Inhibitors of neuraminidasesEnantiomerically enriched compounds having the absolute stereochemistry of t he formula (I) or a pharmaceutically acceptable salt, ester or prodrug thereof, which are useful for inhibiting neuraminidases from disease-causing microorganisms, especially, influenza neuraminidase. Also disclosed are compositions and methods for preventing and treating diseases caused by microorganisms having a neuraminidase, processes for preparing the compounds and synthetic intermediates used in these processes.The compound of enantiomorph enrichment that has the absolute stereo chemistry of following formula: or its pharmaceutical salts, ester or prodrug, r wherein 1be selected from (b)-co 2h，(b)-ch 2co 2h，(c)-so 3h，(d)-ch 2so 3h，(e)-so 2h， (g)-ch 2so 2h, (g)-po 3h 2, (h)-ch 2po 3h 2, (i)-po 2h, (j)-ch 2po 2h, (i) tetrazyl, (i)-ch 2-tetrazyl, (m)-c (=o)-nh-s (o) 2-r 11, (o)-ch 2c (=o)-nh-s (o) 2-r 11, (o)-so 2n (t-r 11) r 12and (p)-ch 2so 2n(t-r 11)r 12wherein t is selected from(i) key, (ii)-c (=o), (iii)-c (=o) o-, (iv)-c (=o) s-, (v)-(c=o) nr 36-, (vi)-c (=s) o-, (vii)-c (=s) s-, and (viii)-c (=s) nr 36-, r 11be selected from (i) c 1-c 12alkyl, (ii) c 2-c 12alkenyl, (iii) cycloalkyl, (iv) (cycloalkyl) alkyl, (w) (cycloalkyl) alkenyl, (vi) cycloalkenyl, (vii) (cycloalkenyl) alkyl,(ix) (cycloalkenyl) alkenyl, (ix) aryl, (x) (aryl) alkyl,(x) (xi) (aryl) alkenyl,(xvii) heterocyclic radical, (xiii) (heterocyclic radical) alkyl reaches(xviii) (xiv) (heterocyclic radical) alkenyl; andr 12and r 36be independently selected from (i) hydrogen atom, (ii) c 1-c 12alkyl, (iii) c 2-c 12alkenyl, (iv) cycloalkyl, (v) (cycloalkyl) alkyl, (vi) (cycloalkyl) alkenyl, (vii) cycloalkenyl, (viii) (cycloalkenyl) alkyl, (ix) (cycloalkenyl) alkenyl, (x) aryl, (xi) (aryl) alkyl, (xii) (aryl) alkenyl, (xiii) heterocyclic radical, (xiv) (heterocyclic radical) alkyl and (xv) (heterocyclic radical) alkenyl; x is selected from(a)-c (=o)-n (r *)-, (b)-n (r *)-c (=o)-, (c)-c (=s)-n (r *)-, (d)-n (r *)-c (=s)-, (e)-n (r *)-so 2-and (f)-so 2-n (r *)-, be r wherein *be hydrogen atom, c 1-c 3low alkyl group or cyclopropyl; r 2be selected from (a) hydrogen