Oxadiazolo[3,2-a]pyrimidines and thiadiazolo[3,2-a]pyrimidines

摘要

The present invention relates to compounds of formula P-1 and related compounds and compositions useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The definitions of A, Y, R1, R2, Ra, Ra′, Rb, Rb′, Rc, Rc′, Rd, Rd′, Re, and Re′ are provided herein. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.;

主权项

1. A compound of Formula P-I:wherein:
i) A is S, N(H), CH2, or O; ii) R1 is:
phenyl optionally substituted with one or more nitro, —C(O)N(R5)(R6) and/or —N(R5)(R6) and Y is a —C1-C4alkylene (e.g., methylene) or arylene;phenyl substituted with one or more nitro and/or —N(R5)(R6) and Y is a single bond;phenyl substituted with —C(O)OR3 and Y is a —C1-C4alkylene or arylene;heteroaryl wherein said heteroaryl group is optionally substituted with one or more —C1-C4alkyl and Y is a single bond, or —C1-C4alkylene;heteroaryl wherein said heteroaryl group is substituted with halo, C(O)OH, —CH2C(O)OH, or —NH2, and Y is arylene;pyrazolyl, isoxazolyl, furyl or thienyl and Y is arylene wherein said pyrazolyl, isoxazolyl, furyl or thienyl is optionally substituted with one or more —C1-C4alkyl, C0-4alkyl-C(O)OH, —N(R13)(R14), or halo; or—C(O)N(R4)(CH2)1-4—C(O)OR3 and Y is a single bond, —C1-C4alkylene or arylene;—C(O)N(R4)(CH2)1-4—N(R13)(R14) and Y is a single bond, —C1-C4alkylene or arylene;—N(R4)—C(O)-heteroaryl wherein said heteroaryl is optionally substituted with halo and Y is a single bond, —C1-C4alkylene or arylene;—N(R4)—C1-4alkylene-heteroaryl and Y is a single bond, —C1-C4alkylene or arylene;—N(R10)—C(O)—[C(R11)(R12)]1-4—N(R13)(R14), and Y is a single bond, —C1-C4alkylene or arylene;—N(R4)(CH2)1-4—C(O)OR4 and Y is arylene;—N(R4)C(O)C(H)(NH2)CH2CH2—C(O)OR3 and Y is arylene;—N(R4)C(O)C(H)(NH2)CH2-heteroaryl) and Y is arylene;—N(R4)C(O)C(H)(CH3)—NH2 and Y is arylene;—N(R4)C(O)CH2CH2C(H)(NH2)—COOH and Y is arylene;—N(R4)C(O)—C(H)(NH2)CH2CH2—COOH and Y is arylene; or—N(R4)C(O)-heteroaryl (—N(H)C(O)isoxazolyl) and Y is arylene; iii) R2 is H, halo or C1-C4alkyl; iv) Ra, Ra′, Rb, Rb′, Rc, Rd, Rd′, Re, and Re′ are independently H or C1-C4alkyl; V) R3, R4, R5 and R6 are independently H or C1-C4alkyl; vi) R10, R11, R12R13 and R14 are independently H or C1-4alkyl, in free or salt form.