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US 11,724,995 B2Granted
Decalin derivatives, a process for the preparation and pharmaceutical composition thereof
AssigneeCouncil of Scientific and Industrial Research
InventorsDumbala Srinivasa Reddy, Kiran Ashok Kulkarni, Hanuman Popat Kalmode, Paresh Ramesh Athawale, Suhag Sanjay Patil, Raveena Vijay Rajput, Yash Jignasu Mankad, Namrata Nandkishor Patil
Life of this patent
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Abstract
Decalin derivative compounds of formula (I) are provided, including processes for preparation thereof, and pharmaceutical compositions including the decalin derivative compounds. Methods are provided for treating blood related disorders, such as sickle cell anemia, in a subject in need thereof using a compound of formula (I).
Claims7
A process for preparing a decalin derivative compound of formula (A8):
- where:
- R1, R2, R4, and R5, are independently chosen from:
- hydrogen;
- or
- unsubstituted C1-C10 alkyl or substituted C1-C10 alkyl;
- or
- unsubstituted C2-C10 alkenyl or C2-C10 alkenyl substituted with hydroxy, alkoxy, ester, or —OTBS;
- or
- amino, halo, hydroxyl, carbonyl, thiocarbonyl, carboxylate, alkoxy, carbamide, carbamate, or hydrazine,
- the process comprising:
- (a) protecting and following allylic oxidation of a compound according to formula (A5):
- where R6 is hydrogen, to afford a compound according to formula (A6):
- (b) epoxidating and deprotecting the compound according to formula (A6) to afford a compound according to formula (A7):
- and
- (c) reducing the compound according to formula (A7) to afford the compound according to formula (A8),
- wherein:
- R1, R2, R4, and R5 in formulas (A5), (A6), (A7) are as defined in the compound of formula (A8);
- and
- Pg in the compounds of formulas (A6) and (A7) is a protecting group.
16 more elements
A process for the preparation of a decalin derivative compound of formula (A13):
- where:
- R1, R2, R4, R5, R7, and R9 are independently chosen from:
- hydrogen;
- or
- unsubstituted C1-C10 alkyl or substituted C1-C10 alkyl;
- or
- unsubstituted C2-C10 alkenyl or C2-C10 alkenyl substituted with hydroxy, alkoxy, ester, or —OTBS;
- or
- amino, halo, hydroxyl, carbonyl, thiocarbonyl, carboxylate, alkoxy, carbamide, carbamate, or hydrazine,
- or wherein R1, R2, R4, R5, R7, and R9 may be joined to form an unsubstituted or substituted fused cyclic ring, and
- represents a single or double bond, the process comprising:
- (a) halogenating a compound according to formula (A9):
- to afford a compound according to formula (A10):
- where X is a halogen;
- (b) performing Suzuki Coupling on the compound according to formula (A10) in the presence of a compound according to formula (X):
- to afford a compound according to formula (A11):
- (c) forming an epoxide on the compound according to formula (A11) to afford a compound according to formula (Al2):
- and
- (d) reducing the compound according to formula (Al2) to afford the compound according to formula (A13),
- wherein:
- R1, R2, R4, R5, R7, and R9 in of formulas (A9), (A10), (X), (A11), (Al2) are as defined in formula (A13).
18 more elements
A process for preparing a decalin derivative compound of formula (A21):
- where:
- R1, R2, R4, R5, R7, and R10 are independently chosen from:
- hydrogen;
- or
- unsubstituted C1-C10 alkyl or substituted C1-C10 alkyl;
- or
- unsubstituted C2-C10 alkenyl or C2-C10 alkenyl substituted with hydroxy, alkoxy, ester, or —OTBS;
- or
- amino, halo, hydroxyl, carbonyl, thiocarbonyl, carboxylate, alkoxy, carbamide, carbamate, or hydrazine, and
- wherein any of R1, R2, R4, R5, R7, or R10 may be joined to form an unsubstituted or substituted fused cyclic ring,
- the process comprising:
- (a) undergoing ozonolysis on a compound according to formula (A14):
- to afford a compound according to formula (A15):
- (b) rearranging the compound according to formula (A15) to afford a compound according to formula (A16):
- (c) reducing and protecting the compound according to formula (A16) to afford a compound according to formula (A17):
- where R9 is independently chosen from:
- hydrogen;
- or
- unsubstituted C1-C10 alkyl or substituted C1-C10 alkyl;
- or
- unsubstituted C2-C10 alkenyl or C2-C10 alkenyl substituted with hydroxy, alkoxy, ester, or —OTBS, or
- amino, halo, hydroxyl, carbonyl, thiocarbonyl, carboxylate, alkoxy, carbamide, carbamate, or hydrazine;
- (d) epoxidating and reducing the compound according to formula (A17) to afford a compound according to formula (A18):
- (e) oxidating, deprotecting, and rearranging the compound according to formula (A18), to afford a compound according to formula (A19):
- hydrogenating the compound according to formula (A19) to afford a compound according to formula (A20):
- and
- (g) oxidating the compound according to formula (A20) to afford the compound according to formula (A21),
- wherein:
- R1, R2, R4, R5, R7, and R10 in the compounds of formulas (A14), (A15), (A16), (A17), (A18), (A19), and (A20), are as defined in the compound of formula (A21);
- and
- TBS in formulas (A17) and (A18) is tert-butyldimethylsilyl.
28 more elements
A process for preparing a decalin derivative compound of formula (A23) or formula (A25):
- where:
- R′, R2, R4, R5, R7, and R10 are independently chosen from:
- hydrogen;
- or
- unsubstituted C1-C10 alkyl or substituted C1-C10 alkyl;
- or
- unsubstituted C2 -C10 alkenyl or C2-C10 alkenyl substituted with hydroxy, alkoxy, ester, or —OTBS;
- or
- amino, halo, hydroxyl, carbonyl, thiocarbonyl, carboxylate, alkoxy, carbamide, carbamate, or hydrazine,
- wherein any of R1, R2, R4, R5, R7, and R10 may be joined to form an unsubstituted or substituted fused cyclic ring,
- the process comprising:
- dihydroxylating a compound according to formula (A22):
- wherein R6 is hydrogen and wherein R1, R2, R4, R5, R7, and R10 in formula (A22) are as defined in the compound according to formula (A23) to afford the compound according to formula (A23);
- or
- dihydroxylating a compound according to formula (A24):
- wherein R6 is hydrogen and wherein R1, R2, R4, R5, R7, and R10 in formula (A24) are as defined in the compound according to formula (A25) to afford the compound according to formula (A25).
13 more elements
Dependencies are inferred from the claim text.