atom, (b) c 1-c 6alkyl, (c) c 2-c 6alkenyl, (d) c 3-c 6cycloalkyl, (e) c 5-c 6cycloalkenyl, (f) halo c 1-c 6alkyl and (g) halo c 2-c 6alkenyl; perhaps r 2-x-is y wherein 1be-ch 2-,-o-,-s-or-nh-and y 2be-c (=o)-or-c (r aa) (r bb)-, be r wherein aaand r bbbe independently selected from hydrogen atom, c 1-c 3low alkyl group, methylol, 1-hydroxyethyl, 2-hydroxyethyl, amino methyl, 1-amino-ethyl, 2-amino-ethyl, mercapto methyl, 1-mercaptoethyl, 2-mercaptoethyl, methoxymethyl, n-methylamino methyl and methylthiomethyl; r 3and r 4be independently selected from (a) hydrogen atom, (b) cycloalkyl, (c) cycloalkenyl, (d) heterocyclic radical, (e) aryl and (f)-z-r 14, wherein z is(ii)-c(r 37a)(r 37b)-，(ii)-c(r 47)＝c(r 48)-，(iii)-c≡c-，(iv)-c(＝o)-， (v)-c(＝s)-，(vi)-c(＝nr 15)-，(vii)-c(r 37a)(or 37c)-， (viii)-c(r 37a)(sr 37c)-， (ix)-c(r 37a)(n(r 37b)(r 37c))-，(x)-c(r 37a)(r 37b)-o-， (xi)-c(r 37a)(r 37b)-n(r 37c)-，(xii)-c(r 37a)(r 37b)-n(o)(r 37c)-， (xiii)-c(r 37a)(r 37b)-n(oh)-，(xiv)-c(r 37a)(r 37b)-s-， (xv)-c(r 37a)(r 37b)-s(o)-，(xvi)-c(r 37a)(r 37b)-s(o) 2-， (xviii)-c(r 37a)(r 37b)-c(＝o)-，(xviii)-c(r 37a)(r 37b)-c(＝s)-， (xxi)-c(r 37a)(r 37c)-c(＝nr 15)-，(xx)-c(r 37a)(or 37c)-c(＝o)-， (xxi)-c(r 37a)(sr 37c)-c(＝o)-，(xxii)-c(r 37a)(or 37c)-c(＝s)-， (xxiii)-c(r 37a)(sr 37c)-c(＝s)-，(xxiv)-c(＝o)-c(r 37a)(or 37c)-， (xxv)-c(＝o)-c(r 37a)(sr 37c)-，(xxvi)-c(＝s)-c(r 37a)(or 37c)-， (xxvii)-c(＝s)-c(r 37a)(sr 37c)-，(xxviii)-c(r 37a)(or 37c)-c(r 37a)(or 37c)-， (xxix)-c(r 37a)(sr 37c)-c(r 37a)(or 37c)-， (xxx)-c(r 37a)(or 37c)-c(r 37a)(sr 37c)-， (xxxi)-c(r 37a)(sr 37c)-c(r 37a)(sr 37c)-，(xxxii)-c(＝o)-c(＝o)-， (xxxiii)-c(＝s)-c(＝s)-，(xxxiv)-c(＝o)-o-，(xxxv)-c(＝o)-s-，(xxxvi)-c(＝s)-o-，(xxxvii)-c(＝s)-s-，(xxxviii)-c(＝o)-n(r 37a)-， (xxxix)-c(＝s)-n(r 37a)-，(xl)-c(r 37a)(r 37b)-c(＝o)-n(r 37a)-， (xli)-c(r 37a)(r 37b)-c(＝s)-n(r 37a)-，(xlii)-c(r 37a)(r 37b)-c(＝o)-o-， (xliii)-c(r 37a)(r 37b)-c(＝o)-s-，(xliv)-c(r 37a)(r 37b)-c(＝s)-o-， (xlv)-c(r 37a)(r 37b)-c(＝s)-s-，(xlvi)-c(r 37a)(r 37b)-n(r 37b)-c(＝o)-， (xlvii)-c(r 37a)(r 37b)-n(r 37b))-c(＝s)-，(xlviii)-c(r 37a)(r 37b)-o-c(＝o)-， (xlix)-c(r 37a)(r 37b)-s-c(＝o)-，(l)-c(r 37a)(r 37b)-o-c(＝s)-， (li)-c(r 37a)(r 37b)-s-c(＝s)-，(lii)-c(r 