Claims
- 1. A compound of formula I (or a pharmaceutically acceptable salt thereof) wherein:A3, A4, A5 and A6, together with the two carbons to which they are attached, complete a substituted benzene in which A3 is CR3, A4 is CR4, A5 is CR5, and A6 is CR6; whereinR3 is hydrogen; one of R4 and R5 is hydrogen, methyl, fluoro, chloro, RfO2C—, or RgNH—; the other of R4 and R5 is hydrogen; and R6 is hydrogen; in which Rf is hydrogen, (1-4C)alkyl or benzyl; Rg is hydrogen, or RhSO2—; and Rh is (1-4C)alkyl or dimethylamino; L1 is —NH—CO—, —CO—NH— or —CH2—NH— such that —L1—Q1 is —NH—CO—Q1 —CO—NH—Q1 or —CH2—NH—Q1; Q1 is 2-pyridyl-, the 2-pyridyl may bear an amino substituent at the 6-position; and R2 is —NH—CH2—Q2 in which Q2 is Q2A wherein Q2A (showing the —CH2— to which it is attached) is in whichR2A is hydrogen, t-butyl, methylsulfonyl, or —CHRWRX wherein each of RW and RX independently is hydrogen or (1-3C) normal alkyl.
- 2. The compound of claim 1 wherein (1-3C) normal alkyl is methyl, ethyl or propyl; and (1-4C)alkyl is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or t-butyl.
- 3. The compound as claimed in claim 2 wherein Q1 is 2-pyridinyl.
- 4. The compound as claimed in claim 2 wherein R2 is (1-isopropylpiperidin-4-ylmethyl)amino.
- 5. The compound as claimed in any one of claims 1-4 wherein each of R3-R6 is hydrogen, or each of R3, R4 and R6 is hydrogen and R5 is chloro.
- 6. The compound as claimed in any one of claims 1-4 wherein —L1—Q1 is —CO—NH—Q1.
- 7. The pharmaceutically acceptable salt of a compound of formula I as claimed in claim 1 which is an acid-addition salt made from a basic compound of formula I and an acid which provides a pharmaceutically acceptable anion or a salt which is made from an acidic compound of formula I and a base which provides a pharmaceutically acceptable cation.
- 8. A pharmaceutical formulation comprising in association with a pharmaceutically acceptable carrier, diluent or excipient, a novel compound of formula I (or a pharmaceutically acceptable salt thereof) as provided in claim 1.
- 9. A process for preparing a compound of formula I (or a pharmaceutically acceptable salt thereof) as provided in claim 1 which is selected from(A) for a compound of formula I in which —L1—Q1 is —NH—CO—Q1, acylating an amine of formula II, using a corresponding acid of formula HO—CO—Q1, or an activated derivative thereof;(B) for a compound of formula I in which —L1—Q1 is —CO—NH—Q1, substituting the group Ya of a compound of formula III in which Ya is a conventional leaving gruop for nucleophilic aromatic substitution with an amine of formula NH2—CH2—Q2;(C) for a compound of formula I in which —L1—Q1 is —CO—NH—Q1, acylating an amine of formula H2N—Q1, or a deprotonated derivative thereof, using an acid of formula IV, or an activated derivative thereof; (D) alkylating an amine of formula V directly, using a compound of formula Y—CH2—Q2, or indirectly by reductive alkylation using an aldehyde of formula Q2—CHO;(E) for a compound of formula I in which —L1—Q1 is —CH2—NH—Q1, reducing a corresponding compound of formula I in which —L1—Q1 is —CO—NH—Q1; (F) for a compound of formula I in which R2A is methylsulfonyl, substituting the amino nitrogen of a corresponding compound of formula I in which R2A is hydrogen using an activated derivative of methanesulfonic acid; (G) for a compound of formula I in which R2A is or —CHRWRX, alkylating the amino nitrogen of a corresponding compound of formula I in which R2A is hydrogen using an alkylating agent of formula Y—CHRWRX or reductively alkylating the amine using a compound of formula RW—CO—RX; (S) for a compound of formula I in which R4 or R5 is amino, reducing the nitro group of a compound corresponding to a compound of formula I but in which R4 or R5 is nitro; and (T) for a compound of formula I in which R4 or R5 is RgNH— and Rg is RhSO2—, substituting the amino group of a corresponding compound of formula I in which R4 or R5 is amino using an activated derivative of the sulfonic acid RhSO2—OH; whereafter, for any of the above procedures, when a functional group is protected using a protecting group, removing the protecting group; whereafter, for any of the above procedures, when a pharmaceutically acceptable salt of a compound of formula I is required, it is obtained by reacting the basic form of a basic compound of formula I with an acid affording a physiologically acceptable counterion or the acidic form of an acidic compound of formula I with a base affording a physiologically acceptable counterion or by any other conventional procedure; and wherein, unless otherwise specified, A3-A6, L1, Q1 and R2 have any of the values defined in claim 1.
- 10. A method of inhibiting factor Xa comprising administering to a mammal in need of treatment, a compound of formula I as provided in claim 1.
- 11. The compound as claimed in claim 5 wherein —L1—Q1 is —CO—NH—Q1.
Parent Case Info
This application is a divisional of copending application Ser. No. 09/857,747, filed Jun. 8, 2001, now U.S. Pat. No. 6,610,704 B1, the national stage application of PCT/US99/29832, filed Dec. 15, 1999 and claims the benefit of U.S. Provisional Application No. 60/113,778, filed Dec. 23, 1998.
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