| 主权项 |
1. A method of modifying physicochemical, biological, pharmacokinetics, and/or pharmaco dynamics properties of a pharmaceutical compound, comprising
incubating the pharmaceutical compound with a modifying agent having the formula of compound 1, under conditions to cause Y—(CO)—O— to covalently bond to a tertiary nitrogen on the pharmaceutical compound, thereby forming a quaternary nitrogen, wherein X is selected from Cl, Br, I, OTs, or OMs; Y is selected from R2, OR2, or N(R2)2; and R and R1 are independently H, C1-C8 straight or branched chain alkyl; C1-C8 straight or branched chain alkyl that has been substituted with 1-3 hetero atoms selected from O, N, S, SO, or SO2; 3-7 membered cycloalkyl; 3-7 membered cyclo alkyl that has been substituted with 1-3 hetero atoms selected from O, N, S, SO, or SO2 and/or lower alkyl, straight or branched alkyl, alkoxy; alkaryl, aryl, heteroaryl, or alkheteroaryl; R and R1 can also be joined to form a 3-7 membered carbocyclic ring optionally containing 1-2 heteroatoms selected from, O, N, S, SO, SO2 and also be optionally substituted with alkoxy, F or Cl; R2 independently is H, C1-C8 straight or branch chain alkyl; C1-C8 straight or branched chain alkyl that has been substituted with 1-3 heteroatoms selected from O, N, S, SO, or SO2; 3-7 membered cyclo alkyl; 3-7 membered cyclo alkyl that has been substituted with 1-3 heteroatoms selected from O, N, S, SO, or SO2 and/or lower alkyl, straight or branched alkyl, alkoxy; alkaryl, aryl, heteroaryl, or alkheteroaryl; or is independently part of a 3-7 membered ring optionally containing additional 1-2 heteroatoms selected from, O, N, S, SO, SO2 and also be optionally substituted with alkoxy, F or Cl; wherein when Y=OR2 then compound 1 is selected from the group consisting of: i. chloromethyl isopropyl carbonate; ii. benzyl chloromethyl carbonate; iii. chloromethylmorpholinomethyl carbonate; iv. chloromethyl isobutyl carbonate; v. (S)-sec-butyl chloromethyl carbonate; vi. (R)-sec-butyl chloromethyl carbonate; vii. chloromethyl ((3S,5R)-3,5-dimethylmorpholino)methyl carbonate; viii. chloromethyl 2-methylcyclopropyl carbonate; ix. chloromethyl2-methoxyethyl carbonate; x. chloromethyl propyl carbonate; xi. chloromethylcyclobutyl carbonate; xii. chloromethylcyclopropyl carbonate; xiii. chloromethyl 2,2-dimethylcyclobutyl carbonate; xiv. chloromethylcyclopentyl carbonate; xv. chloromethyloxetan-3-yl carbonate; xv. (S)-chloromethyltetrahydrofuran-3-yl carbonate; xvii. chloromethylcyclohexylmethyl carbonate; xviii. chloromethyl 3-methoxycyclohexyl carbonate; xix. (R)-chloromethyltetrahydrofuran-3-yl carbonate; xx. chloromethvlethoxymethyl carbonate; xxi. chloromethyloxepan-4-yl carbonate; xxii. (1R,2S,4S)-bicyclo[2.2.1]heptan-2-ylchloromethyl carbonate; xxiii. chloromethyl 2,3-dihydro-1H-inden-1-yl carbonate; xxiv. benzyl chloromethyl carbonate; xxv. (S)-chloromethyl 1-phenylethyl carbonate; xxvi. chloromethylcyclohexyl carbonate; xxvii. chloromethyl isobutyl carbonate; xxviii. chloromethyl 4-methylcyclohexyl carbonate; xxix. chloromethyl 2-(methylthio)ethyl carbonate; xxx. chloromethyl 3-methylcyclohexyl carbonate; xxxi. chloromethylpentan-2-yl