wherein

A is a bivalent radical selected from the group consisting of —C(O)—, —C(O)NH—, —NHC(O)—, —N(R⁷)—CH₂—, —CH₂—N(R⁷)—, —CH(NR⁸R⁹)— and —C(═NR¹⁰)—;

R¹ is —O(CH₂)_dXR¹¹;

R² is hydrogen or a hydroxyl protecting group;

R³ is hydrogen, C_1-4alkyl, or C_3-6alkenyl optionally substituted by 9 to 10 membered fused bicyclic heteroaryl;

R⁴ is hydroxyl, C_2-6alkenyloxy optionally substituted by 9 to 10 membered fused bicyclic heteroaryl, or C_1-6alkoxy optionally substituted by C_1-6alkoxy or —O(CH₂)_eNR⁷R¹²,

R⁵ is hydroxyl, or

R⁴ and R⁵ taken together with the intervening atoms form a cyclic group having the following structure:

R⁶ is hydrogen or fluorine;

R⁷ is hydrogen or C_1-6alkyl;

R⁸ and R⁹ are each independently hydrogen, C_1-6alkyl, —C(═NR¹⁰)NR¹⁴R¹⁵ or —C(O)R¹⁴, or R⁸ and R⁹ together form ═CH(CR¹⁴R¹⁵)_faryl, ═CH(CR¹⁴R¹⁵)_fheterocyclyl, ═CR¹⁴R¹⁵ or ═C(R¹⁴)C(O)OR¹⁴, wherein the alkyl, aryl and heterocyclyl groups are optionally substituted by up to three groups independently selected from R¹⁶;

R¹⁰ is —OR¹⁷, C_1-6alkyl, —(CH₂)_garyl, —(CH₂)_gheterocyclyl or —(CH₂)_hO(CH₂)_iOR⁷, wherein each R¹⁰ group is optionally substituted by up to three groups independently selected from the group consisting of R¹⁶;

R¹¹ is a heterocyclic group having the following structure:

R¹² is hydrogen or C_1-6alkyl;

R¹³ is hydrogen or C_1-4alkyl substituted by a group selected from the group consisting of optionally substituted phenyl, optionally substituted 5 or 6 membered heteroaryl and optionally substituted 9 to 10 membered fused bicyclic heteroaryl;

R¹⁴ and R¹⁵ are each independently hydrogen or C_1-6alkyl;

R¹⁶ is halogen, cyano, nitro, trifluoromethyl, azido, —C(O)R²¹, —C(O)OR²¹, —OC(O)R²¹, —OC(O)OR²¹, —NR²²C(O)R²³, —C(O)NR²²R²³, —NR²²R²³, hydroxyl, C_1-6alkyl, —S(O)_kC_1-6alkyl, C_1-6alkoxy, —(CH₂)_maryl or —(CH₂)_mheteroaryl, wherein the alkoxy group is optionally substituted by up to three groups independently selected from the group consisting of —NR¹⁴R¹⁵, halogen and —OR¹⁴, and the aryl and heteroaryl groups are optionally substituted by up to five groups independently selected from the group consisting of halogen, cyano, nitro, trifluoromethyl, azido, —C(O)R²⁴, —C(O)OR²⁴, —OC(O)OR²⁴, —NR²⁵ C(O)R²⁶, —C(O)NR²⁵R²⁶, —NR²⁵R²⁶, hydroxyl, C_1-6alkyl and C_1-6alkoxy;

R¹⁷ is hydrogen, C_1-6alkyl, C_3-7cycloalkyl, C_3-6alkenyl or a 5 or 6 membered heterocyclic group, wherein the alkyl, cycloalkyl, alkenyl and heterocyclic groups are optionally substituted by up to three substituents independently selected from the group consisting of optionally substituted 5 or 6 membered heterocyclic group, optionally substituted 5 or 6 membered heteroaryl, —OR²⁷, —S(O)_nR²⁷, —NR²⁷R²⁸, —CONR²⁷R²⁸, halogen and cyano;

