyl-4-phenyl-2(3H)-quinazo- linthione (1.50 g, 5.02 mmol) suspended in dry THF to which (30 mL) sodium acetylide (4.02 g, 15.1 mmol, 187, slurry in xylene) was added via syringe at -25oC.
- reaction mixture Upon warming to room temperature over 3 hours, the reaction mixture was poured into 107. aqueous citric acid and ethyl acetate, washed with water, brine, dried (Na 2 SO 4 ), filtered and concentrated in vacuo.
- 6-chloro-4-phenyl-4-methylsulfinylmethyl- 3,4-dihydromethyl-2(1H)quinazolinone was prepared from 6-chloro-4-phenyl-3-methyl-2-(3H)-quinazolinone (1.0 g, 3.7 mmol) by addition to a solution of sodium hydride (0.200 g of a 50% suspension in mineral oil) in dry dimethylsulfoxide (5.0 mL) at room temperature. The mixture was quenched on ice and acetic acid, and the semi-solid chloro-4-phenyl-4-methylsulfinylmethyl-3, 4-dihydromethyl-2(1H)quinazolinone was extracted with EtOAc.
- the reaction was chilled to -74°C in a dry ice-acetone bath and freshly distilled t-butyl acetate (1.28 g, 1.49 ml, 11.03 mmol) was added via syringe keeping the temperature ⁇ -70°C then stirred at -74oC for 1 hour before adding the tetraene.
- reaction mixture was chilled to 0oC, 1.0 M LiAIH 4 in THF (4.78 ml, 4.78 mmol) was added over 5 minutes via syringe and stirred at 0°C for 1 hour.
- 1.0 M LiAIH 4 in THF (4.78 ml, 4.78 mmol) was added over 5 minutes via syringe and stirred at 0°C for 1 hour.
- reaction mixture was quenched into aqueous saturated Na K tartrate, extracted with EtOAc, washed with water, brine, dried (Na 2 SO 4 ), filtered and concentrated in vacuo to affored 1.6 g of an expanded foam.
- 6-chloro-3- methyl-4-phenyl-2(3H)quinazolinthione (0.666'g, 2.0 mmol) and dry methylene chloride (15 mL).
- Trimethylsilyl cyanide (0.750 g, 7.5 mmol) was added at room temperature, the reaction mixture was chilled to 0oC, boron trifluoride (492 ⁇ l, 4.0 mmol) was added with a syringe, the bath was removed and the mixture was stirred at room temperature for 18 hours. The mixture was poured into ethyl acetate and saturated aqueous sodium bicarbonate.
- cyclobutylamine (0.6 mL, 7 mmol) was added to a solution of 5-chloro-2-(1-imidazolecarbonylamino) benzophenone (1.95 g, 6 mmol) in 10 mL of dry THF under N 2 .
- the mixture was heated and stirred 24h at 50°C and then 40h at 25°.
- Example 2 326.00 mg (1.00 mmol) of 5-chloro- 2,1-imidazole-carbonylaminobenzophenone and 103.00 mg (1.00 mmol) (R)-valinol were reacted, with subsequent heating in anhydrous DMSO at 120°C for 72h, to give 210.00 mg (60%) of title compound as a white solid, MP 146-147oC.
- Example, 300.00 mg (1.04 mmol) (5-chloro- 2-imidazole-carbonylamino)phenylcyclopropyl ketone and 63.52 mg (1.04 mmol) ethanolamine were reacted, with subsequent heating at 100oC for 18h in anhydrous DMSO, to give 180.00 mg (65%) of title compound as a white solid, MP 193-194oC.
- 6-chloro-3,4-dihydro-4-propyl-3-methyl-4-phenyl-2(1H)- quinazolinthione there was obtained 6-chloro-3,4- dihydro-4-ethyl-3-methyl-4-phenyl-2(1H)quinazolinone.
- 6-chloro- 3,4-dihydro-4-ethyl-3-methyl-2-methylthio-4-phenyl- 3(1H)quinazoline (248 mg, 0.75 mmol)
- lead cyanamide 370 mg, 1.50 mmol
- cyanamide 400 mg, 9.51 mmol
- dry DMF 5.00 mL
- reaction mixture was heated to reflux for 1 hour, cooled to room temperature and 0.15 mL (1.17 mmol) of trimethylsilylchloride added. The reaction mixture was reheated to reflux for 30 minutes and allowed to stand at room temperature. The reaction mixture diluted with water, extracted with EtOAc and the organic layer washed with brine, dried over Na 2 SO 4 , and the solvents stripped under reduced pressure to give 800 mg of a residue which was chromatographed on silica gel using 1:2 EtOAc-hexanes to give 147 mg of the title compound as a colorless solid:
- Step A 5-chloro-2-(1-imidazolecarbonylamino)benzo- phenone
- Step B 6-chloro-4-phenyl-4-hydroxy-3-methyl-3,4- dihydroquinazoline-2(1H)one
- Step D 6-Chloro-3,4-dihydro-4-ethynyl-3-methyl-4- phenyl-2(1H)-quinazolinone
- 6-chloro-3-methyl-4-phenyl-2(3H)-quinazoli- none (6.0 g, 22.2 mmol) was suspended in dry THF (200 ml) to which sodium acetylide (17.74 g, 66.5 mmol, 18% slurry in xylene) was added via syringe at -25°C. Upon warming to room temperature over 3 hours the yellow color had discharged.
- the reaction mixture was poured into 10% aqueous citric acid and extracted with ethyl acetate, washed with water, brine, dried (MgSO 4 ), filtered and concentrated in vacuo.
- the crude product was chromatographed on silica gel using 20%
- Step A 5-chloro-2-(1-imidazolecarbonylamino)benzo- phenone was prepared in the exact manner as outlined in Example 10, Step A, from 5-chloro-2-aminobenzo- phenone and carbonyldiimidazole in CH 2 CI2.
- Step B 6-chloro-4-phenyl-4-hydroxy-3-isopropyl-3 ,4- dihydroquinazoline-2(1H)one
- reaction mixture was heated to 40oC and stirred under argon.
