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US 7,256,178 B2Granted
Physiologically active substances
AssigneesEisai Co., Ltd., Mercian Corporation
InventorsYoshihiko Kotake, Jun Niijima, Yoshio Fukuda, Mitsuo Nagai, Regina Mikie Kanada, Susumu Takeda, Takashi Nakashima, Masashi Yoshida, Toshio Tsuchida, Tomohiro Sameshima
Life of this patent
Estimating the term…
Abstract
Compounds represented by the following general formula (I), pharmacologically acceptable salts thereof or hydrates of the same: (I) wherein W represents and R3, R7, R16, R17, R20, R21 and R21′ are the same or different and each represents hydrogen, etc. Because of inhibiting angiogenesis and inhibiting the production of VEGF particularly in hypoxia, the compounds (I) are useful as remedies for solid cancer.
Claims39
A compound represented by the formula (I):
- wherein W represents
- and R3, R7, R16, R17, R20, R21 and R21′, the same or different, independently represent
- 1) a hydrogen atom,
- 2) a hydroxyl group or oxo group, provided that the oxo group is limited to an oxo group formed by R3 or R7 in combination with a carbon atom to which R3 or R7 is bonded, and an oxo group formed by R21 and R21′ together in combination with the carbon atom to which R21 and R21′ are bonded,
- 3) a C1 to C22 alkoxy group which may have a substituent,
- 4) an unsaturated C2 to C22 alkoxy group which may have a substituent,
- 5) a C7 to C22 aralkyloxy group which may have a substituent,
- 6) a 5-membered to 14-membered heteroaralkyloxy group which may have a substituent,
- 7) RC(═Y)—O—, wherein Y represents an oxygen atom or sulfur atom, and R represents
- a) a hydrogen atom,
- b) a C1 to C22 alkyl group which may have a substituent,
- c) an unsaturated C2 to C22 alkyl group which may have a substituent,
- d) a C6 to C14 aryl group which may have a substituent,
- e) a 5-membered to 14-membered heteroaryl group which may have a substituent,
- f) a C7 to C22 aralkyl group which may have a substituent,
- g) a 5-membered to 14-membered heteroaralkyl group which may have a substituent,
- h) a C1 to C22 alkoxy group which may have a substituent,
- i) an unsaturated C2 to C22 alkoxy group which may have a substituent,
- j) a C6 to C14 aryloxy group which may have a substituent,
- k) a C3 to C14 cycloalkyl group which may have a substituent,
- l) a 3-membered to 14-membered non-aromatic heterocyclic group which may have a substituent or
- m) a 5-membered to 14-membered heteroaryloxy group which may have a substituent,
- 8) RS1RS2RS3SiO—, wherein RS1, RS2 and RS3, the same or different, independently represent
- a) a C1 to C6 alkyl group or
- b) a C6 to C14 aryl group,
- 9) a halogen atom,
- 10) RN1RN2N—RM—, wherein RM represents
- a) a single bond,
- b) —CO—O—,
- c) —SO2—O—,
- d) —CS—O— or
- e) —CO—NRN3—, wherein RN3 represents a hydrogen atom or a C1 to C6 alkyl group which may have a substituent, provided that, the leftmost bond in b) to e) is bonded to the nitrogen atom,
- RN1 and RN2, the same or different, independently represent
- a) a hydrogen atom,
- b) a C1 to C22 alkyl group which may have a substituent,
- c) an unsaturated C2 to C22 alkyl group which may have a substituent,
- d) an aliphatic C2 to C22 acyl group which may have a substituent,
- e) an aromatic C7 to C15 acyl group which may have a substituent,
- f) a C6 to C14 aryl group which may have a substituent,
- g) a 5-membered to 14-membered heteroaryl group which may have a substituent,
- h) a C7 to C22 aralkyl group which may have a substituent,
- i) a C1 to C22 alkylsulfonyl group which may have a substituent,
- j) a C6 to C14 arylsulfonyl group which may have a substituent,
- k) a 3-membered to 14-membered non-aromatic heterocyclic group formed by RN1 and RN2 together in combination with the nitrogen atom to which RN1 and RN2 are bonded, wherein the 3-membered to 14-membered non-aromatic heterocyclic group may have a substituent,