37a)(r 37b)-n(r 37b)-c(＝o)-n(r 37a)-， (liii)-c(r 37a)(r 37b)-n(r 37b)-c(＝s)-n(r 37a)-， (iiv)-c(r 37a)(r 37b)-n(r 37b)-c(＝o)-o-， (lv)-c(r 37a)(r 37b)-n(r 37b)-c(＝o)-s-， (lvi)-c(r 37a)(r 37b)-n(r 37b)-c(＝s)-o-， (lvii)-c(r 37a)(r 37b)-n(r 37b)-c(＝s)-s-， (lviii)-c(r 37a)(r 37b)-o-c(＝o)-n(r 37a)-， (lix)-c(r 37a)(r 37b)-s-c(＝o)-n(r 37a)-， (lx)-c(r 37a)(r 37b)-o-c(＝s)-n(r 37a)-， (lxi)-c(r 37a)(r 37b)-s-c(＝s)-n(r 37a)-，-(lxii)-c(r 37a)(r 37b)-o-c(＝o)-o-， (lxiii)-c(r 37a)(r 37b)-s-c(＝o)-o-，(lxiv)-c(r 37a)(r 37b)-o-c(＝o)-s-， (lxv)-c(r 37a)(r 37b)-s-c(＝o)-s-，(lxvi)-c(r 37a)(r 37b)-o-c(＝s)-o-， (lxvii)-c(r 37a)(r 37b)-s-c(＝s)-o-，(lxviii)-c(r 37a)(r 37b)-o-c(＝s)-s-， (lxix)-c(r 37a)(r 37b)-s-c(＝s)-s-or(lxx)-c(r 37a)(r 37b)-c(r 37a)(or 37c)-； r 14be (i) hydrogen atom, (ii) c 1-c 12alkyl, (iii) haloalkyl, (iv) hydroxyalkyl, (the v) alkyl of sulfydryl-replacement, (vi) r 37cthe alkyl that o-replaces, (vii) r 37cthe alkyl that s-replaces, (viii) aminoalkyl group, (ix) (r 37c) alkyl that replaces of nh-, (x) (r 37a) (r 37c) alkyl that replaces of n-, (xi) r 37athe alkyl that o-(o=) c-replaces, (xii) r 37athe alkyl that s-(o=) c-replaces, (xiii) r 37athe alkyl that o-(s=) c-replaces, (xix) r 37...
뉴라미니다제의 억제제본원에는 질환-유발성 미생물로부터의 뉴라미니다제, 특히 인플루엔자 뉴라미니다제를 억제하는 데 유용한 화학식 I의 화합물이 기재되어 있다. 또한, 본원에는 뉴라미니다제를 갖는 미생물에 의해 유발되는 질환을 예방하고 치료하기 위한 조성물 및 방법, 당해 화합물의 제조방법 및 이러한 방법에 사용되는 합성 중간체도 기재되어 있다. 화학식 I  위의 화학식 I에서, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X 및 Y는 본원에 정의한 바와 같다. 화학식 I의 절대적인 입체화학을 갖는 에난티오머적으로 풍부한 화합물 또는 이의 약제학적으로 허용되는 염, 에스테르 또는 프로드럭. 화학식 I [이미지] 위의 화학식 I에서, R1은 (a) -CO2H, (b) -CH2CO2H, (c) -SO3H, (d) -CH2SO3H, (e) -SO2H, (f) -CH2SO2H, (g) -PO3H2, (h) -CH2PO3H 2, (i) -PO2H, (j) -CH2PO2H, (k) 테트라졸릴, (l) -CH2-테트라졸릴, (m) -C(=O)-NH-S(O)2-R11, (n) -CH2C(=O)-NH-S(O) 2-R11, (o) -SO2N(T-R11)R12 및 (p) -CH2SO2N(T-R11)R 12[여기서, T는 (i) 결합, (ii) -C(=O)-, (iii) -C(=O)O-, (iv) -C(=O)S-, (v) -C(=O)NR36-, (vi) -C(=S)O-, (vii) -C(=S)S- 및 (viii) -C(=S)NR36-으로 이루어진 그룹으로부터 선택되고, R11은 (i) C1-C 12 알킬, (ii) C2-C12 알케닐, (iii) 사이클로알킬, (iv) (사이클로알킬)알킬, (v) (사이클로알킬)알케닐, (vi) 사이클로알케닐, (vii) (사이클로알케닐)알킬, (viii) (사이클로알케닐)알케닐, (ix) 아릴, (x) (아릴)알킬, (xi) (아릴)알케닐, (xii) 