- the resulting clear solution was evaporated in vacuo. dissolved in ethyl acetate, washed with 10% aqueous citric acid, water, brine, dried over MgSO 4 , filtered, concentrated, and chromatographed using
- Step D 6-chloro-3,4-dihydro-4-ethynyl-3-isopropyl-
- 6-chloro-3-isopropyl-4-phenyl-2(3H)-quina- zolinone (1.50 g, 5.02 mmol) was suspended in dry THF to which (30 mL) sodium acetylide (4.02 g, 15.1 mmol, 18% slurry in xylene) was added via syringe at -25°C. After warming to room temperature over 3 hours, the reaction was poured into 10% aqueous citric acid and ethyl acetate, washed with water, brine, dried
- Step B 6-Chloro-3,4-dihydro-3-ethyl-4-ethynyl-4- phenyl-2(1H)quinazolinone
- Step B 6-chloro-4-cyclopropyl-3-methyl-3,4-dihydro-
- Step C (+/-) 6-chloro-4-cyclopropyl-3-methyl-4-(2- propenyl)-3, 4-dihydroquinazolin-2(1H)-one
- step B The product from step B (0.071g, 0.179 mmol) was dissolved in 2 mL of a 1:1 solution of
- Step A 6-Chloro-4-cyclopropyl-4-cyclopropylmethyl-3,4- 4-dihydro-1-(4-methoxybenzyl)quinazolin-2(1H)- one
- 6-Chloro-4-cyclopropyl-3,4-dihydro-1-(4- methoxybenzyl)-4-(2-propenyl)quinazolin-2(1H)-one (96 mg, 0.251 mmol) was dissolved in 5 ml ethyl ether and 2 ml ether solution of diazomethane was added at 0°C.
- Step B 6-Chloro-4-cyclopropyl-4-cyclopropylmethyl-3, 4-dihydro-1-(4-methoxybenzyl)-3-methylquinazolin-2(1H)-one
- step B the title compound was prepared from 100 mg (0.251 mmol) of the product from step A to give 110 mg of an oil.
- Step C (+/-) 6-Chloro-4-cyclopropyl-4-cyclopropyl- methyl-3-methyl-3,4-dihydroquinazolin-2(1H)- one
- step C the title compound was prepared from 110 mg (0.251 mmol) of the product from step B to give 32 mg (44%) of a solid:
- Step A 9-Chloro-10b-cyclopropyl-6-(4-methoxybenzyl)- 1,2,3,10b-tetrahydropyrrolo[l,2-c]quinazolin-
- step E the title compound was prepared as the product from 24 mg (0.060 mmol) 6-chloro-4-cyclopropyl- 4-(3-hydroxypropyl)-1-(4-methoxybenzyl)-3,4-dihydroquin- azolin-2(1H)-one to give 20 mg of an oil.
- Step B 9-Chloro-10b-cyclopropyl-l,2,3,10b-tetrahydro- pyrrolo[1,2-c]quinazolin-5(6H)-one
- step C the title compound was prepared from 20 mg (0.052 mmol) of the product from above to give 7 mg (51%) of a solid:
- Step A 6-Chloro-4-cyclopropyl-4-(2-hydroxyethyl)-3,
- step A the title compound was prepared from 6-chloro-4- cyclopropyl-4-(2-propenyl)-3,4-dihydroquinazolin-2(1H)- one (130 mg, 0.495 mmol) to give 87 mg of a solid.
- Step B 10-Chloro-11b-cyclopropyl-1,11b-dihydro-2H,
- step C the title compound was prepared from 6-chloro-4- cyclopropyl-4-(2-hydroxyethyl)-3,4-dihydroquinazolin- 2(1H)-one (87 mg, 0.326 mmol) to give 34 mg (37%) of a colorless solid.
- Step A 6-Chloro-4-cyclopropyl-4-(2-thiopheneyl)-3,
- step A the title compound was prepared from 6-chloro-
- Step B 6-Chloro-4-cyclopropyl-1-(4-methoxybenzyl)-3- methyl-4-(2-thiopheneyl)-3,4-dihydroquinazolin-
- step B the title compound was prepared from 187 mg (0.440 mmol) of the product from step A to give 80 mg of an oil.
- Step C (+/-) 6-Chloro-4-cyclopropyl-3-methyl-4-(2- thiopheneyl)-3,4-dihydroquinazolin-2(1H)-one Ceric ammonium nitrate (400 mg, 0.729 mmol) was dissolved in 1.6 ml water and added to the product from step B. (80 mg, 0.182 mmol) dissolved in 8 ml acetonitrile and stirred overnight.
- Step A 6-Chloro-4-cyclopropyl-4-(2,2-dimethyl- propyl)-3,4-dihydro-1-(4-methoxybehzyl)quinazolin-2(1H)-one
- step A the title compound was prepared from 6-chloro-4- cyclopropyl-1-(4-methoxybenzyl)quinazolin-2(1H)-one (200 mg, 0.587 mmol) and 2,2-dimethylpropylmagnesium bromide to give 66 mg of a solid.
- Step B 6-Chloro-4-cyclopropyl-4-(2,2-dimethyl- propyl)-3, 4-dihydro-1-(4-methoxybenzyl)-3- methylquinazolin-2(1H)-one
- step B the title compound was prepared from 66 mg (0.160 mmol) of the product from step A to give 85 mg of an oil.
- Step C (+/-) 6-Chloro-4-cyclo ⁇ ropyl-4-(2,2-dimethyl- propyl)-3-methyl-3,4-dihydroquinazolin- 2(1H)-one
- step C the title compound was prepared from 85 mg (0.160 mmol) of the product from step B to give 12 mg (24%) of a colorless solid:
- step C the title compound was prepared from 60 mg(0.150 mmol) 6-chloro-4-cyclopropyl-4-(2-hydroxyethyl)-1-(4-methoxybe nzyl)-3-methyl-3,4-dihydroquinazolin-2(1H)-one to give 14 mg (34%) of a solid:
- Step B 6-Chloro-4-cyclopropyl-1-(4-methoxybenzyl)-
- step B the title compound was prepared from 745 mg (1.18 mmol) of the product from step A to give 491 mg of an oil.
- Step C (+/-) 6-Chloro-4-cyclopropyl-4-(2-methoxy- ethyl)-3-methyl-3,4-dihydroquinazolin-
- step C the title compound was prepared from 491 mg(1.18 mmol) of the product from step B to give 225 mg (65%) of a colorless solid:
- step B the title compound was prepared from 6-chloro-4- cyclopropyl-4-(2-hydroxyethyl)-1-(4-methoxybenzyl)-3, 4-dihydroquinazolin-2(1H)-one (248 mg, 0.522 mmol) and ethyl iodide (1 ml) to give 100 mg of an oil.
- Step B 6-Chloro-4-cyclopropyl-4-(2-ethoxyethyl)-3- ethyl-3,4-dihydroquinazolin-2(1H)-one
- step C the title compound was prepared from 6-chloro-4-cyclo- propyl-4-(2-ethoxyethyl)-3-ethyl-1-(4-methoxybenzyl)-3, 4-dihydroquinazolin-2(1H)-one (100 mg, 0.226 mmol) to give 25 mg (34%) of a solid:
- Step A 6-Chloro-4-cyclopropyl-4-(2-propenyl)-3,4- dihydroquinazolin-2(1H)-one
- step A the title compound was prepared from 6-chloro-4- cyclopropylquinazolin-2(1H)-one (2.0 g, 9.06 mmol) to give 2.2 g of a yellow solid.
