Application US20200330602

METHOD FOR IMPROVING THE ORAL BIOAVAILABILITY OF A DRUG
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US20200330602

1. A method for increasing the oral bioavailability of a drug HX-DM. wherein HX represents an OH or SH functional group, (1) (2)

comprising the step of linking a sugar-carbamoylalkylidene unit of formula (II)

Sugar is selected from the group consisting of alpha- and beta-linked monosaccharides and disaccharides, wherein optionally one or more OH groups are replaced by a group R4; wherein R4 is selected from the group consisting of C₁-C₆alkoxy, chlorine, fluorine, cyano, CF₃, NH₂, C₁-C₆alkyl-NH, C₁-C₆dialkyl-N, C₁-C₆cycloalkyl-N, C₁-C₆alkyl-C(O)NH, C₁-C₆alkyl-C(O)(C₁-C₆alkyl)—N, HC(O)(C₁-C₆alkyl)—N, C₁-C₆alkyl-O—C(O)NH, C₁-C₆alkyl-O—C(O)(C₁-C₆alkyl)—N, and C₁-C₆alkyl-O—C(O)—O;

R1 is selected from the group consisting of H, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, —R5—O—R7, —R5—S—R7, —R6—C(O)—R7, —R6—C(O)—O—R7, —R5—SO₂—R7, —R5—SO₂—NR7R8, C₃-C₇cycloalkyl, C₄-C₇cycloalkenyl, a 4 to 7 membered heterocycle, aryl and (C₁-C₃alkyl)-aryl;

wherein R5 is C₂or C₃alkyl, R6 is C₁-C₃alkyl, R7 and R8 are independently hydrogen or C₁-C₃-alkyl;

and wherein the C₃-C₇cycloalkyl, C₄-C₇cycloalkenyl, a 4 to 7 membered heterocycle, aryl and (C₁-C₃alkyl)-aryl groups can be optionally substituted by R9,

wherein R9 is selected from the group consisting of C₁-C₄alkyl, C₁-C₄alkoxy, chlorine, fluorine, cyano, CF₃, amine, amide, carbamate and —C(O)O—(C₁-C₄-alkyl);

R2 and R3 are both H, or one of R2 and R3 is H and the other is C₁-C₆alkyl; and wherein ----- represents a leaving group,

2. The method according to claim 1, wherein R1 is selected from the group consisting of H, C₁-C₄alkyl, C₂-C₄alkenyl, —R5—O—R7, —R5—S—R7, —R6—C(O)—R7, —R6—C(O)—O—R7, —R5—SO₂—R7, —R5—SO₂—NR7R8, C₃-C₇cycloalkyl, wherein C₃-C₇cycloalkyl is optionally substituted by one or two fluorine; pyranyl, tetrahydrofuranyl and benzyl, wherein R5 is C₂or C₃alkyl, R6 is C₁-C₃alkyl, R7 and R8 are independently hydrogen or C₁-C₃-alkyl. (1) (0)

8. The method according to any one of the preceding claims wherein R2 and R3 are both H. (0)

9. The method according to any one of the preceding claims, wherein the drug moiety is selected from the group consisting of quetiapine, montelukast, venlafaxine, mesalazine, desvenlafaxine, metoprolol, paliperidone, buprenorphine, morphine, ganciclovir, tapentadol, rotigotine, abiraterone, acetaminophen, saxagliptin, fulvestrant, afimoxifene, testosterone, simvastatin, tolterodine, tramadol, atenolol, naloxone, nabilone, metaraminol, dihydroartemisinin, orciprenaline, labetalol, kalydeco, azacitidine, niclosamide, tetrahydrocannabinol, raloxifene, propofol, gemcitabine, cannabidiol, carvedilol, edavarone, cytaribine, dasatinib, perrilyl alcohol, butorphanol and bazedoxifene. (0)

17. The compound according to any one of the preceding claims wherein R2 and R3 are both H. (0)

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Application US20200330602

METHOD FOR IMPROVING THE ORAL BIOAVAILABILITY OF A DRUG

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