헤테로사이클릭, (xiii) (헤테로사이클릭)알킬 및 (xiv) (헤테로사이클릭)알케닐로 이루어진 그룹으로부터 선택되며, R12 및 R36은 독립적으로 (i) 수소, (ii) C1-C 12 알킬, (iii) C2-C12 알케닐, (iv) 사이클로알킬, (v) (사이클로알킬)알킬, (vi) (사이클로알킬)알케닐, (vii) 사이클로알케닐, (viii) (사이클로알케닐)알킬, (ix) (사이클로알케닐)알케닐, (x) 아릴, (xi) (아릴)알킬, (xii) (아릴)알케닐, (xiii) 헤테로사이클릭, (xiv) (헤테로사이클릭)알킬 및 (xv) (헤테로사이클릭)알케닐로 이루어진 그룹으로부터 선택된다]로 이루어진 그룹으로부터 선택되고; X는 (a) -C(=O)-N(R*)-, (b) -N(R*)-C(=O)-, (c) -C(=S)-N(R*)-, (d) -N(R *)-C(=S)-, (e) -N(R*)-SO2- 및 (f) -SO2-N(R*)-(여기서, R* 는 수소, C1-C3 저급 알킬 또는 사이클로프로필이다)로 이루어진 그룹으로부터 선택되며; R2는 (a) 수소, (b) C1-C6 알킬, (c) C2-C6 알케닐, (d) C3-C6 사이클로알킬, (e) C5-C6 사이클로알케닐, (f) 할로 C1-C6 알킬 및 (g) 할로 C2-C6 알케닐로 이루어진 그룹으로부터 선택되거나, R2-X는 [이미지][여기서, Y1은 -CH2-, -O-, -S- 또는 -NH-이고, Y2는 -C(=O)- 또는 -C(Raa)(Rbb)-(여기서, Raa 및 Rbb는 독립적으로 수소, C1-C3 저급 알킬, 하이드록시메틸, 1-하이드록시에틸, 2-하이드록시에틸, 아미노메틸, 1-아미노에틸, 2-아미노에틸, 티올메틸, 1-티올에틸, 2-티올에틸, 메톡시메틸, N-메틸아미노메틸 및 메틸티오메틸로 이루어진 그룹으로부터 선택된다)이다]이고; R3 및 R4는 독립적으로 (a) 수소, (b) 사이클로알킬, (c) 사이클로알케닐, (d) 헤테로사이클릭, (e) 아릴 및 (f) -Z-R14[여기서, Z는 (i) -C(R37a)(R37b)-, (ii) -C(R47)=C(R48)-, (iii) -C≡C-, (iv) -C(=O)-, (v) -C(=S)-, (vi) -C(=NR15)-, (vii) -C(R37a)(OR37c)-, (viii) -C(R37a )(SR37c)-, (ix) -C(R37a)(N(R37b)(R37c))-, (x) -C(R37a)(R37b)-O-, (xi) -C(R37a)(R37b)-N(R37c)-, (xii) -C(R37a)(R37b)-N(O)(R37c)-, (xiii) -C(R37a)(R37b)-N(OH)-, (xiv) -C(R37a)(R37b)-S-, (xv) -C(R37a)(R37b)-S(O)-, (xvi) -C(R37a)(R37b)-S(O)2 -, (xvii) -C(R37a)(R37b)-C(=O)-, (xviii) -C(R37a)(R37b)-C(=S)-, (xix) -C(R37a)(R37b)-C(=NR 15)-, (xx) -C(R37a)(OR37c)-C(=O)-, (xxi) -C(R37a)(SR37c)-C(=O)-, (xxii) -C(R37a)(OR37c)C(=S)-, (xxiii) -C(R37a)(SR37c)-C(=S)-, (xxiv) -C(=O)-C(R37a)(OR37c)-, (xxv) -C(=O)-C(R37a)(SR37c)-, (xxvi) -C(=S)-C(R37a)(OR37c)-, (xxvii) -C(=S)-C(R37a)(SR37c)-, (xxviii) -C(R37a)(OR37c)-C(R37a)(OR37c)-, (xxix) -C(R37a )(SR37c)-C(R37a)(OR37c)-, (xxx) -C(R37a)(OR37c)-C(R37a)(SR37c)-, (xxxi) -C(R37a )(SR37c)-C(R37a)(SR37c)-, (xxxii) -C(=O)-C(=O)-, (xxxiii) -C(=S)-C(=S)-, (xxiv) -C(=O)-O-, (xxxv) -C(=O)-S-, (xxxvi) -C(=S)-O-, (xxxvii) -C(=S)-S-, (xxxviii) -C(=O)-N(R37a)- (xxxix) -C(=S)-N(R37a)-, (xI) -C(R37a)(R37b)-C(=O)-N(R37a)-, (xIi) -C(R37a)(R37b)-C(=S)-N(R37a)-, (xIii) -C(R37a)(R37b)-C(=O)-O-, (xIiii) -C(R37a)(R 