- step A the title compound was prepared from 300 mg (1.14 mmol) of the product from above to give 217 mg (69%) of a foam:
- Step B 6-Chloro-4-cyclopropyl-4-(3-t-butyldimethyl- silyloxypropyl)-1-(4-methoxybenzyl)-3,4-di- hydroquinazolin-2(1H)-one
- 6-Chloro-4-cyclopropyl-4-(3-t-butyldimethyl- silyloxypropyl)-1-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one 400 mg, 0.776 mmol
- NaH 67 mg, 1.68 mmol, 60% slurry in oil
- 4-Methoxybenzyl chloride (0.105 ml, 0.776 mmol) was added and the mixture was stirred for 2 days.
- Step D 6-Chloro-4-cyclopropyl-4-(3-hydroxypropyl)-1,
- 6-Chloro-4-cyclopropyl-4-(3-t-butyldimethyl- silyloxypropyl)-1,3-di(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one (493 mg, 0.776 mmol) was dissolved in 6 ml 1M tetrabutylammonium fluoride in THF and stirred for 30 min. EtOAc was added , then washed with water, brine, dried over MgSO 4 , filtered, the solvent removed in vacuo. and chromatographed on silica gel using 50% EtOAc/hexanes to give 243 mg of a clear oil.
- Step E 6-Chloro-4-cyclopropyl-4-(3-fluoropropyl)-l
- Step F 6-Chloro-4-cyclopropyl-4-(3-fluoropropyl)-3,
- step C the title compound was prepared from 240 mg (0.459 mmol) of 6-chloro-4-cyclopropyl-4-(3-fluoropropyl)-1, 3-di(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one to give 22 mg (17%) of a colorless solid:
- Step A 6-Chloro-3-cyano-4-cyclopropyl-4-cyclopropyl- methyl-3,4-dihydro-1-(4-methoxybenzyl)quinazolin-2(1H)-one
- Step B 6-Chloro-3-cyano-4-cyclopropyl-4-cyclopropyl- methyl-3,4-dihydroquinazolin-2(1H)-one
- step C the title compound was prepared from 6-chloro-3-cyano- 4-cyclopropyl-4-cyclopropylmethyl-3,4-dihydro-1-(4- methoxybenzyl)quinazolin-2(1H)-one (35 mg, 0.083 mmol) to give 7 mg (28%) of a solid.
- step B from 85.00 mg(0.22 mmol) of 3,4-dihydro-1-(4-methoxy- benzyl)-3-methyl-4,4-dicyclopropyl-6-chloroquinazolin-
- Step A 3,4-dihydro-1-(4-methoxybenzyl)-3-allyl-4- cyclopropyl-4-cyclopropymethyl-6-chloroquinaz ⁇ lin-2 (1H )
- step B from 490 mg(1.12 mmol) 3,4-dihydro-1-(4-methoxy- benzyl)-3-allyl-4-cyclo ⁇ ropyl-4-cyclopropylmethyl-6- chloroquinazolin-2(1H)one and 1 ml methylene chloride/1 ml TFA over 2 hrs., was obtained 285 mg(82%) of title compound as a white crystalline solid, mp:160-162°C.
- Step A 3,4-dihydro-1-(4-methoxybenzyl)-4-cyclopropyl-4- (4-(trimethylsilyl)-3-butyn-1-yl)-6-chloroquinazolin-2(1H)one
- Step B 3,4-dihydro-1-(4-methoxybenzyl)-4-cyclopropyl- 4-(3-butyn-1-yl)-6-chloroquinazolin-2(1H)one
- a solution of 53.45 mg(0.92 mmol) of KF in 42 ml water/2 ml DMF was added a solution of 105.00 mg(0.23 mmol)3,4-dihydro-1-(4-methoxybenzyl)-4-cyclo- propyl-4-(4-trimethylsilyl-3-butyn-1-yl)-6-chloroquinazo lin-2(1H)one in 2 ml DMF.
- step B from 55.00 mg(0.14 mmol) of 3,4-dihydro-1-(4-methoxy- benzyl)-4-cyclopropyl-4-(3-butyn-1-yl)-6-chloroquina- zolin-2(1H)one in 1ml methylene chloride/lml TFA over
- Step A 3,4-dihydro -1-(4-methoxybenzyl)-4-cyclopropyl-4-(2-butyn-1-yl)-6-chloroquinazolin- 2(1H)one
- Step B 3,4-dihydro -1-(4-methoxybenzyl)-3-methy1-4- cyclopropyl-4-(2-butyn-1-yl)-6-chloro- quinazolin-2(1H)one
- step C from 1.30 g(3.41 mmol) of 3, 4-dihydro-1-(4-methoxybenzyl)-4-cyclopropyl-4-(2-butyn-1-yl)-6-chloroquinazolin-2(1H)one, 163.68 mg(3.50 mmol) NaH, and 484.00 mg(3.41 mmol) of methyl iodide was obtained 1.17g(87%) of title compound as a white crystalline solid,
- step B from 1.00g(2.53 mmol) of 3,4-dihydro-1-(4-methoxy- benzyl)-3-methyl-4-cyclopropyl-4-(2-butyn-1-yl)-6- chloroquinazolin-2(1H)one and 8 ml methylene chloride/8 ml TFA over 18 hrs. was obtained 0.64g(91%) of the title compound as a white solid, mp: 204.0-205.5°C.
- Step A (+/-)-6-Chloro-4-cyclopropyl-3,4-dihydro-1- (4-methoxybenzyl)-4-isopropylquinazolin- 2(1H)-one
- step A the title compound was prepared from (+/-) 6-chloro- 4-cyclopropyl-3,4-dihydro-1-(4-4-methoxybenzyl)-4-
- Step A (+/-)-6-Chloro-4-cyclopropyl-3-propargyl-3,
- Example 35 the title compound was prepared from (+/-) 6-chloro-4-cyclo- propyl-3,4-dihydro-1-(4-methoxybenzyl)-4-cyclopropyl- methylquinazolin-2(1H)-one.
- Step B (+/-)-6-Chloro-4-cyclopropyl-3-propargyl-3,
- step A the title compound was prepared from (+/-)-6-chloro-4- cyclopropyl-3-propargyl-3,4-dihydro-1-(4-methoxybenzyl)- 4-cyclopropylmethylquinazolin-2(1H)-one.
- Step A (+)-6-Chloro-4-cyclopropyl-3 , 4-dihydro-1-
- Step B (+)-6-Chloro-4-cyclopropyl-3-ethyl-3,
- Example 35, step A the title compound was prepared from (+)-6-Chloro-4- cyclopropyl-3,4-dihydro-1-(4-methoxybenzyl)-4-propyl- quinazolin-2(1H)-one .