R¹⁸ is hydrogen, —C(O)OR²⁹, —C(O)NHR²⁹, —C(O)CH₂NO₂, or —C(O)CH₂SO₂R⁷;

R¹⁹ is hydrogen; C_1-4alkyl optionally substituted by hydroxyl, cyano, C_1-4alkoxy, NH₂, —NH(C_1-4alkyl) or —N(C_1-4alkyl)₂; C_2-4alkenyl optionally substituted by hydroxyl, cyano, C_1-4alkoxy, NH₂, —NH(C_1-4alkyl) or —N(C_1-4alkyl)₂; C_1-4alkoxy; C_3-7cycloalkyl; —NH₂; —NH(C_1-4alkyl); —N(C_1-4alkyl)₂; (C_1-4alkyl)OC(O)N(C_1-4alkyl); or optionally substituted phenyl or benzyl;

R²⁰ is halogen, C_1-4alkyl, C_1-4thioalkyl, C_1-4alkoxy, —NH₂, —NH(C_1-4alkyl) or —N(C_1-4alkyl)₂;

R²¹ is hydrogen, C_1-10alkyl, —(CH₂)_paryl or —(CH₂)_pheteroaryl;

R²² and R²³ are each independently hydrogen, —OR¹⁴, C_1-6alkyl, —(CH₂)_qaryl or —(CH₂)_qheterocyclyl;

R²⁴ is hydrogen, C_1-10alkyl, —(CH₂)_raryl or —(CH₂)_rheteroaryl;

R²⁵ and R²⁶ are each independently hydrogen, —OR¹⁴, C_1-6alkyl, —(CH₂)_saryl or —(CH₂)_sheterocyclyl;

R²⁷ and R²⁸ are each independently hydrogen, C_1-4alkyl or C_1-4alkoxyC_1-4alkyl;

R²⁹ is hydrogen or C_1-6alkyl optionally substituted by up to three groups independently selected from the group consisting of halogen, C_1-4alkoxy, —OC(O)C_1-6alkyl and —OC(O)OC_1-6alkyl, or —(CH₂)_qheterocyclyl, —(CH₂)_qheteroaryl, —(CH₂)_qaryl, —(CH₂)_qC_3-7cycloalkyl;

R³⁰ is hydrogen, C_1-4alkyl, C_3-7cycloalkyl, optionally substituted phenyl or benzyl, acetyl or benzoyl;

R³¹ is hydrogen or R²⁰, or R³¹ and R¹⁹ are linked to form the bivalent radical selected from the group consisting of —O(CH₂)₂—,

—(CH₂)_t—, —NR⁷(CH₂)_a—, —OCH₂NR⁷—, —SCH₂NR⁷—, —CH₂NR⁷CH²—, —CH₂OCH₂—, —CH₂SCH₂, and —(CH₂)_aNR⁷—;

R³² is hydrogen, or R³² and R¹⁹ are linked to form the bivalent radical selected from the group consisting of —S(CH₂)_b—, —N(R⁷)(CH₂)_b—, and —O(CH₂)_b—;

R³³ is C_1-8alkyl, C_2-6alkenyl or C_2-6alkynyl;

X is —U(CH₂)_vB(CH₂)_vD-, —U(CH₂)_vB—R³³—, —U(CH₂)_vB(CH₂)_vD(CH₂)_vE-, or —U(CH₂)_vB(CH₂)_vD-R³³—

or X is a group selected from the group consisting of:

U, B, D and E are independently divalent radicals selected from —N(R³⁰)—, —O—, —S(O)_z—, —N(R³⁰)C(O)—, —C(O)N(R³⁰)— and —N[C(O)R³⁰]—;

W is —C(R³¹)— or —N—;

a is 1 or 2

b is an integer from 1 to 3;

d is an integer from 2 to 6;

e is an integer from 2 to 4;

f, g, h, m, p, q, r and s are each independently integers from 0 to 4;

i is an integer from 1 to 6;

j, k, n and z are each independently integers from 0 to 2;

t is 2 or 3;

v is an integer independently selected for each occurrence from 1 to 8;

or a pharmaceutically acceptable salt thereof.