37b)-C(=O)-S-, (xIiv) -C(R37a)(R37b)-C(=S)-O-, (xIv) -C(R37a)(R37b)-C(=S)-S-, (xIvi) -C(R37a)(R37b)-N(R37b)-C(=O)-, (xIvii) -C(R37a)(R37b)-N(R37b)-C(=S)-, (xIviii) -C(R37a )(R37b)-O-C(=O)-, (xIix) -C(R37a)(R37b)-S-C(=O)-, (I) -C(R37a)(R37b)-O-C(=S)-, (Ii) -C(R37a)(R37b)-S-C(=S)-, (Iii) -C(R37a)(R37b)-N(R37b)-C(=O)-N(R37a)-, (Iiii) -C(R37a)(R37b)-N(R37b)-C(=S)-N(R37a)-, (Iiv) -C(R37a)(R37b)-N(R37b)-C(=O)-O-, (Iv) -C(R37a)(R37b)-N(R37b)-C(=O)-S-, (Ivi) -C(R37a)(R37b)-N(R37b)-C(=S)-O-, (Ivii) -C(R37a )(R37b)-N(R37b)-C(=S)-S-, (Iviii) -C(R37a)(R37b)-O-C(=O)-N(R37a)-, (Iix) -C(R37a )(R37b)-S-C(=O)-N(R37a)-, (Ix) -C(R37a)(R37b)-O-C(=S)-N(R37a)-, (Ixi) -C(R 37a)(R37b)-S-C(=S)-N(R37a)-, (Ixii) -C(R37a)(R37b)-O-C(=O)-O-, (Ixiii) -C(R37a)(R37b)-S-C(=O)-O-, (Ixiv) -C(R37a)(R37b)-O-C(=O)-S-, (Ixv) -C(R37a)(R37b)-S-C(=O)-S-, (Ixvi) -C(R37a)(R37b)-O-C(=S)-O-, (Ixvii) -C(R37a)(R37b)-S-C(=S)-O-, (Ixviii) -C(R37a)(R37b )-O-C(=S)-S-, (Ixix) -C(R37a)(R37b)-S-C(=S)-S- 또는 (Ixx) -C(R37a)(R37b)-C(R 37a)(OR37c)-이고, R14는 (i) 수소, (ii) C1-C12 알킬, (iii) 할로알킬, (iv) 하이드록시알킬, (v) 티올-치환된 알킬, (vi) R37cO-치환된 알킬, (vii) R37cS-치환된 알킬, (viii) 아미노알킬, (ix) (R37c)NH-치환된 알킬, (x) (R37a)(R37c)N-치환된 알킬, (xi) R37aO-(O=)C-치환된 알킬, (xii) R37aS-(O=)C-치환된 알킬, (xiii) R37aO-(S=)C-치환된 알킬, (xiv) R37aS-(S=)C-치환된 알킬, (xv) (R37aO)2-P(=O)-치환된 알킬, (xvi) 시아노알킬, (xvii) C2-C12 알케닐, (xviii) 할로알케닐, (xix) C2-C12 알키닐, (xx) 사이클로알킬, (xxi) (사이클로알킬)알킬, (xxii) (사이클로알킬)알케닐, (xxiii) (사이클로알킬)알키닐, (xxiv) 사이클로알케닐, (xxv) (사이클로알케닐)알킬, (xxvi)(사이클로알케닐)알케닐, (xxvii) (사이클로알케닐)알키닐, (xxviii) 아릴, (xxix) (아릴)알킬, (xxx) (아릴)알케닐, (xxxi) (아릴)알키닐, (xxxii) 헤테로사이클릭, (xxxiii) (헤테로사이클릭)알킬, (xxxiv) (헤테로사이클릭)알케닐 또는 (xxxv) (헤테로사이클릭)알키닐이며, 단 R14가 수소가 아닌 경우, Z는 -C(R37a)(R37b)-N(R37b)-C(=O)-O-, -C(R37a)(R37b)-N(R37b)-C(=S)-O-, -C(R37a)(R37b)-N(R 37b)-C(=O)-S-, -C(R37a)(R37b)-N(R37b)-C(=S)-S-, -C(R37a)(R37b)-O-C(=O)-O-, -C(R37a)(R37b)-O-C(=S)-O-, -C(R37a)(R37b)-S-C(=O)-O-, -C(R37a)(R37b)-S-C(=S)-O-, -C(R37a)(R37b)-O-C(=O)-S-, -C(R37a)(R37b)-O-C(=S)-S-, -C(R37a)(R37b)-S-C(=O)-S- 또는 -C(R37a)(R37b)-S-C(=S)-S-이고, R37a, R37b, R47 및 R48은 각각 독립적으로 (i) 수소, (ii) C1-C12 알킬, (iii) 할로알킬, (iv) 하이드록시알킬, (v) 알콕시알킬, (v...