- Step A (+/-)-6-Chloro-4-cyclopropyl-3,4-dihydro-1- (4-methoxybenzyl)-4-isopropylmethylquinazolin-2(1H)-one
- step A the title compound was prepared from 6-chloro-4- cyclopropyl-1-(4-methoxybenzyl)quinazolin-2(1H)-one.
- Step B (+/-)-6-Chloro-4-cyclopropyl-3-methyl-3,
- step A the title compound was prepared from (+/-)-6-Chloro-4- cyclopropyl-3,4-dihydro-1-(4-methoxybenzyl)-4-isopropyl methylquinazolin-2(1H)-one.
- step A the title compound was prepared from (+/-)-6-Chloro-4- cyclopropyl-3-methyl-3,4-dihydro-1-(4-methoxybenzyl)-4- isopropylmethylquinazolin-2(1H)-one.
- Step B (+/-)-6-Chloro-4-cyclopropyl-3,4-dihydro-
- step A the title compound was prepared from (+/-)-6-Chloro-4- cyclopropyl-3,4-dihydro-1-(4-methoxybenzyl)-4-n-butyl- quinazolin-2(1H)-one.
- step A the title compound was prepared from (+)-6-Chloro-4- cyclopropyl-3,4-dihydro-1-(4-methoxybenzyl)-4-propyl- quinazolin-2(1H)-one.
- step A the title compound was prepared from (+)-6-Chloro-4- cyclopropyl-3-methyl-3,4-dihydro-1-(4-methoxybenzyl)-4- n-propylquinazolin-2(1H)-one.
- step A the title compound was prepared from 6-chloro-4- cyclopropylquinazolin-2(1H)-one.
- Step A (+)-6-Chloro-4-cyclopropyl-3,4-dihydro-1- camphanyl-4-propylquinazolin-2(1H)-one
Abstract
On décrit des composés possédant un noyau quinazolin-2-(thi)one. Ces composés peuvent être utilisés pour l'inhibition de la transcriptase inverse d'HIV, pour la prévention ou le traitement d'une infection par le virus HIV, ainsi que pour le traitement du SIDA, notamment sous forme de composés, de sels pharmaceutiquement acceptables, ou de principes de composition pharmaceutique, combinés ou non avec d'autres agents antiviraux, immunomodulateurs, antibiotiques ou vaccins. On décrit également des procédés de traitement du SIDA ainsi que des procédés de prévention ou de traitement d'une infection par le virus HIV.
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US880,121 | 1978-02-22 | ||
US74644591A | 1991-08-16 | 1991-08-16 | |
US746,445 | 1991-08-16 | ||
US84587592A | 1992-03-03 | 1992-03-03 | |
US845,875 | 1992-03-03 | ||
US88012192A | 1992-05-07 | 1992-05-07 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1993004047A1 true WO1993004047A1 (fr) | 1993-03-04 |
Family
ID=27419344
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1992/006576 WO1993004047A1 (fr) | 1991-08-16 | 1992-08-06 | Derives de quinazoline utilises comme inhibiteurs de transcriptase inverse d'hiv |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU2436792A (fr) |
WO (1) | WO1993004047A1 (fr) |
Cited By (56)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2281296A (en) * | 1993-08-27 | 1995-03-01 | Merck & Co Inc | Preparation of 4-chloro-2-acyl-anilines |
EP0664128A1 (fr) * | 1992-10-07 | 1995-07-26 | Sumitomo Pharmaceuticals Company, Limited | Composition pharmaceutique utilisee pour inhiber la production des facteurs de necrose tumorale |
US5556860A (en) * | 1993-05-26 | 1996-09-17 | Sumitomo Pharmaceuticals Co., Ltd. | Quinazolinone derivatives possessing calcium uptake inhibiting activity |
WO1998028301A1 (fr) * | 1996-12-21 | 1998-07-02 | Astra Pharmaceuticals Ltd. | Derives de pyrrolo[3,4-d]pyrimidinone et leur utilisation comme medicaments |
WO1998045276A3 (fr) * | 1997-04-09 | 1999-01-14 | Du Pont Pharm Co | 4,4-disubstituees-3,4-dihydro-2(1h)-quinazolinones utilisees comme inhibiteurs de la transcriptase inverse du vih |
WO1999050253A1 (fr) * | 1998-03-27 | 1999-10-07 | Du Pont Pharmaceuticals Company | 3,4-dihydro-2(1h)-quinazolinthiones substitues en 4,4, leur preparation et leur utilisation en tant qu'inhibiteurs de la transcriptase inverse du vih |
US6077981A (en) * | 1998-08-28 | 2000-06-20 | Eastman Chemical Company | Process for the production of cyclopropylmethyl halides |
US6090982A (en) * | 1999-08-03 | 2000-07-18 | Eastman Chemical Company | Process for the preparation of cyclopropylglycine |
US6124302A (en) * | 1997-04-09 | 2000-09-26 | Dupont Pharmaceuticals | 4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones useful as HIV reverse transcriptase inhibitors |
US6175009B1 (en) | 1999-11-18 | 2001-01-16 | Dupont Pharmaceuticals Company | Process for the preparation of quinazolinones |
US6207854B1 (en) | 1999-12-15 | 2001-03-27 | Eastman Chemical Company | Preparation of 3-amino-3-cyclopropylpropanoate esters |
WO2000073284A3 (fr) * | 1999-05-26 | 2001-04-05 | Du Pont Pharm Co | Inhibiteurs de transcriptase inverse du vih a base de 1,4-benzodiazepin-2-ones |
WO2002008226A3 (fr) * | 2000-07-20 | 2002-06-20 | Du Pont Pharm Co | Composants pyridone-2 tricycliques servant d'inhibiteurs de la transcriptase inverse du hiv |
US6593337B1 (en) | 1999-10-19 | 2003-07-15 | Bristol-Myers Squibb Pharma Company | Tricyclic compounds useful as HIV reverse transcriptase inhibitors |
US6809109B2 (en) | 2002-06-27 | 2004-10-26 | Bristol-Myers Squibb Company | 2, 4-disubstituted-pyridine N-oxides useful as HIV reverse transcriptase inhibitors |
US6825210B2 (en) | 2001-04-19 | 2004-11-30 | Bristol-Myers Squibb Pharma Company | Tricyclic compounds useful as HIV reverse transcriptase inhibitors |
US6946469B2 (en) | 2001-03-28 | 2005-09-20 | Bristol-Myers Squibb Pharma Company | Cyanamide, alkoxyamino, and urea derivatives of 4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones as HIV reverse transcriptase inhibitors |
US7015214B2 (en) | 2001-03-28 | 2006-03-21 | Bristol-Myers Squibb Pharma Company | Cyanamide, alkoxyamino, and urea derivatives of 1,3-benzodiazepine as HIV reverse transcriptase inhibitors |