carbonate; xxxii. chloromethylneopentyl carbonate; xxxiii. methyl 1-((chloromethoxy)carbonyloxy)cyclopropanecarboxylate; xxxiv. chloromethylcyclopropylmethyl carbonate; xxxv. chloromethyl 2,2-diethoxyethyl carbonate; xxxvi. chloromethylcyclopentylmethyl carbonate; xxxvii. methyl 2-((chloromethoxy)carbonyloxy)propanoate; xxxviii. (S)-chloromethyl 2,2,4-trimethylcyclopent-3-enyl carbonate; xxxix. chloromethyl 1,3-dioxolan-2-yl carbonate; xl. chloromethyl (2,6-dimethylcyclohexyl)methyl carbonate; xli. chloromethyl 2-(tetrahydro-2H-pyran-2-yl)ethyl carbonate; xlii. chloromethyl(tetrahydro-2H-pyran-4-yl)methyl carbonate; xliii. chloromethyltetrahydro-2H-pyran-4-yl carbonate; xliv. chloromethyl 1-methylcyclopentyl carbonate; xlv. chloromethyl 1-cyclopentylethyl carbonate; xlvi. chloromethyl 3-methylcyclopentyl carbonate; xlvii. chloromethyl 3,3-dimethylcyclohexyl carbonate; xlviii. chloromethyl 2,5-dimethylcyclohexyl carbonate; xlix. chloromethyl 1-(4-methylcyclohexyl)ethyl carbonate; l. chloromethyl (3-methyloxetan-3-yl)methyl carbonate; li. chloromethyl (3-methyloxetan-3-yl)methyl carbonate; lii. chloromethyl 2-isopropoxyethyl carbonate; liii. (chloromethyl carbonic) 5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoic anhydride; liv. 4-((chloromethoxy)carbonyloxy)-2-hydroxy-4-oxobutanoic acid; lv. chloromethyl 4-formyl-2-methoxyphenyl carbonate; lvi. chloromethyl 3-oxobutan-2-yl carbonate; lvii. methyl 4-((chloromethoxy)carbonyloxy)benzoate; lviii. (R)-2-amino-3-((chloromethoxy)carbonyloxy)propanoic acid; lix. 3-tert-butyl-4-methoxyphenylchloromethyl carbonate; lx. (R)-2-amino-3-(4-((chloromethoxy)carbonyloxy)phenyl)propanoic acid; lxi. (R)-2-amino-4-((chloromethoxy)carbonyloxy)-4-oxobutanoic acid; lxii. (E)-chloromethyl 3,7-dimethylocta-2,6-dienyl carbonate; lxiii. methyl 4-((chloromethoxy)carbonyloxy)benzoate; lxiv. chloromethyl 2-(4-methylcyclohex-3-enyl)propan-2-yl carbonate; lxv. chloromethyl 3,7-dimethylocta-1,6-dien-3-yl carbonate; lxvi. 4-allyl-2-methoxyphenylchloromethyl carbonate; lxvii. chloromethyl (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl carbonate; lxviii. propyl 4-((chloromethoxy)carbonyloxy)benzoate; and (E)-chloromethyl 3,7-dimethylocta-2,6-dienyl carbonate; when Y=R2 then compound 1 is selected from the group consisting of: i. Chloromethylcyclohexanecarboxylate; ii. chloromethyl 2-cyclohexylacetate; iii. chloromethyl 4-methylcyclohexanecarboxylate; iv. chloromethyl 1-methylcyclohexanecarboxylate; v. chloromethylcyclopentanecarboxylate; vi. chloromethyl 1-(trifluoromethyl)cyclopentanecarboxylate; vii. chloromethylcyclobutanecarboxylate; viii. chloromethyl 2-ethylhexanoate; ix. chloromethyl 3-cyclopentylpropanoate; x. chloromethylcyclopropanecarboxylate; xi. chloromethylpentanoate; xii. chloromethyl 2-methylpentanoate; xiii. chloromethyl 3,5,5-trimethylhexanoate; xiv. chloromethyl 2,2-dimethylbutanoate; xv. chloromethyl 2-methylbutanoate; xvi. chloromethylhexanoate; xvii. chloromethyl 2-ethylbutanoate; xviii. chloromethyl butyrate; xix. chloromethyl 3-phenylpropanoate; xx. chloromethyl 2-phenylpropanoate; xxi. (R)-chloromethyl 2-phenylpropanoate; xxii. (S)-chloromethyl 2-phenylpropanoate; xxiii. (1r,4r)-chloromethyl 