- l) a 5-membered to 14-membered heteroaralkyl group which may have a substituent,
- m) a C3 to C14 cycloalkyl group which may have a substituent or
- n) a 3-membered to 14-membered non-aromatic heterocyclic group which may have a substituent,
- 11) RN4SO2—O—, wherein RN4 represents
- a) a C1 to C22 alkyl group which may have a substituent,
- b) a C6 to C14 aryl group which may have a substituent,
- c) a C1 to C22 alkoxy group which may have a substituent,
- d) an unsaturated C2 to C22 alkoxy group which may have a substituent,
- e) a C6 to C14 aryloxy group which may have a substituent,
- f) a 5-membered to 14-membered heteroaryloxy group which may have a substituent,
- g) a C7 to C22 aralkyloxy group which may have a substituent or
- h) a 5-membered to 14-membered heteroaralkyloxy group which may have a substituent,
- 12) (RN5O)2PO—O—, wherein RN5 represents
- a) a C1 to C22 alkyl group which may have a substituent,
- b) an unsaturated C2 to C22 alkyl group which may have a substituent,
- c) a C6 to C14 aryl group which may have a substituent,
- d) a 5-membered to 14-membered heteroaryl group which may have a substituent,
- e) a C7 to C22 aralkyl group which may have a substituent or
- f) a 5-membered to 14-membered heteroaralkyl group which may have a substituent,
- 13) (RN1RN2N)2PO—O—, wherein RN1 and RN2 are the same as defined above or
- 14) (RN1RN2N)(RN5O)PO—O—, wherein RN1, RN2 and RN5 are the same as defined above;
- or a pharmacologically acceptable salt thereof.
63 more elements
A method for producing a chemical compound, comprising:
- culturing a microorganism belonging to the genus Streptomyces, which is capable of producing a compound of the following chemical formula (I):
- wherein [1] W is
- R3 and R2 are a hydroxyl group, R7 is an acetoxy group, and R16, R17, R20 and R21′ are a hydrogen atom or
- [2] W is
- R3 and R21 are a hydroxyl group, R7 is an acetoxy group, and R16, R17, R20 and R21′ are a hydrogen atom;
- and collecting the compound as defined in [1] or [2] from the culture.
3 more elements
Streptomyces sp. strain A-1543 (FERM BP-8442).
A method for producing a chemical compound by bioconversion with a microorganism of a compound of the following chemical formula (I):
- wherein [1] W is
- R3 and R21 are a hydroxyl group, R7 is an acetoxy group, and R16, R17, R20 and R21′ are a hydrogen atom into a compound of the above formula (I), wherein
- [3] W is
- R3, R16 and R21 are a hydroxyl group, R7 is an acetoxy group, and R17, R20 and R21′ are a hydrogen atom,
- [4] W is
- R21 and R21 form an oxo group together with the carbon atom to which R21 and R21′ are bonded,
- R3, R16 and R20 are a hydroxyl group, R7 is an acetoxy group, and R17 is a hydrogen atom,
- [5] W is
- R3, R16, R20 and R12 are a hydroxyl group, R7 is an acetoxy group, and R17 and R21′ are a hydrogen atom,
- [6] W is
- R3, R7, R16 and R21 are a hydroxyl group, and R17, R20 and R21′ are a hydrogen atom,
- [7] W is
- R3, R17, R16 and R21 are a hydroxyl group, R7 is an acetoxy group, and R20 and R21′ are a hydrogen atom or
- [8] W is
- R21 and R21′ form an oxo group together with the carbon atom to which R21 and R21′ are bonded, R3 and R16 are a hydroxyl group, R7is an acetoxy group, and R17 and R20 are a hydrogen atom comprising:
- 1) a step of incubating a compound of the above formula (I) in the presence of a culture solution of a strain selected from microorganisms belonging to bacteria or a product prepared from culture cells of the strain, and
- 2) collecting the resulting compound from the incubated solution.
14 more elements
Strain A-1544 (FERM BP-8446) or strain A-1545 (FERM BP-8447).
Dependencies are inferred from the claim text.