WO2006138192A1 (fr) * | 2005-06-14 | 2006-12-28 | Schering Corporation | Inhibiteurs de l'aspartyl protease |
WO2006138264A2 (fr) | 2005-06-14 | 2006-12-28 | Schering Corporation | Inhibiteurs d'aspartyl protease |
WO2006098969A3 (fr) * | 2005-03-09 | 2007-03-01 | Merck & Co Inc | Antagonistes de canaux calciques de type t a base de quinazolinone |
WO2008073365A1 (fr) | 2006-12-12 | 2008-06-19 | Schering Corporation | Inhibiteurs de la protéase d'aspartyle |
WO2009044788A1 (fr) * | 2007-10-05 | 2009-04-09 | Banyu Pharmaceutical Co., Ltd. | Dérivé de benzoxazinone |
USRE41065E1 (en) | 1995-06-06 | 2009-12-29 | Pfizer, Inc. | Alkynl and azido-substituted 4-anilinoquinazolines |
JP2010515763A (ja) * | 2007-01-16 | 2010-05-13 | ベイジン・モレキュール・サイエンス・アンド・テクノロジー・カンパニー・リミテッド | テトラヒドロキナゾリン化合物、ならびに、ウィルス疾病を処置および予防するための薬を調製することにおけるその使用 |
EP2194047A1 (fr) | 2005-06-14 | 2010-06-09 | Schering Corporation | Préparation et utilisation d'inhibiteurs d'aspartyl protease |
US7759353B2 (en) | 2005-06-14 | 2010-07-20 | Schering Corporation | Substituted spiro iminopyrimidinones as aspartyl protease inhibitors, compositions, and methods of treatment |
JP2011503117A (ja) * | 2007-11-15 | 2011-01-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ヒト免疫不全ウイルス複製のインヒビター |
JP2011503116A (ja) * | 2007-11-16 | 2011-01-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ヒト免疫不全ウイルスの複製阻害薬 |
JP2011503118A (ja) * | 2007-11-15 | 2011-01-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ヒト免疫不全ウイルスの複製阻害薬 |
JP2011503119A (ja) * | 2007-11-16 | 2011-01-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ヒト免疫不全ウイルス複製のインヒビター |
EP2345411A1 (fr) | 2005-06-14 | 2011-07-20 | Schering Corporation | Inhibiteurs hétérocycliques d'aspartyl protéase, leurs préparations et utilisations |
US8440693B2 (en) | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
US8557826B2 (en) | 2009-10-08 | 2013-10-15 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions, and their use |
US8563543B2 (en) | 2009-10-08 | 2013-10-22 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
US8569310B2 (en) | 2009-10-08 | 2013-10-29 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions and their use |
US8686002B2 (en) | 2005-08-21 | 2014-04-01 | AbbVie Deutschland GmbH & Co. KG | Heterocyclic compounds and their use as binding partners for 5-HT5 receptors |
US8729071B2 (en) | 2009-10-08 | 2014-05-20 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as BACE inhibitors, compositions and their use |
US8969351B2 (en) | 2010-11-19 | 2015-03-03 | Novartis Ag | Crystalline form of an inhibitor of MDM2/4 and p53 interaction |
US9145426B2 (en) | 2011-04-07 | 2015-09-29 | Merck Sharp & Dohme Corp. | Pyrrolidine-fused thiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
US9181236B2 (en) | 2011-08-22 | 2015-11-10 | Merck Sharp & Dohme Corp. | 2-spiro-substituted iminothiazines and their mono-and dioxides as bace inhibitors, compositions and their use |
US9221839B2 (en) | 2011-04-07 | 2015-12-29 | Merck Sharp & Dohme Corp. | C5-C6 oxacyclic-fused thiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
US9365576B2 (en) | 2012-05-24 | 2016-06-14 | Novartis Ag | Pyrrolopyrrolidinone compounds |
US9403827B2 (en) | 2013-01-22 | 2016-08-02 | Novartis Ag | Substituted purinone compounds |
US9550796B2 (en) | 2013-11-21 | 2017-01-24 | Novartis Ag | Pyrrolopyrrolone derivatives and their use as BET inhibitors |
US9556180B2 (en) | 2013-01-22 | 2017-01-31 | Novartis Ag | Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the P53/MDM2 interaction |
US9624247B2 (en) | 2013-05-28 | 2017-04-18 | Novartis Ag | Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease |
US9714249B2 (en) | 2013-05-28 | 2017-07-25 | Novartis Ag | Pyrazolo-pyrrolidin-4-one derivatives and their use in the treatment of disease |
US9890166B2 (en) | 2013-05-27 | 2018-02-13 | Novartis Ag | Imidazopyrrolidine derivatives and their use in the treatment of disease |
US9902703B2 (en) | 2015-07-01 | 2018-02-27 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators and uses thereof |
US11028068B2 (en) | 2017-07-25 | 2021-06-08 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators and uses thereof |
US11130750B2 (en) | 2017-02-15 | 2021-09-28 | Cavion, Inc. | Calcium channel inhibitors |
US11273218B2 (en) | 2015-10-22 | 2022-03-15 | Cavion, Inc. | Methods for treating Angelman syndrome and related disorders |
US11311522B1 (en) | 2018-10-03 | 2022-04-26 | Cavion, Inc. | Treating essential tremor using (R)-2-(4-Isopropylphenyl)-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)acetamide |
US11324733B2 (en) | 2017-04-26 | 2022-05-10 | Cavion, Inc. | Methods for improving memory and cognition and for treating memory and cognitive disorders |
US11427540B2 (en) | 2019-07-11 | 2022-08-30 | Praxis Precision Medicines, Inc. | Formulations of T-type calcium channel modulators and methods of use thereof |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2012062A1 (fr) * | 1968-07-01 | 1970-03-13 | Sandoz Sa | |
FR2027023A1 (en) * | 1968-12-24 | 1970-09-25 | Farmaceutici Italia | Substd quinazoline derivs prepn cns depress - ants |
FR2103544A1 (fr) * | 1970-08-27 | 1972-04-14 | Sumitomo Chemical Co | |
FR2118932A1 (en) * | 1970-12-23 | 1972-08-04 | Sumitomo Chemical Co | 2-oxo-1, 2, 3, 4-tetrahydroquinazoline derivs - sedatives antiinflammatories, analgesics, uricosurics and antimicrobials |
US3764600A (en) * | 1970-10-06 | 1973-10-09 | Sandoz Ag | 1-substituted-quinazoline-2(1h)-thiones |