4-methylcyclohexanecarboxylate; xxiv. chloromethyl 4-methoxycyclohexanecarboxylate; xxv. chloromethyl 4,4-difluorocyclohexanecarboxylate; xxvi. chloromethyl 3-methoxycyclohexanecarboxylate; xxvii. (2R)-chloromethyl 2-methylcyclopentanecarboxylate; xxviii. (R)-chloromethyl 2-methylbutanoate; xxix. (S)-chloromethyl 2-methylbutanoate; xxx. (S)-chloromethyl 2-methoxy-2-phenylacetate; xxxi. (S)-chloromethyl 2-phenylpropanoate; xxxii. (S)-chloromethyl 2-phenylbutanoate; xxxiii. (S)-chloromethyl 3-phenylbutanoate; xxxiv. bis(chloromethyl) 2,2-dimethylmalonate; xxxv. bis(chloromethyl) oxalate; xxxvi. chloromethyl 2-cyclopropylacetate; xxxvii. chloromethyl 2-cyclobutylacetate; xxxviii. chloromethyl 2-cyclopentylacetate; xxxix. chloromethyl 2-(tetrahydrofuran-3-yl)acetate; xl. chloromethyl 2-(tetrahydro-2H-pyran-4-yl)acetate; xli. chloromethyl 2-methylcyclopropanecarboxylate; xlii. chloromethyl 2-(1-methylcyclobutyl)acetate; xliii. chloromethyl 2-(1-methylcyclopropyl)acetate; xliv. chloromethyl propionate; xlv. chloromethyl acetate; xlvi. chloromethylisobutyrate; xlvii. chloromethyl 2-isopropyl-3-methylbutanoate; xlviii. chloromethyl 3,5-dimethylcyclohexanecarboxylate; xlix. chloromethyl 2-propylpentanoate; l. chloromethyl 4-methoxybenzoate; li. chloromethyl 4-methylbenzoate; lii. chloromethyl 3-methylbenzoate; liii. chloromethyl 2,2,2-trifluoroacetate; liv. chloromethyl 5,5-dimethyl-3-oxohexanoate; lv. bis(chloromethyl) cyclopropane-1,1-dicarboxylate; lvi. chloromethyl 1,2-dihydrocyclobutabenzene-1-carboxylate; lvii. chloromethyl 2-cyclopentenylacetate; lviii. chloromethyl 2-phenylbutanoate; lix. chloromethyl 2,2-difluoroacetate; lx. chloromethyl 4-fluorobenzoate; lxi. chloromethyl 3-cyclohexylpropanoate; lxii. chloromethyl 2-cyclohexylacetate; lxiii. chloromethyl 3-(tetrahydro-2H-pyran-4-yl)propanoate; lxiv. chloromethyl 2-(tetrahydro-2H-pyran-3-yl)acetate; and lxv. chloromethyl 3-(tetrahydro-2H-pyran-3-yl)propanoate and when Y=NR2 then compound 1 is selected from the group consisting of: i. chloromethylbenzylcarbamate; ii. chloromethylisopropylcarbamate; iii. chloromethyldiisopropylcarbamate; iv. iodomethyldiisopropylcarbamate; v. chloromethyl benzyl(methyl)carbamate; vi. chloromethylpiperidine-1-carboxylate; vii. (S)-chloromethyl (1-cyclohexylethyl)carbamate; viii. (R)-chloromethyl (1-cyclohexylethyl)carbamate; ix. chloromethyl (1-phenylethyl)carbamate; x. (S)-chloromethyl (1-phenylethyl)carbamate; xi. chloromethylcyclohexylcarbamate; xii. (S)-chloromethyl (3-methylbutan-2-yl)carbamate; xiii. (S)-chloromethyl sec-butylcarbamate; xiv. chloromethyl 2-methylpiperidine-1-carboxylate; xv. chloromethyl sec-butylcarbamate; xvi. chloromethylmorpholine-4-carboxylate; xvii. chloromethylpyrrolidine-1-carboxylate; xviii. iodomethylisopropylcarbamate; xix. chloromethyldimethylcarbamate; xx. iodomethyldimethylcarbamate; xxi. chloromethyl 4-methylpiperazine-1-carboxylate; xxii. 1-chloroethyldiisopropylcarbamate; xxiii. 1-chloroethylisopropylcarbamate; xxiv. 1-chloroethylmorpholine-4-carboxylate; xxv. 1-chloroethylpiperidine-1-carboxylate; xxvi. chloromethyl 4-methylpiperidine-1-carboxylate; and xxvii. bromomethylmorpholine-4-carboxylate. |