SU470423A1 (ru) * | 1973-06-27 | 1975-05-15 | Центральное Проектно-Конструкторское Бюро Главтехмонтажа Министерства Монтажных И Специальных Строительных Работ Ссср | Устройство дл намотки несущего каната канатной дороги на анкеррный барабан |
FR2328700A1 (fr) * | 1975-10-24 | 1977-05-20 | Sumitomo Chemical Co | Procede pour la preparation de derives 3,4-dihydro-2-(1h)-quinazolinoniques |
EP0107398A1 (fr) * | 1982-09-30 | 1984-05-02 | Ortho Pharmaceutical Corporation | Acides dihydroxy 1H-quinazolinone-2-alcanoiques-1 ortho substitués |
WO1991009024A1 (fr) * | 1989-12-11 | 1991-06-27 | Kyorin Pharmaceutical Co., Ltd. | Derive de l'acide quinazoline-3-alcanoique, sels derives de ce compose et sa production |
-
1992
- 1992-08-06 AU AU24367/92A patent/AU2436792A/en not_active Abandoned
- 1992-08-06 WO PCT/US1992/006576 patent/WO1993004047A1/fr unknown
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2012062A1 (fr) * | 1968-07-01 | 1970-03-13 | Sandoz Sa | |
FR2027023A1 (en) * | 1968-12-24 | 1970-09-25 | Farmaceutici Italia | Substd quinazoline derivs prepn cns depress - ants |
FR2103544A1 (fr) * | 1970-08-27 | 1972-04-14 | Sumitomo Chemical Co | |
US3764600A (en) * | 1970-10-06 | 1973-10-09 | Sandoz Ag | 1-substituted-quinazoline-2(1h)-thiones |
FR2118932A1 (en) * | 1970-12-23 | 1972-08-04 | Sumitomo Chemical Co | 2-oxo-1, 2, 3, 4-tetrahydroquinazoline derivs - sedatives antiinflammatories, analgesics, uricosurics and antimicrobials |
SU470423A1 (ru) * | 1973-06-27 | 1975-05-15 | Центральное Проектно-Конструкторское Бюро Главтехмонтажа Министерства Монтажных И Специальных Строительных Работ Ссср | Устройство дл намотки несущего каната канатной дороги на анкеррный барабан |
FR2328700A1 (fr) * | 1975-10-24 | 1977-05-20 | Sumitomo Chemical Co | Procede pour la preparation de derives 3,4-dihydro-2-(1h)-quinazolinoniques |
EP0107398A1 (fr) * | 1982-09-30 | 1984-05-02 | Ortho Pharmaceutical Corporation | Acides dihydroxy 1H-quinazolinone-2-alcanoiques-1 ortho substitués |
EP0220786A2 (fr) * | 1982-09-30 | 1987-05-06 | Ortho Pharmaceutical Corporation | Quinazolinones substituées |
WO1991009024A1 (fr) * | 1989-12-11 | 1991-06-27 | Kyorin Pharmaceutical Co., Ltd. | Derive de l'acide quinazoline-3-alcanoique, sels derives de ce compose et sa production |
Non-Patent Citations (2)
Title |
---|
Patent Abstracts of Japan, vol. 6, no. 180 (C-125)(1058), 14 September 1982, & JP,A,5795966 (SUMITOMO) 15 June 1982, see abstract * |
Soviet Patents Abstracts, week 9105, 20 March 1991, class B02, accession no. 91-035113/05, Derwent Publications Ltd, London, GB, & SU,A,470423 (TOMSK POLY) 30 May 1990, see abstract * |
Cited By (85)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0664128A1 (fr) * | 1992-10-07 | 1995-07-26 | Sumitomo Pharmaceuticals Company, Limited | Composition pharmaceutique utilisee pour inhiber la production des facteurs de necrose tumorale |
EP0664128A4 (fr) * | 1992-10-07 | 1997-12-17 | Sumitomo Pharma | Composition pharmaceutique utilisee pour inhiber la production des facteurs de necrose tumorale. |
US5556860A (en) * | 1993-05-26 | 1996-09-17 | Sumitomo Pharmaceuticals Co., Ltd. | Quinazolinone derivatives possessing calcium uptake inhibiting activity |
US5426230A (en) * | 1993-08-27 | 1995-06-20 | Merck & Co., Inc. | Process for the preparation of 4-chloro-2-cyclopropylcarbonylaniline |
GB2281296A (en) * | 1993-08-27 | 1995-03-01 | Merck & Co Inc | Preparation of 4-chloro-2-acyl-anilines |
USRE41065E1 (en) | 1995-06-06 | 2009-12-29 | Pfizer, Inc. | Alkynl and azido-substituted 4-anilinoquinazolines |
US6046204A (en) * | 1996-12-21 | 2000-04-04 | Astra Pharmaceuticals Limited | Pyrrolo[3,4-D] pyrimidinone derivatives and their use as medicaments |
US6211368B1 (en) | 1996-12-21 | 2001-04-03 | Astrazeneca Uk Limited | Pyrrolo(3,4-d)pyrimidinone derivatives and their use as medicaments |
WO1998028301A1 (fr) * | 1996-12-21 | 1998-07-02 | Astra Pharmaceuticals Ltd. | Derives de pyrrolo[3,4-d]pyrimidinone et leur utilisation comme medicaments |
US6306863B1 (en) | 1996-12-21 | 2001-10-23 | Astrazeneca Ab | Pyrrolo[3,4-d]pyrimidinone derivatives and their use as medicaments |
US6136974A (en) * | 1996-12-21 | 2000-10-24 | Astrazeneca Uk Limited | Pyrrolo[3,4-D]Pyrimidinone derivatives and their use as medicaments |
US6166206A (en) * | 1996-12-21 | 2000-12-26 | Astrazeneca Uk Limited | Pyrrolo[3,4-D]Pyrimidinone derivatives and their use as medicaments |
US6229013B1 (en) | 1996-12-21 | 2001-05-08 | Astrazeneca Uk Limited | Pyrrolo[3,4-d]pyrimidinone derivatives and their use as medicaments |
WO1998045276A3 (fr) * | 1997-04-09 | 1999-01-14 | Du Pont Pharm Co | 4,4-disubstituees-3,4-dihydro-2(1h)-quinazolinones utilisees comme inhibiteurs de la transcriptase inverse du vih |
US6423718B1 (en) | 1997-04-09 | 2002-07-23 | Bristol-Myers Squibb Pharma Company | 4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones useful as HIV reverse transcriptase inhibitors |
US6124302A (en) * | 1997-04-09 | 2000-09-26 | Dupont Pharmaceuticals | 4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones useful as HIV reverse transcriptase inhibitors |
WO1999050253A1 (fr) * | 1998-03-27 | 1999-10-07 | Du Pont Pharmaceuticals Company | 3,4-dihydro-2(1h)-quinazolinthiones substitues en 4,4, leur preparation et leur utilisation en tant qu'inhibiteurs de la transcriptase inverse du vih |
US6077981A (en) * | 1998-08-28 | 2000-06-20 | Eastman Chemical Company | Process for the production of cyclopropylmethyl halides |
WO2000073284A3 (fr) * | 1999-05-26 | 2001-04-05 | Du Pont Pharm Co | Inhibiteurs de transcriptase inverse du vih a base de 1,4-benzodiazepin-2-ones |
US6103929A (en) * | 1999-08-03 | 2000-08-15 | Eastman Chemical Company | Process for the preparation of cyclopropylglycine |
US6090982A (en) * | 1999-08-03 | 2000-07-18 | Eastman Chemical Company | Process for the preparation of cyclopropylglycine |
US6593337B1 (en) | 1999-10-19 | 2003-07-15 | Bristol-Myers Squibb Pharma Company | Tricyclic compounds useful as HIV reverse transcriptase inhibitors |
US6175009B1 (en) | 1999-11-18 | 2001-01-16 | Dupont Pharmaceuticals Company | Process for the preparation of quinazolinones |
US6207854B1 (en) | 1999-12-15 | 2001-03-27 | Eastman Chemical Company | Preparation of 3-amino-3-cyclopropylpropanoate esters |
WO2002008226A3 (fr) * | 2000-07-20 | 2002-06-20 | Du Pont Pharm Co | Composants pyridone-2 tricycliques servant d'inhibiteurs de la transcriptase inverse du hiv |
US6946469B2 (en) | 2001-03-28 | 2005-09-20 | Bristol-Myers Squibb Pharma Company | Cyanamide, alkoxyamino, and urea derivatives of 4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones as HIV reverse transcriptase inhibitors |
US7015214B2 (en) | 2001-03-28 | 2006-03-21 | Bristol-Myers Squibb Pharma Company | Cyanamide, alkoxyamino, and urea derivatives of 1,3-benzodiazepine as HIV reverse transcriptase inhibitors |
US6825210B2 (en) | 2001-04-19 | 2004-11-30 | Bristol-Myers Squibb Pharma Company | Tricyclic compounds useful as HIV reverse transcriptase inhibitors |
US6809109B2 (en) | 2002-06-27 | 2004-10-26 | Bristol-Myers Squibb Company | 2, 4-disubstituted-pyridine N-oxides useful as HIV reverse transcriptase inhibitors |
WO2006098969A3 (fr) * | 2005-03-09 | 2007-03-01 | Merck & Co Inc | Antagonistes de canaux calciques de type t a base de quinazolinone |
US7745452B2 (en) | 2005-03-09 | 2010-06-29 | Merck Sharp & Dohme Corp. | Quinazolinone T-type calcium channel antagonists |
EP2194047A1 (fr) | 2005-06-14 | 2010-06-09 | Schering Corporation | Préparation et utilisation d'inhibiteurs d'aspartyl protease |
US8722708B2 (en) | 2005-06-14 | 2014-05-13 | Merck Sharp & Dohme Inc. | Substituted isoindolines as aspartyl protease inhibitors |
JP2008543849A (ja) * | 2005-06-14 | 2008-12-04 | シェーリング コーポレイション | アスパルチルプロテアーゼ阻害剤 |
EP2345411A1 (fr) | 2005-06-14 | 2011-07-20 | Schering Corporation | Inhibiteurs hétérocycliques d'aspartyl protéase, leurs préparations et utilisations |
WO2006138192A1 (fr) * | 2005-06-14 | 2006-12-28 | Schering Corporation | Inhibiteurs de l'aspartyl protease |
US9382242B2 (en) | 2005-06-14 | 2016-07-05 | Merck Sharp & Dohme Corp. | Preparation and use of compounds as protease inhibitors |
WO2006138264A2 (fr) | 2005-06-14 | 2006-12-28 | Schering Corporation | Inhibiteurs d'aspartyl protease |
WO2006138264A3 (fr) * | 2005-06-14 | 2007-03-01 | Schering Corp | Inhibiteurs d'aspartyl protease |
US7759354B2 (en) | 2005-06-14 | 2010-07-20 | Schering Corporation | Bicyclic guanidine derivatives as asparyl protease inhibitors, compositions, and uses thereof |
US7759353B2 (en) | 2005-06-14 | 2010-07-20 | Schering Corporation | Substituted spiro iminopyrimidinones as aspartyl protease inhibitors, compositions, and methods of treatment |
US7868000B2 (en) | 2005-06-14 | 2011-01-11 | Schering Corporation | Aspartyl protease inhibitors |
US8110682B2 (en) | 2005-06-14 | 2012-02-07 | Schering Corporation | Preparation and use of compounds as aspartyl protease inhibitors |
US8686002B2 (en) | 2005-08-21 | 2014-04-01 | AbbVie Deutschland GmbH & Co. KG | Heterocyclic compounds and their use as binding partners for 5-HT5 receptors |
WO2008073365A1 (fr) | 2006-12-12 | 2008-06-19 | Schering Corporation | Inhibiteurs de la protéase d'aspartyle |
US8093254B2 (en) | 2006-12-12 | 2012-01-10 | Schering Corporation | Aspartyl protease inhibitors |
JP2010515763A (ja) * | 2007-01-16 | 2010-05-13 | ベイジン・モレキュール・サイエンス・アンド・テクノロジー・カンパニー・リミテッド | テトラヒドロキナゾリン化合物、ならびに、ウィルス疾病を処置および予防するための薬を調製することにおけるその使用 |
WO2009044788A1 (fr) * | 2007-10-05 | 2009-04-09 | Banyu Pharmaceutical Co., Ltd. | Dérivé de benzoxazinone |
JP2011503117A (ja) * | 2007-11-15 | 2011-01-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ヒト免疫不全ウイルス複製のインヒビター |
JP2011503118A (ja) * | 2007-11-15 | 2011-01-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ヒト免疫不全ウイルスの複製阻害薬 |
JP2011503119A (ja) * | 2007-11-16 | 2011-01-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ヒト免疫不全ウイルス複製のインヒビター |
JP2011503116A (ja) * | 2007-11-16 | 2011-01-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ヒト免疫不全ウイルスの複製阻害薬 |
US8710230B2 (en) | 2007-11-16 | 2014-04-29 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
JP2013241410A (ja) * | 2007-11-16 | 2013-12-05 | Gilead Sciences Inc | ヒト免疫不全ウイルスの複製阻害薬 |
US8940748B2 (en) | 2009-10-08 | 2015-01-27 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
US8557826B2 (en) | 2009-10-08 | 2013-10-15 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions, and their use |
US8563543B2 (en) | 2009-10-08 | 2013-10-22 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
US8729071B2 (en) | 2009-10-08 | 2014-05-20 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as BACE inhibitors, compositions and their use |
US9687494B2 (en) | 2009-10-08 | 2017-06-27 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
US9029362B2 (en) | 2009-10-08 | 2015-05-12 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as brace inhibitors, compositions, and their use |
US8569310B2 (en) | 2009-10-08 | 2013-10-29 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions and their use |
US9475785B2 (en) | 2009-10-08 | 2016-10-25 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as BACE inhibitors, compositions and their use |
US9428475B2 (en) | 2009-10-08 | 2016-08-30 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
US8440693B2 (en) | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
US9051279B2 (en) | 2009-12-22 | 2015-06-09 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
US9073898B2 (en) | 2010-11-19 | 2015-07-07 | Novartis Ag | Crystalline form of an inhibitor of MDM2/4 and p53 interaction |
US8969351B2 (en) | 2010-11-19 | 2015-03-03 | Novartis Ag | Crystalline form of an inhibitor of MDM2/4 and p53 interaction |
US9145426B2 (en) | 2011-04-07 | 2015-09-29 | Merck Sharp & Dohme Corp. | Pyrrolidine-fused thiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
US9221839B2 (en) | 2011-04-07 | 2015-12-29 | Merck Sharp & Dohme Corp. | C5-C6 oxacyclic-fused thiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
US9181236B2 (en) | 2011-08-22 | 2015-11-10 | Merck Sharp & Dohme Corp. | 2-spiro-substituted iminothiazines and their mono-and dioxides as bace inhibitors, compositions and their use |
US9365576B2 (en) | 2012-05-24 | 2016-06-14 | Novartis Ag | Pyrrolopyrrolidinone compounds |
US9556180B2 (en) | 2013-01-22 | 2017-01-31 | Novartis Ag | Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the P53/MDM2 interaction |
US9403827B2 (en) | 2013-01-22 | 2016-08-02 | Novartis Ag | Substituted purinone compounds |
US9890166B2 (en) | 2013-05-27 | 2018-02-13 | Novartis Ag | Imidazopyrrolidine derivatives and their use in the treatment of disease |
US9624247B2 (en) | 2013-05-28 | 2017-04-18 | Novartis Ag | Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease |
US9714249B2 (en) | 2013-05-28 | 2017-07-25 | Novartis Ag | Pyrazolo-pyrrolidin-4-one derivatives and their use in the treatment of disease |
US9550796B2 (en) | 2013-11-21 | 2017-01-24 | Novartis Ag | Pyrrolopyrrolone derivatives and their use as BET inhibitors |
US9902703B2 (en) | 2015-07-01 | 2018-02-27 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators and uses thereof |
US11273218B2 (en) | 2015-10-22 | 2022-03-15 | Cavion, Inc. | Methods for treating Angelman syndrome and related disorders |
US11130750B2 (en) | 2017-02-15 | 2021-09-28 | Cavion, Inc. | Calcium channel inhibitors |
US11324733B2 (en) | 2017-04-26 | 2022-05-10 | Cavion, Inc. | Methods for improving memory and cognition and for treating memory and cognitive disorders |
US11028068B2 (en) | 2017-07-25 | 2021-06-08 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators and uses thereof |
US11311522B1 (en) | 2018-10-03 | 2022-04-26 | Cavion, Inc. | Treating essential tremor using (R)-2-(4-Isopropylphenyl)-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)acetamide |
US11427540B2 (en) | 2019-07-11 | 2022-08-30 | Praxis Precision Medicines, Inc. | Formulations of T-type calcium channel modulators and methods of use thereof |
US11649207B2 (en) | 2019-07-11 | 2023-05-16 | Praxis Precision Medicines, Inc. | Formulations of T-type calcium channel modulators and methods of use thereof |
Also Published As
Publication number | Publication date |
---|---|
AU2436792A (en) | 1993-03-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO1993004047A1 (fr) | Derives de quinazoline utilises comme inhibiteurs de transcriptase inverse d'hiv | |
EP0530994A1 (fr) | Dérivés de quinazoline utilisés comme inhibiteurs de transcriptase inverse de HIV | |
AU719392B2 (en) | Nitrogen-containing heterocyclic compounds | |
US5308854A (en) | Inhibitors of HIV reverse transcriptase | |
US5424311A (en) | Azaquinoxalines and their use | |
JP4625838B2 (ja) | Hivインテグラーゼ阻害薬 | |
CA2607151C (fr) | Inhibiteurs de l'integrase du vih | |
US20050171101A1 (en) | Phenanthridinones as parp inhibitors | |
NZ238576A (en) | Pyridinone derivatives, preparation and pharmaceutical compositions thereof | |
PL175615B1 (pl) | Benzoksazynony będące inhibitorami odwrotnej transkryptazy HIV, zawierające je środki farmaceutyczne oraz sposób wytwarzania (-)-6-chloro-4-cyklopropyloetynylo-4-trifluorometylo-1,4-dihydro-2H-3,1-benzoksazyn-2-onu | |
WO1995012583A1 (fr) | Nouvelles quinazolines utilisees comme inhibtiteurs de la transcriptase inverse du vih | |
EP2415767A1 (fr) | Inhibiteurs de la poly(ADP-ribose)polymérase (PARP) | |
IL94062A (en) | History of Pyrimidine Process for their preparation and pharmaceutical preparations containing them | |
NZ248583A (en) | (iso) quinoline derivatives, preparation and pharmaceutical compositions therof | |
KR20010049859A (ko) | β-카르볼린 화합물, 이를 제조하는 방법 및 이를함유하는 약제 조성물 | |
US20150210713A1 (en) | Griseofulvin derivatives | |
SI9300244A (sl) | Novi kinazolini kot inhibitorji HIV reverzne transkriptaze | |
EP0096214B1 (fr) | Composés pyrimidiques antibactériens | |
US5693640A (en) | Pyridazino-indole derivatives | |
US5376748A (en) | Nitroquinolone derivatives | |
GB2282808A (en) | 3-substituted heterocyclic indoles as inhibitors of HIV reverse transcriptase | |
US5747540A (en) | HIV protease inhibitors useful for the treatment of AIDS | |
KR900006745B1 (ko) | 5-아미노-1,2-디티올-3-온 화합물 및 그의 제법 | |
AU712120B2 (en) | HIV protease inhibitors useful for the treatment of AIDS | |
US3291824A (en) | Nu-(2-halo-lower alkanoyl) anthranilic acid derivatives |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU BG CA CS FI HU JP KR NO PL RO RU |
|
NENP | Non-entry into the national phase |
Ref country code: CA |